10-year-old's condition stable at follow-up after 10 months Plasma exchange therapy followed by treatment with Soliris (eculizumab) was effective at managing atypical hemolytic uremic syndrome (aHUS) in a boy in China The case was described in the report, “Plasma exchange combined with eculizumab in the management of atypical hemolytic uremic in pediatric patients: A case report,” which was published in Medicine aHUS is a rare disorder in which part of the immune system called the complement cascade becomes abnormally activated leading to the formation of blood clots in small blood vessels that can restrict or block blood flow to internal organs Soliris is a widely approved aHUS treatment that works by blocking the activation of the complement cascade Plasma exchange aims to replace a patient’s plasma to remove components of the complement cascade that are driving the disease Plasma exchange has historically been a key tool for managing aHUS While complement-blocking therapies like Soliris are now generally regarded as the best available treatment especially if these medications aren’t immediately accessible The researchers in China described the case of a 10-year-old boy who was brought to their hospital with symptoms that included weakness and jaundice (yellowing of the skin and eyes) Tests revealed that the boy had hemolytic anemia (low red blood cell counts driven by the destruction of these cells) thrombocytopenia (a low number of platelets which are cell fragments involved in clotting) and kidney damage are a telltale characteristic of aHUS When the boy was diagnosed with aHUS in early 2023, Soliris had only been approved in China for a couple of months The boy initially underwent three rounds of treatment with plasma exchange he started treatment with the therapy according to standard protocols for three months his condition stabilized and lab tests showed resolution of hemolytic anemia and thrombocytopenia The boy has shown no further signs of aHUS-related medical problems for nearly a year after stopping Soliris “The patient successfully completed a 3-month treatment regimen with [Soliris] and has been followed up for an additional 10 months without any recurrence of the condition demonstrating favorable treatment outcomes,” the researchers wrote noting that the report shows it’s possible for children with aHUS given both plasma exchange and Soliris to achieve favorable outcomes Soliris is sold by Alexion, AstraZeneca Rare Disease This site is strictly a news and information website about the disease This content is not intended to be a substitute for professional medical advice Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition Never disregard professional medical advice or delay in seeking it because of something you have read on this website Metrics details Atypical haemolytic uremic syndrome (aHUS) is a rare disorder characterised by complement-mediated thrombotic microangiopathy (TMA) the diagnosis and treatment of aHUS in its early stages remains challenging This study examined the annual trends in aHUS clinical practices in Japan and explored factors influencing early diagnosis and treatment Using data from the 2011–2020 Diagnosis Procedure Combination database 3096 cases with the HUS disease code were identified of which 217 were confirmed as aHUS and treated with eculizumab or plasma exchange defined as starting eculizumab or plasma exchange within 7 days of admission Our study revealed no significant changes over time in the number of aHUS diagnoses Early initiation cases underwent haemodialysis earlier and had ADAMTS13 activity measured earlier and lower hospitalisation costs than late initiation cases we found no increase in the number of newly diagnosed aHUS cases or early treatment initiation over time Early recognition of TMA and differentiation of the causative disease are crucial for identifying potential aHUS cases which may lead to better patient prognoses half of the patients with a clinical diagnosis of aHUS do not have complement-related genetic abnormalities despite the turnaround time of the genetic tests While some tests to prove complement activation have been reported none of the currently available tests are highly specific or sensitive although disease-specific treatment with anti-complement drugs has been developed the diagnostic methods have not been refined While the registry data showed detailed genetic variations it did not provide information regarding changes in clinical practices or medical costs that would allow a thorough understanding of practice patterns over time and the current difficulties clinicians face in early case identification and treatment initiation clinicians in Japan face challenges to make clinical decisions as they do not have complete access to epidemiological data Data from a Japanese epidemiological study show that 74% of aHUS patients were treated with PE; however the reason for this high percentage of PE use is unclear and the effectiveness of PE as a treatment is not mentioned the role of PE in the process from the diagnosis of TMA to the definitive diagnosis of aHUS cannot be ignored The database contains information on the patient's age information such as whether a test was ordered and the date of the test can be acquired although specific test results cannot be obtained Since 90% of tertiary emergency hospitals in Japan participate in the DPC this database can possibly be used to collect data suitable for epidemiological studies of serious and rare diseases we aimed to depict the annual trends in the number of newly diagnosed aHUS cases to clarify the clinical practices for aHUS in Japan and to identify the factors that could contribute to early treatment initiation using DPC data The findings of this study would shed light on the changes in practice patterns before and after the publication of the guidelines and the status of PE treatment in the post-Ecu era The aHUS group was defined as a group of cases in which the disease name "aHUS" was described and the patients were treated with PE or Ecu we compared the characteristics of aHUS group patients with those of unspecified HUS group patients (Analysis A) we compared the characteristics between those who were treated early (the early initiation group) and those who were treated late (the late initiation group) (Analysis B) the Ecu-first group (patients whose treatment was initiated with eculizumab) and PE-first group (those whose treatment was initiated with PE) were compared (Analysis C) A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity was measured more frequently in the aHUS group than in the unspecified HUS group (22.1% vs the aHUS group had more patients who underwent blood purification (60.4% vs P < 0.001) and had hypertension (27.2% vs patients in the aHUS group had longer hospital stays (44 vs and more readmissions than those in the unspecified HUS group (48.8% vs Of the 106 readmissions that were treated with any therapy Eight patients were diagnosed with aHUS between 2011 and 2013, before the implementation of insurance coverage for Ecu. The number of patients with aHUS notably increased to 31 in 2014, but the annual number of aHUS patients did not change significantly between 2014 and 2019 (Table 2) No significant annual trend was observed in terms of the ratio of early vs as well as between Ecu-first and PE-first groups No annual changes in hospitalisation costs A total of 42 (19.4%) patients received dialysis immediately before discharge from the hospital and no significant annual trend was observed in this context readmissions significantly decreased over time (P for trend = 0.008) This study demonstrated the clinical practices for aHUS over approximately a decade during which the guidelines for aHUS were published and Ecu was approved in Japan Our study showed that early initiation with either PE or Ecu was associated with a shorter length of hospital stay and reduced medical expenses Early blood purification and measurement of ADAMTS13 activity were associated with early treatment initiation Our findings provide a temporal trend of clinical practice in patients with aHUS before and after the introduction of guidelines and Ecu we were also able to identify several associated problems with aHUS which means that approximately 200–300 patients would potentially be diagnosed with aHUS annually in Japan the estimated number of patients over a 9-year study period would be 1800–2700 The data from this study shows that even the sum of unspecified HUS and aHUS cases did not correspond with the number of cases that can be inferred from the previous reports The number of aHUS diagnoses and the number of patients receiving Ecu have not changed significantly since 2014 the year after the Ecu was approved for insurance the number of patients readmitted to hospital decreased This may be because maintenance treatment with Ecu for patients with a confirmed diagnosis of aHUS stabilised their condition and allowed for continued treatment in an outpatient setting initiating Ecu as a disease-specific treatment is not difficult the reason why the number of cases treated with Ecu has not increased is not because of the Ecu itself but rather because of the difficulty in diagnosing aHUS One possible reason for this may be that the diagnostic flow and treatment strategies suggested in the clinical guidelines are not refined and straightforward the diagnostic process of aHUS has been divided into three phases: Phase 1 microangiopathic haemolytic anaemia (often accompanied by thrombocytopenia identification of schistocyte and decreased haptoglobin) and major organ damage (primarily kidney failure) allow the physician to recognise TMA since blood investigation results were not available for this study it was not possible to confirm whether TMA cases were accurately incorporated we analysed the initiation of blood purification therapy as a surrogate indicator of renal dysfunction to analogise whether clinicians recalled the possibility of TMA and secondary TMA must be excluded to arrive at the clinical diagnosis of aHUS Measurement of ADAMTS13 activity is performed at the beginning of phase 2 to differentiate TTP and is therefore a surrogate marker of TMA recognition The lack of TMA recognition is reflected in the low frequency of testing for ADAMTS13 activity in patients belonging to the late initiation group All clinicians should be aware of the concept of TMA as Phases 1 and 2 may involve any category of healthcare setting and not just tertiary hospitals PE was performed in approximately 80% of patients with aHUS PE in the aHUS group was started 8 days earlier than Ecu (4 vs and PE-first was more common than Ecu-first (23% vs indicating a tendency for PE to be pre-emptively performed analysing not only Ecu but also PE as an initial treatment was justified we believe that PE is a non-negligible bridging therapy before anti-complement therapy: the replenishment of complement regulating factors and the removal of anti-CFH antibodies (for only positive cases) it is justified to analyse not only Ecu but also PE as initial therapy and PE can be performed at several tertiary care facilities in Japan even in the treatment of readmission cases which may have also been unique to the Japanese population There was no evidence that PE was preferred because of the high prevalence of meningitis (only 1 in 106 readmission cases were given antibiotics for more than 2 weeks with meningitis as the disease name) Reasons for the diagnostic process that PE is more likely to be performed ahead of Ecu include the complexity of aHUS disease and the lack of knowledge and experience of physicians is difficult to use in the early stages unless there is a strong diagnostic basis PE is often used as a pre-emptive treatment until the results of genetic and anti-CFH antibody tests are available the proportion of PE was higher in the late-initiation group than in the early-initial group and corticosteroids (which were rarely given to patients with aHUS) were used more frequently suggesting that the late-initiation group included more cases with difficult diagnosis patients in the Ecu-first group was younger than those in the PE-first group had a lower proportion of those on haemodialysis suggesting that patients who could be administered Ecu early had fewer complications and were easier to diagnose it would be short-sighted to interpret the results of lower hospitalisation costs and shorter length of stay in the Ecu-first group too favourably towards Ecu we believe that in cases with fewer comorbidities and less difficulties in diagnosis Ecu-first interventions should be performed earlier and more aggressively than that in the past Multivariable analysis showed that early treatment initiation was associated with 21 fewer days of hospitalisation than late treatment initiation with more than 11 days difference in the treatment starting date hospitalisation costs were also reduced by approximately 26% in the early treatment initiation group the DPC data demonstrated that early initiation was associated with shorter hospital stays and lower hospitalisation costs Although the establishment of practice guidelines and introduction of Ecu were expected to increase clinicians' awareness of aHUS and accelerate the timing of therapeutic intervention the percentage of patients in the early-initiation group did not actually increase Further disease awareness is warranted for both aHUS and TMA owing to the retrospective design of the study the association between the timing of treatment initiation and clinical outcomes was not causal our main objective was to describe the current clinical practices for aHUS and not the efficacy of medical interventions Our study clearly demonstrated that early initiation of PE or anti-complement therapy was associated with favourable clinical outcomes we used disease codes and documented disease names to classify aHUS cases The possibility that the unspecified HUS group included undiagnosed aHUS could not be ruled out it is unlikely that our results or discussion would be significantly changed even if all 7.7% of this unspecified HUS group were aHUS patients because the difference in the proportion of Ecu use between the aHUS and unspecified HUS groups was large (66.8 vs Excluding untreated cases may have also led to the exclusion of aHUS cases that resolved spontaneously the topic of interest for clinicians is the diagnosis and therapeutic intervention in severe cases our study still adheres to the main aim of our study using DPC data which is to provide realistic clinical practice data that can be used as a reference for clinicians who are involved actively in the ongoing care of patients with severe TMA some duplicate cases may have been present due to transfers from other facilities their proportion was so small that it would not substantially affect the results of this study including platelet counts and levels of haemoglobin we could not judge the severity of the cases the items and dates of laboratory testing performed were available which allowed us to evaluate the clinical practices followed by the physicians the results of genetic variants were not available since genetic testing for the disease was not covered by health insurance during the period of data acquisition Phase 3 was considered to be beyond the scope of the present study We are currently conducting a prospective study of aHUS and unexplained TMA cases consulted by hospitals throughout Japan We are waiting for the results of long-term prognosis and genetic tests in this registry to be available early recognition of TMA and early diagnosis of clinical aHUS were insufficient irrespective of the introduction of anti-complement agents and the establishment of specific practice guidelines Enlightening physicians about these entities will promote a rapid definitive diagnosis of aHUS and early therapeutic intervention This retrospective cohort study was conducted using the DPC data between April 1 We enrolled patients who were registered with the disease code of haemolytic uremic syndrome (HUS) (ICD-10 code: D593) as the primary disease or the disease for which most of the medical resources were invested we defined patients with aHUS as those who had been provided a specific aHUS disease name and were treated with PE or Ecu for the first time Patients with HUS other than aHUS were classified as those with unspecified HUS Patients with other diagnoses who were treated with Ecu including paroxysmal nocturnal haemoglobinuria the Ecu-first and PE-first groups were compared Data regarding ADAMTS13 activity were available in 2018 and 2019 since the measurement of ADAMTS13 activity was covered by health insurance in the middle of the year 2018 We also examined whether and when a percutaneous kidney biopsy was performed as a sign of kidney injury we investigated whether the patient was on blood purification or PE and whether and how much Ecu or glucocorticoids were administered The cases in which treatment was initiated with Ecu were defined as Ecu-first and the cases in which treatment was initiated with PE were defined as PE-first Cases in which both treatment modalities were started on the same day were defined as Ecu-first To determine the proportion of patients who ultimately required kidney replacement therapy after discharge we ascertained whether they had been on dialysis for up to 2 days before discharge Student's t-test or Wilcoxon rank sum test was performed for continuous variables and Chi-square test for categorical variables The following trend tests were conducted to assess the annual trend: The Cochran-Armitage trend test was used when the outcome variable was binary and the explanatory variable was ordinal or numeric The Jonckheere-Terpstra trend test was used when the outcome variable was continuous a trend test was performed with data from 2014 to 2019 after the introduction of Ecu Multiple regression analysis was performed for hospitalisation costs Logistic regression analysis was performed for death during hospitalisation and readmission and whether blood purification was performed Since blood purification was performed in patients with severe conditions such as kidney failure we considered blood purification a proxy for severe kidney disease and thus added it to the covariates Hospitalisation costs were log-transformed as they violated the assumptions of linear regression All statistical analyses were conducted using Stata Statistical significance was set at P < 0.05 The study was performed following the tenets of the Declaration of Helsinki This study was approved by the Institutional Review Board of the University of Tokyo [approval number: 3501-(3) the requirement for patient informed consent was waived by the committee Owing to personal information protection laws The data underlying this article will be shared upon reasonable request to the corresponding author Genetic studies into inherited and sporadic hemolytic uremic syndrome Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome Clinical guides for atypical hemolytic uremic syndrome in Japan Atypical hemolytic uremic syndrome and C3 glomerulopathy: Conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome PhRMA Japan Medical Affairs Committee Working Group 1 and future perspectives of real-world data and real-world evidence in Japan Economic impact of early-in-hospital diagnosis and initiation of eculizumab in atypical haemolytic uraemic syndrome Real world data in Japan: Chapter II the diagnosis procedure combination database Improved renal recovery in patients with atypical hemolytic uremic syndrome following rapid initiation of eculizumab treatment von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome Download references We would like to thank Editage (www.editage.co.kr) for English language editing Nagoya University Graduate School of Medicine National Center for Global Health and Medicine Department of Clinical Epidemiology and Health Economics School of Public Health Department of Health Policy and Informatics Tokyo Medical and Dental University Graduate School substantially contributed to the study conceptualization significantly contributed to data analysis and interpretation organized this research project and interpreted the results substantially contributed to the manuscript drafting All authors critically reviewed and revised the manuscript draft and approved the final version for submission Shoichi Maruyama received lecture fee from Alexion Pharmaceuticals Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-024-68736-6 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science Adults and children with atypical hemolytic uremic syndrome who switched from eculizumab to ravulizumab had stable renal function and hematologic values with similar safety seen in clinical trials “Atypical hemolytic uremic syndrome (aHUS) is a progressive rare disease that can result in severe organ damage and death a humanized monoclonal antibody that blocks terminal complement activation by inhibiting was approved for the treatment of aHUS in 2011 and revolutionized the clinical management of aHUS,” Franz Schaefer professor of pediatrics and chief of pediatric nephrology at Heidelberg University Hospital in Germany and colleagues wrote in background to the study published in KI Reports “The efficacy and safety of [the next-generation terminal complement inhibitor] ravulizumab [Ultomiris Alexion] in patients with aHUS have been demonstrated in clinical trials in which ravulizumab was shown to provide immediate complete and sustained complement C5 inhibition.” To assess real-world efficacy and safety of ravulizumab among adult and pediatric patients researchers analyzed data from the Global aHUS Registry an ongoing registry sponsored by Alexion Pharmaceuticals begun in 2012 that includes data on patients in 23 countries “The registry has the largest real-world cohort of patients with aHUS and is open to all patients providing reasonable representation of the global aHUS patient population,” the researchers wrote researchers evaluated data on all registry patients who switched from eculizumab to ravulizumab therapy — 43 adults (73% women; median age at start of ravulizumab 23 months) and 17 children (78% girls; median age at start of ravulizumab No unexpected adverse events were reported during treatment with ravulizumab 20 adverse events were reported among 13 patients Two were deemed related to treatment: an infusion reaction that resolved within 24 hours and headache and fatigue that led the patient to discontinue the medication Two other patients discontinued ravulizumab on the advice of their physicians Three serious adverse events occurred: squamous cell carcinoma atrial fibrillation and SARS-CoV-2 infection The most common adverse event was infection and there were no cases of meningococcal infection and no deaths the researchers focused on data from patients who were prescribed eculizumab and switched less than 1 month later to ravulizumab for at least 3 months beginning on or after Oct No patients proceeded to dialysis or kidney transplantation after switching to ravulizumab one patient switched back to eculizumab for a planned kidney transplant No new thrombotic microangiopathy symptoms developed after switching to ravulizumab and relevant laboratory values remained stable “These data provide further evidence for the safety and effectiveness of ravulizumab treatment in patients with aHUS who switched from eculizumab and reinforce a positive risk-benefit profile of ravulizumab Further studies in other aHUS subpopulations would be beneficial to guide clinical practice,” the researchers wrote Atypical hemolytic uremic syndrome is a thrombotic microangiopathy caused by complement dysregulation Uncontrolled terminal complement activation can result in severe organ damage and death which affects fewer than 625 patients in the U.S. which blocks terminal complement activation and is effective for 90% of patients but is expensive and is associated with frequent meningococcal disease Changing four amino acids in its complement binding and neonatal Fc regions led to the development of ravulizumab with a longer half-life and Schaefer and colleagues aimed to evaluate the safety and efficacy of ravulizumab in real-world usage by analyzing data from a global aHUS registry that was initiated in April 2012 by 23 countries Patients were included in the efficacy analysis after 3 months of ravulizumab Patients were excluded if they had less than 1 month between eculizumab discontinuation and ravulizumab initiation or if they discontinued eculizumab relapsed and then initiated treatment with ravulizumab Sixty patients were entered into the registry: 43 were adults; 17 were pediatric All were included in the safety analysis; 49 were included in the efficacy analysis There were insufficient data on genetic analyses to draw conclusions Among patients who switched to ravulizumab there were no new dialysis or transplant events and no new thrombotic microangiopathy symptoms Twenty adverse events were reported in 13 patients There were no reports of meningococcal disease Ravuzliumab appears to have similar safety and efficacy profiles as eculizumab for treatment of aHUS with an advantageous administration protocol The expense of these drugs and the risk of meningococcal disease warrant an ongoing search for better treatment options Get the latest news and education delivered to your inbox The email address associated with your Healio account is: If you would like to edit or change the email address that your subscriptions and alerts are sent to You'll receive reminders to complete your saved activities from Healio CME Soliris® (eculizumab) is the first targeted therapy approved for paediatric patients with gMG in Europe Paroxysmal nocturnal haemoglobinuria (PNH) atypical haemolytic uraemic syndrome (aHUS) neuromyelitis optica spectrum disorder (NMOSD) Soliris® (eculizumab) is a monoclonal antibody indicated for the treatment of rare and severe blood disorders including paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) It is also indicated to treat rare autoimmune disorders such as generalised myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD) The drug is developed and manufactured by Alexion Pharmaceuticals a biopharmaceutical company based in the US and a subsidiary of AstraZeneca clear solution in a single-dose vial in 300mg/30ml (10mg/ml) dosage strength for intravenous infusion The National Medical Products Administration (NMPA) in China authorised Soliris for treating NMOSD in adults who are anti-aquaporin-4 (AQP4) antibody-positive in October 2023, based on results of the Phase III PREVENT clinical trial Labour and Welfare (MHLW) approved the drug for paediatric patients with gMG who are anti-acetylcholine receptor (AChR) antibody-positive in August 2023 The European Union (EU) sanctioned the drug’s use in children and adolescents with refractory gMG in July 2023 Soliris was approved in China for the treatment of refractory gMG in AChR antibody-positive adults based on the Phase III REGAIN trial results The US Food and Drug Administration (FDA) approved the drug for treating NMOSD in adults who are AQP4 antibody-positive in June 2019 while the European Commission (EC) granted marketing authorisation for the same indication in August 2019 Japan’s MHLW approved the drug for NMOSD relapse prevention in November 2019 Soliris was approved by the FDA for gMG in AChR antibody-positive adults in August 2017 and by the EC in October 2017 The Japanese MHLW sanctioned its use in patients with difficult-to-control symptoms despite high-dose IVIG therapy or plasmapheresis in December 2017 The drug is also approved in the European Union The drug was made available in Australia for PNH treatment in February 2009 following the initial FDA approval for the same indication in 2007 Soliris was designated as an orphan drug by the FDA in October 2003 Soliris is being explored as an experimental emergency treatment for Covid-19 infection and severe pneumonia in a limited number of patients with its potential role or efficacy still under investigation PNH and aHUS are caused due to defects in protein (CD59) present on the surface of red blood cells (RBCs) The protein hinders complement protein from attacking the cells PNH is the breakdown of the RBC at an early stage It usually occurs in people with the missing PIG-A gene aHUS is a chronic illness in which a genetic deficiency may lead to uncontrolled activation of complement protein causing small clots to form in blood vessels all over the body The uncontrolled complement activation may lead to reduced platelet count (thrombocytopaenia) and the destruction of RBCs It may also cause damage to many vital organs gMG is a chronic autoimmune neuromuscular disease which begins with muscle weakness around the eyeballs and eyelids and leads to weakness in the head It occurs due to the generation of antibodies by the patient’s own body to attack the AChR receptor present in the muscle cells of the neuromuscular junction debilitating disorder that affects the central nervous system particularly the optic nerves and spinal cord the patient’s own body generates auto-antibodies against the AQP4 protein The protein is present in the nerve cells of the eyes brain and spinal cord for its growth and survival The AQP4 auto-antibodies destroy the essential cells in the CNS and neurons Eculizumab is a first-in-class C5 complement inhibitor It functions by inhibiting the C5 protein within the terminal complement cascade an integral component of the body’s immune system When this cascade becomes overly activated causing the body to mistakenly target its own healthy cells Soliris has demonstrated efficacy and safety in treating PNH through three multi-national clinical studies The 26-week Phase III TRIUMPH placebo-controlled trial involved 87 patients while the 52-week SHEPHERD open-label Phase III trial included 97 patients the long-term extension study E05-001 further supported the findings from the trial The primary endpoint of reduced haemolysis was consistently met across the studies with a significant decrease from a baseline lactate dehydrogenase level (LDH) level of 2,032u/l to 239u/l at week 26 occurring within the first week of treatment and was maintained for up to 54 months with ongoing Soliris therapy there was an increase in circulating PNH cells and an improvement in haemoglobin levels the co-primary endpoints of haemoglobin stabilisation and reduction in the need for RBC transfusions were achieved About 50% of the Soliris-treated patients experienced haemoglobin stabilisation in stark contrast to none in the placebo group The median number of transfusions dropped from ten units per patient to zero Patients on Soliris also reported less fatigue and an enhanced health-related quality of life the incidence of thrombotic events was reduced during Soliris treatment compared to the period before treatment The FDA’s approval of Soliris for aHUS was based on three Phase II studies conducted to evaluate the drug’s safety and efficacy in aHUS patients undergoing plasma therapy paediatric aHUS patients and plasma therapy-resistant patients The first Phase II study enrolled 17 plasma therapy-resistant or sensitive patients Haematologic normalisation was observed in 76% of the patients Around 87% of the patients treated with Soliris achieved thrombotic microangiopathy (TMA) free status The second trial was conducted in aHUS patients undergoing plasma therapy Haematologic normalisation was observed in 90% of the patients The third trial recruited 19 paediatric aHUS patients Haematologic normalisation was reported in 89% of the patients The FDA’s approval of the drug for gMG was based on a Phase III The approval for NMOSD was based on the results of PREVENT The 26-week REGAIN Phase III randomised, double-blind, placebo-controlled, multi-centre clinical study, enrolled 125 gMG patients. The trial’s primary endpoint was the change in the total score of the MG-Specific Activities of Daily Living scale (MG-ADL) The total score was -4.2 in Soliris-treated patients compared with -2.3 in patients receiving a placebo A lower score indicates a better clinical outcome A total of 143 NMOSD patients were enrolled in the PREVENT Phase III randomised Soliris demonstrated efficacy in meeting its primary endpoint by prolonging the time to the first adjudicated relapse and reducing the risk of relapse 98% of patients administered Soliris remained relapse-free compared to only 63% of those who received a placebo 96% of patients treated with Soliris remained relapse-free contrasting with just 45% of patients who received a placebo Give your business an edge with our leading industry insights View all newsletters from across the GlobalData Media network The global atypical hemolytic uremic syndrome (aHUS) treatment market is on a growth trajectory expected to attain a value of US$ 2,308.84 million by 2033 expanding at a CAGR of 4.9% from 2023 to 2033 Currently valued at US$ 1,431 million in 2023 recording a CAGR of 3.4% between 2018 and 2022 The growth of the aHUS treatment market is largely driven by intensified research and development initiatives aimed at delivering effective treatment options for this rare and life-threatening condition As aHUS patients often face critical health complications due to complement system dysregulation there is a pressing demand for advanced therapies that can effectively manage symptoms and improve patient outcomes thanks to robust healthcare infrastructure and active investment in rare disease research the Asia-Pacific region is emerging as a promising area for growth supported by increasing healthcare spending With the growing focus on developing innovative and effective treatments the global aHUS treatment market is expected to see significant advancements Key industry players are anticipated to prioritize new product development and strategic partnerships to accelerate therapeutic progress and support patients living with atypical hemolytic uremic syndrome worldwide Key players in the atypical hemolytic uremic syndrome (ahus) treatment market are Alexion Pharmaceuticals A Full Report Overview Key Segments Profiled in the Atypical Hemolytic Uremic Syndrome (aHUS) Treatment Industry Survey and a member of the Greater New York Chamber of Commerce) offers profound insights into the driving factors that are boosting demand in the market FMI stands as the leading global provider of market intelligence With a vast team of over 400 analysts worldwide and local expertise on diverse domains and industry trends across more than 110 countries Contact Us: PharmiWeb.com is Europe's leading industry-sponsored portal for the Pharmaceutical sector features and events listings.The information provided on PharmiWeb.com is designed to support the relationship that exists between a patient/site visitor and his/her 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always verify the information obtained from linked websites before acting upon this information please be aware that the security and privacy policies on these sites may be different than PharmiWeb.com policies so please read third party privacy and security policies closely If you have any questions or concerns about the products and services offered on linked third party websites Treatment with plasma exchange therapy helped teen recover COVID-19 triggered atypical hemolytic uremic syndrome (aHUS) in a 13-year-old boy with a genetic predisposition to the syndrome “This case highlights the potential of COVID-19 to trigger aHUS particularly in individuals with underlying genetic predispositions,” the researchers wrote The report, “Atypical hemolytic uremic syndrome with a C3 variant following COVID-19: a case report,” was published in Frontiers in Pediatrics aHUS is a rare type of thrombotic microangiopathy (TMA) a group of diseases characterized by the formation of blood clots in the body’s small vessels the abnormal activity of the complement system causes blood clots to form in small blood vessels While most people with aHUS have mutations in genes involved in complement regulation, these mutations alone are typically not sufficient to cause the disease on their own. Usually, the onset of symptoms is triggered by an immune-activating stimulus researchers at the Gifu University Hospital in Japan described the case of a 13-year-old boy infected with SARS-CoV2 The boy had a headache and sore throat for two days He was positive for SARS-CoV2 and blood work revealed he had low platelet counts Platelets are tiny cell fragments involved in blood clotting and he had signs of microangiopathic hemolytic anemia anemia driven by the destruction of red blood cells associated with the obstruction of small blood vessels and he was fully conscious and well oriented Blood work showed signs of hemolytic anemia including high levels of lactate dehydrogenase and he presented severe thrombocytopenia and hematuria The activity of the ADAMTS13 enzyme was normal (85%) indicating he did not have a TMA called thrombocytopenic purpura (TTP) in which the enzyme’s activity is severely reduced with the exception of a slight decrease in the levels of the C3 complement protein The boy also tested negative for Shiga toxin a compound that can indicate the presence of typical HUS accompanied by a rise in creatinine levels Because the results of the ADAMTS13 activity tests were still pending he began treatment with plasma exchange therapy this procedure replaces a person’s plasma — the liquid portion of blood — and is believed to be helpful for patients with aHUS and TTP The boy recovered fully after undergoing plasma exchange and was discharged after 18 days He remained free of relapses in the year following Genetic testing revealed the boy had a disease-causing mutation in one of the copies of the C3 gene, confirming the diagnosis of aHUS who had a medical history of unexplained TMA This case reinforces the notion that COVID-19 even in the absence of severe respiratory symptoms particularly in individuals with genetic predisposition to develop the disease “Clinicians should be vigilant for signs of aHUS in children with COVID-19 especially those with a family history of TMA or complement system abnormalities as early diagnosis and intervention can lead to favorable outcome,” they wrote New storybook for ages 6-10 developed by pharmaceutical An interactive electronic storybook, or e-book, designed to help children with atypical hemolytic uremic syndrome (aHUS) better understand their rare disease, has been launched by Alexion, AstraZeneca Rare Disease Called “Revealing the Secrets of aHUS,” the fantasy e-book uses imaginative play to educate children and provide clarity about aHUS in ways that are fun and engaging — and appropriate for young children It’s designed to be read by youth ages 6-10 The interactive e-book is available on Healthinote a website that bills itself as an “aHUS support hub.” Alexion, which markets the aHUS therapies Soliris (eculizumab) and Ultomiris (ravulizumab-cwvz), developed the book in collaboration with the patient support charity Kidney Care UK and the Newcastle National Renal Complement Therapeutics Center “Navigating through a disease is hard for anyone, at any age, but it can be particularly tough for children to fully understand the implications and support available,” Christine Maville, a nurse consultant for NRCTC, said in an Alexion press release adding that “this book clearly explains the complexities of aHUS and how to cope with the challenges of living with a rare disease.” and hopefully one which can brighten and engage the imagination of children diagnosed with aHUS and remind them they are not alone.” aHUS is a very rare disease in which the abnormal activation of the immune system’s complement cascade causes blood clots to form in small blood vessels. This drives progressive organ damage, especially in the kidneys. Symptoms can emerge at any age though it’s a little more common for them to first manifest during childhood rather than later in life The goal of the new e-book is to guide children through the journey of aHUS diagnosis and treatment in an engaging way “Working with medical and patient advocacy partners we’re now able to provide children with a way to learn about their disease and importantly help them feel in control,” explained Deborah Richards The story follows the fictional Guardian of Healthoria whose mission is to restore a mythical land that’s been overrun by naughty pixies To help readers take ownership of the mission they’re able to personalize the hero by choosing a name and the things they can do to minimize the impact aHUS has on their body and mental health the book works to translate complex medical terms in ways that are more easily understandable to youngsters Working with medical and patient advocacy partners we’re now able to provide children with a way to learn about their disease and importantly help them feel in control There are four major learning objectives in the book: what to expect in the patient journey how to deal with emotions and find support and understanding the impact aHUS can have on a child’s daily life As children complete different activities within the interactive story they collect rewards and are provided recaps on what they’ve learned The ultimate goal is to help children engage with important information about their health while having fun marketing and communications for Kidney Care UK a patient-centered charity in Great Britain notes that the book “gives children the chance to see themselves in a character and story as well as learning more about their condition.” The interactive e-book can be accessed via laptop A noninteractive version of the story can also be downloaded as a PDF after children have created their character this storybook “helps to create a space where parents and carers can learn more about aHUS together and how they can support their child to live with this complex condition.” List price of new medicine expected to be 30% lower than brand name drug Epysqli (eculizumab-aagh), a biosimilar of Soliris (eculizumab), is now available for patients in the U.S., according to an announcement from Samsung Bioepis and Teva Pharmaceuticals The biosimilar is authorized to treat people with atypical hemolytic uremic syndrome (aHUS), as well as paroxysmal nocturnal hemoglobinuria, and generalized myasthenia gravis — all of which are conditions that Soliris is approved to treat Biosimilars are treatments that are highly similar in terms of purity and efficacy to a brand-name biological medicine They’re comparable to generics for traditional medicines because biological therapies are made using living cells rather than being chemically synthesized the regulatory requirements and naming conventions for biosimilars are more complex biosimilars are typically marketed at a lower price than the reference product Teva, which is marketing Epysqli in the U.S. under an agreement with developer Samsung Bioepis said that the biosimilar treatment will be available at approximately a 30% reduced list price relative to Soliris The release calls Epysqli “one of the greatest cost-saving biosimilars to Soliris in the U.S.” executive vice president and head of the global commercial division of Samsung Bioepis said the company “will work closely with Teva to ensure access of this medicine for payers healthcare professionals and patients in the U.S.” “the availability of Epysqli means that patients now have an additional treatment option available at a lower cost safety and efficacy comparable to the reference product.” Soliris is an antibody-based medication that works to block the activation of the complement cascade a group of immune proteins whose activation helps to drive disease activity in aHUS and other conditions For aHUS, the recommended dosing schedule in adults is 900 mg weekly for the first four weeks, then 1,200 mg in the fifth week, and 1,200 mg every other week thereafter. In children and adolescents, dosing is based on body weight. Epysqli is dosed in the same way, as stated in its prescribing information The availability of Epysqli means that patients now have an additional treatment option available at a lower cost safety and efficacy comparable to the reference product Similar to Soliris, Epysqli’s label comes with a boxed warning for serious meningococcal infections. Complement inhibitors and products containing eculizumab, the active agent in both Soliris and Epysqli, are known to increase the risk of such infections. Due to this increased risk, Epysqli is only available in the U.S. through a restricted access program, called Epysqli REMS The U.S. Food and Drug Administration approved Epysqli for aHUS last year based on clinical trial data showing that it had similar pharmacological properties to Soliris in healthy volunteers and that it showed similar efficacy in people with PNH Nonprofit's RareCare program aims to ease disease's financial burden The National Organization for Rare Disorders (NORD) is offering patient assistance programs specifically for people in the U.S. with atypical hemolytic uremic syndrome (aHUS) to help cover out-of-pocket medical costs and emergency nonmedical expenses in their daily lives These initiatives come under NORD’s RareCare program which was created to offer various types of support to people living with rare diseases Two programs specifically aim to help those with aHUS: one dubbed Atypical Hemolytic Uremic Syndrome (aHUS) Premium & Copay Assistance and the other called Atypical Hemolytic Uremic Syndrome (aHUS) Emergency Relief “Our RareCare program helps patients obtain life-saving or life-sustaining medication they could not otherwise afford The program also provides financial assistance with insurance premiums and co-pays and travel assistance for clinical trials or consultation with disease specialists,” NORD states on its patient assistance programs webpage aHUS is a rare disease in which blood clots form in the body’s small blood vessels It is driven by the abnormal activation of the immune system’s complement cascade NORD’s RareCare patient assistance programs are designed to help support rare disease patients and caregivers by offering financial support connecting patients with diagnostic testing and providing travel assistance for clinical trials or disease specialist consultations NORD offers a program providing caregiver respite The aHUS premium and copay assistance program helps aHUS patients and caregivers cover the out-of-pocket costs associated with disease-related medical care Types of expenses NORD can help cover include: U.S. citizens or residents of at least six months who have been diagnosed with aHUS are eligible to apply if they or their caregiver meet certain financial eligibility criteria and patients can reapply annually if they continue to need assistance The aHUS emergency relief program aims to help patients and caregivers pay for unexpected or emergency non-medical expenses that are necessary for daily life Among the expenses NORD can help cover are: Other types of emergency requests will be considered on a case-by-case basis Patients and caregivers in need can apply online Individuals who need help with either application or have additional questions can also email NORD’s aHUS program NORD also offers other types of assistance programs that are not specifically targeted for aHUS but that are intended to help all families affected by a rare disease That includes its Rare Disease Educational Support Programs which aim to help patients and caregivers participate in rare disease educational programming Patients, immediate family members, and caregivers in the U.S. may be eligible, but interested individuals should contact NORD by email or phone (860-556-2208/203-635-7486) and speak with a patient service representative who can guide them on whether the education programming they’d like to attend might be covered Samsung Bioepis therapy approved last year for use by aHUS Under a new commercialization agreement with Samsung Bioepis, the developer of Epysqli (eculizumab-aagh), Teva Pharmaceuticals will have exclusive marketing rights in the U.S. for the Soliris (eculizumab) biosimilar — an approved treatment for atypical hemolytic uremic syndrome (aHUS) A biosimilar is a biological product that is highly similar to an already approved biological medicine It has no clinically meaningful differences in terms of safety or efficacy compared with the original therapy such therapies usually are more affordable an autoimmune disorder also thought to be driven by the excessive activity of the complement system Under the terms of the agreement, Samsung Bioepis will remain responsible for the development The deal’s financial terms were not disclosed “We are excited to enter this partnership with Samsung Bioepis, who share our commitment to accelerate the delivery of impactful and accessible medicines to patients,” Chris Fox, executive vice president of U.S. commercial at Teva, said in a joint press release from the two companies “The collaboration enables us to leverage our extensive commercial capabilities and is aligned with our pivot to growth strategy introducing a new biosimilar to our broad biosimilar portfolio accelerating access to affordable treatment options.” the company “will work closely with Teva to accelerate access to this important biologic medicine for rare disease patients in the U.S.” Teva will be responsible for Epysqli’s commercialization in the country “This collaboration is a testament of our long-term commitment in the biosimilars business as a leading biopharmaceutical company with a mission to innovate access to treatments for healthcare systems Soliris — originally developed by Alexion Pharmaceuticals and later acquired by AstraZeneca — is an antibody-based therapy approved for aHUS in the U.S blocks complement activation by targeting a complement protein called C5 We are excited to announce this new strategic partnership for a biosimilar which has a significant potential to increase access for rare disease patients who are suffering from the high cost and the limited availability of … treatment Epysqli’s approval in the U.S. was based on data from both preclinical and clinical studies, including a Phase 1 trial (NCT03722329) in healthy volunteers and a Phase 3 trial (NCT04058158) in patients with PNH the overactivation of the complement system leads to the destruction of red blood cells Both studies confirmed that Epysqli matched Soliris in terms of efficacy In the Phase 1 study, Epysqli was shown to be comparable to Soliris in safety The biosimilar also was found to have similar pharmacokinetics — how a therapy moves into “We are excited to announce this new strategic partnership for a biosimilar which has a significant potential to increase access for rare disease patients who are suffering from the high cost and the limited availability of … treatment,” Kim said weakness started 15 days after vaccination A woman developed atypical hemolytic uremic syndrome (aHUS) after receiving the first dose of a COVID-19 vaccine The researchers said the “connection of symptoms post-COVID-19 vaccination to aHUS … emphasizes the need for ongoing monitoring and research into vaccine-related complications.” The case was described in the study, “Atypical hemolytic-uremic syndrome after COVID-19 vaccine: A case report,” published in Immunity Recent studies have indicated that COVID-19 vaccination may be associated with uncommon adverse events including thrombotic microangiopathy (TMA) TMAs are disorders that are marked by the formation of blood clots in small blood vessels leading to organ damage researchers described the case of a 25-year-old woman who started experiencing general discomfort and physical weakness 15 days after receiving the first dose of the AstraZeneca COVID-19 vaccine She subsequently developed swelling in both legs and shortness of breath during periods of exertion She also had persistent abdominal pain and nausea The woman was treated for her symptoms in the emergency department and was discharged after 10 days she returned to the emergency department with the same symptoms Initial laboratory tests revealed she had kidney dysfunction but there were no changes in blood cell counts her condition improved and she was discharged with instructions to take a blood pressure-lowering medication she returned with acute hypertensive pulmonary edema — a condition characterized by the accumulation of fluid in the lungs — along with worsened kidney function high levels of neutrophils (a type of immune cell) Further laboratory tests were consistent with a TMA diagnosis including the presence of schistocytes (red blood cell fragments) in the blood high levels of lactate dehydrogenase (a marker of cell and tissue injury) No mutations were found in genes encoding proteins of the complement system and there was no evidence of viral infections A kidney biopsy revealed a pattern of tissue damage characteristic of TMA and indicative of an aHUS diagnosis Clinical improvement was achieved with early initiation of invasive breathing support intravenous (into-the-vein) treatment with blood pressure-lowering medication The woman was discharged after two weeks and continued receiving outpatient follow-up care and hemodialysis treatment for insufficient urine production have been reported after a first vaccine dose and without previous alterations to kidney function The researchers said their case differed from previous reports “by presenting itself in a patient of age below the average age of the cases reported in addition to having been caused after the application of an adenoviral vector vaccine … starting symptoms after 15 days of the administration and not showing complete remission of the case and still requiring hemodialysis.” “Despite the critical role of vaccination in pandemic control must be recognized and investigated,” they wrote “Additional clinical trials are imperative to comprehend the clinical features and pathophysiological [disease] mechanisms underlying TMA associated with COVID-19 vaccination.” Patients of all ages see benefits with treatment up to 2 years in trials Long-term treatment with Ultomiris (ravulizumab) led to sustained clinical improvements for adults and children with atypical hemolytic uremic syndrome (aHUS) according to new two-year data from a pair of clinical trials Patients in both age groups saw improvements in blood-related health factors and kidney function and experienced less fatigue than they had before treatment started “These results from a 2-year analysis of Phase 3 trial data demonstrated that the improved clinical outcomes and quality of life benefits achieved in adult and pediatric patients with aHUS treated with [Ultomiris] are maintained long-term,” the researchers wrote noting that treatment was given “over 2 years with maintenance dosing every 4-8 weeks.” “we found that treating patients for 2 years with [Ultomiris] was associated with improved blood health and quality of life and was well tolerated,” the team wrote The study, “Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials,” was published in the journal Kidney Medicine. The work was funded by Alexion, Astrazeneca Rare Disease, which markets Ultomiris and Soliris (eculizumab) In aHUS, abnormal activation of the immune system’s complement cascade causes blood clots to form in the body’s small blood vessels driving damage to the kidneys and other organs aHUS is a type of thrombotic microangiopathy, or TMA, disorders in which small blood vessel damage is associated with three core symptoms: red blood cell destruction Both Ultomiris and Soliris work to block complement activation by targeting a protein called C5 Ultomiris is designed to last longer in the bloodstream and requires less frequent dosing than the older medication To know more about the safety and efficacy of Ultomiris, a pair of open-label Phase 3 clinical trials evaluated the therapy in either adults or children with aHUS. One trial (NCT02949128) enrolled 58 adults who had never been on a C5 inhibitor. The other trial (NCT03131219) recruited 34 children 24 of whom were C5 inhibitor-naïve and 10 who switched from Soliris participants received infusions of Ultomiris into the bloodstream every one or two months at a weight-based dose after an initial loading dose patients could continue on for up to 4.5 years or until the therapy’s regulatory approval the main goal was to evaluate the proportion of those who achieved a complete TMA response after six months That was defined as achieving normalized platelet counts as well as a minimum 25% improvement in blood creatinine concentrations This response had to be seen at two consecutive assessments taken at least a month apart the scientists are reporting two-year follow-up findings from both studies which generally indicated that the benefits of treatment had been sustained and that the proportion of treatment responders slightly increased over time 61% of adults and 90% of inhibitor-naïve children had achieved a complete TMA response at the two-year mark and 63% saw at least a 25% improvement in creatinine LDH and platelet normalization occurred in 95% while creatinine improvements occurred in 90% Improvements in kidney function that had been observed after six months were also generally maintained at the two-year follow-up mark More than half of adults who required dialysis to support kidney function at baseline were able to discontinue it All inhibitor-naïve children who required dialysis at the study’s start were able to stop such treatment over the course of two years improvements in kidney function seen with that medication were generally maintained after starting Ultomiris Reductions in fatigue were observed as soon as six months after starting treatment and were also maintained over the two-year period which had been rapidly reduced once Ultomiris was started These 2-year data support the favorable benefit/risk profile of [Ultomiris] and its long-term use in all patients with aHUS The treatment was generally well tolerated with a safety profile similar to previous reports and with most side effects occurring during the first six months of treatment “long-term treatment with [Ultomiris] was well tolerated and associated with continual improvement in TMA response and kidney function in adults and pediatric patients with aHUS,” the team wrote “These 2-year data support the favorable benefit/risk profile of [Ultomiris] and its long-term use in all patients with aHUS,” the researchers wrote Decision based on data including evidence from PNH trial The U.S. Food and Drug Administration (FDA) has approved Epysqli (eculizumab-aagh), a biosimilar to Soliris (eculizumab), as an atypical hemolytic uremic syndrome (aHUS) treatment Epysqli, from Samsung Bioepis, has also been approved to treat people with paroxysmal nocturnal hemoglobinuria (PNH) occurs when the complement system that forms part of the body’s immune defenses becomes overly active causing red blood cells to break down (hemolysis) The medication is not indicated for people with typical HUS a disorder caused by toxins produced by certain bacteria Epysqli joins other Soliris biosimilars previously approved. Bkemv (eculizumab-aeeb) this year became the first interchangeable biosimilar of Soliris to become available in the U.S A biosimilar is a medication that’s similar to an existing It’s designed to have the same properties as the reference medicine and to have similar safety and effectiveness it’s often cheaper than the original medication Epysqli was previously approved in Europe and South Korea and always will be improving the lives of patients by providing quality-assured and our work to fulfill this mission is expanding into rare disease areas where patients continue to suffer from limited access to life-enhancing medicines,” Hansung Ko said Originally developed by Alexion Pharmaceuticals, later acquired by AstraZeneca eculizumab is designed to prevent formation of the C5b-9 complement protein complex and stop clotting within small blood vessels The FDA’s decision was based on evidence from non-clinical and clinical data, including a Phase 1 trial (NCT03722329) in healthy volunteers and a Phase 3 trial (NCT04058158) in PNH patients which supported similar efficacy and safety to Soliris The Phase 1 trial showed that Epysqli was equivalent to Soliris with regard to the therapy’s safety Pharmacokinetics refers to the movement of a therapy into In the Phase 3 study, patients with PNH were randomly assigned to receive the same dose of Epysqli or Soliris for 26 weeks (about six months), after which they switched treatments over a similar period. Results showed Epysqli to be therapeutically equivalent to Soliris in its ability to reduce hemolysis and the need for blood transfusions Case underscores importance of early intervention Early treatment with plasma exchange, or plasmapheresis, followed by the immunosuppressant rituximab helped a 2-year-old girl who was diagnosed with a case of severe atypical hemolytic uremic syndrome (aHUS) a form of thrombotic microangiopathy (TMA) is marked by the destruction of red blood cells (RBCs) more quickly than they’re produced The disease is driven by an abnormal activation of the complement system a set of more than 50 proteins that contribute to the body’s natural immune defenses about 50% of children with aHUS have self-reacting antibodies against complement factor H (CFH) but reports show mutations in complement-regulating genes in 60% of patients While the standard treatment for children without anti-CFH antibodies is Soliris (eculizumab) “due to cost and accessibility issues in India plasmapheresis or plasma infusions often serve as alternatives.” In plasma exchange disease-causing antibodies are removed from the bloodstream The girl was first seen in the hospital in March 2023 with swelling around the eyes She showed an unusual lack of energy and mental alertness on examination and had high blood pressure and a fast heartbeat Blood work showed severe acute kidney injury and severe anemia with low levels of the hemoglobin protein The girl was given immediate peritoneal dialysis for kidney failure and a blood transfusion fluid is inserted into the abdomen to remove waste from the blood physicians examined her to determine the cause of the acute kidney injury The girl had blood and protein in her urine, and tests revealed red blood cell fragments, called schistocytes, in a blood smear. Her complement and platelet levels were normal. She tested negative for self-reacting antibodies that mark ANCA-associated vasculitis (AAV) but was positive for antinuclear antibodies (ANA) Her urine output was still low after 10 days and she developed rapidly worsening glomerulonephritis or inflammation and damage to the kidneys’ filtering units (glomeruli) she started treatment with the corticosteroid methylprednisolone for three days Further blood tests showed a decrease in hemoglobin and a gradual onset of thrombocytopenia with 59% of glomeruli showing restricted or reduced blood flow and a shrunken appearance her blood vessels were blocked and fragmented RBCs in the wall of the glomeruli were visible the girl was diagnosed with aHUS and began treatment with the oral immunosuppressant mycophenolate mofetil followed by seven plasma exchange sessions No immediate clinical improvements were observed She had a hypertension emergency that affected her brain and was given treatment into the vein with nitroglycerin which causes blood vessels to relax and widen A brain CT scan showed signs of a posterior reversible encephalopathy syndrome (PRES) with small blood clots which arises due to swelling in parts of the brain The girl was given a single rituximab dose which improved her kidney function in two days as shown by a gradual increase in urine output and improved kidney function Her hemoglobin and platelet counts normalized and blood work confirmed she was negative for self-reacting antibodies targeting targeting CFH but wasn’t performed due to financial constraints The girl was discharged after a month with a prescription of oral prednisolone and mycophenolate mofetil with no signs of red blood cell destruction “early initiation of plasmapheresis within 24 hours is crucial for a desired response in severe [hemolytic uremic syndrome] cases,” the report reads 22-year-old in 2nd trimester went to hospital with headache Researchers in Mexico described the series of events that led to a diagnosis of atypical hemolytic uremic syndrome (aHUS) in a 22-year-old pregnant woman The case highlights the need for vigilance, as well as prompt diagnosis and treatment, they said. The report, “Pregnancy-associated atypical hemolytic uremic syndrome. Case report,” was published in the Journal of Obstetrics and Gynaecology Research aHUS belongs to a group of disorders called thrombotic microangiopathies These disorders are marked by the formation of blood clots inside small blood vessels that can damage internal organs Patients typically show signs of red blood cell destruction and have low platelet counts as well aHUS is associated with mutations in genes that regulate the complement cascade The complement system comprises a set of proteins that are part of the body’s immune defenses Mutations alone are usually not enough to cause aHUS to develop is necessary to induce the onset of the disease most reports of aHUS occur during the postpartum period The woman in the case report was in the 26th week of her second pregnancy when she went to a hospital with a generalized Her attending physician prescribed aspirin and paracetamol Her doctor prescribed the antibiotic cephalexin and she had petechiae — tiny spots of blood — on the palms of her hands and inner thighs Tests showed she had low blood pressure and tachycardia Blood work revealed the presence of mild anemia Additional signs of liver and kidney damage were also detected The woman was transferred to another hospital She was drowsy on arrival and was admitted to the obstetric intensive care unit where she received treatment with a vasopressor a type of medication used to increase blood pressure An ultrasound indicated the baby’s growth was being restricted but two days later she had vaginal bleeding and her platelet count dropped even further Additional blood tests revealed the presence of red blood cell fragments (schistocytes) typically very low in a type of TMA called thrombotic thrombocytopenic purpura a compound that can indicate the presence of typical HUS when detected Overall, these signs confirmed the diagnosis of aHUS She was then prescribed six plasmapheresis and six hemodialysis sessions Her platelet counts improved following the plasma exchange sessions she tested positive for methicillin-resistant Staphylococcus aureus (MRSA) a bacteria that is resistant to many of the antibiotics usually used to treat ordinary staph infections She received intravenous (into-the-vein) antibiotic treatment with vancomycin for MRSA along with a seven-day course of the broad spectrum antibiotic imipenem she was diagnosed with severe inflammation of the inner lining of the large intestine caused by the Clostridioides difficile bacterium She received treatment with oral and intravenous vancomycin for eight days By day 18, treatment with Soliris (eculizumab) was initiated her levels of kidney dysfunction markers started to drop and she no longer required hemodialysis She was discharged after 97 days in the hospital A follow-up consultation confirmed she had mild to moderate chronic kidney disease but treatment halted its progression and prevented the need for a kidney transplant with clinical features overlapping with other pregnancy-related conditions causing diagnostic delays,” the researchers wrote “Early diagnosis and early treatment are extremely important for the prognosis posing a genuine challenge for physicians.” Neumann has been involved in health care writing and editing since 1985 He received his BA in Journalism from Rider College and has covered various specialties He has been the editor-in-chief of Nephrology News & Issues since 1989 he has received APEX Awards for Publication Excellence for editorials and feature articles along with recognition from various nephrology organizations the National Association of Nephrology Technicians/Technologists and the American Association of Kidney Patients Mark enjoys spending time restoring vintage automobiles and outdoor activities. Connect with him on LinkedIn here Ravulizumab was successful in improving blood health kidney function and quality of life while maintaining eGFR in pediatric and adult patients with atypical hemolytic uremic syndrome “These results support ravulizumab as a long-term treatment for people with [atypical hemolytic uremic syndrome] aHUS,” Bradley P professor of pediatrics and medicine and head of the renal section of the department of pediatrics at the University of Colorado School of Medicine “aHUS is a rare genetic disease that is caused by the inability of the body’s complement system to be properly regulated,” Dixon told Healio “The endothelial cells become injured by this uncontrolled complement activation and this causes tiny clots to form in the capillaries of the body causing a consumption of platelets and low platelet counts in the blood; hemolysis as the red blood cells are passing through the capillaries containing the tiny clots and organ dysfunction including kidney dysfunction from the clots choking off blood supply and oxygen and nutrients that it carries,” he said “This condition looks clinically very similar to the [Escherichia coli] E coli (Shiga toxin) form of hemolytic uremic syndrome caused by food poisoning from undercooked food but is a very different form of HUS.” a complement C5 inhibitor (C5i) approved for the treatment of aHUS turns off the complement system and stops the injury to endothelial cells “Ravulizumab was developed from an earlier form of the complement-blocking drug eculizumab but has a much longer duration in the body so fewer/less frequent doses of ravulizumab have to be given compared to eculizumab to control the disease,” Dixon told Healio Dixon and colleagues analyzed data from two clinical trials involving children and adults with aHUS who received ravulizumab intravenously every 4 to 8 weeks and the second study included two cohorts of pediatric patients (C5i-naive and those who switched to ravulizumab from eculizumab) “The primary endpoint in the studies of C5i-naive patients was complete [thrombotic microangiopathy] TMA response which consisted of platelet count normalization lactate dehydrogenase normalization and [at least] 25% improvement in serum creatinine from baseline at two consecutive assessments at least 4 weeks apart,” the researchers wrote “Complete TMA response rates over 2 years were 61% and 90% in C5i-naive adults and pediatric patients respectively,” the researchers wrote “The median increase in eGFR from baseline was maintained over 2 years in C5i-naive adults (35 mL/min/1.73 m2) and pediatric patients (82.5 mL/min/1.73 m2).” The researchers wrote that quality of life scores improved for patients who had to take fewer treatment doses compared with eculizumab and no meningococcal infections were reported The U.S. Food and Drug Administration (FDA) has approved Bkemv (eculizumab-aeeb), the first interchangeable biosimilar to Soliris (eculizumab), to treat people with atypical hemolytic uremic syndrome (aHUS) A biosimilar is a medication highly similar to a reference biologic — a medication made from natural living sources like bacteria — already approved by the FDA It is expected to be as safe and work as well over the course of treatment as its reference biologic product a clinically equivalent biosimilar with an “interchangeable” designation can be substituted for its reference biologic at the pharmacy without consulting the prescribing doctor Bkemv, by Amgen, also was approved to treat paroxysmal nocturnal hemoglobinuria (PNH) occurs when the complement system — part of the immune system — becomes overly active “Many rare conditions are life-threatening, and many do not have treatments,” Sarah Yim, who directs the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in an agency press release “The FDA is committed to help facilitate the development of safe and effective interchangeable biosimilar treatments that can expand access for individuals with rare diseases whose current treatment options are limited,” Yim added Like Alexion’s Soliris, Bkemv works by binding to C5, a complement protein, preventing the complement system from becoming overly active and breaking down red blood cells, thereby helping to control aHUS symptoms Inhibiting complement activity in people with aHUS is expected to ease thrombotic microangiopathy which occurs when clots form in small blood vessels blocking blood flow to tissues and damaging organs In an Amgen-funded study involving 217 healthy men, a single 300 mg intravenous (into-the-vein) infusion of Bkemv — then known as ABP 959 — matched Soliris in terms of how fast it was taken up into the bloodstream and how long it stayed in the body It also was seen to be as safe and to inhibit complement activity as well as Soliris None of the participants developed neutralizing antibodies against Bkemv or Soliris which could prevent either medication from working as expected In a Phase 3 clinical study called DAHLIA (NCT03818607) 42 adults with PNH were assigned to receive 900 mg of Bkemv or Soliris for two periods of treatment in a random order Patients receiving Bkemv in the first period of treatment (lasting around one year) then switched to Soliris in the second treatment period (lasting about six months) Bkemv showed similar clinical efficacy to Soliris as measured by the levels of lactate dehydrogenase an enzyme released from red blood cells when they break down While Bkemv has not been tested in people with aHUS, researchers found that it can block the C5 complement protein in a way similar to Soliris in a lab model of simulated blood from the disease supporting its use in aHUS to ease thrombotic microangiopathy Like Soliris, Bkemv’s label carries a boxed warning noting that products containing eculizumab can increase risk of serious and life-threatening meningococcal infection Patients must complete meningococcal vaccination before starting treatment Bkemv will be available only through a restricted program, called a Risk Evaluation and Mitigation Strategy (REMS) which the FDA requires for certain medications with serious safety concerns to help ensure treatment benefits outweigh potential risks All 5 Releases Teva Pharmaceuticals and Samsung Bioepis have announced the U.S availability of EPYSQLI® (eculizumab-aagh) The treatment is now accessible for patients with rare diseases including paroxysmal nocturnal hemoglobinuria (PNH) and generalized myasthenia gravis (gMG) in AchR antibody positive adults EPYSQLI will be offered at a 30% discount compared to Soliris's Wholesale Acquisition Cost making it one of the most cost-effective biosimilars in the U.S The FDA approved EPYSQLI in July 2024 for PNH and aHUS treatments with gMG indication added in November 2024 The FDA has provisionally determined EPYSQLI to be interchangeable with Soliris® after exclusivity expiration for the first interchangeable biosimilar Teva Pharmaceuticals e Samsung Bioepis hanno annunciato la disponibilità negli Stati Uniti di EPYSQLI® (eculizumab-aagh) Il trattamento è ora accessibile per i pazienti con malattie rare tra cui emoglobinuria notturna parossistica (PNH) sindrome emolitica uremica atipica (aHUS) e miastenia grave generalizzata (gMG) negli adulti positivi agli anticorpi AchR EPYSQLI sarà offerto con un sconto del 30% rispetto al costo di acquisizione all'ingrosso di Soliris rendendolo uno dei biosimilari più convenienti negli Stati Uniti La FDA ha approvato EPYSQLI a luglio 2024 per i trattamenti di PNH e aHUS con l'indicazione gMG aggiunta a novembre 2024 mentre Teva si occupa della commercializzazione negli Stati Uniti La FDA ha determinato provvisoriamente che EPYSQLI è intercambiabile con Soliris® dopo la scadenza dell'esclusività per il primo biosimilare intercambiabile Teva Pharmaceuticals y Samsung Bioepis han anunciado la disponibilidad en EE El tratamiento ya está accesible para pacientes con enfermedades raras incluyendo hemoglobinuria nocturna paroxística (PNH) síndrome hemolítico urémico atípico (aHUS) y miastenia grave generalizada (gMG) en adultos positivos para anticuerpos AchR EPYSQLI se ofrecerá con un descuento del 30% en comparación con el costo de adquisición al por mayor de Soliris convirtiéndolo en uno de los biosimilares más rentables en EE La FDA aprobó EPYSQLI en julio de 2024 para tratamientos de PNH y aHUS con la indicación de gMG añadida en noviembre de 2024 mientras que Teva se encarga de la comercialización en EE La FDA ha determinado provisionalmente que EPYSQLI es intercambiable con Soliris® después de la expiración de la exclusividad para el primer biosimilar intercambiable 테바 제약과 삼성바이오에피스는 EPYSQLI® (에쿨리주맙-aagh)의 미국 내 출시를 발표했습니다 그리고 AchR 항체 양성 성인에서의 일반화된 중증 근무력증 (gMG)과 같은 희귀 질환을 가진 환자들에게 접근 가능해졌습니다 EPYSQLI는 솔리리스의 도매 인수 비용에 비해 30% 할인된 가격으로 제공될 예정이며 FDA는 2024년 7월 PNH 및 aHUS 치료를 위해 EPYSQLI를 승인했으며 FDA는 EPYSQLI가 첫 번째 바이오시밀러의 독점 기간 만료 후 솔리리스®와 교환 가능하다고 잠정적으로 결정했습니다 Teva Pharmaceuticals et Samsung Bioepis ont annoncé la disponibilité aux États-Unis de EPYSQLI® (éculizumab-aagh) Ce traitement est désormais accessible aux patients atteints de maladies rares notamment l'hémoglobinurie nocturne paroxystique (PNH) le syndrome hémolytique et urémique atypique (aHUS) et la myasthénie grave généralisée (gMG) chez les adultes positifs aux anticorps AchR EPYSQLI sera proposé avec un rabais de 30% par rapport au coût d'acquisition en gros de Soliris ce qui en fait l'un des biosimilaires les plus rentables aux États-Unis La FDA a approuvé EPYSQLI en juillet 2024 pour les traitements de PNH et aHUS avec l'indication gMG ajoutée en novembre 2024 Dans le cadre de leur partenariat de janvier 2025 tandis que Teva s'occupe de la commercialisation aux États-Unis La FDA a provisoirement déterminé qu'EPYSQLI est interchangeable avec Soliris® après l'expiration de l'exclusivité pour le premier biosimilaire interchangeable Teva Pharmaceuticals und Samsung Bioepis haben die Verfügbarkeit von EPYSQLI® (eculizumab-aagh) in den USA angekündigt Die Behandlung ist nun für Patienten mit seltenen Krankheiten zugänglich darunter paroxysmale nächtliche Hämoglobinurie (PNH) atypisches hämolytisch-urämisches Syndrom (aHUS) und generalisierte Myasthenia gravis (gMG) bei AchR-Antikörper-positiven Erwachsenen EPYSQLI wird mit einem 30% Rabatt im Vergleich zu den Großhandelskosten von Soliris angeboten was es zu einem der kosteneffektivsten Biosimilars in den USA macht Die FDA hat EPYSQLI im Juli 2024 für die Behandlung von PNH und aHUS genehmigt wobei die gMG-Indikation im November 2024 hinzugefügt wurde Im Rahmen ihrer Partnerschaft im Januar 2025 verwaltet Samsung Bioepis die Entwicklung während Teva die Vermarktung in den USA übernimmt dass EPYSQLI nach Ablauf der Exklusivität für das erste austauschbare Biosimilar mit Soliris® austauschbar ist Teva's launch of EPYSQLI marks a strategic entry into the high-value rare disease market with a biosimilar offered at a 30% discount to Soliris's wholesale acquisition cost This presents a meaningful competitive advantage in diseases where treatment costs have been prohibitive and gMG—represent small but lucrative patient populations with approximately 50,000 PNH and 5,000 aHUS patients in the US Current market dynamics reveal significant opportunities: 70% of PNH patients receive non-label-compliant dosing and two-thirds discontinue therapy within 1.5 years The partnership structure optimizes capital efficiency with Teva leveraging its established commercial infrastructure while Samsung Bioepis handles development and manufacturing This arrangement allows Teva to enter a specialized therapeutic area without substantial upfront investment in manufacturing capabilities The pending interchangeability designation represents a future catalyst that could accelerate market penetration once exclusivity expires In rare disease markets where annual treatment costs frequently exceed $500,000 per patient the 30% discount has potential to significantly expand the treated patient population by addressing the primary barrier to continued therapy The EPYSQLI launch represents a significant advancement in rare disease treatment accessibility The 30% price reduction versus Soliris creates one of the largest cost-saving opportunities among biosimilars in the US market particularly meaningful given the ultra-high price points of complement inhibitor therapy Three critical market access factors stand out: First the high discontinuation rate (two-thirds within 1.5 years) among current Soliris patients signals substantial opportunity for a more affordable alternative to improve persistence the provisional interchangeability designation will eventually remove key prescribing barriers though the timeline remains dependent on exclusivity expiration for the first interchangeable biosimilar the partnership leverages Teva's established payer relationships and rare disease market experience while utilizing Samsung Bioepis's manufacturing expertise This combination addresses both supply reliability concerns and formulary access requirements critical for specialty products For payers managing high-cost specialty categories EPYSQLI offers immediate savings opportunities while potentially expanding the treatable population for these severe conditions The biosimilar could ultimately normalize treatment patterns closer to label recommendations by removing cost barriers that currently drive suboptimal dosing in 70% of PNH patients 30% discount of the Wholesale Acquisition Cost (WAC) of the reference product making it one of the greatest cost-saving biosimilars to Soliris® in the U.S.Teva and Samsung Bioepis entered into a strategic partnership in January 2025 for the commercialization of EPYSQLI in the U.S. furthering both companies’ commitment to bring more accessible treatment options to rare disease patients PARSIPPANY 2025 (GLOBE NEWSWIRE) -- Teva Pharmaceuticals affiliate of Teva Pharmaceutical Industries Ltd today announced the availability of EPYSQLI® (eculizumab-aagh) in the U.S EPYSQLI is a biosimilar to Soliris® (eculizumab) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) atypical hemolytic uremic syndrome (aHUS) and generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AchR) antibody positive EPYSQLI will be offered at a 30% discount of the Wholesale Acquisition Cost (WAC) of the reference product offering one of the greatest cost-saving biosimilars to Soliris® in the U.S including paroxysmal nocturnal hemoglobinuria atypical hemolytic uremic syndrome and generalized myasthenia gravis often have limited access to life-enhancing medicines,” said Thomas Rainey “We are proud to launch EPYSQLI in the U.S more affordable treatment option to help expand access to these underserved communities further expanding our biosimilars medicine portfolio and efforts to deliver important medicines to patients through strategic partnerships that leverage our proven commercialization abilities.” and it is important for patients to have early access to treatment The availability of EPYSQLI means that patients now have an additional treatment option available at a lower cost Based on our robust track record supplying biosimilars in the U.S. we are well-positioned to deliver this life-changing medicine to patients,” said Linda MacDonald Executive Vice President and Head of Global Commercial Division of Samsung Bioepis “Our mission is to positively impact and ensure the sustainability of health care systems by offering affordable We will work closely with Teva to ensure access of this medicine for payers healthcare professionals and patients in the U.S.,” she added The monoclonal antibody and anti-C5 complement inhibitor eculizumab is a well-established standard of care to treat PNH and aHUS prevalence of approximately 50,000 and 5,000 respectively.1,2 Approximately 70% of eculizumab-treated PNH patients are not dosed according to the label and two-thirds of patients discontinue eculizumab within an average of 1.5 years which can be attributed to several factors including the high treatment cost.3 Biosimilars are highly similar to their reference product with no clinically meaningful differences in safety and can increase the affordability and accessibility associated with these therapies Biosimilars are approved according to the same standards of pharmaceutical quality that apply to all biological medicines with comparable safety and efficacy to the reference product expected.4 The introduction of biosimilars leads to higher utilization of the molecule as lower costs offer increased access to patients.5 Food and Drug Administration (FDA) as a biosimilar to Soliris® for the treatment of patients with PNH to reduce hemolysis and aHUS to inhibit complement-mediated thrombotic microangiopathy its indication was expanded to include the treatment of gMG in adult patients who are AchR antibody positive The FDA has provisionally determined that EPYSQLI will be interchangeable with the reference biologic Soliris® following the expiration of exclusivity for the first interchangeable biosimilar Teva and Samsung Bioepis entered into a strategic partnership for the commercialization of EPYSQLI in the U.S while Teva is responsible for the commercialization of the product in the U.S. leveraging its experience and extensive sales and marketing infrastructure About EPYSQLI® (eculizumab-aagh) injection for intravenous useEPYSQLI is a complement inhibitor indicated for the treatment of patients with: Limitation of Use: EPYSQLI is not indicated for the treatment of patients with Shiga toxin E coli related hemolytic uremic syndrome (STEC-HUS) Use of Trademarks Soliris® is a registered trademark of Alexion Pharmaceuticals increase the risk of serious infections caused by Neisseria meningitidis Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors These infections may become rapidly life-threatening or fatal if not recognized and treated early Because of the risk of serious meningococcal infections EPYSQLI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called EPYSQLI REMS CONTRAINDICATIONSEPYSQLI is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection Serious Meningococcal InfectionsEculizumab products increase a patient's susceptibility to serious or fatal infections caused by meningococcal bacteria (septicemia and/or meningitis) in any serogroup Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors The initiation of EPYSQLI treatment is contraindicated in patients with unresolved serious Neisseria meningitidis infection Complete or update meningococcal vaccination (for serogroups A and B) at least 2 weeks prior to administration of the first dose of EPYSQLI according to current ACIP recommendations for patients receiving a complement inhibitor Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EPYSQLI Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information If urgent EPYSQLI therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations provide the patient with antibacterial drug prophylaxis and administer meningococcal vaccines as soon as possible Various durations and regimens of antibacterial drug prophylaxis have been considered but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors The benefits and risks of treatment with EPYSQLI as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients must be considered against the known risks for serious infections caused by Neisseria meningitidis Vaccination does not eliminate the risk of serious meningococcal infections despite development of antibodies following vaccination Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur Meningococcal infection may become rapidly life- threatening or fatal if not recognized and treated early Consider interruption of EPYSQLI in patients who are undergoing treatment for serious meningococcal infection depending on the risks of interrupting treatment in the disease being treated EPYSQLI REMSEPYSQLI is available only through a restricted program under a REMS called EPYSQLI REMS because of the risk of serious meningococcal infections Notable requirements of the EPYSQLI REMS include the following: Further information is available at www.EPYSQLIREMS.com or 1-866-318-0342 Other InfectionsSerious infections with Neisseria species (other than Neisseria meningitidis) including disseminated gonococcal infections Eculizumab products block terminal complement activation; therefore patients may have increased susceptibility to infections such as infections with Neisseria meningitidis but also Streptococcus pneumoniae Aspergillus infections have occurred in immunocompromised and neutropenic patients Children treated with eculizumab products may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP recommendations Patients receiving eculizumab products are at increased risk for infections due to these organisms even if they develop antibodies following vaccination Monitoring Disease Manifestations after EPYSQLI DiscontinuationTreatment Discontinuation for PNHMonitor patients after discontinuing EPYSQLI for at least 8 weeks to detect hemolysis Treatment Discontinuation for aHUSAfter discontinuing EPYSQLI monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks 18 patients (5 in the prospective studies) discontinued eculizumab treatment TMA complications occurred following a missed dose in 5 patients and eculizumab was reinitiated in 4 of these 5 patients Clinical signs and symptoms of TMA include changes in mental status the following changes in laboratory parameters may identify a TMA complication: occurrence of two or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during EPYSQLI treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during EPYSQLI treatment; or an increase in serum LDH by 25% or more over baseline or nadir during EPYSQLI treatment If TMA complications occur after EPYSQLI discontinuation consider reinstitution of EPYSQLI treatment or appropriate organ-specific supportive measures Thrombosis Prevention and ManagementThe effect of withdrawal of anticoagulant therapy during eculizumab products treatment has not been established treatment with eculizumab products should not alter anticoagulant management Infusion-Related ReactionsAdministration of eculizumab products may result in infusion-related reactions including anaphylaxis or other hypersensitivity reactions no patients experienced an infusion-related reaction which required discontinuation of eculizumab Interrupt EPYSQLI infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur ADVERSE REACTIONSThe most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) are: headache The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) are: headache The most frequently reported adverse reaction in the gMG placebo-controlled clinical trial (≥10%) is: musculoskeletal pain or Fresh Frozen Plasma InfusionConcomitant use of eculizumab products with plasma exchange (PE) plasmapheresis (PP) or fresh frozen plasma infusion (PE/PI) treatment can reduce serum eculizumab product concentrations and requires a supplemental dose of EPYSQLI Neonatal Fc Receptor BlockersConcomitant use of eculizumab products with neonatal Fc receptor (FcRn) blockers may lower systemic exposures and reduce effectiveness of eculizumab products Closely monitor for reduced effectiveness of EPYSQLI contact Teva Pharmaceuticals at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch Please click here for full Prescribing Information for EPYSQLI Teva Cautionary Note Regarding Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 which are based on management’s current beliefs and expectations and are subject to substantial risks and uncertainties performance or achievements to differ significantly from that expressed or implied by such forward-looking statements You can identify these forward-looking statements by the use of words such as “should,” “expect,” “anticipate,” “estimate,” “target,” “may,” “project,” “guidance,” “intend,” “plan,” “believe” and other words and terms of similar meaning and expression in connection with any discussion of future operating or financial performance Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully commercialize EPYSQLI (eculizumab-aagh) in the U.S for the treatment of the rare diseases: paroxysmal nocturnal hemoglobinuria (PNH) and generalized myasthenia gravis (gMG); our ability to successfully compete in the marketplace including our ability to develop and commercialize additional pharmaceutical products; our ability to successfully execute our Pivot to Growth strategy including to expand our innovative and biosimilar medicines pipeline and profitably commercialize the innovative medicines and biosimilar portfolio whether organically or through business development; and other factors discussed in our Annual Report on Form 10-K for the year ended December 31 including in the section captioned “Risk Factors” and “Forward Looking Statements.” Forward-looking statements speak only as of the date on which they are made and we assume no obligation to update or revise any forward-looking statements or other information contained herein You are cautioned not to put undue reliance on these forward-looking statements Already have an account? Login with plenty of festivities leading up to it Check back for more ways to celebrate Easter as we update this roundup with the latest SEE ALSO: Your Roundup of Easter Menus From All Over O‘ahu Visit the Easter Bunny in his house in the Macy’s wing between Zales and Sephora Photo packages are $35 for an Easter Bunny photo USB with copyright release (3–5 different images) Prints may be ordered through the Expressions Hawai‘i website BOOK NOW 91-5431 Kapolei Parkway, Kapolei, (808) 628-4800, kamakanaalii.com Snap a picture with the Easter Bunny on the second level in the Wai Makai Center Court Walk-in visits and appointments are available daily Photo packages start at $35 for three to five digital photos and print photos available for purchase BOOK NOW Pearlridge Center, 98-1005 Moanalua Road, ‘Aiea, (808) 488-0981, pearlridgeonline.com, @pearlridge Kids will get a 5-minute photo session and the rights to three to five images with the bunny starting at $35 Each child can also receive a “free CPKids meal” card redeemable at CPK Kāhala The spring photo garden is located between Sunglass Hut and the Hawaiian Telcom kiosk BOOK NOW Kāhala Mall, 4211 Wai‘alae Ave., (808) 732-7736, kahalamallcenter.com Hop over to the first floor of the Mauka Court in International Market Place for pictures with the Easter Bunny and each session is 15 minutes long with multiple families scheduled per session as reservations include printable activity sheets BOOK NOW International Market Place, 2330 Kalākaua Ave., (808) 921-0536, shopinternationalmarketplace.com, @intlmktplace Put on your finest spring attire and hop over to Windward Mall to get your photo with the Easter Bunny in Storybook Entertainment’s Easter Garden and photos are available for purchase starting at $25 and including a digital download and two 4×6 prints Windward Mall, 46-056 Kamehameha Highway, Kāne‘ohe, (808) 235-1143, windwardmall.com, @windwardmall Bring your ‘ohana to meet Aunty Lele and Uncle Lapaki the Easter Bunnies of the Royal Hawaiian Center Royal Hawaiian Center, 2201 Kalākaua Ave., royalhawaiiancenter.com, @royalhwnctr SEE ALSO: Things to Do on O‘ahu in April 2025 Enjoy a festive and delicious Easter Brunch at any of the participating Grand Lānai restaurants at the International Marketplace so booking in advance is highly recommended Participating restaurants include Eating House 1849 Spend $100 or more in combined receipts to receive an Easter Egg surprise gift at the customer service on Level One International Market Place, 2330 Kalākaua Ave., (808) 921-0536, shopinternationalmarketplace.com, @intlmktplace SEE ALSO: HONOLULU Family Easter Craft: Hawai‘i-Inspired Eggs Visit Kapolei Commons to take photos with the Easter backdrop photo station located outside the Regal Kapolei Theatre This photo booth is self-serve and open at all times during the shopping center’s daily hours Free, Kapolei Commons, 4450 Kapolei Parkway, Kapolei, kapoleicommons.com, @kapoleicommons Hunt for Easter eggs at the First Assembly of God campuses at Red Hill food and free prizes available for these family-friendly events First Assembly of God, 3400 Moanalua Rd., firstaog.com, @faoghawaii Bring the whole family to enjoy keiki crafts glitter tattoos and photos with the Easter Bunny Keiki are welcome to pick up Easter passports and collect Easter eggs and treats at each station with grand prizes awaiting those who complete the quest Free, Mānoa Marketplace, 2752 Woodlawn Dr., manoamarketplace.com, @manoamarketplace ride a pony and make some egg-cellent Easter Bunny stickers at the Joy of Easter event at Mililani Shopping Center Find a list of participating merchants that will be handing out Easter eggs on the website Free, 95-221 Kīpapa Dr., Mililani, (808) 521-2611, mililanishoppingcenter.com, @mililanishoppingcenter SEE ALSO: HONOLULU Family Easter Craft: Mini Egg Planters Photo: Courtesy of Town Center of Mililani enjoy keiki crafts and visit the petting zoo Join the festivities at Center Court and enjoy performances from UFC Gym and Hālau ‘O Napuala‘ikauika‘iu bags of popcorn and shave ice will be available while supplies last Town Center of Mililani, 95-1249 Meheula Parkway, towncenterofmililani.com, @towncenterofmililani make egg-citing crafts and play in the center Reservations include a one-hour program and admission into the center’s interactive galleries until 3 p.m $15 per person, $10 for members, 111 ‘Ohe St., (808) 524-5437, discoverycenterhawaii.org, @hawaiichildrensdiscoverycenter SEE ALSO: Kid-Friendly Easter Desserts Enjoy an afternoon of ‘ohana-friendly activities at the Ka Lewa Lānai in the Royal Hawaiian Center Keiki can participate in an Easter egg hunt (for ages 7 and under) paint and take home Easter eggs and get their faces painted REGISTER Royal Hawaiian Center, 2201 Kalākaua Ave., royalhawaiiancenter.com, @royalhwnctr SEE ALSO: HONOLULU Family Easter Craft: Washi Tape Eggs Visit Sea Life Park for their Springtime Celebration where keiki can participate in a fun Easter Egg Scavenger Hunt kids will receive a list of clues and a stamp card for the scavenger hunt which can be filled throughout various habitats throughout the park the card can be brought to the Keiki Prize Station to redeem for prizes Free keiki admission with adult admission purchase ($59.99), Sea Life Park, 41-202 Kalaniana‘ole Highway, Waimānalo, sealifeparkhawaii.com, @sealifepark Brighten up your Easter by painting your own miniature ceramic Easter Egg light and participate in an Easter Egg hunt with exciting prizes on the Kuilima Point Lawn While this event is being hosted at the Ritz-Carlton O‘ahu it is also open to non-resort guests attending the Easter Brunch Buffet by reservation only BOOK NOW $50 for resort guests, $75 for non-resort guests, The Ritz-Carlton O‘ahu, Turtle Bay, 57-091 Kamehameha Hwy, Kahuku, turtlebayresort.com, @turtlebayresort Fit4Mom is organizing free community workouts and egg hunts Participating families are asked to bring 20 eggs filled with treats stickers or toys to contribute to the hunt The Easter Bunny will make a special appearance The Easter egg hunt will run simultaneously for separate age groups (4 and under and look out for eggs with special offers and prizes BOOK NOW Free with pre-booked Wai Kai activities, $5 general admission, waikai.com, @waikaiexperience Create a fairy garden with cute little plants and Easter-themed accessories; all supplies are provided along with refreshments you’ll get an exclusive offer to take 10% off any purchase on the day of the event $40, Mari’s Gardens Mililani, 94-415 Makapipipi St, Mililani, marisgardens.com, @maris_gardens Meet the Easter Bunny at Hard Rock Café as you breakfast BOOK NOW Reservations required, Hard Rock Café, 280 Beach Walk, cafe.hardrock.com, @hrchonolulu take photos with an Easter-themed backdrop play games and win prizes from KDNN Radio and even pet real bunnies Free, Salt Lake Shopping Center, 848 Ala Liliko‘i St., saltlakeshoppingcenter.com, @saltlakeshopping SEE ALSO: HONOLULU Family Easter Recipe: Colorful, Layered Springtime Treats Photo: Courtesy of Hawai‘i Kai Towne Center Spring into the Easter festivities at the Hawai‘i Kai Towne Center’s Marina Docks Bring your own cameras or phones to take selfies with the Easter Bunny in a beautifully decorated Easter selfie station There will also be special twisted balloon animals and Easter giveaways while supplies last Hawai‘i Kai Towne Center, 333 Keahole St., (808) 440-2917, hawaiikaitownecenter.com, @hawaiikaitownecenter Receive expert guidance from Kasey Matschat of Island Bloom Florals on how to pair dried and fresh flowers with Easter adornments All supplies and farm-to-table refreshments will be provided $75, gates open at 4:45 p.m., Mari’s Gardens Kailua, 1127 Kailua Rd, Kailua, marisgardens.com, @maris_gardens Lōkahi Kailua Market and other local businesses are teaming up to host a fun egg hunt on Easter morning And this one isn’t just for kids—moms and dads are welcome to participate too Eggs hidden in a designated obstacle area at Lōkahi Market will be filled with toys BUY TICKETS All proceeds will go to KidzArt Hawai‘i’s financial aid program Note: You can leave your Easter baskets at home as baskets will be provided for all participants $15 to $20 with a small online booking fee, Lōkahi Kailua Market, 340 Uluniu St., Kailua, @kidzarthawaii Spend Easter Sunday outdoors cheering on polo matches there will be an Easter egg hunt on the field Enjoy Spanish and Mediterranean cuisine from Mayas Tapas and live music by The Imposters as well From $23, free for keiki 12 and under, Hawai‘i Polo Club, 68-411 Farrington Hwy, Waialua, hawaii-polo.org, @hawaiipolo Photo: Courtesy of Salt at Our Kaka‘ako Visit Salt’s colorful Springtime-themed photo station to take selfies with the Easter Bunny (bring your own cameras or phones to take pictures free of charge) Keiki will also enjoy Spring/Easter crafts (while supplies last) and balloon art and everyone is welcome to enter the spin-to-win prizes from their favorite Salt merchants Salt at Our Kaka‘ako, 691 Auahi St., saltatkakaako.com, @saltourkakaako SEE ALSO: HONOLULU Family Easter Craft: Sock Bunnies Photo: Courtesy of Wet ’n’ Wild Hawaii This is not your traditional egg hunt—huge prizes are inside the 24 eggs that will be hidden within Keiki Kove Lil Kahuna Beach and Hawaiian Waters Wave Pool area one-day tickets and food certificates to Crumbl Cookie and Little Caesar Pizza Two platinum eggs even contain one of two special prizes One egg contains a staycation package for four people which includes a one-night accommodation in a Studio Suite at Residence Inn by Marriott and Kāhuna Season Passes; and the other platinum egg includes passes for a birthday party for 10 (10 daily ticket admissions fruit punch and a reserved area for the entire day) The first 200 keiki (ages 12 and under) through the gate before 11:30 a.m or while supplies last will receive an Easter goodie bag filled with treats and the Easter Bunny will make a special appearance for a photo op Free with park admission, kama‘āina and military get 50% off 1-day general admission before 11:30 a.m., Wet ’n’ Wild Hawai‘i, 400 Farrington Highway, Kapolei, wetnwildhawaii.com, @wetnwildhawaii We are a leading healthcare campus encompassing all fields of health: from healthcare and research to teaching and management commitment and research by professionals on the Campus are the key elements in offering patients excellent care We are committed to research as a tool to provide solutions to the daily challenges we face in the field of medical healthcare we work to incorporate new knowledge to generate value for patients transform and transmit knowledge in all areas of the health sciences helping to train the professionals of the future We are defined by our vocation for communication We invite you to share everything that happens at Vall d'Hebron Barcelona Hospital Campus A study from the Vall d’Hebron Campus demonstrates that the Ex Vivo C5b-9 deposition test is useful for monitoring the activity of the complement system (CS) in patients with aHUS or transplant-associated TMA Atypical hemolytic uremic syndrome (aHUS) is a rare genetic disease that causes the formation of clots in the blood capillaries (thrombotic microangiopathy but with greater impact on the kidney vasculature It is caused by a malfunction of the complement system (CS) a group of blood proteins involved in the innate immune system the CS is chronically and uncontrollably activated leading to excessive formation of the C5b-9 component on the cells of the blood vessels The CS can also be secondarily altered for other reasons The Ex Vivo C5b-9 deposition test is an in vitro test that detects abnormal CS activity on cultured endothelial cells we can determine if the affected person has TMA associated with CS alterations (whether aHUS or secondary TMA) and determine the degree of disease activity the Ex Vivo C5b-9 test is a useful tool not only for detecting CS activity in patients with aHUS and transplant-associated TMA but also for monitoring the activity level This allows for a broader spectrum of patients to benefit from the test and also to personalize the medication plan based on the disease activity level Have you ever heard of a disease so rare that even medical experts have trouble diagnosing it Atypical Haemolytic Uremic Syndrome (aHUS) is such a condition It strikes only a few individuals globally causing kidney failure and other life-threatening complications the journey to diagnosis is long and uncertain To understand this condition, we spoke to Dr (Prof) Arvind Bagga, Senior Consultant, Department of Paediatric Nephrology, Apollo Indraprastha,New Delhi, who explained aHUS, its signs, causes, diagnosis, and treatment. What is atypical HUS (aHUS) “Haemolytic Uremic Syndrome (HUS) is a serious condition that causes damage to the inner lining of blood vessels, resulting in tiny clots that lead to platelet deficiency The most common form of HUS is associated with infection by food-borne bacteria that produce the ‘Shiga toxin.’ This form is more common in children and is prevalent across the world but less so in South Asia,” explained Dr Bagga Also Read: Can High Blood Sugar Damage Your Kidneys? Here Is What An Expert Has To Say! Importance of Prompt Management Timely diagnosis and appropriate management are essential for managing aHUS this might be a challenge as the clinical features of the disease often overlap with other conditions nearly one out of every two patients with aHUS will need dialysis these patients need prompt referral to a nephrologist (kidney specialist) for prompt initiation of specific therapy “aHUS can significantly impact patients' quality of life Their families may also struggle with guilt the need for frequent dialysis leads to poor quality of life,” highlighted Dr Bagga Diagnosis of aHUS Key tests for diagnosing aHUS include stool tests for Shiga toxin and investigations for associated conditions Also Read: Kidney Failure Symptoms: Early Warning Signs You Shouldn’t Ignore Treatment for aHUS Treatment depends on the severity of aHUS and the underlying cause the patient may be monitored regularly and receive supportive treatment such as blood transfusions and medications to manage hypertension “Plasma exchanges are considered an important form of therapy for aHUS Plasma exchanges or infusions are required frequently and the medium-term outcome of these interventions is not satisfactory,” said Dr Bagga Early use of complement inhibitors has significantly improved outcomes in patients with aHUS Some patients may require prolonged dialysis Kidney transplant patients with aHUS face a high risk of recurrence “Although the journey with aHUS is challenging timely diagnosis and targeted therapies have significantly improved patient outcomes,” concluded Dr Bagga [Disclaimer: This article contains information provided by an expert and is for informational purposes only. Hence, we advise you to consult your professional if you are dealing with any health issue to avoid complications.]Read NextDietary Changes That May Help Manage An Overactive BladderDisclaimer All possible measures have been taken to ensure accuracy timeliness and authenticity of the information; however Onlymyhealth.com does not take any liability for the same Using any information provided by the website is solely at the viewers’ discretion In case of any medical exigencies/ persistent health issues we advise you to seek a qualified medical practitioner before putting to use any advice/tips given by our team or any third party in form of answers/comments on the above mentioned website This website follows the DNPA’s code of conduct Bayview Golf Course has just launched its weekly Saturday night market, where you can enjoy manapuas from Island Manapua, sweet refreshers from Sugar Mami, bar specials from Jolene’s by the Bay live music and family-friendly activities at the mini-putt and golf park Follow the Instagram to stay updated on the vendors and activities Free, 45-285 Kāne‘ohe Bay Dr., Kāne‘ohe, bayviewgolfcourse.us, @bayviewnightmarket SEE ALSO: Your Guide to Farmers Markets on O‘ahu Enjoy live music, food vendors, specialty drinks by D’lish at the Beach and an evening at the beach at the Kapilina Night Market Follow the market on Instagram and Facebook for the latest updates Free, Pilikai Beach Park, 5100 Iroquois Ave., ‘Ewa Beach, @KapilinaBeachHomes, @livekapilina Free, Wai Kai, 91-1621 Keone‘ula Blvd., ‘Ewa Beach, onogrindzandmakeke.com, @onogrindzandmakeke SEE ALSO: Date Night Market: A $60 Sunset Date at ‘Ono Grindz & Mākeke Every Saturday, head to the Pearlridge Center for the Village Market in front of TJ Maxx. Explore Central O‘ahu’s best food trucks and craft vendors, including Corn Onoz Hawai‘i, Waba Snacks and Maguro Brothers while indulging in cocktails at the open-air beer garden and enjoying live music from local artists Check the Instagram for weekly vendor lists and entertainment lineups Free, Pearlridge Center, 98-1005 Moanalua Rd., ‘Aiea, pearlridgeonline.com, @village.events.hawaii SEE ALSO: Date Night Market: $60 Feast for Two at Pearlridge’s Village Night Market Follow Art + Flea’s Instagram to stay updated on participating vendors and entertainment lineups Free, Capitol Modern, 250 South Hotel St., Downtown, artandflea.com, @artandflea Free, Waikele Center, 94-849 Lumi‘aina St., Waipahu, by-my-standards.com, @whatthetruck.hawaii Head over to Windward Mall every second Friday of the month for the Ko‘olau Night Market, where you can grab summer rolls from Ono Viet, baked goodies from Brave Hearts Bakery, handcrafted resin jewelry from Tide Pool Bangles and more Enjoy live entertainment and free admission at this monthly night market Free, Windward Mall parking lot next to Leonard’s Malasadas Truck, 46-056 Kamehameha Hwy., Kāne‘ohe, islandcraftfairs.org, @islandcraftfairs Free, Waterfront Plaza, 500 Ala Moana Blvd., Kaka‘ako, tasteofalohahi.com, @tasteofalohahi Follow the night market’s Instagram for vendor updates and information on reserving your plant from Grow Aloha Free, Bishop Museum, 1525 Bernice St., Kalihi, @kaiwiulanightmarket enjoy an evening of live music while you eat Free, Pearl at Kalauao, 98-535 Kaonohi St., ‘Aiea, pearlatkalauao.com, @nightmarketcentral Those living in Mililani no longer have to drive to Kapolei or town for a local night market—the new and upcoming annual Mililani Garden Nights at Mari’s Gardens offers family-friendly fun with local vendors there will be trolley rides from the parking area and a VIP ticketing option with two beer gardens for adults 21 and older BUY TICKETS Free, $10 for 21+ VIP tickets, $10 for hidden garden concert tickets, $9 for parking pass and family trolley rides, $4 for solo trolley ride, 94-415 Makapipipi St., Mililani, @mililanigardennights drinks and gifts from over 100 vendors at Windward Oahu’s largest outdoor night market Support local vendors and enjoy live music and performances Follow the Instagram and check the website for updated information on vendors Free, 21+ VIP tickets, parking pass and family trolley ride tickets available, Windward Mall, Lot 44, 46-68 Alaloa St., Kāne‘ohe, kaneohenightmarket.com, @kaneohenightmarket No night market roundup would be complete without mentioning the island’s biggest—the Honolulu Night Market This biannual event takes place in June and November at Our Kaka‘ako and always boasts an impressive lineup of food vendors Check the website and Instagram and sign up for the email list for the most up-to-date information on the upcoming events Free, The Barn at Salt at Our Kaka‘ako, Auahi, Coral and Keawe St., Kaka‘ako, ourkakaako.com, @hnlnightmarket By Paul Honda Editors' Picks MARCO GARCIA/SPECIAL TO THE HONOLULU STAR ADVERTISER University Lab’s Alika Ahu (23) tries to grab a loose ball over Punahou’s Tate Takamiya (1) and Dane Kellner (11) during the first half of the state boy’s basketball semifinal play off game at McKinley Gym on Thursday University Lab’s Alika Ahu (23) makes a layup over Punahou’s Tate Takamiya (1) during the first half of the state boy’s basketball semifinal play off game at McKinley Gym on Thursday DARRYL OUMI / SPECIAL TO THE STAR-ADVERTISER Alika Ahu is a two-way threat in baseball as a pitcher and batter for the Wolfpack He posed on Saturay at Keehi Lagoon baseball field DARRYL OUMI / SPECIAL TO THE HONOLULU STAR-ADVERTISER Alika Ahu sat in the dugout during a practice for the Pac-Five Wolfpack on Saturday Already a Honolulu Star-Advertiser subscriber? Log in now to continue reading It was the week of a baseball tournament on Maui days before the HHSAA Boys Basketball State Championships arrive in Kahului and play shortstop for the Pac-Five Wolfpack fly into HNL and get to basketball practice with the University Lab Jr but few have done the daily commute for two sports which means her oldest son can travel stand-by “I just remember being grateful that my mom has flight benefits that allow me to fly back and forth like that for free,” Alika Ahu said “Without that it wouldn’t have been possible.” The double-duty life is just part of the world Ahu lives in while maintaining a 4.0 grade-point average 190-pound junior is one of the top baseball prospects in the state and has already committed to Stanford fast athletes often connect to football and Pylon year round Ahu was born into a family with basketball and baseball roots was a 6-1 forward who starred in three sports at Waiakea the same size Alika Ahu is now as a high school junior “I’ve seen him do things from 13 he’s way better than I was,” Jaime Ahu said Just unstoppable with his strength and size I see him process it and use it to get better.” Former Pac-Five coach Paul Ah Yat coached Ahu as a freshman two years ago He has a gift of being able to just focus on the things that matter that’s what they teach you when you’re in pro ball.” Making a diving play is more thrilling,” he said “I don’t put a lot into pitching maybe one or two (workouts) a week for my arm but I don’t work on it that much.” Current Pac-Five coach Reyn Sugai is also a ULS alum “I saw Alika play in eighth grade on the intermediate team He always had great hands and footwork defensively,” Sugai said “He just carried himself differently from most guys His leadership this year has definitely surpassed expectations even with him playing basketball a lot of people don’t really see.” Ahu and his father headed back to campus and loaded up the pitching machine “The discipline day to day is something you see in pro athletes He and his (younger) brothers balance their schoolwork and have that work ethic,” Sugai added University and Pac-Five are in maximum efficiency mode “The pride is coming back,” Sugai said Basketball was instrumental when Ahu went from Manoa Elementary School to ULS in sixth grade Kenna Quitan and Ahu were busy playing club basketball in the offseason everyday talk-story was about academic challenges and rumination on weekend games with their club teams The group played for former boys varsity coach Walt Quitan “I’m a Kamehameha graduate,” Tiare Ahu said “But when Alika got to University Lab he found an immediate community with those boys in basketball The seniors on that team were so awesome.” is a big reason why the straight-A son of a Kamehameha administrator stayed at ULS rather than become a Warrior scholar-athlete At no other school did I think our boys would play varsity sports from freshman year,” Jaime Ahu said 1 starter and UH commit Colten Amai-Nakagawa Alika Ahu is passing down what was gifted to him during his first year in varsity sports “He always gravitated toward the older kids They always hung out at school and they were good role models for the younger kids,” Jaime Ahu said “They made the younger ones feel welcome and part of the team.” University caught a wave in hoops with the current core of multi-sport athletes ‘Bows reached the semifinal round and lost There were plenty of highlights for Ahu and the Jr He scored a team-high 20 points in a 49-48 win at No 2-ranked Punahou that vaulted ULS into a second-place tie When the teams met a week later in a tiebreaker playoff for second place and a state-tournament berth Coach Ryan Tong’s squad qualified for the state championships by finishing third in the brutally tough ILH Ahu’s tip-in with three-tenths of a second left lifted ULS over Kamehameha all seven ILH D-I teams were ranked in the Top 10 at least once Overcoming early- and mid-season injuries and illnesses The team was relatively healthy at the right time This is when Ahu weighed his options and decided he would not miss any ULS basketball practices or Pac-Five baseball games Ahu and his University teammates flew to Maui for the opening round of the state basketball tournament Ahu scored 11 points in the program’s biggest D-I state-tournament win in years ’Bows run came to an end in the semifinals a 49-46 loss to eventual state champion Punahou In the three games with a potential title at stake Ahu averaged 12 points on 16-for-30 shooting from the field (53%) University (21-13) closed the season at No The bond and pride of wearing the green and white hasn’t been this strong in a generation “Alika has always been even-keeled through the highs and lows He was expressing a lot of intensity on the basketball court this year,” Jaime Ahu said The team will return most of the roster next season though filling the void of outgoing senior Laboy will be a major task “I’m hoping everyone comes back If we can stay healthy and continue to progress and develop I’m excited about next year,” Tong said “Alika’s obviously going to have to play a major role for us again He’s always had to guard the best player He’s one of the best defenders in the state A lot of our success is the result of Alika’s performance It’s a luxury to have a player that is able to not just play 1 through 5 It’s extremely rare and it’s extremely valuable.” Ahu batted .326 with an on-base percentage of .466 in ILH play He had 14 runs scored and seven stolen bases Ahu had a 3.49 ERA with 11 strikeouts and four walks in 24 innings pitched Ahu was at a baseball combine for incoming juniors unable to directly contact parents and players until Aug “I love the way your son plays,” he said Alika Ahu was on a flight back to Honolulu when the clock struck midnight “His phone just blew up,” Jaime Ahu said All these big schools trying to be the first to talk to him My wife calls me a half-hour after they got off the phone This is too much for us to handle.’” mom had already set up a spreadsheet listing 30 coaches and their phone numbers That was roughly half of all the texts and calls Alika Ahu knew who he wanted to spend his college years with “It was 10 a.m.,” Jaime Ahu recalled ‘I want to go to Stanford.’ I asked him ‘You don’t want to visit other colleges?’ He said I can use the weekends to train.’” Alika Ahu got on his phone and replied to all 60-plus schools “I told them I was committed to Stanford “Most of them were professional about it.” Pac-Five is 2-4-1 after two weeks of a tough nonconference schedule The ‘Pack opens ILH action March 12 against Saint Louis at Ala Wai Field Last year’s team was 2-15 in ILH play “They’re going to be special this year,” Ah Yat said We’re pretty tight together,” he said Everyone here is just used to playing at different fields.” Sunday morning is a rare moment of relative stillness The Ahu ohana attends C4 Christ-Centered Community Church in East Honolulu “My favorite thing about church is worship,” Alika Ahu said “The atmosphere when everyone is singing and worshipping God.” “I’ve seen ‘Sandlot” around 15 times ‘Moneyball’ is about doing what you got to do to win.” Korean fried chicken and chili plate (Zippy’s) “My grandpa (Henry Butch Robinson) is a huge Cubs fan.’ “But he left (the Cubs) and he’s not good anymore Funniest teammate: Ethan Kamahele or Thomas Mitchell “One is from basketball and the other is from baseball “Because he’s going to Stanford.” “I get my homework done early at school so I can get sleep.” “She teaches well and she’s nice Favorite scripture: Joshua 1:9 “Be strong and courageous Do not be afraid; do not be discouraged for the Lord your God will be with you wherever you go.” and my two younger brothers Aaron and Austen.” Subscribe! Honolulu Magazine | Honolulu Family and lucky as we are to abound in gau and jai in this season these traditional foods are joined by so much more Lunar New Year is the biggest day of the year not just for the Chinese world Honolulu’s multiethnic food scene joins in with treats like gau mochi almond float sherbet and Year of the Snake shave ice Click on the images below to find out more about these Lunar New Year menus And keep checking back as we update this roundup with more finds SEE ALSO: Ring in the Year of the Snake With Lion Dances, Firecrackers, Parades and More Industry news and insights from Europe and around the World Keep up-to-date with the latest new products and technology UK: Ciat has supplied three ClimaCiat AirAccess AHUs to a brand new purpose-built new hub for the performing arts in the Chiltern Hills is a multi-purpose resource for rehearsals Garsington Studios is a greenfield project committed to renewable energy sources aiming to be a beacon of sustainable design. The Studios’ acoustic and thermal requirements were stringent demanding precise control over noise levels and temperatures across multiple rooms including recording studios and the main auditorium. These stringent noise ratings were addressed with acoustically lined plenums and ducting minimising ventilation noise to create an optimal acoustic environment for performances and recordings The supply air noise level was kept to 58dBA Attention was paid to energy efficiency with the inclusion of a thermal wheel and the availability of a free cooling mode The greenfield site and unpredictable weather conditions presented unique challenges Ciat’s team proactively managed the project in phases to ensure the installation stayed on track despite the adverse conditions Huntingdon-based Arcade UK were the mechanical design and build contractors for the project Cooling Post is the leading online resource covering latest news and developments in the cooling industry air conditioning news and the latest heat pump developments Privacy & Cookie Policy © Copyright 2025, Cooling Post Ltd - All Rights Reserved | Website by Capital Web Metrics details Studies of complement genetics have changed the landscape of thrombotic microangiopathies (TMAs) particularly atypical haemolytic uraemic syndrome (aHUS) Knowledge of complement genetics paved the way for the design of the first specific treatment for aHUS and is increasingly being used to aid decisions regarding discontinuation of anti-complement treatment in this setting Complement genetic studies have also been used to investigate the pathogenic mechanisms that underlie other forms of HUS and provided evidence that contributed to the reclassification of pregnancy- and postpartum-associated HUS within the spectrum of complement-mediated aHUS complement genetics has not provided definite evidence of a link between constitutional complement dysregulation and secondary forms of HUS the available data do not support systematic testing of complement genes in patients with typical HUS or secondary HUS The potential relevance of complement genetics for distinguishing the underlying mechanisms of malignant hypertension-associated TMA should be assessed with caution owing to the overlap between aHUS and other causes of malignant hypertension the interpretation of complement genetics results remains complex as even complement-mediated aHUS is not a classical monogenic disease Such interpretation requires the input of trained geneticists and experts who have a comprehensive view of complement biology Knowledge of complement genetics has transformed the landscape of atypical haemolytic uraemic syndrome (aHUS) and other forms of HUS aHUS is the only form of HUS that has been clearly associated with genetic susceptibility factors related to complement regulation Pregnancy- and postpartum-associated HUS is part of the spectrum of complement-mediated HUS Secondary forms of HUS do not share genetic risk factors with aHUS Malignant hypertension is highly prevalent in patients with aHUS; however aHUS is a rare cause of malignant hypertension Interpretation of complement genetics results requires comprehensive expertise in complement biology Prices may be subject to local taxes which are calculated during checkout Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency predispose to development of familial hemolytic uremic syndrome Familial haemolytic uraemic syndrome and an MCP mutation The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults High-throughput genetic testing for thrombotic microangiopathies and C3 glomerulopathies Statistical validation of rare complement variants provides insights into the molecular basis of atypical hemolytic uremic syndrome and C3 glomerulopathy Complement system Part I — molecular mechanisms of activation and regulation Complement gene variants and shiga toxin-producing escherichia coli-associated hemolytic uremic syndrome: retrospective genetic and clinical study Impact of hypertensive emergency and complement rare variants on presentation and outcome of atypical hemolytic uremic syndrome Genetic analysis of 400 patients refines understanding and implicates a new gene in atypical hemolytic uremic syndrome Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors The genetic fingerprint of susceptibility for transplant-associated thrombotic microangiopathy Acquired complement regulatory gene mutations and hematopoietic stem cell transplant-related thrombotic microangiopathy Pretransplant genetic susceptibility: clinical relevance in transplant-associated thrombotic microangiopathy A global reference for human genetic variation Hemolytic uremic syndrome in pregnancy and postpartum Maternal and fetal outcomes of pregnancies in women with atypical hemolytic uremic syndrome A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome Germline mutations in the alternative pathway of complement predispose to HELLP syndrome and factor I mutations in patients with hemolysis The genetics of the alternative pathway of complement in the pathogenesis of HELLP syndrome Familial risk of developing atypical hemolytic-uremic syndrome Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology Complete functional characterization of disease-associated genetic variants in the complement factor H gene Complement factor B mutations in atypical hemolytic uremic syndrome-disease-relevant or benign C3 and C9 are associated with high risk of advanced age-related macular degeneration A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis Dynamics of complement activation in aHUS and how to monitor eculizumab therapy Complement activation and thrombotic microangiopathies C5b9 formation on endothelial cells reflects complement defects among patients with renal thrombotic microangiopathy and severe hypertension An Ex vivo test of complement activation on endothelium for individualized eculizumab therapy in hemolytic uremic syndrome Targeted strategies in the prevention and management of atypical HUS recurrence after kidney transplantation Discontinuation of eculizumab treatment in atypical hemolytic uremic syndrome: an update Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome Use of highly individualized complement blockade has revolutionized clinical outcomes after kidney transplantation and renal epidemiology of atypical hemolytic uremic syndrome Fakhouri, F. et al. Eculizumab discontinuation in children and adults with atypical haemolytic uremic syndrome: a prospective multicentric study. Blood https://doi.org/10.1182/blood.2020009280 (2020) Thrombomodulin mutations in atypical hemolytic-uremic syndrome Determining the population frequency of the CFHR3/CFHR1 deletion at 1q32 Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome Clinical and immunological profile of anti-factor h antibody associated atypical hemolytic uremic syndrome: a nationwide database Thrombotic microangiopathy in inverted formin 2-mediated renal disease A novel mutation in the complement regulator clusterin in recurrent hemolytic uremic syndrome The phenotypic spectrum of nephropathies associated with mutations in diacylglycerol kinase epsilon Loss of DGKepsilon induces endothelial cell activation and death independently of complement activation Adult-onset renal thrombotic microangiopathy and pulmonary arterial hypertension in cobalamin C deficiency Eculizumab for the treatment of pregnancy-related atypical hemolytic uremic syndrome Suspected atypical haemolytic uraemic syndrome in two post-partum patients with foetal-death in utero responding to eculizumab Eculizumab in pregnancy-associated atypical hemolytic uremic syndrome: insights for optimizing management Post-partum atypical haemolytic-uraemic syndrome treated with eculizumab: terminal complement activity assessment in clinical practice Postpartum thrombotic microangiopathy revealed as atypical hemolytic uremic syndrome successfully treated with eculizumab: a case report Successful treatment of the postpartum atypical hemolytic uremic syndrome with eculizumab Etiology and outcomes of thrombotic microangiopathies Renal cortical necrosis in postpartum hemorrhage: a case series Increased release of tumor necrosis factor-alpha and interleukin-6 in women with the syndrome of hemolysis Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome Mutations in complement regulatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort Classical complement pathway activation in the kidneys of women with preeclampsia Placental sFLT1 is associated with complement activation and syncytiotrophoblast damage in preeclampsia Soluble c5b-9 as a biomarker for complement activation in atypical hemolytic uremic syndrome Atypical haemolytic uraemic syndrome and pregnancy: outcome with ongoing eculizumab Eculizumab in pregnant patients with paroxysmal nocturnal hemoglobinuria Eculizumab in secondary atypical haemolytic uraemic syndrome Insights from the use in clinical practice of eculizumab in adult patients with atypical hemolytic uremic syndrome affecting the native kidneys: an analysis of 19 cases Patients with hypertension-associated thrombotic microangiopathy may present with complement abnormalities ESC Council on hypertension position document on the management of hypertensive emergencies Diagnostic and risk factors for complement defects in hypertensive emergency and thrombotic microangiopathy Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference treatment and prognosis with experience from the Bordeaux cohort A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy Improving survival of malignant hypertension patients over 40 years Complications and survival of 315 patients with malignant-phase hypertension Increasing trend in admissions for malignant hypertension and hypertensive encephalopathy in the United States presentation and complications of malignant hypertension Predictors of 5-year outcomes in malignant phase hypertension: the West Birmingham Malignant Hypertension Registry Genetic testing of complement and coagulation pathways in patients with severe hypertension and renal microangiopathy Download references Lausanne University Hospital and University of Lausanne The authors contributed equally to all aspects of this article has received consultancy and/or speaker honoraria from Roche V.F.-B has received fees from Alexion Pharmaceuticals Novartis and Baxter for invited lectures and/or board membership and is the recipient of a research grant from Alexion Pharmaceuticals and Apellis Nature Reviews Nephrology thanks the anonymous reviewer(s) for their contribution to the peer review of this work Genome Aggregation Database (gnomAD): https://gnomad.broadinstitute.org/ A high-throughput methodology that enables rapid sequencing of the base pairs in DNA samples This ‘first-generation’ DNA sequencing method is considered to be the gold standard for validating DNA sequences including those that have been obtained using next-generation sequencing A multiplex assay to detect copy number variations of genomic DNA sequences A molecular mechanism of exchange between two long segments of DNA (~300 bp or longer) that have very high sequence homology An in silico tool that is designed to predict the pathogenicity of variants CADD scores are based on diverse genomic features derived from the surrounding sequence context epigenetic measurements and functional predictions In silico predictive scores should be used Download citation DOI: https://doi.org/10.1038/s41581-021-00424-4 Here’s where to go and what to do to get into the holiday spirit this year whether you’re looking for Christmas lights or searching for Santa himself Bookmark this roundup since it’ll be updated regularly Click to the holiday events you want to explore: Await the arrival of Aloha Santa with live local music Aloha Santa will lead the lighting of the 34-foot holiday tree decked in Hawaiian ornaments Stick around to take a free professional photo with him Free, Royal Hawaiian Center Royal Grove, 2201 Kalākaua Ave., royalhawaiiancenter.com, @royalhwnctr The Royal Hawaiian will be fully decked out with 30,000 lights Free, The Royal Hawaiian, 2259 Kalākaua Ave., marriott.com, @royal_hawaiian This holiday parade honors survivors of the Dec attack on Pearl Harbor and members of the U.S The torch-lit 1.5-mile night parade begins at Fort DeRussy continues along Kalākaua Avenue and ends at Kapi‘olani Park Free, Waikīkī, waikikiholidayparade.com The parade will start at the corner of Lunalilo Home Road and Hawai‘i Kai Drive (by the HK Skate Park) and march down Lunalilo Home Road Stick around for the afterparty from 11 a.m Bring a toy donation to receive 10 free tickets to play the carnival games Free, Koko Marina Center, 7192 Kalaniana‘ole Hwy, kokomarinacenter.com, @kokomarinacenter Join the Leeward O‘ahu community at a festive block party along Ala Kahawai and Ulu‘ōhi‘a St luminous displays of holiday cheer and a holiday parade The parade will begin outside of Kapolei High School and end at Kama‘aha Street The holiday lights will be displayed nightly until 11 p.m Free, 1000 Ulu‘ōhia St., Kapolei, honolulu.gov, @kapoleisanta The Kaimukī Christmas Parade returns with marching bands The Christmas tree on top of Pu‘u O Kaimukī will also be lit Free, Wai‘alae Ave., kaimukihawaii.com See Wahiawā light up in its biggest event of the holiday season The parade will start at Ka‘ala Elementary Free, California Ave., ourwahiawa.com, @ourwahiawa Photo: Courtesy of City and County of Honolulu View Christmas trees decorated in various themes by City and County of Honolulu departments Tūtū Mele and the snowman family will also be there spreading holiday cheer Mayor Rick Blangiardi will light the city’s 50-foot holiday tree as well as the lights strung up around Honolulu Hale and the Civic Center grounds Get a free photo with Santa on opening night Free, parking available in the municipal lot at Alapai and Beretania St., 530 S. King St., honolulucitylights.org, @friendshonolulucitylights SEE ALSO: Your Insider Guide to Honolulu City Lights The parade starts at Kāne‘ohe Bay Shopping Center and ends at Castle High School Street closures along Kamehameha Hwy begin at 8:30 a.m Free, kaneohechristmasparade.org, @kaneohechristmasparade Santa Claus and more starts at Mililani High School’s Kauinana Stadium and ends at the Town Center of Mililani Come see the resort’s Christmas tree centerpiece in the lobby light up for the first time amid the decked out halls Free, Moana Surfrider, A Westin Resort & Spa, Waikīkī Beach, 2365 Kalākaua Ave., marriott.com, @themoanasurfrider Photo: Courtesy of Hawai‘i Kai Marina Community Association Come see the marina boats decked out and lit up in a parade on the water Free, Hawai‘i Kai Marina, hawaiikaimarina.com, @hkmca_hawaii Spend $200 or more at Ward Village retailers and show your receipts to receive two free tickets to Consolidated Theatres at Ward (while supplies last). Receipts can be during business hours at Crazy Shirts and Paul Brown Salons in Ward Centre and House of Mana Up in South Shore Market. More details online Ward Village, 1240 Ala Moana Blvd., wardvillage.com, @wardvillage SEE ALSO: Can’t-Miss Local Holiday Markets and Craft Fairs on O‘ahu Receive a travel tote featuring a Big Santa enamel charm when you spend $500 from Nov. 9 to Dec. 24 (while supplies last). Redeem your receipts at Guest Services on the ground floor. See the terms and conditions online Ala Moana Center, 1450 Ala Moana Blvd., alamoanacenter.com, @alamoanacenter Have a bubbly holiday shopping experience with different wine tastings using your commemorative wine glass light bites and exclusive deals at participating Kāhala Mall retailers stick around for the giveaways at the end of the holiday event held at Center Court BUY TICKETS $50 general admission tickets online, $60 at the door, Kāhala Mall, 4211 Wai‘alae Ave., kahalamallcenter.com, @kahalamall Head to this family farm in Wahiawā to pick your own Norfolk pine or cypress tree grown right here in Hawai‘i The whole ‘ohana (even dogs!) can search the farm for the perfect tree $60–$250 for Norfolk pine (up to 12 feet), $70–$320 for a cypress (up to 12 feet), 1750 Whitmore Ave., Wahiawā, helemanofarms.com SEE ALSO: HONOLULU Magazine Team’s 2024 Holiday Gift Guide Richard Tajiri’s Christmas Hawai‘i will be selling Noble firs Douglas firs and Grand firs on the Coral Level near the Atkinson Trolley Depot at Ala Moana Center Near the Atkinson Trolley Depot at Ala Moana Center, 1450 Ala Moana Blvd., christmastreesinhawaii.com grand and Douglas firs for your holiday décor Proceeds go toward the nonprofit that’s been working to help people overcome substance abuse and other antisocial behaviors for more than 40 years This year’s retail locations are at Central Union Church Stadium Mall and Kāne‘ohe Safeway Tree prices from $82, habilitat.com Browse the artistic creations of local artists and craftspeople and even take some home as unique holiday gifts Free admission, The Arts at Marks Garage, 1159 Nu‘uanu Ave., associationhawaiiartists.com, windwardartistsguild.org Palama Settlement and Habilitat Honolulu have partnered to host a Christmas tree giveaway for the community Free, Palama Settlement, 810 N. Vineyard Blvd., palamasettlement.org, @palamasettlement Shop exclusive deals from more than 20 local Kailua shops while enjoying refreshments Adult participants can grab an event passport at the Lau Hala Shops lobby (by the UFC gym entrance) and fill it out with stamps for a chance to win a $500 Kailua Town gift package Try to get there early since the first 75 people to check in will receive exclusive holiday Kailua Town tote bags All ticket sales will benefit Shop Small Hawai‘i BUY TICKETS Early bird tickets (purchase by Dec. 11) $10, at the door $15, Lau Hala Shops, 573 Kailua Road, Kailua, kailuatownhi.com, @kailuatownhi Buy Very Merry Event ticket pamphlets to support your favorite nonprofits. The pamphlet is full of offers from 50+ participating Kāhala Mall merchants You can also enter to win a one-night staycation at the Kāhala Hotel & Resort with a breakfast for two at The Plumeria Beach House and $100 Kāhala Mall gift cards $5 for a ticket pamphlet, Kāhala Mall, 4211 Wai‘alae Ave., kahalamallcenter.com, @kahalamall Spend $250 at Kāhala Mall and receive a free, limited-edition Kāhala Mall x Kākou Collective belt bag and a Kākou Collective vinyl lei wrap sticker (while supplies last). Redeem your receipts at center court. See the terms and conditions online Kāhala Mall, 4211 Wai‘alae Ave., kahalamallcenter.com, @kahalamall The Mele Kalikimaka Marketplace showcases local food products crafts and more gifts from more than 250 vendors $6 for adults, $4 for seniors 60+, students, military (ID required for all), keiki 12 years and under free with a paid adult, Blaisdell Exhibition Hall, 777 Ward Ave., melekalikimakamarketplace.com Island Craft Fairs will also be collecting school supply donations for our hardworking teachers at the info booth at Center Stage Ka Makana Ali‘i, 91-5431 Kapolei Pkwy, Kapolei, islandcraftfairs.org, @islandcraftfairs If you’re still scrambling for gifts on Christmas Eve head to Town Center of Mililani for some comfort in the form of free donuts from Zippy’s and coffee and hot cocoa from Starbucks at Center Court (while supplies last) the Rotary Club of Mililani Sunrise will provide complimentary gift wrapping Free, Town Center of Mililani, 95-1249 Mehe‘ula Pkwy, Mililani, towncenterofmililani.com, @towncenterofmililani Call (808) 888-2060 to pre-order baked goods or go online, Kapa Hale, 4614 Kilauea Ave. Suite 102, kapahale.com, @4614kapahale SEE ALSO: Christmas Pop-Up Bars to Get You in the Holiday Spirit Enjoy an assortment of festive craft cocktails with a tiki twist and small bites that will put any Scrooge in the holiday spirit—all while enjoying live local music. See what the bar looks like in this reel 21+, validated parking, Prince Waikīkī, 100 Holomoana St. princewaikiki.com, @princewaikiki SEE ALSO: Christmas and New Year’s Special Menus at O‘ahu Restaurants New this year, this pop-up bar transports you to a cozy ski lodge with festive drinks and a secret speakeasy. Get a sneak peek of the bar in this reel 21+, former Chili’s space at Pearlridge Center, 98-1005 Moanalua Road, ‘Aiea, @christmaslodgehawaii SEE ALSO: Frolic Foodie Advent Calendar: Local Kine Gifts for 25 Days of Giving Have holiday-themed brews like frozen butterbeer in this cozy, Christmassy pop-up bar decked out in ornaments and lights. Find it on the street level in the ‘Ewa wing of Ala Moana Center. See what the bar looks like in this reel 21+, Ala Moana Center, 1450 Ala Moana Blvd., winterwonderlandhonolulu.com, @winterwonderlandhonolulu The Boardroom is bringing the holiday cheer with a pop-up bar featuring signature cocktails and food specials a festive eggnog and a Candy Cane Lane Dessert The Boardroom Kailua, 44 Kainehe St., Kailua, theboardroomkailua.com, @theboardroomkailua Pick up kits at the Concierge that will include freshly baked cookies The resort’s pastry chefs will share tips and tricks as you get to decorating BUY TICKETS $50 for resort guests, $75 for non-guests, The Ritz-Carlton O‘ahu, Turtle Bay, 57-091 Kamehameha Highway, Kahuku, turtlebayresort.com, @ritzcarltonoahuturtlebay The Moana Surfrider will unveil its annual gingerbread display This year’s “Nightmare Before Christmas” themed creation is the result of five skilled pastry chefs’ efforts over 189 hours The 12 Bars of Christmas crawl takes you to 12 themed venues across Chinatown with festive drinks BUY TICKETS 21+, $20 presale, $30 at the door, various locations around Chinatown, @12barshnl Visit Common Ground to take advantage of holiday specials the week of Dec Common Ground, 1111 Bishop St., commongroundhnl.com, @commongroundhnl This make-and-take workshop will teach you how to craft a Christmas wreath charcuterie board plus you’ll enjoy light pūpū during the class BOOK YOUR SPOT $75, Fig & Ginger Honolulu, 1960 Kapiolani Blvd. #103, fghonolulu.com, @fig.gingerhonolulu The Wahiawā Value-Added Product Development Center is hosting a workshop with Chibi Confectionery to teach you how to decorate sugar cookies BUY TICKETS Early bird rate (until Dec. 13) $30 per person, regular rate $50 per person, registration covers one adult and up to two keiki, who must be 5 or older, email vapdc@hawaii.edu to RSVP for keiki, leeward.hawaii.edu/wvapdc/, @wahiawafoodinnovation Enjoy complimentary hot cocoa and cookies in the Ka La‘i Waikīkī Beach lobby Free, Ka La‘i Waikīkī Beach lobby, 223 Saratoga Road, hilton.com, @kalaiwaikikibeachlxr holiday-themed game area and coloring pages The Mean One will make a special appearance for family photos Adults will receive a complimentary welcome mimosa and exclusive $5 drink specials BUY TICKETS $35, Hard Rock Café, 280 Beach Walk, cafe.hardrock.com, @hrchonolulu Enjoy complimentary candy cane decorating in the Ka La‘i Waikīkī Beach lobby Enjoy a breakfast buffet with Santa along with festive activities A Santa Ticket will also get you a photo with him and a $10 Power Card to play video games BUY TICKETS From $28.22, free for children under the age of 2, Dave and Buster’s, 1030 Auahi St., daveandbusters.com, @daveandbusters Stop by Kai Market for breakfast and stick around for a meet-and-greet with Santa Free, Kai Market, 2255 Kalākaua Ave., kaimarketwaikiki.com Enjoy complimentary cookie decorating in the Ka La‘i Waikīkī Beach lobby Enjoy live music by Brandon Tatupu alongside a holiday buffet featuring dishes like grilled island fish Hawaiian salt-crusted prime rib and sugar cane-brined Santa Claus will make an appearance from 6 to 8 p.m Guests can receive 4 hours of validated self-parking MAKE A RESERVATION Pā‘ina Terrace on Queensbreak Rooftop, Waikīkī Beach Marriott Resort & Spa, 2552 Kalākaua Ave., marriott.com, @marriottwaikiki Enjoy live music by Sunny Kapu alongside a holiday buffet featuring dishes like Waialua Eggs Benedict and crispy pork belly bao buns plus an eggnog station Santa Claus will make an appearance from 8:30 to 10:30 a.m Kūhiō Beach Grill, Waikīkī Beach Marriott Resort & Spa, 2552 Kalākaua Ave., marriott.com, @marriottwaikiki Keiki of all ages are invited to write their wishes to Ala Moana Center’s Big Santa Free stationery is provided at the mailbox located on level 3 in the mauka wing Free, Ala Moana Center, 1450 Ala Moana Blvd., alamoanacenter.com, @alamoanacenter SEE ALSO: Holiday Crafts and Recipes to Try with Your Family This Year Escape game enthusiasts, try your hand at this scavenger hunt twist where instead of trying to get out of the room, you scour it for tokens. The previous sushi restaurant theme is now Christmassy with lots of puzzles and clue-hunting for the whole family to get into. Preview what the game is like in this reel BUY TICKETS $42/person for 2 players, $38/person for 3–8 players, free for keiki 5 and under, Room With a Clue, 1023 Pensacola St. Ste. G, roomwithaclue.com, @roomwithaclue SEE ALSO: 15 Fun Group Activities to Do with Visiting Friends and Family This Holiday Season Catch these carolers on the move around the mall singing holiday classics acapella Free, 1450 Ala Moana Blvd., alamoanacenter.com, @alamoanacenter A unique immersive experience transforms the Convention Center into a Christmas wonderland with enchanting backdrops whimsical light sculptures and festive scenes Don’t forget to grab a themed drink and check out the gift shop BUY TICKETS From $31.99 (discounts available for keiki, kūpuna and military), free for keiki age 2 and younger, Hawai‘i Convention Center, 1801 Kalākaua Ave., alohaimmersive.com, @twas.honolulu SEE ALSO: Your Insider Guide to ‘Twas the Light Before Christmas Queen Emma Ballet presents an original two-act ballet following the story of a girl who enters another world after seeing a sugar plum fairy in a store window display BUY TICKETS $33, free parking, Palikū Theatre at Windward Community College, 45-720 Kea‘ahala Road, Kāne‘ohe, queenemmaballet.com, @queenemmaballet where there will be an interactive Storybook Station Flurry and Snow Show The first 200 keiki to arrive will receive free holiday goody bags bring canned goods for the Kāne‘ohe Salvation Army to donate to those in need Free, Windward Mall, 46-056 Kamehameha Highway, Kāne‘ohe, windwardmall.com, @windwardmall The holiday-themed hula show series kicks off on Black Friday presenting traditional Hawaiian and classic holiday songs with a snowfall finale check out the keiki hula dancers on Sundays Enjoy the mele of Kimié Miner and more special guests plus stick around for the chance to win gift cards to International Market Place merchants throughout the show Free, International Market Place, Level 1, Queen’s Court, 2330 Kalākaua Ave., shopinternationalmarketplace.com, @intlmktplace SEE ALSO: Your Ultimate Guide to Concerts and Live Music in Honolulu Admire the works of artists The Twins Fine Art Kristine Provenza and Kimo and even get the chance to meet them There will be music and refreshments as well Validated parking, Kaikoa Gallery, 2005 Kalia Road, thekaikoagallery.com, @kaikoagallery bands and hālau hula will take Center Stage to share holiday joy through song and dance Free, Kāhala Mall, 4211 Wai‘alae Ave., kahalamallcenter.com, @kahalamall Get in the Christmas spirit with holiday films Arthur Christmas Seuss’ How the Grinch Stole Christmas From $14.75, Consolidated Theatres Ward, Kāhala, Kapolei and Mililani, consolidatedtheatres.com, @consolidatedhi Learn how to make your own holiday wreath using local greenery and flowers there will be lei po‘o raffles and more giveaways and flowers to create your own beautiful wreath creation A portion of the proceeds will support Halau Kahiwahiwa’s efforts to preserve the hula ki‘i art form BUY TICKETS $70, Nov. 30 workshop will be in The Secret Spot in The Laylow, 2299 Kūhiō Ave. Space A, Dec. 7 workshop will be on the beach if the weather permits, ecomindfullei.com, @eco.mindful.lei SEE ALSO: In the Mood for Lei: Where to Take Lei-Making Classes on O‘ahu All materials are provided for this paint-and-take creative workshop and a local artist will lead the session with a holiday theme BUY TICKETS $25, validated self-parking, Prince Waikīkī, 100 Holomoana St. princewaikiki.com, @princewaikiki The elves return to Ward Village this holiday season—find them for a chance to win a $100 gift card to the store or restaurant of your choice. Take photos of the elves and post them to your social media account to enter. More details and rules online Free, Ward Village, 1240 Ala Moana Blvd., wardvillage.com, @wardvillage tackle holiday-themed photo challenges and solve riddles at the Turtle Bay resort to win prizes and treats BUY TICKETS Free for resort guests, $50 for non-guests, The Ritz-Carlton O‘ahu, Turtle Bay, 57-091 Kamehameha Highway, Kahuku, turtlebayresort.com, @ritzcarltonoahuturtlebay The Nā Hōkū Hanohano Award-winning Ho‘okena take the stage with Maila Gibson to perform Hawaiian holiday music BUY TICKETS $35–$45, Blue Note Hawai‘i, 2335 Kalākaua Ave., bluenotejazz.com, @bluenotehawaii All materials are provided for this make-and-take creative workshop BUY TICKETS $25, validated self-parking, Prince Waikīkī, 100 Holomoana St. princewaikiki.com, @princewaikiki It’s a Wonderful Life and Love Actually on the big screen From $14.75, Consolidated Theatres Ward, Kāhala, Kapolei and Mililani, consolidatedtheatres.com, @consolidatedhi BUY TICKETS $25, validated self-parking, Prince Waikīkī, 100 Holomoana St. princewaikiki.com, @princewaikiki Stop by the South Shore Market Courtyard on Friday night to catch live holiday music by local artists alongside a light show. See the music lineup online Free, Ward Village, 1240 Ala Moana Blvd., wardvillage.com, @wardvillage Join Henry Kapono for a night of joy, laughter and holiday music along with special guests Alx Kawakami and the Henry Kapono Foundation’s (HKF) On the Rise Artists BUY TICKETS: DEC. 6 6:30 PM BUY TICKETS: DEC. 6 9 PM $35–$45, Blue Note Hawai‘i, 2335 Kalākaua Ave., bluenotejazz.com, @bluenotehawaii make s’mores and decorate a gingerbread house don’t miss the musical The Year Christmas Was Almost Canceled in the auditorium below the chapel This event is cashless—use card or mobile payments Join your keiki in creating a unique letter to send to Santa There are 15 seats available for every 30 minutes Registration is recommended to secure a spot REGISTER Free, City Mill, 660 North Nimitz Highway, hnltix.com, @honolulufamily festive activities include a meet-and-greet with Santa Claus and Snowy the Snowman; a Christmas tree bounce house and photo ops at a storybook-themed backdrop Keiki 12 years and under can receive a free candy cane from Santa and an activity book There will also be a food drive for the Hawai‘i Foodbank Free, Mililani Shopping Center, 95-221 Kipapa Dr., Mililani, mililanishoppingcenter.com The Mililani Holiday Parade ends at Town Center of Mililani Head to Kapolei Shopping Center to meet Santa and Rudolph play keiki carnival games and marvel at a stilt-walker Free, Kapolei Shopping Center, 590 Farrington Hwy., kapoleishopping.com, @kapoleishoppingctr Make your own letterpress-printed items at Cravings Media so you just need to pull the lever to print The following items will be available for printing: Cravings Media, 547 Halekauwila St., Suite 102, cravingsmedia.com, @findyourcraving The Hawai‘i Symphony Orchestra presents local-style holiday music with sing-alongs and special guest appearances BUY TICKETS $10.50–$109, Hawai‘i Theatre, 1130 Bethel St., hawaiitheatre.com, @hawaiitheatre Conceptualized and directed by Asian Performance PhD student Mariah Massengill this production explores holiday themes and spirituality through the provocative stories of its performers $5–$10, tickets sold at the box office one hour before the show, Earle Ernst Lab Theatre at Kennedy Theatre 1770 East-West Road, manoa.hawaii.edu, @uhmkennedytheatre BUY TICKETS $25, validated self-parking, Prince Waikīkī, 100 Holomoana St. princewaikiki.com, @princewaikiki See the classic Christmas movie on the big screen accompanied by a live rendition of the score by the  Hawai‘i Symphony Orchestra BUY TICKETS: DEC. 11 BUY TICKETS: DEC. 12 $25–$89, Hawai‘i Theatre, 1130 Bethel St., hawaiitheatre.com, @hawaiitheatre Deaf and hard-of-hearing keiki are invited to meet the islands’ only Deaf and signing Santa and tell him their Christmas wishes There will also be live entertainment by the Golden Angels Free, Pearlridge Center Wai Makai, second level, in the former Inspiration space, 98-1005 Moanalua Road, ‘Aiea, pearlridgeonline.com, @pearlridge This two-night event in the heart of Downtown Honolulu will feature music The first 50 guests to check in get free milk and cookies RSVP FOR DEC. 13 RSVP FOR DEC. 14 Free with RSVP, Downtown Art Center, 1041 Nu‘uanu Ave., downtownarthi.org, @downtownartcenter Discover new holiday delights throughout the 12 Days of Christmas at the Sheraton Waikīkī Free, Sheraton Waikīkī Beach Resort, 2255 Kalākaua Ave., marriott.com, @sheratonwaikiki Have holiday fun at the Hawai‘i Children’s Discovery Center with a workshop and play The program fee covers one adult per child REGISTER $35 for non-members, $25 for members, Hawai‘i Children’s Discovery Center, 111 Ohe St., discoverycenterhawaii.org, @hawaiichildrensdiscoverycenter Have loads of holiday fun at Wet ’n’ Wild from photos with Santa to a movie in the wave pool The first 200 keiki who arrive will receive a special treat from Santa (while supplies last) Celebrate the season with local entertainment Free, Waipahu Town Center, 94-050 Farrington Hwy, Waipahu, waipahutowncenter.com, @waipahutowncenter Enjoy songs from The Nutcracker and more holiday classics in the ambiance of a candlelit room BUY TICKETS $45–$70.50, The Cathedral of St. Andrew, 229 Queen Emma Square, feverup.com Head to the South Shore Market courtyard for a holiday light show The Mākaha Sons lead a holiday performance with special guests Darlene Ahuna BUY TICKETS $40–$55, Hawai‘i Theatre, 1130 Bethel St., hawaiitheatre.com, @hawaiitheatre Ballet Hawai‘i returns with its special rendition of The Nutcracker set in 1858 in the Kingdom of Hawai‘i BUY TICKETS: DEC 14 BUY TICKETS: DEC 15 $50 to $130, Blaisdell Arena, 777 Ward Ave., blaisdellcenter.com, @blaisdellcenter then spruce it up with all kind of materials at the decorating station BUY TICKETS Free for resort guests, $50 for non-guests, The Ritz-Carlton O‘ahu, Turtle Bay, 57-091 Kamehameha Highway, Kahuku, turtlebayresort.com, @ritzcarltonoahuturtlebay Enjoy brunch with a side of laughs with beloved local comedian Frank De Lima BUY TICKETS $35–$45, Blue Note Hawai‘i, 2335 Kalākaua Ave., bluenotejazz.com, @bluenotehawaii Sacred Hearts Academy presents the beautiful holiday classic The Nutcracker featuring stunning ballet choreography and timeless music BUY TICKETS $15–$25, Hawai‘i Theatre, 1130 Bethel St., hawaiitheatre.com, @hawaiitheatre Kuana Torres Kahele and his band will perform with guest dancers Theresa and Iokia Ramento BUY TICKETS: DEC. 15 6:30 PM BUY TICKETS: DEC. 15 9 PM $35–$45, Blue Note Hawai‘i, 2335 Kalākaua Ave., bluenotejazz.com, @bluenotehawaii Photo: Courtesy of Hawaiian Humane Society Bring your keiki to spend quality time reading to shelter animals They’ll also get to decorate kennel cards and take home milk and cookies Sign up fast since there are only 16 spaces for each time slot REGISTER: HŌ‘OPILI REGISTER: MŌ‘ILI‘ILI Free, registration required, Hawaiian Humane Society Kosasa Family Campus at Ho‘opili, 91-1945 Fort Weaver Road, ‘Ewa Beach; Hawaiian Humane Society Mō‘ili‘ili Campus, 2700 Wai‘alae Ave.; hawaiianhumane.org, @hawaiianhumane The internet-famous Fashion Santa will appear at various stores throughout Ala Moana Center for meet-and-greets and photos treats from Big Island Candies and a limited-edition Fashion Santa postcard Ala Moana Center, 1450 Ala Moana Blvd., alamoanacenter.com, @alamoanacenter The Honolulu Brass Quintet will fill the hall with Christmas cheer and popular seasonal tunes BUY TICKETS $25–$35, Blue Note Hawai‘i, 2335 Kalākaua Ave., bluenotejazz.com, @bluenotehawaii including Santa’s Workshop Stick Christmas Ornaments Christmas Tree Glasses and Gingerbread Wreaths and receive a free snack from Zippy’s Free, Town Center of Mililani center court, 95-1249 Mehe‘ula Pkwy, Mililani, towncenterofmililani.com, @towncenterofmililani Hang out with adoptable cats and enjoy exclusive holiday drinks Pick your favorite feline friend to make an ornament with their paw print MAKE A RESERVATION $26, Hawai‘i Cat Cafe, 415 Kapahulu Ave., hawaiicatcafe.org, @hawaiicatcafe Take free photos with Santa and shop local at the ‘Ono Grindz & Mākeke Farmers Market Add an additional $5 for a gingerbread house Free admission, Wai Kai, 91-1621 Keoneula Blvd., waikai.com, @waikaiexperience Don’t forget to bring your own blankets or mats to sit on BUY TICKETS $50 (includes entry for one father and daughter, additional daughters free), Ke‘ehi Lagoon Beach Park, 465 Lagoon Dr., salvationarmyhawaii.org, @fathers_with_daughters Don McLean will perform his greatest hits like “American Pie” and “Castles in the Air” alongside festive tunes like “Winter Wonderland” and “White Christmas.” BUY TICKETS $49–$99, Hawai‘i Theatre, 1130 Bethel St., hawaiitheatre.com, @hawaiitheatre Free admission, Gunstock Ranch, 56-250 Kamehameha Hwy, Kahuku, gunstockranch.com, @gunstockranch Enjoy holiday tunes sung by a community choir The nonprofit performs free concerts at rehabilitation facilities senior communities and public venues to share the joy of music Free, donations welcome, voicesofaloha.com, @voicesofaloha Experience the magic of Christmas in Hawai‘i with the Islands’ beloved songbird Kimié Miner BUY TICKETS: DEC. 21 6:30 PM BUY TICKETS: DEC. 21 9 PM $35–$45, Blue Note Hawai‘i, 2335 Kalākaua Ave., bluenotejazz.com, @bluenotehawaii SEE ALSO: 13 Things You Didn’t Know About Kimié Miner Celebrate the warmth and aloha of the season with this three-time Grammy Award-winning artist This special holiday performance will also include Kumu Hula Olana Ai BUY TICKETS $45–$100, Hawai‘i Theatre, 1130 Bethel St., hawaiitheatre.com, @hawaiitheatre Enjoy complimentary ornament crafting in the Ka La‘i Waikīkī Beach lobby Dive into childhood nostalgia with the Christmas music of the Peanuts performed live BUY TICKETS: DEC. 24 6:30 PM BUY TICKETS: DEC. 25 6:30 PM Family-friendly, $25–$35, Blue Note Hawai‘i, 2335 Kalākaua Ave., bluenotejazz.com, @bluenotehawaii Watch your little ones’ eyes light up as they ride the custom miniature train across Pearlridge Center Mauka’s festive landscape filled with oversized toys Taking a ride on Hawai‘i’s only scale-model fully functioning locomotive has become a holiday tradition for many train booklets this year will include a free photo with Santa at the Pearlridge Center Santa Set in Wai Makai Keep in mind that the train staff will be on break from 2 to 3 p.m $6 per ride, $41 10-ride coupon books, keiki must be under 48 inches tall, 98-1005 Moanalua Road, ‘Aiea, pearlridgeonline.com, @pearlridge Photo: Courtesy of Waikīkī Trolley Hop on the trolley at Prince Waikīkī and enjoy a round-trip ride to see the holiday decorations at Honolulu City Lights The last of the Friday night rides is a little later so you and your ‘ohana can watch the Waikīkī fireworks before getting on the trolley BUY TICKETS $20 for adults and keiki ages 3 and up, lap children are free, pickup at Prince Waikīkī, 100 Holomoana St., princewaikiki.com, @princewaikiki Take a joyful 30-minute ride to Honolulu Hale to see Shaka Santa, then spend about an hour exploring all the lights and scenes throughout the area. Reservations are required and can fill up quickly. Tickets also include free cocoa, entry into the Waikīkī Trolley Winter Wonderland and a photo with Santa Claus. A shuttle service from Waikīkī to Winter Wonderland is available BUY TICKETS $35 for adults; $25 for keiki 3 to 11 years old; kids 2 years and younger are free but must sit on an adult’s lap, pickup at the corner of Richards St. and Aloha Tower Dr., holidaylightshi.com, @holidaylightshi BOOK A SPOT From $39.99, no personal cameras allowed, 1450 Ala Moana Blvd., alamoanacenter.com, @alamoanacenter Check for dedicated times for those with sensory needs and pets Receive parking validation with your purchase of a photo package BOOK A SPOT From $39.99, 2330 Kalākaua Ave., shopinternationalmarketplace.com, @intlmktplace Visit Santa in his sleigh between Zales and Sephora Clause will also be available for photos on weekdays BOOK A SPOT From $35, 91-5431 Kapolei Pkwy, Kapolei, kamakanaalii.com, @kamakanaalii Guests will receive a Royal Santa Savings Pass while keiki can enjoy free peppermint cookies from Honolulu Cookie Company Free, The Royal Grove, 2201 Kalākaua Ave., royalhawaiiancenter.com, @royalhwnctr you can win prizes from Raising Cane’s lunch and drink coupons and stuffed animals Free, Town Center of Mililani center court, 95-1249 Mehe‘ula Pkwy, Mililani, towncenterofmililani.com, @towncenterofmililani Photo: Courtesy of Surfjack Hotel & Swim Club Feed him a treat and receive a Surfjack keychain Free, Surfjack Hotel & Swim Club, 412 Lewers St., surfjack.com, @thesurfjack Stop by the holiday backdrop in front of Regal Theater for a free photo with Santa and an elf Free, 4450 Kapolei Pkwy, Kapolei, kapoleicommons.com, @kapoleicommons Resort guests are invited to take a photo with Santa shot by Pacific Dream Photography Free for resort guests, 57-091 Kamehameha Highway, Kahuku, turtlebayresort.com, @ritzcarltonoahuturtlebay Enjoy complimentary photos with Santa in the Ka La‘i Waikīkī Beach lobby Take an ornament from a Wishing Tree at one of the above participating locations then bring the requested gift back to where you picked up the ornament helpinghandshawaii.org, @helpinghandshawaii Toys for Tots – Nov unwrapped toys at the donation bins in South Shore Market or Ward Centre Senior Giving Tree – Nov In partnership with Catholic Charities Hawai‘i Ward Village has set up Giving Trees at Logos Bookstore Select an ornament to fulfill the wish of a senior in need Ward Village, 1240 Ala Moana Blvd., wardvillage.com, @wardvillage Clear out your storage spaces and take your donations to the Goodwill Hawai‘i locations in Kapolei Kaimukī and Windward City Shopping Center on Saturday Goodwill will give away $6,500 in Aloha Gas cards Car Wash 808 Express tickets and Popeyes Hawai‘i promo cards (while supplies last) across those locations plus there’ll be free cookies from Diamond Bakery Hawai‘i and local entertainment anyone who donates to a Goodwill on O‘ahu or Hawai‘i Island will receive a 10% off Popeyes coupon Multiple locations, goodwillhawaii.org, @goodwill_hawaii Ronald McDonald House Charities will be at Hawai‘i’s Shop Local Pop-Up at Ala Moana Center near Target then bring it back to the donation box at the RMHC booth Ala Moana Center, 1450 Ala Moana Blvd., ronaldhousehawaii.org, @ronaldhousehi Easter is hopping around the corner and let’s be honest—everyone loves a good brunch This holiday is the perfect eggs-cuse to indulge so we’ve rounded up menus for festive brunches dinners and sweet Easter-themed bites at restaurants and eateries across O‘ahu Keep checking back—we’ll be updating this list as more specials roll in SEE ALSO: Easter Events on O‘ahu Kaka‘ako Waikīkī has been updated with new photos from our April 2025 issue When you just need a way for your kiddo to burn off energy, sometimes the best thing to do is let them run around your neighborhood playground. There’s actually a lot of benefits to playground play. In fact, pediatric physical therapist Dr. Suma Metla wrote about it here head to one of the hundreds of playgrounds on O‘ahu Below are just a few of the best playgrounds on O‘ahu according to our team of contributors (and their keiki). We’re always exploring more and would love to know which ones you’d like us to review next! Feel free to email your recommendations or suggestions to web@honolulumagazine.com SEE ALSO: Playgrounds With Swings on O‘ahu UPDATE: The park offers lots of options for play but the playground itself is in need of repair Best to hold off on this one until its slide gets fixed SEE ALSO: The Importance of Playground Play some standalone and others across multiple sessions Saturday’s Making Art for Art’s Sake 1041 Nu‘uanu Ave., downtownarthi.org, @downtownartcenter SEE ALSO: 40 Amazing Things to Do The Fishschool art studio within Fishcake hosts various workshops, from bookbinding to making clay trinkets. If you’ve ever wanted to try wheel throwing, intro classes are offered periodically. And if you fall in love with it, you can apply for the open studio membership to continue your pottery practice 307C Kamani st., fishcake.us, @fishschoolhawaii SEE ALSO: Feed Your Artistic Appetite With Fishschool Classes Photos: Courtesy of Hawai‘i Ceramic Supply This ceramic studio offers introductory wheel throwing classes that can be taken as a series or individually There are even private lessons for one to three students Or if you’d like to take on a single project at a time check out the upcoming one- to two-day ceramic workshops 1920 Colburn St. Suite A, hawaiiceramicsupply.com, @hawaiiceramicsupply SEE ALSO: 5 Wellness Classes to Try There’s also a weekly class dedicated to empowering women with rope and lead climbing skills 825 Ilaniwai St., hawaiiclimb.com, @hiclimbhawaii For the spring session that runs from April to June Multimedia and Metalsmithing and Jewelry-Making from sketching to oil painting to printmaking look out for the three-day keiki summer camps for ages 6 to 8 and 9 to 12 that will cover Sculpture; Drawing and Painting; and Printmaking and Collage 900 S Beretania St., honolulumuseum.org, @honolulumuseum Learn how to prepare three to four new dishes at KCC’s culinary school Local Japanese Favorites and Local Korean Favorites are scheduled for August; you can fill out a Course Inquiry to get notified when registration opens Check back for new listings throughout the year 4303 Diamond Head Road, continuinged.kapiolani.hawaii.edu, @kccculinary SEE ALSO: Expand Your Culinary Horizons in Expert-Led Cooking Classes Recently reopened at Capitol Modern, Mori is bringing back its workshops taught by local artists. First up in February, a songpyeon workshop in collaboration with Rice Blossoms; next in March a basket-making workshop with recycled materials 250 S Hotel St., morihawaii.com, @mori_hawaii Registration is open for the Parks & Rec Spring Program The activities range from archery and canoeing to cooking and lei-making with many tailored for keiki and kūpuna Click on “Activities” at pros8.hnl.info Learn how to do yoga mixed with Hawaiian healing practices sew a Hawaiian quilt and dance hula ‘auana at Hānaiakamalama and general admission is just $5 ($2 for members) 2913 Pali Highway, daughtersofhawaii.org, @queenemmasummerpalace L iving in Hawai‘i means that the perfect holiday is always just down the road all of them in a big hurry to shuttle themselves to our world-class beaches and scenic coastlines—but why should they have all the fun With some of the best oceanfront resorts in the world and a wide range of prices and styles Here are some of our favorite kama‘āina deals for your next staycation on O‘ahu which gets bonus points for its affordability and fabulous on-site bar/restaurant kama‘āina can save up to 30% off the best available room rate room prices for the property which was remodeled and rebranded in a hip style Locals can also snag a discounted amenity fee of $15 the hotel will throw in a $20 daily food and beverage credit (credits cannot be stacked) at the property’s delightful poolside Heyday restaurant ultra-tropical vibes (including swings at the bar!) and casual-meets-elevated entrees BOOK NOW 431 Nohonani St., (808) 924-7263, whitesandshotel.com, @whitesandshotel SEE ALSO: Our Favorite O‘ahu Hotels for Staycations The Prince Hotel, located at the entrance to Waikīkī next to the marina, doesn’t get as much attention as it should. It has a beautiful lobby, a chef’s-kiss buffet that’s one of the best on the island and a fantastic rooftop bar. But maybe the Kama‘āina Staycation deal will change that and enjoy an Ocean Room starting at $199 (plus tax per night) and 50% off self or valet parking for one vehicle a pool cabana discount and a kids-eat-free program for children 5 years and younger You can also plan ahead for this summer and beyond—this staycation deal applies for dates through Dec BOOK NOW 100 Holomoana St., (855) 277-3123, princewaikiki.com, @princewaikiki SEE ALSO: Our Tips for the Best Family Staycation in Hawai‘i The Wayfinder Waikīkī was recently rebranded and upgraded into a boutique hotel on the Lē‘ahi end of the neighborhood Voted one of the Top 10 Hotels in Hawai‘i by Conde Nast Traveler’s readers the Wayfinder Waikīkī offers the perfect oasis for a staycation Just five minutes from International Market Place the hotel boasts 228 rooms with lively tropical designs with some overlooking the 70-foot saltwater pool Book with the kama‘āina offer to receive a special rate two complimentary welcome drinks and early check-in (upon availability) BOOK NOW 2375 Ala Wai Blvd., (808) 922-4744, wayfinderwaikiki.com, @wayfinderwaikiki SEE ALSO: Is the New Wayfinder Waikīkī Hotel Your Next Staycation Spot? more private experience and feels like luxury the moment you step into its gorgeous airy lobby with its high ceilings and dramatic blown-glass chandeliers And the price tag reflects it: Room nights at this beauty start in the $500 range But thanks to its incredible 40% off kama‘āina deal on most dates locals can treat themselves to a taste of that luxury BOOK NOW 5000 Kāhala Ave., (808) 739-8620, kahalaresort.com, @kahala_resort SEE ALSO: The Best Things To Do Outdoors While You Staycation on O‘ahu just not have to fight traffic on your commute into town Ko Olina’s lagoons are perfect for families doing a little weekend holoholo but even more fun when you treat the kids to a weekday stay at Disney’s ‘Aulani where they can visit all their favorite Disney characters and enjoy the lazy river Plan ahead for this winter with up to 30% savings on select rooms and villas on most Sunday through Thursday nights for stays of two nights or longer from Jan BOOK NOW 92-1185 Ali‘inui Dr., Kapolei, (866) 443-4763, disneyaulani.com, @disneyaulani SEE ALSO: Your Guide to a Staycation at Disney’s ‘Aulani Resort BOOK NOW 2863 Kalākaua Ave., (808) 757-7426, kaimana.com, @kaimanabeach SEE ALSO: 8 Things To Do in Waikīkī BOOK NOW 2199 Kālia Road, (808) 923-2311, halekulani.com, @halekulanihotel Photo: Courtesy of the Ritz-Carlton O‘ahu Whether you’re looking for some spa day pampering or a premier golf experience Turtle Bay has everything you need to curate an unforgettable staycation The iconic North Shore resort has a limited-time kama‘āina special for stays now through March 5 with rates starting from $495 and 40% savings when you upgrade to a premium room kama‘āina can get a waived resort fee and self-parking for one vehicle per room—along with other discounted offerings for the spa BOOK NOW 57-091 Kamehameha Hwy., Kahuku, (866) 475-2567, turtlebayresort.com, @ritzcarltonoahuturtlebay Photo: Courtesy of ‘Alohilani Resort Waikīkī Beach As soon as you step into the ‘Alohilani Resort a 280,000 gallon “Oceanarium” filled with a colorful variety of Hawaiian reef fish Whether you’re dining at Morimoto Asia or sipping a cocktail by the Swell Pool the ‘Alohilani Resort offers a remarkable staycation destination With the hotel’s Love Hawai‘i staycation experience kama‘āina can save up to 25% on their entire stay complimentary early check-in and late check-out (upon availability) and 10% off at the Swell Restaurant and Pool Bar BOOK NOW 2490 Kalākaua Ave., (808) 922-1233, alohilaniresort.com, @alohilaniresort the stress of daily life can become overbearing and you may just want to lay low and unwind—at the Laylow What better way to escape than at this mid-century modern oasis in the middle of Waikīkī From pet-friendly rooms to nightly live music and daily included activities the Laylow has a great atmosphere for relaxation residents can enjoy up to 25% off room rates a discounted daily destination fee and valet parking through 2025 BOOK NOW 2299 Kūhiō Ave., (808) 922-6600, laylowwaikiki.com, @laylowwaikiki Where a few years ago we had just a handful of choices there are now at least nine sources for local eggs on O‘ahu—and with mainland eggs in short supply our local poultry farms are more essential than ever Here’s where to find eggs from KLK Farm What: Educational tropical fruit farm that also raises honeybees and chickens that graze under the fruit trees. The farm practices permaculture and regenerative farming methods using a zero-waste model. Fun fact: You can attend a coconut workshop by contacting klkfarm.com raises free-range chickens on organic feed Kōkua Market carried its eggs for years and continues to carry them inside Hapa Market in Palolo Price: Grade A eggs in three sizes: medium $11.50/dozen Rhode Island Red (brown eggs) and Americana (blue eggs) hens on this North Shore farm are raised without antibiotics The brown eggs are bigger and the blue eggs are creamier with bigger yolks according to interviews with co-owner Channon Harris What: Kahumana purchases hens and eggs from local growers and farmers around the community each carton labeled with information on where they are from SEE ALSO: Worth the Drive: Kahumana Farm Café in Lualualei Valley but asked not to be included in this listing is a family farm in Wai‘anae that has been around since 1975 These brown and white Grade A organic eggs can be found at most grocery stores on island What: Established in 1910 and run by the fourth and fifth generations of the Peterson family the oldest egg operation on O‘ahu sold fresh eggs at the farm five days a week They came in different sizes and were beloved by local chefs this family-run farm raises cage-free chickens and markets their eggs under the Shaka Moa brand You can find them in grocery stores all over the island or pick them up fresh from the farm SEE ALSO: Local Online Grocer Farm Link Builds Up Hawai‘i’s Food Systems What: This sustainable farm’s 300 off-grid acres were developed to lessen Hawai‘i’s dependency on imported eggs Pick up these cage-free eggs from the farmstand near the entrance to Sweet Land Farm or at grocery stores islandwide Find eggs at: Kapi‘olani Community College farmers market Faria feels like what would happen if our Portuguese grandma’s dining room got a makeover by a creative cousin who’s been itching to add her own spin a wall of rosaries overlooks a pillow embroidered with Vovo—Portuguese for grandmother The overall effect is homey and as respectful as it is playful and it’s clear that Faria—a Pasifika-Portuguese Restaurant as it describes itself—has plenty of talent It’s the years-long dream of chef-owner Kawehi Haug who with business partners Kim Potter and Sheldon Lo previously ran Downtown’s Hukilau Café and Bethel Street Tap Room handle administration and logistics and jump in “as prep cooks dishwashers and laundry ladies,” Haug says “We’re not trying to be Lisbon or Massachusetts or San Jose We are specifically Hawai‘i Portuguese,” she says “It struck me as so odd that there were no Portuguese restaurants in a place with such a large Portuguese population and I wanted to bring familiar local family recipes into the local restaurant scape to honor the deep Portuguese heritage.” (Full disclosure: Haug has written freelance articles for HONOLULU Magazine and Frolic and we worked together at The Honolulu Advertiser.) Some of our early favorites are an appetizer of sardines ($19) simmered in a tomato-garlic confit so good we wipe the skillet clean with house-made bread fine-ground cornmeal deep-fried until the crispy crust wisps apart on the palate; smear it with Potter’s grandmother’s Hawaiian chile pepper jelly for a tangy finish Next on our list to try are the appetizer platter and tinned fish board and maybe the linguiça sausages or what’s listed as Pocho Trinity—boiled peanuts Go early to order the velvety whole branzino ($45) served alongside fresh tomatoes sprigs of thyme and grilled lemons—it often sells out a slow-cooked pot roast hinting of cinnamon with mashed potatoes and cabbage you will recognize classic dishes featuring bacalhau One version at Faria presents cod as an entrée of gratin with potatoes and onions baked with béchamel ($28) Other favorites are Granny Pereira’s Piripiri Chicken ($24) two roasted legs with tangy lemon potatoes and melty cabbage; as well as a Fishermen’s Stew ($26) with shrimp full-flavored cabbage—which is having a heyday among home cooks—accompanies many entrées and is so memorable that you might find yourselves arguing over the leftovers The familiar flavors of Hawai‘i-style Portuguese bean soup ($10) get kicked up a notch with a savory broth of ham hock The same is true of vinha d’ahlos ($26) or pickled pork—it’s tender in a garlicky wine sauce whose flavor is not exactly what your auntie makes for Christmas brunch The Pasifika part of Faria’s tagline refers to other cuisines that influence the menu: a laulau stew a burger with smoked Provolone and Portuguese sausage mayo and Auntie Jan-Marie’s Almond Butter Mochi SEE ALSO: Sweet Treats: Kailua’s New Ice Cream Parlor Has One Request similar to focaccia; and oval-shaped loaves of bolo de caco a flatbread from Madeira made with sweet potato The shape is different from the traditional rounds because that’s how the recipe came down from family members And leave room for dessert—Haug has been refining her pasteis de nata for years including trips to taste and study them in Lisbon these become a silky Portuguese burnt custard tinged with cinnamon and baked in crisp layers of laminated pastry The restaurant serves wines and spirits from Portugal and beyond along with cocktails that showcase the team’s family ties and traditions SEE ALSO: Restaurants We Love: Resonant Stories From the Best Restaurants in Honolulu Portuguese eateries have been exceedingly rare on O‘ahu Adega restaurant offered a mix of Portuguese and Brazilian fare in Downtown Lisboa restaurant served a white tablecloth version of Portuguese food at the Pacific Grand Hotel Faria is the island’s only Portuguese restaurant Its 70 seats have been filling up as word gets around so best to make a reservation via the website or by phone The team plans to expand hours—and eventually hope to roll out a food truck selling those creamy custard tarts Open Wednesday to Saturday 5 to 10 p.m., 306 Ku‘ulei Road, Kailua, (808) 200-4953, fariahawaii.com, @fariahawaii Hawai‘i Police DepartmentSouth Hilo Patrol DivisionOfficer Macintyre FeltonPhone: (808) 961-2213Report No. 24-081122 Hawai’i Island Police are requesting the public’s assistance in locating 21-year-old Jaykob Ahu of Hilo, who was reported missing. Ahu was last seen on Lama Street in Hilo on Wednesday, September 4, 2024, at approximately 6:00 a.m., wearing a camouflage printed jacket with black pants. He is described as Hawaiian and has a light brown complexion, 5-feet and 11-inches tall, 135 pounds, with short black wavy hair and brown eyes. Ahu may be in need of medical attention. Police ask anyone who may have information about Ahu’s whereabouts to please call the police department’s non-emergency line at (808) 935-3311 or contact Officer Macintyre Felton of South Hilo Patrol at (808) 961-2213. Tipsters who prefer to remain anonymous may call the island-wide Crime Stoppers number at 961-8300 and may be eligible for a reward of up to $1,000.00. Crime Stoppers is a volunteer program run by ordinary citizens who want to keep their community safe. Crime Stoppers does not record calls or subscribe to any Caller ID service. All Crime Stoppers information is kept confidential. The Crime Stoppers TV Program is available on-demand from Nā Leo TV. This site is only for accessing historical media releases prior to November 12 Visit our new site for up to date information In addition to Black Friday and Small Business Saturday deals at retailers across the island local craft fairs and holiday markets ramp up in November and December Expect to find wares from across the state from Native Hawaiian-owned and mom-run brands Skip the big-box retailers and online marketplaces to keep your dollars in Hawai‘i and support the small makers who pour their hearts into every individual piece SEE ALSO: The Ultimate Guide to Holiday Happenings on O‘ahu One of the biggest draws for this event, other than the more than 200 vendors is the chance to win one of five 65-inch TVs that will be given away hawaiiholidayfair.com, @hawaiiholidayfair This fundraiser for Ali‘iōlani Elementary School features dozens of vendors and live entertainment from Deven Camat islandcraftfairs.org, @islandcraftfairs Some of the biggest outdoor craft fairs offer trendy handmade items 808craftandgiftfairs.com, @808craftandgiftfairshawaii Created to mālama Hawai‘i’s small local businesses plus live music and food and drink vendors malamahawaiimarket.com, @malamahawaiimarket SEE ALSO: Your Ultimate Guide to Concerts and Live Music in Honolulu Dozens of mom-made businesses return to Kāhala Mall for two days of local shopping. Look for clothing, jewelry, stickers, totes, bedding and more. A portion of proceeds will be donated to the Make Lemonade Project @themommademarkethawaii The popular Kaka‘ako block party returns with an evening filled with entertainment delicious food truck eats and a holiday market plus The Barn at Salt at Our Kaka‘ako ourkakaako.com, @hnlnightmarket SEE ALSO: Your Insider Guide to Honolulu Night Market: November 2024 Expect crafters who offer things like press-on nails The historic clubhouse will host 40 local vendors once again on the property in Kailua kalamabeachclub.com, @kalamabeachclub this pop-up market was designed to support creators artists and entrepreneurs who perpetuate Hawaiian culture and language A portion of proceeds will be donated to Native Hawaiian nonprofits and organizations Kūpuna over 65 are welcome to shop early on Sunday at 9 a.m hoomaumarket.com, @hoomaumarket SEE ALSO: Your Insider Guide to the Ho‘omau Market There will be entertainment from 12:30–1:30 p.m crafts and treats for everyone on your list To support McKinley’s chorus and theater group students will be selling Krispy Kreme doughnuts among craft December’s event is a little different and benefits the band and orchestra Church of the Crossroads joins up with Waiwai Collective Hawai‘i Potters’ Guild and others for a rummage sale churchofthecrossroadshawaii.org More than 80 vendors come together to raise money to maintain Lanikai Park and beach access points in the neighborhood lanikaiassociation.org, @lanikaiassociation Created by Hawai‘i real estate agent Danielle Sherman There will be locally made items at each market 22 for pet adoptions in partnership with the Hawaiian Humane Society There will also be a keiki clothing swap on Nov alohahomemarket.com, @alohahomemarket Unique gifts help raise money for nonprofits eventbrite.com, @quirkycrafters808 More than 200 craft and food vendors draw upward of 20,000 attendees to this expo that started back in 1987 islandwideexpos.com, @islandwideexpos Find made-in-Hawai‘i gifts such as glass artwork More than 40 vendors will participate in Honolulu’s oldest craft fair Hawaiian Mission Houses Historic Site and Archives missionhouses.org, @hawaiian_mission_houses Aloha Stadium Swap Meet & Marketplace goes with a holiday theme on these select dates In addition to more than 400 local businesses a beer garden and a giveaway from Alaska Airlines when you donate a new toy during these times alohastadium.hawaii.gov, @alohastadiumhi the festival will include a pop-up holiday market at Ali‘iōlani Elementary School where you can snag goodies from 30-plus food and retail vendors plus attend a petting zoo and take photos with a giant snow globe keepitkaimuki.com, @keepitkaimuki SEE ALSO: O‘ahu’s Great Neighborhoods: Kaimukī The Windward Artists Guild and Association of Hawai‘i Artists gather many types of art from painting and ceramics to photography and mixed media windwardartistsguild.org, @windwardartistsguild and associationhawaiiartists.com, @associationofhawaiiartists Shop for the anime and K-pop fans in your life with collectibles supersaturdayhawaii.com, @supersaturdayhi The hub of Kaka‘ako hosts a one-day shopping event with plenty of local designers saltatkakaako.com, @saltourkakaako the Institute for Native Pacific Education and Culture hosts its second annual market in Kapolei in collaboration with HI Street Grindz & Crafts Fest inpeace.org, @inpeacehawaii Curated by the team behind local womenswear boutique Here this holiday market brings together independent makers Admission: Will be available for purchase online 100% of proceeds from entry fees will be donated to local charities and nonprofits here-shop-here.com, @sunshinepeoplemarket SEE ALSO: O‘ahu Pop-Up Market Guide: Where and When to Find Them Pacific Expos and Special Events Hawai‘i bring hundreds of vendors together with their locally made unique wares for the eighth year There will also be a pet zone (as long as your pet is leashed) and a petting zoo Admission: $6 for general admission; $4 for ages 60 and up students and military with ID; free for keiki 12 years and younger with a paying adult melekalikimakamarketplace.com Say thank you to the teachers in your keiki’s life by donating school supplies at this fair where you’ll also be able to find plenty of stocking stuffers hosts its second annual holiday market that showcases Native Hawaiian and Indigenous artisans The organization also recently celebrated the grand opening of its retail pop-up at Salt for the holidays kukolu.org, @kukoluorg Put off your shopping until the final weekend before Christmas You can still buy from local makers such as Ho‘onani Love and Wick’d Essentials This new market features Fishcake’s vendors: Plant Bar fishcake.us, @fishcakehawaii Volume 10 - 2019 | https://doi.org/10.3389/fimmu.2019.00853 This article is part of the Research TopicAutoantibodies in Kidney DiseasesView all 11 articles Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia It is caused by genetic or acquired defects of the complement alternative pathway Factor H autoantibodies (anti-FHs) have been reported in 10% of aHUS patients and are associated with the deficiency of factor H-related 1 (FHR1) FHR1 deficiency is not enough to cause aHUS since it is also present in about 5% of Caucasian healthy subjects In this study we evaluated the prevalence of genetic variants in CFH using healthy subjects with FHR1 deficiency here defined “supercontrols,” as a reference group “Supercontrols” are more informative than general population because they share at least one risk factor (FHR1 deficiency) with aHUS patients We analyzed anti-FHs in 305 patients and 30 were positive The large majority were children (median age: 7.7 [IQR 6.6–9.9] years) and 83% lacked FHR1 (n = 25 cases) due to the homozygous CFHR3-CFHR1 deletion (n = 20) or the compound heterozygous CFHR3-CFHR1 and CFHR1-CFHR4 deletions (n = 4) or the heterozygous CFHR3-CFHR1 deletion combined with a frameshift mutation in CFHR1 that generates a premature stop codon (n = 1) Of the 960 healthy adult subjects 48 had the FHR1 deficiency (“supercontrols”) and C3 were found in 24% of cases (n = 6) compared to 2.1% of the “supercontrols” (P-value = 0.005) We also found that the CFH H3 and the CD46GGAAC haplotypes are not associated with anti-FHs aHUS whereas these haplotypes are enriched in aHUS patients without anti-FHs which highlights the differences in the genetic basis of the two forms of the disease we confirm that common infections are environmental factors that contribute to the development of anti-FHs aHUS in genetically predisposed individuals which fits with the sharp peak of incidence during scholar-age Further studies are needed to fully elucidate the complex genetic and environmental factors underlying anti-FHs aHUS and to establish whether the combination of anti-FHs with likely pathogenetic variants or other risk factors influences disease outcome and response to therapies Previous studies reported that about 14.7% of aHUS patients with anti-FHs also carry LPVs in complement genes (18, 19, 21–23, 32); however the prevalence of LPVs in patients with anti-FHs should be compared to that in the general population or This would support the hypothesis that LPVs have a role in anti-FHs aHUS In this study we investigated the genetic determinants of anti-FH-associated aHUS by comparing patients with anti-FHs and FHR1 deficiency (defined here as “cases”) and adult healthy subjects carrying the homozygous CFHR1 deletion (defined here as “supercontrols”) as a homogeneous to optimize the power to detect differences We hypothesized that the “supercontrols” were depleted for risk variants or even enriched in protective variants since they evaded the development of aHUS despite carrying the known risk factor represented by the FHR1 deficiency Specifically, we compared the prevalence of rare LPVs in complement genes between cases and “supercontrols.” We also investigated the association with anti-FHs aHUS of common variants in complement genes, which in previous studies were reported to increase the risk of aHUS or of other immune-mediated glomerulopathies (33–38) We found that rare LPVs but not common complement gene variants are enriched to a significant extent in cases compared to “supercontrols,” suggesting they are involved in the development of anti-FHs aHUS atypical HUS was diagnosed based on microangiopathic hemolytic anemia and thrombocytopenia defined as hematocrit <30% serum lactate dehydrogenase level above 500 U/l fragmented erythrocytes in peripheral blood smear and platelets below 150 × 103/μl associated with acute renal failure (serum creatinine >1.3 mg/dl for adults >0.5 mg/dl for children under 5 years of age and >0.8 mg/dl for children aged 5–10 years old; and/or urinary protein/creatinine ratio >200 mg/g; or an increase of serum creatinine or urinary protein/creatinine ratio >15% compared to baseline levels) All aHUS patients (n = 305) were recruited through the International Registry of HUS/TTP (Ranica Healthy adult subjects (n = 960) were from internal donors and from the Piedmont Regional Registry of the Italian Bone Marrow Donors Registry (Azienda Ospedaliera–Universitaria Città della Salute e della Scienza Patient and healthy subject data were handled with respect for confidentiality and anonymity All subjects provided informed written consent in accordance with the Declaration of Helsinki The study was approved by the Ethics Committee of Azienda Sanitaria Locale goat anti-human IgG antibody conjugated with horseradish peroxidase (HRP Sigma-Aldrich) was added and incubated for 1 h Enzymatic activity was revealed using the 3,3′,5,5′-tetramethylbenzidine (TMB) substrate with 2,000 AU/ml titer was used at 1:100 dilution The positive threshold was set up at the mean titer +2 standard deviations (SD) found in plasma samples of 98 healthy controls with 1 or 2 copies of CFHR1 (56 AU/ml) The sample concentrations expressed in arbitrary units/ml (AU/ml) were extrapolated from a sigmoidal curve and the background derived from wells without FH coating was subtracted The ELISA was repeated in positive samples adding 15 μg of FH into each sample to verify antibody specificity Samples showing at least a 50% decrease of the ELISA absorbance in the assay performed in the presence of exogenous FH were considered as true positive This ELISA protocol was also used to evaluate the binding of autoantibodies to SCRs 1–5 and 15–20 FH fragments obtained by baculovirus transfection of Spodoptera frugiperda cells as reported (40) The plate was coated with molar equivalents of FH SCRs 1–5 and 15–20 and the results were expressed as absorbance at 450 nm additional wells were coated with full length FH (positive control) or bovine serum albumin (BSA Serum-induced C5b-9 deposition on a human microvascular endothelial cell line (HMEC-1) was analyzed as previously described, with minor modifications (41) HMEC-1 were plated on glass coverslips and used when confluent Cells were activated with 10 μM ADP for 10 min and incubated for 4 h with serum from patients (ID: 18 and 20) or healthy controls diluted 1:2 with test medium (Hank's Balanced Salt Solution—HBSS +0.5% BSA) HMEC-1 were fixed and stained with rabbit anti-human C5b-9 antibody Fluorescent staining on cell surface was acquired in 15 fields through confocal microscopy and the staining area was evaluated using Image J software Results were expressed as the percentage of staining in relation to a pooled control sera (n = 10 subjects) run in parallel The sera from additional 35 controls were analyzed separately and the percentages of C5b-9 deposits vs control serum pool were calculated to establish the normal range (mean ± 2SD of % C5b-9 deposits of the control sera vs Microtiter plates were coated with 0.15 μg of purified sheep polyclonal anti-human factor H antibody (Abcam) the plate was blocked with 200 μl of PBS 100 μl of plasma samples at 1:10,000 dilution were added to duplicated wells 100 μl of mouse monoclonal anti-human factor H (OX-23 which recognizes the SCRs 1–4 of the FH N-terminal domain were added at a 1:10,000 dilution in blocking solution this anti-human factor H antibody also detected the FH-like 1 (FHL1) which shares the N-terminal domain with FH The plate was washed and 100 μl of goat anti-mouse antibody conjugated with HRP (1:2,000 Thermo Fisher) were added and incubated for 1 h Enzymatic activity was revealed using the TMB substrate which recognizes the N-terminal domains of FHR1 The binding of the antibody was detected by 1 h incubation with HRP goat anti-mouse IgG (1:5,000) followed by enhanced chemiluminescence (ECL) substrate (Amersham) Multiplex-ligation dependent probe amplification (SALSA MLPA P236-A3 ARMD, MCR-Holland, Netherlands) was used to evaluate the presence of copy number variations (CNVs) in CFH, CFHR3, CFHR1, CFHR2, CFHR5 genes in the 30 aHUS patients with anti-FHs. The CFHR4 CNV was evaluated in aHUS patients with anti-FHs by a multiplex PCR, as reported by Moore et al. (22) To evaluate the presence of the homozygous deletion of CFHR1 in all 305 aHUS patients and in the 960 healthy adult controls a multiplex PCR was set up that amplifies a 133 bp fragment in intron 3 of CFHR1 and a 83 bp fragment in the promoter of RNAseP Primers: CFHR1-For 5′-ATCACTACACATGGACCTGAAA-3′; CFHR1-Rev 5′-GATGTGGAAAAATAAAAGAAAATAAGTC-3′; RNAseP-For 5′-TAGATACCGTGTGCGTGCAT-3′; RNaseP-Rev 5′-GGGGTTCCAATTCCCAACTA-3′ Through next-generation sequencing we performed genetic screening of all exons and flanking regions of CFH, CD46, CFI, CFB, C3, and THBD by highly multiplex PCR using the Ion AmpliSeq™ Library Kit on an Ion PGM Sequencer (Life Technologies) (34) The CFH promoter and the coding and flanking regions of CFHR1 were analyzed by direct sequencing All statistical tests were executed using MedCalc software The Chi-square test or the Fisher's exact test were used to compare the allele frequencies between cases and “supercontrols,” as appropriate The expectation maximization algorithm by Haploview software was used to estimate each CFH haplotype frequency Findings were considered statistically significant at P-values <0.05 after Bonferroni correction Odds ratio (OR) was reported with the 95% confidence interval ANOVA or Kruskal-Wallis tests were used to compare the mean or the median of variables The presence of anti-FHs was assessed in 305 consecutive aHUS patients of the International Registry of HUS for whom serum or plasma was available. Thirty patients (9.8%) were positive for anti-FHs (anti-FHs titer threshold >56 AU/ml); in all of them the specificity of the result was confirmed in a replicated assay, in which an excess of FH was added to the serum/plasma sample and competed for the anti-FHs with FH coated on the well (Figure 1) The mean ± SD of anti-FH titers was 1,164.7 ± 1,189.5 AU/ml in samples collected during the acute phase of the disease (n = 4) and 521.8 ± 504.3 AU/ml in samples collected during remission (n = 26; ANOVA Anti-FHs in aHUS patients and healthy controls 305 aHUS patients were analyzed for anti-FHs through ELISA: 254 were carriers of 1 or 2 copies of CFHR1 (aHUS with CFHR1) and 51 had 0 copies of CFHR1 (aHUS with HomCFHR1Del) carrying the heterozygous CFHR1Del and a frameshift variant in CFHR1 exon 2 (c.104delAfsX) which resulted in a complete deficiency of FHR1 has been also included in the group of patients defined as “aHUS with HomCFHR1Del.” Ninety-eight healthy controls with 1 or 2 copies of CFHR1 were also analyzed for anti-FHs (CTR) The positive threshold was set at mean +2SD of values recorded in the 98 controls (56 AU/mL) and is shown with the horizontal red dashed line and CFHR4 and LPVs in complement genes observed in aHUS patients with anti-FHs Direct sequencing of CFHR1 was performed in the 6 patients with anti-FHs and at least one copy of CFHR1. In patient 23, who carried the heterozygous CFHR1 deletion, a frameshift variant in CFHR1 exon 2 (c.104delAfsX) that resulted in a premature stop codon (p.D35fsX36) was observed. In all six patients, the presence of FHR1 in serum was verified by Western blot (Figure 2) The normal pattern of two FHR1 bands was observed in patients 13 and 26 (all with one copy of CFHR1) and patients 21 and 30 (both with two copies of CFHR1) who had one copy of CFHR1 plus the c.104delAfsX frameshift mutation did not have any FHR1 band confirming that the mutation resulted in a non-secreted truncated protein 25/30 (83.3%) patients with anti-FHs showed a complete deficiency of FHR1 and are defined as cases here Detection of FHR1 by Western blotting in aHUS patients with anti-FHs and at least one copy of CFHR1 19 and 26: patients with 1 copy of CFHR1; ID numbers 21 and 30: patients with 2 copies of CFHR1; ID number 23: patient with 1 copy of CFHR1 and a frameshift mutation in exon 2 (c.104delAfsX); ID number 12: patient with 0 copies of CFHR1; CTR: an healthy control with two copies of CFHR1 We also evaluated the prevalence of the acidic and basic FHR1 isoforms in patients with anti-FHs and with at least one copy of CFHR1. In the basic FHR1 isoform that has been associated with the risk of aHUS (21) which make the SCR3 of FHR1 identical to the SCR18 of FH In patients with the heterozygous CFHR3-CFHR1 deletion one exhibited the basic isoform and two the acidic isoform Both patients with two copies of CFHR3 and CFHR1 were compound heterozygous for the two FHR1 isoforms we did not find an enrichment of a specific FHR1 isoform in our aHUS patients with anti-FHs Prevalence of homozygous CFHR1 deletion in aHUS patients (n = 305) and healthy controls (n = 960) Binding site localization of anti-FHs detected in aHUS patients Anti-FH binding to FH N-terminal fragment (SCRs 1–5) and FH C-terminal fragment (SCRs 15–20) evaluated in 12 aHUS patients Seven patients were carriers of the homozygous CFHR1 deletion (HomCFHR1Δ) while 5 patients presented at least one copy of CFHR1 (No HomCFHR1Δ) BSA coating was used as negative control and full length FH coating as positive control Absorbance of serum from a healthy subject was used as an additional control The absorbance is shown on the ordinate axis Data are representative of three experiments An ex-vivo test to evaluate complement activation at the endothelial cell level showed that serum from two patients (ID: 18 and 20, without LPVs and with homozygous CFHR1 deletion) taken after aHUS remission induced higher than normal (>149%) C5b-9 deposits on cultured ADP-activated human microvascular endothelial cells (Figure 4) Complement activation on endothelial cells Endothelial surface area covered by C5b-9 staining after incubation of ADP-activated HMEC-1 with serum from aHUS patients with anti-FHs studied at remission (patients 18 and 20) values were expressed as the percentage of C5b-9 deposits induced by a pool of sera from 10 healthy controls run in parallel (reference 100%) The red dashed lines indicated the normal range (60–149%) determined by testing single sera from 35 different healthy controls CFH, CD46, CFI, CFB, C3, and THBD were sequenced in all patients with anti-FHs and 9 were found to be carriers of LPVs as defined in methods (30%, Table 1) In an Italian case we found the C3 heterozygous c.1909G>C which is located in the Linker domain of the C3 molecule and has not been reported in patients with aHUS before We identified two THBD heterozygous LPVs: the c.1693G>T, p.Asp486Tyr (rs41348347, MAF (ExAC) = 0.006, CADD = 6.12) was identified in an Italian case and the c.241G>A, p.Val81Ile (rs772288987, MAF (ExAC) = 9 × 10−6, CADD = 8.28) was found in a case from Yemen. Both THBD variants have already been reported in patients with aHUS (3, 49) Of the 48 adult healthy “supercontrols” with the homozygous deletion of CFHR1, only one carried a LPV, namely the heterozygous CFI c.949 G>A, p.Arg317Trp [rs121964917, MAF (ExAC) = 9.9 × 10−5, CADD = 16.27]. The FI 317Trp variant has previously been reported to have 30% C3b and C4b cofactor activity compared to wild type FI, but conflicting results have been found by other authors (50, 51) in cases the prevalence of LPVs was significantly higher than in “supercontrols” (24 vs We then investigated whether common genetic variants in CFH contribute to determining susceptibility to anti-FHs mediated aHUS by comparing the prevalence of CFH c.1-332C>T (rs3753394), c.184G>A p.Val62Ile (rs800292), c.1204T>C p.Tyr402His (rs1061170), c.2016A>G Gln572Gln (rs3753396), c.2237-543G>A (rs1410996), c.2808G>T Glu936Asp (rs1065489) in the 25 cases and in the 48 “supercontrols.” As shown in Table 3 allele frequencies did not differ between cases and “supercontrols.” and THBD in cases (n = 25) and “supercontrols” (n = 48) the frequency of the CFH H3 haplotype in aHUS patients without anti-FHs of our cohort (n = 275) was 0.292 and was significantly higher compared to cases (P-value = 0.0002) “supercontrols” (P-value = 5.6 × 10−8) as well as the general population (H3 haplotype frequency = 0.203 among 2,504 controls from 1,000 genomes project Estimated CFH haplotypes in the 25 cases and the 48 “supercontrols.” no significant association has been found between CFH haplotypes and anti-FHs mediated aHUS using “supercontrols” as the reference group In our cohort of aHUS patients with anti-FHs, the H4a and H4b CFH haplotypes were in strong LD with the CFHR3-CFHR1 deletion (Table 5), which is consistent with published data (16), while the H5 and H3 haplotypes were associated with the CFHR1-CFHR4 deletion (Table 5) Linkage disequilibrium between CFH haplotypes and CFHR3-CFHR1 or CFHR1-CFHR4 deletions in the 30 aHUS patients with anti-FHs The frequency of the CD46 c.*783C allele (rs7144) that tags the CD46GGAAC aHUS risk haplotype (52), did not differ between cases (0.38) and “supercontrols” (0.35, Table 3) the frequency of the C allele was significantly higher in our aHUS patients without anti-FHs (0.45) as compared with the 2,504 controls (allele frequency: 0.35) from the 1,000 genomes project (P-value = 0.001) Finally, we analyzed the combination of the three variants FH Val62, FB Arg32, and C3 102Gly, which in functional studies (53, 54) have been associated with higher C3 convertase activity (risk complotype) and we did not find any difference in the prevalence of the risk complotype between cases (0.24) and “supercontrols” (0.17 We then wondered whether rare variants in the CFH promoter that could affect FH expression in the thymus may predispose to a lack of central tolerance toward FH and to the development of anti-FHs HUS. The analysis through Matinspector software (Genomatix) revealed the presence of two sequences predicted with a good score as consensus motifs for the “autoimmune regulator” transcription factor (AIRE, Figure 6) a DNA binding molecule that is involved in central thymic tolerance by promoting the expression of tissue-specific antigens in medullary thymic epithelial cells We sequenced the c.1-1070 region upstream the CFH gene including the two predicted AIRE consensus regions and two AIRE consensus sequences predicted by Matinspector software–Genomatix (underlined) are shown We did not find any rare variant (with MAF ≤ 0.01) in the two DNA sequences predicted as AIRE consensus regions or in the entire sequenced CFH promoter region Clinical and biochemical features at onset for all the 30 patients with anti-FHs are reported in Table 6 Clinical and biological data at onset of the 30 patients with anti-FH associated aHUS Distribution of age at disease onset in aHUS patients analyzed for anti-FHs (A) Patients with anti-FHs (n = 30); (B) Patients without anti-FHs (n = 275) and (C) Patients without anti-FHs and carrying LPVs in complement genes (n = 99) Estimate of the risk of an aHUS patient having anti-FHs in the presence of CFHR1 homozygous deletion and/or age at disease onset between 4 and 12 years Among patients with anti-FHs, we did not find any significant difference in the age of onset and in clinical complement parameters between cases with FHR1 deficiency and patients with one or two copies of CFHR1 (Table 6), as well as between patients with or without LPVs (Table 6) and plasma FH + FHL1 levels evaluated at the time of anti-FH measurement During a median of 36 months follow-up (IQR = 12–72 months) 11 patients with anti-FHs experienced relapses of the disease (37%): 9 had the FHR1 deficiency one the FHR1 deficiency plus a LPV in CFH and one a LPV in CD46 and 1 copy of CFHR1 15 patients (50%) developed end stage renal disease (ESRD): 8 had the FHR1 deficiency 2 the FHR1 deficiency plus a LPV in C3 and CFH respectively and 2 a LPV in THBD (and 1 copy of CFHR1) and C3 (and 2 copies of CFHR1) The prevalence of relapses or ESRD during the follow-up did not differ statistically between patients with or without LPVs (relapses: patients with LPVs 22% Four patients received kidney transplantation and aHUS recurrence was observed in one of them who also carried the C3 heterozygous LPV p.Arg592Trp Another patient died following the transplant due to clinical complications unrelated to aHUS Here we report the results of a retrospective study in a large cohort of patients with aHUS in which we described the clinical and genetic features of 30 patients with anti-FHs Through combined CNV analysis and CFHR1 sequencing we confirm that the FHR1 deficiency is strongly associated with anti-FHs aHUS through an approach based on the inclusion of “supercontrols,” we demonstrate that patients with anti-FHs are enriched in complement gene LPVs while common complement gene variants known to increase the risk of aHUS or other immune -mediated diseases do not significantly contribute to anti-FHs aHUS The prevalence of anti-FHs in our cohort of aHUS patients (10%) is consistent with data from other European cohorts (5–13%) (28), but is lower than that observed in an Indian aHUS cohort in which the percentage of anti-FH positive patients was dramatically higher up to 56.1% (57) we found 5 patients with anti-FHs carrying at least one normal copy of CFHR1 indicating that autoantibodies against FH can also be formed in the presence of FHR1 the failure to find any variant in the CFH promoter in our patients with anti-FHs aHUS does not support the hypothesis that there is a defect of central tolerance related to AIRE in anti-FHs development The authors proposed that binding of this domain with certain microbes induces a conformation change in FH SCR20 generating a neoepitope similar to FHR1 which might predispose to the development of the autoantibodies against FH in subjects with the FHR1 deficiency the possibility that AP dysregulation associated with LPVs per se could favor the proliferation of the self-reactive T cell clones and the formation of anti-FHs is worth investigating further studies are required to clarify the mechanisms through which LPVs predispose to anti-FHs aHUS We found only one LPV in the “supercontrol” group, namely the p.Arg317Trp in FI. This variant was previously reported to have a lower cofactor activity compared to wild type FI (50). However, later on Nilsson and colleagues found that the activity of the 317Trp variant was not impaired in any functional assay, rather this variant was more efficient than wild type FI in C3b cleavage on the surface of endothelial cells (51) we did not observe any difference between cases and “supercontrols,” whereas the frequency of this allele was significantly enriched in our aHUS patients without anti-FHs Altogether our data demonstrate that the CFH H3 and the CD46GGAAC haplotypes are risk factors for aHUS without anti-FHs but do not contribute to development of anti-FHs aHUS The marked difference we observed in the age of onset between patients with anti-FHs and those negative for anti-FHs further supports the hypothesis that diverse predisposing factors underlying the two forms of the disease are involved but these drugs may have serious side effects particularly in children we have confirmed in our cohort of patients the strong association between FHR1 deficiency and aHUS with anti-FH autoantibodies Through an innovative approach based on the comparison with “supercontrols” carrying the homozygous CFHR1 deletion identified by screening a large number of healthy adult subjects we have documented that patients with anti-FHs aHUS are enriched in complement gene LPVs This observation indicates that the pathogenesis of anti-FHs aHUS is complex and multiple “hits” are required for its clinical manifestation We also document that the CFH H3 and the CD46GGAAC haplotypes are not associated with anti-FHs aHUS we confirm the role of common infections as environmental factors that contribute to the development of anti-FHs aHUS in genetically predisposed individuals The latter finding fits with the sharp peak of disease onset during scholar-age Further studies are needed to fully elucidate the genetic and environmental factors underlying anti-FHs aHUS and to establish whether the combination of anti-FHs with LPVs or other risk factors influences the course of the disease and the response to therapies and SA performed the research and analyzed the data EB provided detailed clinical information of patients AB and AA analyzed the data and critically revised the manuscript MN has received honoraria from Alexion Pharmaceuticals for giving lectures and for participating in advisory boards and research grants from Omeros GR has consultancy agreements with AbbVie* compensation is paid to his institution for research and educational activities None of these activities have had any influence on the results or interpretations in this article The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest Paola Cuccarolo and Flavio Gaspari for biochemical evaluation of FH Sara Gastoldi for the evaluation of serum-induced C5b-9 deposits on HMEC-1 Kerstin Mierke for editing the manuscript and Manuela Passera for secretarial assistance This work was partially supported by the FP7 EURenOmics grant EV and MB are the recipients of a fellowship from Fondazione Aiuti per la Ricerca sulle Malattie Rare ARMR ONLUS (Bergamo RP is the recipient of a research contract from Progetto DDD Onlus—Associazione per la lotta alla DDD The funding sources had no role in study design nor in the writing of the report or in the decision to submit the paper for publication CrossRef Full Text | Google Scholar CrossRef Full Text | Google Scholar New functional and structural insights from updated mutational databases for complement factor H Screening for complement system abnormalities in patients with atypical hemolytic uremic syndrome A novel C3 mutation causing increased formation of the C3 convertase in familial atypical hemolytic uremic syndrome Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T the A2089G 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complement factor H autoantibodies Gastrointestinal pathogens in anti-FH antibody positive and negative Hemolytic Uremic Syndrome Structural basis for complement evasion by Lyme disease pathogen Borrelia burgdorferi Microbes bind complement inhibitor factor H via a common site Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes CrossRef Full Text Complement system part II: role in immunity Factor H-related protein 1 neutralizes anti-factor H autoantibodies in autoimmune hemolytic uremic syndrome Remuzzi G and Noris M (2019) Rare Functional Variants in Complement Genes and Anti-FH Autoantibodies-Associated aHUS Received: 10 December 2018; Accepted: 02 April 2019; Published: 01 May 2019 Copyright © 2019 Valoti, Alberti, Iatropoulos, Piras, Mele, Breno, Cremaschi, Bresin, Donadelli, Alizzi, Amoroso, Benigni, Remuzzi and Noris. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Marina Noris, bWFyaW5hLm5vcmlzQG1hcmlvbmVncmkuaXQ= Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish Metrics details Haematopoietic stem-cell transplantation (HSCT)-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with high mortality Accumulating evidence suggests that complement dysregulation is potentially involved in the development of HSCT-TMA We retrospectively analysed the clinical characteristics and outcomes of thirteen paediatric patients who were diagnosed with atypical haemolytic uremic syndrome and treated with eculizumab to manage HSCT-TMA during post-marketing surveillance in Japan The median time from HSCT to TMA was 31 days (Interquartile range IQR;21–58) and the median doses of eculizumab was three (IQR;2–5) Seven patients (54%) were alive at the last follow-up while six died due to complications related to HSCT Six of seven survivors initiated eculizumab after insufficient response to plasma therapy median platelet counts and LDH levels in all survivors significantly improved and renal function improved in 4/7 patients All survivors possessed potential risk factors of complement overactivation During the follow-up period after eculizumab discontinuation (median;111.5 days eculizumab showed benefit in over half of this paediatric patient population Ongoing clinical studies are expected to optimize the treatment regimen of terminal complement pathway inhibitor and it may become a therapeutic option for paediatric HSCT-TMA in the future Eculizumab is a recombinant humanized monoclonal antibody that binds to and blocks cleavage of C5 to C5a and C5b thereby inhibiting the terminal complement pathway patients who had complications were excluded because it is difficult to distinguish between outcomes from complications and those from aHUS who were clinically diagnosed with aHUS as an indication for eculizumab treatment All of them were excluded in previous analyses; therefore This PMS mandated by the Japanese health authority was conducted in accordance with Good Post-Marketing Study Practice (Ministry of Health Ethical approval by an institutional review board and informed consent from individual patients are non-mandatory for PMS The attending physician provided consent for the use of anonymized data in this report Actual dose and administration intervals could be determined by the attending physician aExclude patients with missing records Overall survival rate after initiating eculzumab Eighteen serious adverse events (SAEs) during eculizumab treatment were recorded in nine patients, among which six patients died due to SAEs such as multiple organ dysfunction, adenovirus infection, TMA, cerebral haemorrhage, pseudomonas sepsis, and pulmonary alveolar haemorrhage (Table S4) None of the SAEs leading to death were considered to be related to eculizumab treatment by treating physicians and d estimated glomerular filtration rate Days after HSCT are shown under each patient number (from HSCT to baseline This study is a real-world analysis of 13 paediatric patients with TMA after HSCT who were treated with eculizumab in accordance with the approved regimen for aHUS Eculizumab treatment appeared to show benefit in over half of these patients with favourable haematologic responses observed after the initiation of eculizumab in survivors Three of seven survivors received less than 4 doses of eculizumab and no TMA recurrence was observed until the last observation Twelve out of thirteen patients experienced hypertension and/or proteinuria Although sC5b-9 level data was not collected all patients fulfilled ≥4 of items of the algorithm satisfying the HSCT-TMA diagnostic criteria as defined by Schoettler CH50 level and blood concentration data were not collected and all patients analysed here did not receive an intensive personalized treatment; therefore we could not assess if eculizumab dosing was adequate to suppress complement activity This difference could explain the better survival outcomes overserved in the Jodele’s cohort both the period from HSCT to TMA onset and the period from TMA onset to eculizumab administration were numerically shorter in survivors (21 days vs Early treatment with complement inhibitor and early evaluation of treatment response can be a preferential treatment strategy once complement dysfunction is suspected in HSCT-TMA the seven surviving patients with HSCT-TMA did not show evidence of platelet count recovery during the first 22 days (median improvements were observed at the last observation; 280 days after eculizumab initiation (median This delay of platelet response might have been due to insufficient haematopoietic recovery after HSCT Renal improvement was not observed in three survivors; there is a possibility that the treatment period or blood concentration of eculizumab might not be enough to observe an improvement in renal function; otherwise renal damage in those patients was already irreversible LDH levels may be a better marker to evaluate an early response to eculizumab in patients with HSCT-TMA one or more of these factors were observed in all six non-survivors These results reflect the complexity of complications after HSCT and suggest that future studies should consider the management of these complications during complement C5 inhibitor treatment for HSCT-TMA The small number of patients and broad variability of patient baseline characteristics prevented us from making robust analyses to identify possible risk factors for HSCT-TMA outcomes only patients clinically diagnosed with aHUS by their treating physician after HSCT were analysed here; in other words patients with HSCT-TMA who did not receive a diagnosis of aHUS were excluded from this analysis These limitations should be carefully considered when interpreting and assessing the generalizability of our findings further research into the risk stratification of HSCT-TMA and the use of C5 inhibitors are needed to confirm appropriate use in HSCT-TMA and to identify factors that might predict patients’ responses to therapy The data underlying this article are available in the article and in its online supplementary data Transplant-associated thrombotic microangiopathy: opening Pandora’s box Hematopoietic Cell Transplantation in Japan Annual Report of Nationwide Survey 2021. http://www.jdchct.or.jp/ Accessed September 28 Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation Hematopoietic stem cell transplant-associated thrombotic microangiopathy Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis and treatment of pediatric hematopoietic stem cell transplantation-associated thrombotic microangiopathy Transplant-associated thrombotic microangiopathy: elucidating prevention strategies and identifying high-risk patients Clinical evaluation of thrombotic microangiopathy: identification of patients with suspected atypical hemolytic uremic syndrome Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplantation-Associated Thrombotic Microangiopathy: A Report on Behalf of the European Society for Blood and Marrow Transplantation American Society for Transplantation and Cellular Therapy Asia-Pacific Blood and Marrow Transplantation Group and Center for International Blood and Marrow Transplant Research Diagnostic criteria for hematopoietic stem cell transplant-associated microangiopathy: results of a consensus process by an International Working Group Transplant-associated thrombotic microangiopathy: theoretical considerations and a practical approach to an unrefined diagnosis Validation of recently proposed consensus criteria for thrombotic microangiopathy after allogeneic hematopoietic stem-cell transplantation Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) controversies conference Early elevation of complement factor Ba is a predictive biomarker for transplant-associated thrombotic microangiopathy Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology Thrombotic microangiopathy following haematopoietic stem cell transplant Eculizumab and thrombotic microangiopathy after hematopoietic stem cell transplantation: a report on its efficacy and safety in two pediatric patients Eculizumab therapy in children with severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy Thrombotic microangiopathy following pediatric autologous hematopoietic cell transplantation: a report of significant end-organ dysfunction in eculizumab-treated survivors Impact of treatment and outcomes for patients with posttransplant drug-associated thrombotic microangiopathy persistent neurotoxicity after transplant-associated thrombotic microangiopathy in a pediatric patient despite treatment with eculizumab SOLIRIS® (eculizumab) 300 mg for intravenous infusion. Interview Form, revised December 2020 (65th edition). https://soliris.jp/-/media/soliris_jp/document-slide/interview_form.pdf Efficacy and safety of eculizumab in childhood atypical hemolytic uremic syndrome in Japan Safety and effectiveness of eculizumab for pediatric patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance Ito S, Hataya H, Ashida A, Hamada R, Ishikawa T, Ishikawa Y, et al. Eculizumab for paediatric patients with atypical haemolytic-uremic syndrome: Full dataset analysis of post-marketing surveillance in Japan. Nephrol Dial Transplant, 2022. https://doi.org/10.1093/ndt/gfac150 Diagnostic criteria for atypical hemolytic uremic syndrome proposed by the Joint Committee of the Japanese Society of Nephrology and the Japan Pediatric Society Controversies of the classification of TMA and the terminology of aHUS Creatinine-based equations to estimate glomerular filtration rate in Japanese children and adolescents with chronic kidney disease Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab Ravulizumab in Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant. https://clinicaltrials.gov/ct2/show/NCT04543591 Accessed August 5 Study of Ravulizumab in Pediatric Participants With HSCT-TMA. https://clinicaltrials.gov/ct2/show/NCT04557735 Accessed August 5 Successful Treatment of Transplantation-associated Atypical Hemolytic Uremic Syndrome With Eculizumab A Heterozygous CFHR3-CFHR1 Gene Deletion in a Pediatric Patient With Transplant-associated Thrombotic Microangiopathy Who was Treated With Eculizumab Prompt Improvement of Transplant-associated Thrombotic Microangiopathy by Eculizumab Administration for Neuroblastoma after Autologous Hematopoietic Stem Cell Transplantation Case Report: Successful Treatment With Anti-C5 Monoclonal Antibody in a Japanese Adolescent Who Developed Thrombotic Microangiopathy After Autologous Bone Marrow Transplantation for Malignant Lymphoma Download references The PMS were mandated by the Japanese government as part of the regulatory approval of eculizumab for aHUS in Japan The authors thank all participating physicians and registered patients who participated in this study and their families and thank Akihiko Shimono for reviewing the manuscript and interpreting the data Smith (EMC K.K.) for medical writing support PMS was conducted by Alexion Pharma GK (Tokyo Japan) the sponsor and funder of this analysis provided medical writing support funded by Alexion Pharma GK Osaka University Graduate School of Medicine SI conceived and supervised the study and reviewed and edited the manuscript HT was responsible for data curation and wrote the original draft of the manuscript and HY registered patients’ data to the PMS All authors commented on previous versions of the manuscript All authors read and approved the final manuscript SI reports payment for lectures and participation on advisory board from Alexion Pharma GK HT is an employee of Alexion Pharma GK and shareholders of Alexion Pharmaceutical Inc All other authors have nothing to disclose Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41409-023-02161-7 the beverage known as ‘awa in Hawai‘i has been around the South Pacific for thousands of years yet it’s not a mainstream pau hana drink It’s consumed more as a cultural practice or to unwind and connect sans alcohol and it’s the latter reason that’s recently brought attention to it nationwide With the steady rise in popularity of low- or no-ABV drinks more places across the country have begun serving kava is known to make you feel relaxed without all the downsides of alcohol sparkling or mixed with flavorings or supplements in wholly nontraditional forms that make it more palatable but some believe that takes away from its cultural purpose and authenticity Though it’s growing in popularity elsewhere (there’s even an O‘ahu Kava Bar in Florida) many of the places where you could sit and drink it freshly prepared have closed: Hale Noa and Kava Kafé in Kapahulu Uluwehi’s and Kava Roots on the North Shore with a new bar now in its soft opening phase in Waialua Here’s where to go to find the drink on O‘ahu SEE ALSO: A Local’s Guide to an O‘ahu Road Trip: Honolulu to North Shore Kava Queen started selling powdered and prepared kava at Farm Lovers markets in 2021 owner Ava Taesali opened her first kava bar at the Waialua Sugar Mill silos Follow the signs to loop around behind North Shore Soap Factory and you’ll see yellow painted silos with gravel and tables out front In the building that also houses Mele Mele Bakery 16- and 32-ounce portions of traditional kava ($5 along with a coconut mango version when available Those more experienced with the drink can try shots of kava concentrate Though she’s also working on some nonalcoholic mocktails featuring kava she says she always leads with traditional kava and loves talking about its history We try some from Vanuatu before watching her make ‘awa from Pu‘u O Hoku Ranch on Moloka‘i tastes more of the scent of fresh-cut grass and yields less than the dried powder but is worth trying for comparison Kava Queen gave us exactly what we came for: community culture and connection in a beautiful space to relax 67-106 Kealohanui St., Waialua, @kavaqueenkavabar The former Diamond Head Cove Health Bar isn’t focused solely on kava but it does feature a chalkboard wall explaining the benefits of the drink and its active ingredients called kavalactones 16 ounces) or an ‘awa coconut smoothie with coconut milk 3045 Monsarrat Ave., #5, dacove.com, @dacovehawaii Daya Nand has been sharing kava from his tucked-away shop off Dillingham Boulevard Parking is in the lot just past the sign when you’re driving from the ‘Ewa side (no left turns from the mauka lane) and you’ll have to walk around the building to find it Nand welcomes you in and gladly shares some of the history of the drink He imports the pure powdered root from Fiji and sells it by the cup or bottle (so you can easily shake it once the sediment settles) or the bag if you want to prepare it yourself $5 per cup, $40 all-you-can-drink on weekends, 1007 Dillingham Blvd., #107b, (808) 295-2450, @fijikava_hi Despite significant advances in therapeutic management of atypical hemolytic uremic syndrome (aHUS), guidelines are not timely updated and achieving a consensus on management recommendations remains a topic of ongoing discussion. A Scientific Committee with five experts was set up. A literature review was conducted and publications addressing the classification of aHUS, patient profiles and therapeutic approach were selected. Recommendations were proposed at an initial meeting, evaluated through an online questionnaire and validated during a second meeting. These recommendations provides physicians who are not familiar with the disease with recommendations for the management of aHUS in adults. The experts who participated advocate early treatment, maintenance for at least 6–12 months and treatment interruption guided by genetic background, trigger factors, risk of relapse and evolution. Volume 10 - 2023 | https://doi.org/10.3389/fmed.2023.1264310 Background: Despite significant advances in therapeutic management of atypical hemolytic uremic syndrome (aHUS) guidelines are not timely updated and achieving a consensus on management recommendations remains a topic of ongoing discussion Methods: A Scientific Committee with five experts was set up A literature review was conducted and publications addressing the classification of aHUS patient profiles and therapeutic approach were selected Recommendations were proposed at an initial meeting evaluated through an online questionnaire and validated during a second meeting Results: Patients with confirmed or clear suspicion of aHUS should be treated with C5 inhibitors within 24 h of the diagnosis or suspicion of aHUS Treatment monitoring and the decision to interrupt treatment should be individualised according to the risk of relapse and each patient’s evolution aHUS with a genetic variant or associated with pregnancy should be treated for at least 6–12 months; de novo aHUS associated with kidney transplant until renal function is recovered and genetic variants are ruled out; aHUS associated with malignant hypertension until genetic variants are ruled out; aHUS associated with non-kidney transplant infection-or drug-induced until the thrombotic microangiopathy is resolved Patients with a high risk of relapse should be treated for longer than 6–12 months Conclusion: These recommendations provides physicians who are not familiar with the disease with recommendations for the management of aHUS in adults The experts who participated advocate early treatment maintenance for at least 6–12 months and treatment interruption guided by genetic background • Atypical hemolytic uremic syndrome (aHUS) is an ultrarare disease for which there is no clearly defined therapeutic approach in the current guidelines • This publication provides a set of recommendations for physicians involved in the clinical management of aHUS • aHUS should be treated with C5 inhibitors within 24 h of clinical suspicion and treatment should be maintained for at least 6–12 months in specific patient profiles Patients with a high risk of relapse might need longer treatment • Treatment interruption is feasible in selected patients with a low risk of relapse as long as close follow-up is possible and C5 inhibitors are accessible in case of relapse • The therapeutic management of aHUS (duration of treatment interruption and follow-up) needs to be individualised according to the patient profiles presented in this publication there is an unmet need to identify patient profiles whose management can be more individualised aHUS was formerly associated with a poor prognosis in terms of mortality and renal function recovery after a first episode (4, 11, 12). The introduction of C5 inhibitors (eculizumab and ravulizumab) improved aHUS prognosis, leading to significant renal function recovery and TMA remission when administered during the acute phase (13–16) Despite considerable progress in aHUS therapeutic management, guidelines are not timely updated, as C5 inhibitors are not universally considered first-line treatment (8, 9) there is no consensus regarding which recommendations should be followed Unequal access to diagnostic tests and to C5 inhibitors in many centres further complicates the development of clear and standardized recommendations The START-aHUS (STrategy for monitoring and disease Risk-adapted Treatment of aHUS) consensus has been developed to address these gaps in aHUS therapeutic management both generally and for specific patient profiles defined by expert consensus This paper provides general and patient-specific recommendations regarding the initiation duration and monitoring of discontinuation of aHUS treatment in adults This study aimed to establish consensus recommendations for therapeutic management of aHUS patients by a group of highly experienced physicians in the field A Scientific Committee comprising five nephrologists all of whom were experts in aHUS management an online meeting involving all members of the Scientific Committee was convened to discuss recommendations to be issued to improve therapeutic management of aHUS patients throughout their journey: treatment initiation The recommendations were compiled in a questionnaire organised in two sections The first section focused on the general recommendations with participants providing their responses personal comments and supporting bibliography The second section covered recommendations on six specific patient profiles The Scientific Committee completed the questionnaire in April 2022 A second online meeting was held in May 2022 to reach consensus on the developed recommendations. This publication summarizes the recommendations discussed and agreed during this final meeting (Supplementary Figure 1) Eculizumab and ravulizumab are anti-C5 monoclonal antibodies, and their efficacy and safety in patients with aHUS have stablished them as the first line therapies. However, their use continues to entail several challenges in terms of treatment initiation, duration, monitoring and interruption. In this regard, a set of recommendations are suggested and an algorithm summarising the general recommendations for the management of aHUS is shown (Figure 1) • C5 inhibitors should be the first-line treatment of aHUS particularly to reduce the need for dialysis and ICU admission time • Patients with a confirmed diagnosis (patients with relapsing aHUS or a confirmed family history of aHUS) must be treated within 24 h of the clinical suspicion • In the presence of a clear clinical suspicion of aHUS diagnosis early initiation of treatment with a C5 inhibitor is recommended (as soon as possible and ideally within 24 h of clinical suspicion) In centres with limited C5 inhibitors access initiate plasmapheresis until obtaining the complement inhibitor C5 inhibitor treatment should be maintained for at least 6 to 12 months • The minimum 6-month period must include at least 3 months of treatment after the normalisation of serum creatinine or the stabilisation of renal function (18) • The duration of treatment with C5 inhibitors depends on the mutation and the trigger factors of aHUS and must be individualised according to each patient’s risk and evolution • Treatment interruption should be considered in specific patient profiles before they have completed 6 months of treatment: ‒ In patients with de novo TMA after kidney transplant maintain C5 inhibitor treatment at least until recovery of renal function and at least until the results of the genetic study are available recovery of renal function may be rapid and require few treatment doses ‒ Development of severe encapsulated infections ‒ Allergy to any component of the drug ‒ Dialysis (renal replacement therapy) without worsening of subclinical manifestations of aHUS or without improvement in TMA parameters during the last 3 months of treatment or more ‒ No pathogenic complement variants or benign variants of the membrane-cofactor protein (MCP) type • A complete recovery of renal function and stability over the last 3 months is achieved • No severe extrarenal manifestations are observed • A renal biopsy should be performed as soon as possible to confirm the diagnosis (rule out other causes such as IgA-associated TMA or C3 glomerulopathy) in cases in which the risk is acceptable and in any aHUS profile • The identification of complement biomarkers by immunohistochemistry in a kidney biopsy can help to understand the pathogenesis of aHUS beyond the information provided by proteinuria • The use of biomarkers for monitoring is currently difficult. The combination of blood C5 inhibitor levels with a complement biomarker (C4d, C3a, C5a, and CH50) or plasma levels of sC5b-9 complex could provide relevant information (19) • Biomarkers should be widely available in routine clinical practice in the future • Further research is needed to identify the optimal biomarkers for monitoring treatment with either eculizumab or ravulizumab • Treatment interruption requires close patient monitoring and immediate access to treatment in case of documented recurrence (18) • Patients must be informed about and trained in the warning signs and symptoms: ‒ Periodic determination of blood pressure ‒ Periodic examination of changes in urine colour and the use of urine strips Distinguishing primary from secondary aHUS is still a challenge in many cases especially when genetic variants are not detected or when they overlap with one of the triggering conditions of secondary aHUS A classification based on easily-defined patient profiles was an important objective and considered to be helpful throughout the START project • aHUS associated with genetic variant of complement • aHUS associated with malignant hypertension (MHT) • aHUS associated with pregnancy (P-aHUS) • aHUS associated with de novo TMA after kidney transplant • aHUS associated with solid-organ non-kidney transplant or drug-induced aHUS (after a non-kidney transplant aHUS is generally induced by drugs such as mTOR inhibitors or calcineurin inhibitors) • aHUS associated with autoimmune disease or with infection The corresponding recommendations regarding treatment duration, monitoring, interruption and post-interruption follow-up were agreed on by the experts (Table 1; Supplementary Figure 2) a significant number of patients with MHT-associated aHUS may present complement-related endothelium damage although mutations are not always identified the recommendation is to give C5 inhibitors until the presence of a pathogenic genetic variant has been excluded regardless of the presence of inherited complement abnormalities they are all candidates for treatment with C5 inhibitors Other profiles for which recommendations throughout the patient journey have been addressed in this work include: patients with aHUS associated with non-kidney transplant (mostly linked to immunosuppressive treatment); and patients with aHUS triggered by an autoimmune disease or an infection (see Table 1) Early initiation of treatment with C5 inhibitors leads to improved renal and extrarenal outcomes. It also leads to less time in the ICU, less dialysis, fewer kidney transplants and lower hospitalisation costs (36, 37) Although it is currently difficult to confirm the diagnosis in advance and to begin treatment with certainty early initiation is always recommended in case of clinical suspicion of aHUS there is currently a gap in the complete and rapid determination of genetic variants to initiate treatment with a clear diagnosis which is also hampered by a lack of resources in certain centres and hospitals Future investment of resources in this field must therefore be prioritised treatment duration must be individualised according to patient’s risk and evolution and interruption should be avoided in patients presenting such characteristics interruption should be discussed extensively with each patient who must be informed about the potential benefits and risks Both physician and patient should be aware of a potential aHUS relapse (patient education for early detection of TMA symptoms) especially in the first year after treatment interruption potentially triggering events (mainly infections) clinically relevant increases in serum creatinine and/or hematuria and/or proteinuria C5 inhibitors should always be available to immediately resume treatment in case of relapse The START consensus provides expert-based recommendations which is intended to serve as a guide for other physicians with less experience in managing suspected aHUS cases covering the entire patients journey from clinical suspicion through post-treatment interruption follow-up effective aHUS patient care relies on individualisation and adaptation of these general recommendations to specific patient profiles Future research into the classification of patient profiles is relevant to improve the individualisation of therapeutic management and clinical response Access to diagnostic tests for aHUS and C5 inhibitors treatment still are unequal and faces challenges ready access to C5 inhibitors should be available to avoid plasmapheresis after a suspected diagnosis of aHUS Other complement-inhibiting therapies are currently under development they may emerge as an intriguing alternative in the treatment of aHUS treatment monitoring tools are not universally accessible in all hospitals the implementation of the standardised recommendations offered in this document is crucial if the prognosis of all patients with aHUS is to be improved regardless of the hospital or region where they are treated The START consensus provides a set of recommendations for the management of patients with aHUS based on the early initiation of C5 inhibitors a minimum duration of 6–12 months and an evaluation of the suitability of interruption depending on genetic background trigger factors and the evolution of each patient The original contributions presented in the study are included in the article/Supplementary material further inquiries can be directed to the corresponding author AÁ: Writing – original draft The author(s) declare financial support was received for the research This project resulted from an advisory board funded by Alexion the attendees independently decided to draft a manuscript based on their discussion; Alexion had no role in this decision yet did sponsor the medical writing for the manuscript which was performed by Cristina Calle from Adelphi Targis S.L Alexion provided a courtesy review of the manuscript just prior to submission; however the authors maintained complete control over the manuscript content The authors did not receive any specific grant from funding agencies in the public The authors would like to acknowledge Cristina Calle All authors had full access to all data in the study and had final responsibility for the decision to submit for publication The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmed.2023.1264310/full#supplementary-material CrossRef Full Text | Google Scholar CrossRef Full Text | Google Scholar CrossRef Full Text | Google Scholar PLASMIC score to aid diagnosis of aHUS: a post-hoc analysis of data from C5 inhibitor trials Google Scholar Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study Actualización en síndrome hemolítico urémico atípico: diagnóstico y tratamiento Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “kidney disease: improving global outcomes” (KDIGO) controversies 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recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome Economic impact of early-in-hospital diagnosis and initiation of Eculizumab in atypical Haemolytic Uraemic syndrome Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies Long-term efficacy and safety of the long-acting complement C5 inhibitor Ravulizumab for the treatment of atypical hemolytic uremic syndrome in adults Belgian consensus statement on the diagnosis and management of patients with atypical hemolytic uremic syndrome Clinical practice guidelines for the Management of Atypical Hemolytic Uremic Syndrome in Korea Early Eculizumab withdrawal in patients with atypical hemolytic uremic syndrome in native kidneys is safe and cost-effective: results of the CUREiHUS study Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study Eculizumab discontinuation 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Ana Ávila, YWFhYXZpbGFiQGdtYWlsLmNvbQ== †These authors have contributed equally to this work and share first authorship Photo: Courtesy of Mō‘ili‘ili Summer Fest The lively tradition of bon dances is returning to O‘ahu this year so dust off your yukata and get ready to make your way around the yagura to the sounds of taiko drums One of the most beloved cultural events in Hawai‘i bon dances take place during Obon season in the summer This Japanese Buddhist tradition is a celebration of life and a way to honor your ancestors Hawai‘i’s Plantation Village opens the 2024 bon season with dancing under the stars Honolulu’s largest and arguably most popular bon dance takes place at Mō‘ili‘ili Summer Fest on July 6 Don’t worry if you miss it—there are more than a dozen other festivals to enjoy throughout the summer too Here is our lineup of bon dances and Obon festivals happening across O‘ahu this summer Note that dates and times may be subject to change SEE ALSO: How to Up Your Bon Dance Cred SEE ALSO: Your Insider Guide to the 2024 Pan-Pacific Festival SEE ALSO: Guide to O‘ahu Bon Dance Food: June & July 2024 Mō‘ili‘ili Summer Fest bon dance SEE ALSO: Your Insider Guide to the 11th Annual Mō‘ili‘ili Summer Fest SEE ALSO: Our Guide: Obon Dances for Beginners SEE ALSO: Your Insider Guide to the 42nd Okinawan Festival SO much choice, O‘ahu. We have that to be thankful for. The roundup of Thanksgiving menus that you’ve been browsing and bookmarking since we started that post has swollen to 65 restaurants So we’re starting a second round here—all new dine-in and takeout menus in addition to those in Part 1 Click the link below to view offerings from the first 65 restaurants and keep checking this post as we add more and more SEE ALSO: O‘ahu Restaurants’ Dine-In and Takeout Menus for Thanksgiving 2024 Photos: Courtesy of Nani Welch Keliihoomalu If you weren’t lucky enough to be in Hilo for the release of Rumi Robertson’s first two womenswear collections for Sig Zane Designs you now have a change to snag some of her pieces on O‘ahu The Kaimukī-based designer’s new Kumukahi Collection will be available exclusively at her pop-up at Kaiao Space in downtown Honolulu Kaiao Space, 1018 Smith St., rumimurakami.com, @rumi_murakami, sigzanedesigns.com, @sigzanedesigns you can shop Dolkii’s buttery-soft graphic tees cozy lounge sets and keiki finds in person at the brand’s pop-up boutique located on the second floor of the Ten Tomorrow store in Kaimukī New releases include Maganda (above left) and Le Kaimukī sweaters plus a pareo (above right) and notebook featuring hand-drawn illustrations inspired by Filipino culture 1114 11th Ave., dolkii.com, @dolkii Dedicated to supporting Native Hawaiian and indigenous entrepreneurs the Kūkolu Organization fosters the growth of early-stage small businesses through its Indigenous Women’s Incubator Program Shop goods and artwork created by members of its most recent cohorts at Kūkolu the group’s pop-up boutique at Salt at Our Kaka‘ako Salt at Our Kaka‘ako, 691 Auahi St., Level 1, kukolu.org, @kukoluorg Photo: Courtesy of The Mākeke Holiday Store Celebrating Hawaiian culture and small Hawai‘i-based businesses the Council for Native Hawaiian Advancement’s The Mākeke Holiday Store returns to Ka Makana Ali‘i food items and more by local makers and check out special spotlights on Maui vendors and youth-owned companies Ka Makana Ali‘i, 91-5431 Kapolei Pkwy. Suite 319 (Macy’s wing), Kapolei, themakeke.com, @themakeke SEE ALSO: Shop Local: Where to Buy Hawai‘i-Designed Activewear If the neon sign and shimmering disco ball didn’t tip you off to the vibe at Small Kine Gift the shop’s floor-to-ceiling candy lei installation should confirm that this is a place where fun and creativity thrive The new Kaimukī boutique from journalist Mitchell Kuga and artist-graphic designer Adam J souvenirs and snacks from design-focused brands that you’ll be hard-pressed to find anywhere else on island—think everyone from Night March and Tropic Editions to Dusen Dusen and Apartmento Magazine The store will also stock its own in-house goodies 3424 Wai‘alae Ave., open Thursday through Sunday, small.kine.gift, @smallkinegift After shuttering its South Shore Market location back in August Aly Ishikuni’s Mori by Art + Flea boutique is back on the scene with a refreshed storefront at the Capitol Modern art museum during the museum’s monthly First Friday event Capitol Modern, 250 S. Hotel St., morihawaii.com, @mori_hawaii Native Hawaiian textile designer Jalene Kanani Bell recently opened a second boutique at Salt at Our Kaka‘ako Highlights include pillow covers topped with the artwork of award-winning vocalist Melveen Leed and a newly released batch of area rugs featuring Hawai‘i-inspired patterns Salt at Our Kaka‘ako, 691 Auahi St., Level 1, nohohomehawaii.com, @nohohome Japanese luxury watch label Grand Seiko opened its first Hawai‘i boutique in Waikīkī in November courtesy of a partnership with Ben Bridge Jewelers the brand’s timepieces feature mechanical quartz and Spring Drive movements paired with elegant aesthetics Outrigger Waikīkī Beachcomber Hotel, 2300 Kalākaua Ave., (808) 830-4995, benbridge.com, @benbridgejwlr Created by two friends from Hilo High School is one of our favorite sustainable swimwear labels thanks to its eco-friendly fabrics (made from recycled plastic bottles) and Hawai‘i-inspired prints The brand already boasts boutiques on Hawai‘i Island and Maui and just opened its first O‘ahu location at Ala Moana Center plus a ton of warm-weather accessories and breezy resortwear Ala Moana Center, 1450 Ala Moana Blvd., Level 2 in the Target wing, coconutave.com, @coconutave Local labels Yireh and MahinaMade have once again teamed up to open shop at South Shore Market Snag the latest from both labels—Kailee Freitas just launched new lei-printed dresses and trucker hats while Emily Jaime recently dropped her holiday-ready Ma‘o Hau Hele Collection South Shore Market, 1170 Auahi St.,shopyireh.com, @yireh_, mahinamade.com, @mahinamade New-York based womenswear label Yumi Kim is known for vibrant hues lively floral prints and vintage-inspired silhouettes Slated to open in Waikīkī on Dec the brand’s first Hawai‘i boutique will stock party-ready sundresses Royal Hawaiian Center, 2201 Kalākaua Ave., Building B, Level 1, (808) 200-3216, yumikim.com, @yumikim SEE ALSO: Can’t-Miss Local Holiday Markets and Craft Fairs on O‘ahu Whether you have a sweet tooth or a need for chicken skin you’ll find something to scream about in this roundup of haunted houses Check back for more Halloween events throughout the month SEE ALSO: Where to Find Spoopy Halloween Treats on O‘ahu Just don’t expect any scare tactics or any funny business—whatever happens on the tour is real $40, various locations, mysteries-of-hawaii.com, @mysteriesofhawaii SEE ALSO: Pumpkin Patches and Fall Festivals on O‘ahu Photo: Courtesy of Waimanalo Country Farms The annual pumpkin patch is back at this beloved family-run farm you can also take hayrides (and selfies) in the sunflower fields shop at the country market for fresh corn and so much more Family-friendly, from $7 for keiki and $12 for adults, children 2 years old and under are free, 41-225 Lupe St., Waimānalo, waimanalocountryfarms.com, @waimanalocountryfarms SEE ALSO: We Tried It: Waimānalo Country Farms’ Fall Harvest Festival Photo: Courtesy of Universal Pictures – Psycho Alfred Hitchcock’s most iconic movies return to the big screen for October Catch the suspenseful films North by Northwest Strangers on a Train and Psycho at Kāhala BUY TICKETS $17.75, Consolidated Theatres Kāhala, 4211 Wai‘alae Ave., consolidatedtheatres.com, @consolidatedhi SEE ALSO: Our Favorite Ghost Stories About Haunted Places on O‘ahu Photo: Courtesy of Paramount Pictures – The Ring Consolidated Theatres is bringing the screams to the big screen with showings of The Texas Chainsaw Massacre BUY TICKETS: WARD BUY TICKETS: MILILANI BUY TICKETS: PEARLRIDGE $17.75, Consolidated Theatres Ward, Mililani and Pearlridge, consolidatedtheatres.com, @consolidatedhi a young vampire who is too empathetic to kill humans she must learn to hunt or find another way to survive BUY TICKETS $15, free for 18 and under, Doris Duke Theatre at Honolulu Museum of Art, 900 S Beretania St., honolulumuseum.org, @honolulumuseum For the month of October, Skull & Crown will pop up in the Treehouse (Banyan Court 21+, International Market Place, 2330 Kalākaua Ave., shopinternationalmarketplace.com, @intlmktplace Don your costume (or not) and sip on seasonally inspired specialty cocktails The concept of this terrifyingly entertaining space is by the creators of Haunted Plantation 21+, Ala Moana Center, 1450 Ala Moana Boulevard, Space 1310 (former Surfers Bakery), nightmarehonolulu.com, @nightmarehonolulu Looking for a costume or accessories for Halloween Check out the assortment the Kaimukī Performing Arts Center has collected Kaimukī High School Auditorium, 2705 Kaimukī Ave., @officialkhspac Immerse yourself in Halloween music live surrounded by candlelight Some of the classics played will include “Thriller” by Michael Jackson “The Addams Family Theme” and the “Ghostbusters Theme.” BUY TICKETS $44–$68.50, The Salvation Army Kroc Center Hawai‘i, 91-3257 Kualaka‘i Parkway, ‘Ewa Beach, feverup.com See the zoo in a new eerie light with this walking tour that delves into its supernatural occurrences The tour accommodates up to 25 guests and is recommended for keiki age 8 and older BUY TICKETS Family-friendly, $20 for Honolulu Zoo Society members, $30 for non-members, 151 Kapahulu Ave., honoluluzoo.org, @thehonoluluzoo Head to the aquarium to seek out the marine masters of disguise carve pumpkins underwater and enjoy delicious food and drinks from local vendors BUY TICKETS Family-friendly, $15 for members ($5 for children 4–12), $20 for non-members ($10 for children 4–12), children 3 and under free, Waikīkī Aquarium, 2777 Kalākaua Ave., fowaquarium.org, @waikikiaquarium You need to overcome three challenges to escape Dr Keep in mind that this escape room experience will include strobe lights BUY TICKETS $35, 1500 Kapiolani Blvd., trialoffearshi.com, @trialoffears Hawai‘i’s Plantation Village is an outdoor museum of historical homes and gardens where you can learn the stories of Hawai‘i’s people this historic sugar plantation in Waipahu turns into a truly scary site It’s even been named one of the scariest haunted houses in the world by media and technology company Pop Sugar this terrifying attraction is geared toward the bravest souls ages 12 and up $20 + $1 online reservation fee, cash only, Hawai‘i’s Plantation Village, 94-695 Waipahu St., Waipahu, hawaiihauntedplantation.com, @hauntedplantation SEE ALSO: Scary Ghost Stories From Hawai‘i’s “Haunted” Plantation Village The creators of Haunted Plantation bring a walkthrough horror experience to Hawai‘i Theatre Meet a hypnotist who claims to be able to raise the dead and watch his captivating show BUY TICKETS $40, 18+ only, 12 guests per showtime, Hawai‘i Theatre, 1130 Bethel St., hawaiitheatre.com, @170six Aloun Farms invites you to Kapolei to harvest your own pumpkins Keep your keiki entertained with activities like free hayrides and a petting zoo Bring a wagon or reusable bags as there is a farmers’ market where you can purchase produce grown on Aloun Farms’ 3,000-acre grounds Family-friendly, $5, free for 2 years and under, free parking, 91-1440 Farrington Highway, alounfarms.com, @alounfarmshawaii Find thrills and chills at the haunted house and onsite Halloween movies There will also be food trucks and carnival games The event proceeds will benefit the American Renaissance Academy BUY TICKETS Family-friendly, $20 haunted house entry, $25 at the door, $10 parking, Kapolei Events Center, 91-1180 Midway St., arahawaii.org, @ara.hawaii, @kapoleieventscenter Celebrate the artsy spirit of Halloween with costumed models posing for your figure drawing You can also dress up for the evening and enjoy music and refreshments Instructions and supplies (if you don’t bring your own) are provided BUY TICKETS $15, limited to 20 participants, Downtown Art Center, 1041 Nu‘uanu Ave., downtownarthi.org, @downtownartcenter Photo: Courtesy of Alexander & Baldwin gather for a quest across Kailua where you’ll solve puzzles and follow clues to treats Keiki who uncover the password will receive a token to redeem a gachapon-style prize capsule Participants who are 18 or older can also enter to win a $250 Kailua Town prize package Family-friendly, free, Lau Hala Shops, 573 Kailua Rd., Kailua, kailuatownhi.com, @kailuatownhi Have a blast decorating Basalt’s famous charcoal buttermilk pancakes with spooky Halloween effects, including ube liliko‘i sabayon, meringue ghosts and pumpkins, ash mascarpone whip, candy corn and Halloween sprinkles. Make a reservation online or by calling (808) 923-5689 Complimentary validation is available for self-parking at the Hyatt Centric Waikīkī Hotel MAKE A RESERVATION Family-friendly, $19, Basalt, 2255 Kūhiō Ave., basaltwaikiki.com, @basaltwaikiki you will receive an email invitation for Trunk O’ Treat SIGN UP FOR KEIKI CLUB Family-friendly, for PBS Hawai‘i Keiki Club member ($30 annual donation to sign up and $25 for each additional sibling), PBS Hawai‘i, 315 Sand Island Access Rd., pbshawaii.org, @pbshawaii And after the thrill of the 45-minute workshop REGISTER Family-friendly, $10 for members, $15 for nonmembers, Children’s Discovery Center, 111 ‘Ohe St., discoverycenterhawaii.org, @hawaiichildrensdiscoverycenter Photo: Courtesy of The Surfjack Hotel & Swim Club is inviting all furry friends to celebrate his birthday in spooky style then register your pet for the costume contest starting at 4 p.m Parking is available at the Hyatt Centric Garage: $8 for four hours with validation from Mahina & Sun’s Free, The Surfjack Hotel & Swim Club, 412 Lewers St., surfjack.com, @thesurfjack Enter your keiki in one of three age groups: 0–4 The three judging categories will be Funniest/Cutest Scariest and Most Creative Costume Made with 50% or More Recycled Materials There will also be one special prize awarded for Judges’ Overall Favorite And stick around for the opening and closing performances by Studio 808 Danceproject Family-friendly, free, Ka Makana Ali‘i, 91-5431 Kapolei Pkwy., Kapolei, kamakanaalii.com, @kamakanaalii Courtesy of Sustainable Coastlines Hawai‘i Help clean up Kaimukī and Pālolo Stream and check out the festival’s live entertainment Come dressed up for the upcycled costume contest REGISTER FOR CLEANUP Family-friendly, free, Ali‘iolani Elementary School, 1240 7th Ave., sustainablecoastlineshawaii.org, @sustainablecoastlineshawaii Photo: Courtesy of Market City Shopping Center Bring your ‘ohana for trick-or-treating The Market City Halloween costume contest is open to keiki try your hand at the 94.7 KUMU prize wheel to win prizes from Market City merchants The Halloween celebration will be held in the back parking lot next to Ben Franklin Crafts with additional parking available at Kaimukī High School Family-friendly, free, Market City Shopping Center, 2919 Kapi‘olani Blvd. #2, marketcityhawaii.com, @marketcityhi Photo: Courtesy of Sea Life Park Hawai‘i Sea Life Park becomes Halloween headquarters with a mermaid encounter and ghost stories with Lopaka Kapanui Come in costume on Saturday to join the costume contest Family-friendly, festivities are included with the price of admission, Sea Life Park, 41-202 Kalaniana‘ole Highway, Waimānalo, sealifeparkhawaii.com, @sealifepark Swimsuit up with your ‘ohana for the Kroc Center’s floating pumpkin patch This event is for keiki ages 6 months to 15 years Each ticket includes entry for one guardian or parent REGISTER Family-friendly, $15 for members, $20 for non-members, The Salvation Army Kroc Center Hawai‘i, 91-3257 Kualaka‘i Parkway, ‘Ewa Beach, kroccenterhawaii.org, @kroccenterhi Drink Elysian Brewing Night Owl beer on tap from a 100 lb There will also be a pumpkin drawing contest with prizes 21+, Village Beer Kapolei, 4450 Kapolei Parkway, Suite 278, villagebeerhawaii.com, @villagebeerkapolei Go on a family-friendly adventure through Hauntopia and enjoy trick-or-treating interactive art and science activities and more Halloween surprises BUY TICKETS Family-friendly, $15, Da Dream Lab, 905 Kalanianaʻole Highway #3304, Kailua, dadreamlab.com, @kidzarthawaii Enter (if you dare) a former clinic haunted by a mad doctor who committed a Chinatown massacre and now seeks more victims in the afterlife BUY TICKETS 13+, $35, meet at 1136 Union Mall, dohoevents.com DLT Stables is hosting a Halloween party with a wild side—come down for pony rides and a petting zoo in addition to trick-or-treating and games BUY TICKETS $25, DLT Stables, 41-631 Mokulama St., Waimānalo, dltstables.com, @dltstables Keiki up through sixth grade can participate in the 45th annual costume contest for a chance to win gifts and gift cards from mall merchants Families dressed in one theme can also enter as a group for a chance to win best overall theme Family-friendly, free, 4211 Wai‘alae Ave., Kāhala, kahalamallcenter.com, @kahalamall Listen to eerie tales and legends from Lopaka Kapanui Hawai‘i’s premier ghost storyteller that will make you confront your supernatural beliefs BUY TICKETS $20, $15 for 18 and under, Doris Duke Theatre at Honolulu Museum of Art, 900 S Beretania St., honolulumuseum.org, @honolulumuseum The only remaining time slot is on Friday at 9:15 p.m call (808) 681-5461 and leave a message with your name Check in and pay 20 minutes before departure; keep in mind that if you’re late you may lose your spot to standby passengers $5 per passenger (ages 2+), cash only, onsite parking, Hawaiian Railway Society Train Yard, 91-1001 Renton Road, ‘Ewa Beach, hawaiianrailway.com from deranged doctors to restless patients All proceeds will benefit Kaimukī High School Performing Arts Center BUY TICKETS $20, recommended for 12+, Kaimukī High School Performing Arts Center, 2705 Kaimukī Ave., @officialkhspac The Flick-or-Treat Drive-In Weekend includes new and timeless favorites: Inside Out 2 explore the Holy Nativity School’s pumpkin patch and enjoy keiki-friendly festival games and this area is free and open to the public BUY TICKETS Family-friendly, $35 festival entry, $45 movie entry for one vehicle, Holy Nativity School, 5286 Kalaniana‘ole Highway, holynativityschool.org, @holynativityschool Nine Chinatown bars are pitching in spooky food and drink specials and there will be a horror movie screening and you will need to check in at Skull & Crown Trading Co GET TICKETS 21+, free, Chinatown, @frightnightshawaii dance all night long and come in costume for the contests to win up to $2,500 in prizes BUY TICKETS 21+, $10 early bird online, $20 at the door, The District Nightclub, 1349 Kapiolani Blvd., thedistricthi.com, @thedistricthi Head to Victoria Ward Park for free Halloween festivities grab free pumpkin spice malasadas and pumpkins from Aloun Farms while supplies last Family-friendly, free, Victoria Ward Park, 1020 Auahi St., wardvillage.com, @wardvillage Bring your hungry little monsters to eat their fill at Hard Rock Café and play in a game area take photos with Beetlejuice and compete in a costume contest BUY TICKETS $35 (covers tax and gratuity), Hard Rock Café, 280 Beach Walk, cafe.hardrock.com, @hrchonolulu Bring your ‘ohana in costume to enjoy a scavenger hunt There will be a costume contest for kids as well as prize giveaways from KDNN radio and participating merchants Family-friendly, free, Salt Lake Shopping Center, 848 Ala Liliko‘i St., saltlakeshoppingcenter.com, @saltlakeshoppingcenter Hana Koa Brewing Co. has brewed up a benefit beer called Fangs for Donating, with 10% of the proceeds benefiting the Blood Bank of Hawai‘i. And if you’re able, you can sign up to donate blood at bbh.org/#blooddrive (Saturday is booked up Every donor will receive a $10 gift card and free plate of fries Free admission, Hana Koa Brewing Co., 962 Kawaiaha‘o St., bbh.org, hanakoabrewing.com SEE ALSO: Just in Time for Halloween, Hana Koa’s “Fangs for Donating” Hazy IPA Is a Plea for the Blood Bank Head over to the Hokulani Imaginarium at Windward Community College to learn about the history of Halloween and its astronomical connections or look back at how ancient Egyptians used the stars while building pyramids The first show will be followed by a special virtual tour of a haunted graveyard brought to life with 3D animation The annual Halloween Spooktacular is happening once again at the marina docks Participating merchants will have “Trick-or-Treat” signs for keiki to snag some sweet treats The keiki costume contest will have three categories based on age (infants to 12 year olds are welcome to participate) plus an ‘ohana category second- and third- place prizes will be awarded to each age group Family-friendly, free, Hawai‘i Kai Towne Center, 333 Keahole St., Hawai‘i Kai, hawaiikaitownecenter.com, @hawaiikaitownecenter play games and make friends during this Halloween-themed dance party REGISTER $60, For kids ages 5–9, Hawai‘i Dance Bomb, hawaiidancebomb.com, @hawaii_dance_bomb Photo: Courtesy of La Pietra–Hawai‘i School for Girls At La Pietra–Hawai‘i School for Girls keiki can trick or treat their way through candy trails play carnival games, join the Keiki Spooky Story Circle and brave a haunted house if they so dare and all ticket proceeds support La Pietra’s Student Council with tickets sold at the door for cash only pending availability BUY TICKETS Family-friendly, $20, 2933 Poni Moi Rd., lapietra.edu, @lapietraschool Chinatown bar owners took it upon themselves to organize their own Halloween crawl with spooky drink specials dance parties and a midnight costume contest BUY TICKETS 21+, $20 presale, $30 at the door, Chinatown, @halloweeninchinatown SEE ALSO: “Plan on Hallowbaloo Not Happening”—But Another Chinatown Bar Crawl Is Coming Marvel as Aloha Ballroom Company takes over the streets of downtown Honolulu performing Michael Jackson’s “Thriller.” The dancers will have zombie makeup on for a frightful effect Free, in front of Hawai‘i Theatre, 1130 Bethel St., alohaballroomcompany.com, @alohaballroomco Dress up and trick-or-treat for laughs at Improv Hawai‘i’s Halloween special-edition of Nerd Nite The show will include a costume contest and prizes $10, Tiny Stage Hawai‘i, 419 South St Suite 163, improvhi.com, @improvhi Photo: Courtesy of Hawai‘i Symphony Orchestra Enjoy ghost stories narrated by HI Now Daily Correspondent Lauren Teruya and spooky music that make your hair stand on end BUY TICKETS: OCT. 26 BUY TICKETS: OCT. 27 Family-friendly, $25 to $45, Hawai‘i Theatre, 1130 Bethel St., myhso.org, @hawaiisymphonyorchestra Enjoy drink specials like the Ghoul’s Night Out while you bop to DJ Hale Life’s beats Hideout at The Laylow, 2299 Kūhiō Ave., hideoutwaikiki.com, @hideoutwaikiki Head to Aloha Stadium for a special fall- and Halloween-themed swap meet with a pumpkin patch and golden prize tickets in addition to the usual vendors and live entertainment Keiki are also invited to trick-or-treat and enjoy face painting balloon art and photo ops with costumed characters Free admission, 99-500 Salt Lake Blvd, ‘Aiea, alohastadium.hawaii.gov, @alohastadswapmeet Get the most out of your keiki’s costumes and play some spoopy games create creepy crafts and go trick-or-treating throughout the Children’s Discovery Center You need to register to join this special event REGISTER Family-friendly, $8 for members, $12 for nonmembers. Children’s Discovery Center, 111 ‘Ohe St., discoverycenterhawaii.org, @hawaiichildrensdiscoverycenter limited-edition Halloween Trick-or-Treat Aloha bag when you spend $50 or more (while supplies last) Family-friendly, free, 2201 Kalākaua Ave., Waikīkī, royalhawaiiancenter.com, @royalhawaiicenter Come in costume and follow clues to collect creature stamps then trek down the Haunted Habitat Treat Trail There will also be activity stations with eerie educational animal bio-facts Participation in this event is included with admission Family-friendly, 151 Kapahulu Ave., honoluluzoo.org, @thehonoluluzoo Bring your little ghouls and goblins to Town Center of Mililani to trick-or-treat at participating stores with signs in their windows You can also enjoy face painting and spin a prize wheel Family-friendly, free, Town Center of Mililani, 95-1249 Meheula Pkwy, Mililani, towncenterofmililani.com, @towncenterofmililani Enter your paw-some costumed critters in this contest to win prizes And don’t miss your chance to get a photo with Cruella Family-friendly, Town Center of Mililani, 95-1249 Meheula Pkwy, Mililani, towncenterofmililani.com, @towncenterofmililani Hale‘iwa Store Lots’ annual trick-or-treating and keiki costume contest is back with three age groups: 0–3 years and participation is limited to 50 keiki per age group and the top three age group winners will receive prizes Participating retailers will pass out candy while supplies last Family-friendly, free, Hale‘iwa Store Lots, 66-111 Kamehameha Highway, Hale‘iwa, haleiwastorelots.com, @haleiwastorelots Hear some spooky mo‘olelo (stories) of Kaimukī from Lopaka Kapanui and learn more about the neighborhood’s history Free, Kaimukī Public Library, 1041 Koko Head Ave., librarieshawaii.org, @hsplshigov Bring the ‘ohana for trick-or-treating and prize raffles Keiki will receive free trick-or-treat bags that include a coupon for a free kids’ meal and 20% off the next bill at Black Angus Steakhouse Participating businesses will also have discounts and giveaways of their own Family-friendly, free, Black Angus Steakhouse, 98-1262 Ka‘ahumanu St., Pearl City, blackangus.com Nalo Keiki Paniolo is hosting a Halloween party with a wild side—come down for pony rides and a petting zoo in addition to trick-or-treating and games BUY TICKETS Family-friendly, $25 for keiki ages 2–12 years, $15 for 13+, Nalo Keiki Paniolo, 41-632 Mokulama St., Waimānalo, nalokeikipaniolo.com, @nalo.keiki.paniolo Photo: Courtesy of The Ritz-Carlton O‘ahu Come in costume with surfboard in hand to this surf competition There will be a live DJ at The Ritz-Carlton O‘ahu Turtle Bay pool as well for spectators to enjoy Registration proceeds will benefit the Kahuku High School surf team $10 registration fee, Jamie O’Brien Surf Experience, 57-091 Kamehameha Highway, Kahuku, turtlebayresort.com, @ritzcarltonoahuturtlebay Look out for branded cauldrons full of treats around Kū‘ono Marketplace. You can also enter the Instagram costume contest for a chance to win a $50 gift card to a Kū‘ono Marketplace merchant of your choice Family-friendly, free, Kū‘ono Marketplace, 4210 Wai‘alae Ave., kuonomarketplace.com, @kuonomarketplace SEE ALSO: Things to Do on Halloween on O‘ahu Head to Wai Kai for free trick-or-treating Join the costume contest at the Wave Deck (family for the chance to win gift certificates for Wai Kai experiences Head to the Surfside Lawn to decorate your own trick-or-treat tote ($5) ‘Ono Grindz & Makeke Farmers Market will also be on at the same time Family-friendly, free admission, Wai Kai, 91-1621 Keoneula Blvd, ‘Ewa Beach, waikai.com, @waikailineup Collect treats from participating retailers with balloons in front of their stores and enjoy the terrifying tunes spun by a live DJ at center stage Family-friendly, free, 4211 Wai‘alae Ave., kahalamallcenter.com, @kahalamall Photo: Courtesy of International Market Place Keiki can trick-or-treat at participating stores and restaurants with orange and black balloons caricature drawing and photo ops with costumed characters Family-friendly, free, International Market Place, 2330 Kalākaua Ave., shopinternationalmarketplace.com, @intlmktplace More than 100 merchants throughout the mall will hand out sweets to trick-or-treaters on Halloween night Find more spooky festivities in the ‘Ewa Wing Court near Bloomingdale’s including a bubble-filled Halloween dance party a haunted house selfie wall and balloon creations Family-friendly, free, Ala Moana Center, 1450 Ala Moana Blvd., alamoanacenter.com, @alamoanacenter Enjoy indoor trick-or-treating with your keiki in Pearlridge Center’s Mauka and Wai Makai wings There will also be a keiki costume contest and giveaways hosted by PBS Hawai‘i Family-friendly, free, Pearlridge Center, 98-1005 Moanalua Rd, ‘Aiea, pearlridgeonline.com, @pearlridge ‘Ohana can trick-or-treat at participating merchants while completing a passport for treasure get your face painted and enter a costume contest Family-friendly, free, Salt at Our Kaka‘ako, 691 Auahi St., saltatkakaako.com, @saltourkakaako Keiki can trick or treat throughout Ka Makana Ali‘i get there early for the Halloween magic show with Torch Entertainment from 5:30 to 6 p.m Family-friendly, free, Ka Makana Ali‘i, 91-5431 Kapolei Pkwy., Kapolei, kamakanaalii.com, @kamakanaalii Participating merchants will be giving out goodies during Windward Mall’s indoor Trick-or-Treat event this Halloween Note: Masks are only permitted on keiki 12 and under during the trick-or-treating event while masks are not permitted before or after and not permitted on adults Family-friendly, free, Windward Mall, 46-056 Kamehameha Hwy, Kāne‘ohe, windwardmall.com, @windwardmall Have a glamorous and spooky Halloween night at this prohibition-themed soirée with dance performances and a live DJ Your ticket includes two specialty cocktails and small bites and you’ll receive a free masquerade mask for added mystery BUY TICKETS $75, Moana Surfrider, 2365 Kalakaua Ave., event.marriott.com, @themoanasurfrider Dress up in your cosplay finest to party on Halloween night with live DJs playing your favorite anime and K-pop tunes There will also be a cosplay contest and local vendors with merch and treats for sale BUY TICKETS 18+, $15, Dave & Buster’s, 1030 Auahi St., supersaturdayhawaii.com, @supersaturdayhi This year’s Halloween at the Hyatt theme is “Creatures Come Alive.” Do the Monster Mash enter the costume contest with up to $2,000 in prizes and join the afterparty at The District Nightclub BUY TICKETS 21+, $20 general admission, $25 at the door, $30 VIP Admission, Hyatt Regency Waikīkī Beach Resort and Spa, 2411 Koa Ave., hyatthalloween.com, @hyattregencywaikiki you get up to two drinks or shots and access to food and drink specials at Bar 35 Off the Wall Craft Beer & Wine and Air Park Karaoke Lounge There will also be an afterparty at NextDoor and Air Park Karaoke Lounge BUY TICKETS 21+, $15 for individuals or $10 for groups of four or more + fees, TJ’s Sports Bar & Grill, 600 Kapiolani Blvd. Ste 100, crawlwith.us People with atypical hemolytic uremic syndrome (aHUS) usually have a genetic predisposition for disorders of the complement system. However, aHUS usually develops only following a triggering factor such as an infection Following is more information about the relationship between aHUS and cancer The complement system is a series of different proteins that play a role in the immune system These proteins usually become active in the presence of foreign invaders in the body such as viruses or bacteria They work together to activate the immune system The complement system usually is kept in check by complement regulatory proteins (CRPs) which ensure it does not target the body’s own cells The exact link between aHUS and cancer is not clear. However, researchers think that cancerous cells cause activation of certain parts of the complement pathway in order to have new blood vessels grow to feed the tumor Certain types of cancer also produce thrombin a molecule that can activate the complement system The extra activation of the complement pathway may lead to aHUS in some people especially if they already have a genetic predisposition due to genetic mutations that control the regulatory proteins Research also has shown that up to 90% of cancer-related aHUS cases involve cancer that has spread (metastatic) Some patients may experience aHUS symptoms due to cancer treatments including chemotherapy and anti-vascular endothelial growth factor (anti-VEGF) — a treatment used to halt the formation of new blood vessels — may induce TMA that can lead to aHUS In most cases of cancer-related aHUS, cancer needs to be treated first. Treatment usually consists of chemotherapy or hormone therapy, while plasma exchange can treat aHUS symptoms A study that looked at medical records of aHUS in cancer patients found that those with gastric (stomach) and lung cancer tended to survive longer when they received chemotherapy or hormone therapy 14 of 16 patients had a good response to plasma exchange aHUS News is strictly a news and information website about the disease Never disregard professional medical advice or delay in seeking it because of something you have read on this website.