Displaying publications 141 - 160 of 384 in total

Abstract:
Sort:
  1. Zhang XC, Wang J, Shao GG, Wang Q, Qu X, Wang B, et al.
    Nat Commun, 2019 04 16;10(1):1772.
    PMID: 30992440 DOI: 10.1038/s41467-019-09762-1
    Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.5%) compared with squamous cell carcinoma (SQCC, 54.4%). The correlation of genomic alterations with immune signatures reveals that low immune infiltration was associated with EGFR mutations in ADC samples, PI3K and/or WNT pathway activation in SQCC. While KRAS mutations are found to be significantly associated with T cell infiltration in ADC samples. The SQCC patients with high antigen presentation machinery and cytotoxic T cell signature scores are found to have a prolonged overall survival time.
  2. Chung KF, Seiffert J, Chen S, Theodorou IG, Goode AE, Leo BF, et al.
    ACS Nano, 2017 03 28;11(3):2652-2664.
    PMID: 28221763 DOI: 10.1021/acsnano.6b07313
    There is a potential for silver nanowires (AgNWs) to be inhaled, but there is little information on their health effects and their chemical transformation inside the lungs in vivo. We studied the effects of short (S-AgNWs; 1.5 μm) and long (L-AgNWs; 10 μm) nanowires instilled into the lungs of Sprague-Dawley rats. S- and L-AgNWs were phagocytosed and degraded by macrophages; there was no frustrated phagocytosis. Interestingly, both AgNWs were internalized in alveolar epithelial cells, with precipitation of Ag2S on their surface as secondary Ag2S nanoparticles. Quantitative serial block face three-dimensional scanning electron microscopy showed a small, but significant, reduction of NW lengths inside alveolar epithelial cells. AgNWs were also present in the lung subpleural space where L-AgNWs exposure resulted in more Ag+ve macrophages situated within the pleura and subpleural alveoli, compared with the S-AgNWs exposure. For both AgNWs, there was lung inflammation at day 1, disappearing by day 21, but in bronchoalveolar lavage fluid (BALF), L-AgNWs caused a delayed neutrophilic and macrophagic inflammation, while S-AgNWs caused only acute transient neutrophilia. Surfactant protein D (SP-D) levels in BALF increased after S- and L-AgNWs exposure at day 7. L-AgNWs induced MIP-1α and S-AgNWs induced IL-18 at day 1. Large airway bronchial responsiveness to acetylcholine increased following L-AgNWs, but not S-AgNWs, exposure. The attenuated response to AgNW instillation may be due to silver inactivation after precipitation of Ag2S with limited dissolution. Our findings have important consequences for the safety of silver-based technologies to human health.
  3. Wong JH, Muthuraju S, Reza F, Senik MH, Zhang J, Mohd Yusuf Yeo NAB, et al.
    Biomed Pharmacother, 2019 Feb;110:168-180.
    PMID: 30469081 DOI: 10.1016/j.biopha.2018.11.044
    Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABAA receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was significantly reduced in the CA3 (at 100, 300, and 600 mg/kg) while no significant changes of subunit expression was observed in CA1 and EC compared to control. The results suggest that the enhanced learning and memory observed in animals administered with CA was mainly mediated through increased expression of AMPAR GluA1 and GluA2 subunits and differential expression of NMDAR GluN2 A and GluN2B subunits in the hippocampal subfields and EC. With these findings, the study revealed a new aspect of cognitive enhancing effect of CA and its therapeutic potentials through modulating receptor subunit expression.
  4. Tay E, Khaing T, Yin W, Posas E, Kao P, Buddhari W, et al.
    AsiaIntervention, 2021 Jul;7(1):54-59.
    PMID: 34913003 DOI: 10.4244/AIJ-D-18-00053
    Aims: The aim of the study was to report the clinical experience, 30-day mortality and acute outcomes of patients undergoing transcatheter aortic valve implantation (TAVI) in the Asia Pacific region.

    Methods and results: The Asia Pacific TAVI registry is an international, multicentre, prospective, observational registry managed under the auspices of the Asian Pacific Society of Interventional Cardiology (APSIC). Patients undergoing TAVI in seven centres from Hong Kong, Japan, Philippines, Singapore and Taiwan, treated with TAVI devices for severe symptomatic aortic stenosis, were assessed. This first review presents the acute results and 30-day mortality. A multivariable analysis was also performed to identify independent predictors of early all-cause mortality. The enrolment was from 2009 to 2017 and a total of 1,125 patients were recruited. The 30-day mortality rate was 2.5%. Baseline logistic EuroSCORE more than 16 was independently associated with a 2.8-times increased risk of 30-day all-cause mortality (p=0.016). Post-procedural stroke (HR 4.9, p=0.008) was also associated with increased mortality.

    Conclusions: This initial report of the Asia Pacific TAVI registry demonstrated good acute success and low 30-day mortality. The preprocedural logistic EuroSCORE and post-procedural stroke incidence were strongly associated with acute mortality. Further attempts to reduce post-procedural stroke should be explored.

  5. Li T, Cheng H, Li Y, Mou Z, Zhu X, Wu W, et al.
    Sci Total Environ, 2023 Jul 10;881:163204.
    PMID: 37044342 DOI: 10.1016/j.scitotenv.2023.163204
    Tropical primary forests are being destroyed at an alarming rate and converted for other land uses which is expected to greatly influence soil carbon (C) cycling. However, our understanding of how tropical forest conversions affect the accumulation of compounds in soil functional C pools remains unclear. Here, we collected soils from primary forests (PF), secondary forests (SF), oil-palm (OP), and rubber plantations (RP), and assessed the accumulation of plant- and microbial-derived compounds within soil organic carbon (SOC), particulate (POC) and mineral-associated (MAOC) organic C. PF conversion to RP greatly decreased SOC, POC, and MAOC concentrations, whereas conversion to SF increased POC concentrations and decreased MAOC concentrations, and conversion to OP only increased POC concentrations. PF conversion to RP decreased lignin concentrations and increased amino sugar concentrations in SOC pools which increased the stability of SOC, whereas conversion to SF only increased the lignin concentrations in POC, and conversion to OP just increased lignin concentrations in POC and decreased it in MAOC. We observed divergent dynamics of amino sugars (decrease) and lignin (increase) in SOC with increasing SOC. Only lignin concentrations increased in POC with increasing POC and amino sugars concentrations decreased in MAOC with increasing MAOC. Conversion to RP significantly decreased soil enzyme activities and microbial biomasses. Lignin accumulation was associated with microbial properties, whereas amino sugar accumulation was mainly associated with soil nutrients and stoichiometries. These results suggest that the divergent accumulation of plant- and microbial-derived C in SOC was delivered by the distribution and original composition of functional C pools under forest conversions. Forest conversions changed the formation and stabilization processes of SOC in the long run which was associated with converted plantations and management. The important roles of soil nutrients and stoichiometry also provide a natural-based solution to enhance SOC sequestration via nutrient management in tropical forests.
  6. Chen L, Xu YY, Lin JY, Ji ZP, Yang F, Tan S, et al.
    Asian J Psychiatr, 2024 Mar;93:103958.
    PMID: 38364597 DOI: 10.1016/j.ajp.2024.103958
    BACKGROUND AND AIM: Suicide is nearly always associated with underlying mental disorders. Risk factors for suicide attempts (SAs) in patients with bipolar disorder (BD) misdiagnosed with major depressive disorder (MDD) remain unelucidated. This study was to evaluate the prevalence and clinical risk factors of SAs in Chinese patients with BD misdiagnosed with MDD.

    METHODS: A total of 1487 patients with MDD from 13 mental health institutions in China were enrolled. Mini International Neuropsychiatric Interview (MINI) was used to identify patients with BD who are misdiagnosed as MDD. The general sociodemographic and clinical data of the patients were collected and MINI suicide module was used to identify patients with SAs in these misdiagnosed patients.

    RESULTS: In China, 20.6% of patients with BD were incorrectly diagnosed as having MDD. Among these misdiagnosed patients, 26.5% had attempted suicide. These patients tended to be older, had a higher number of hospitalizations, and were more likely to experience frequent and seasonal depressive episodes with atypical features, psychotic symptoms, and suicidal thoughts. Frequent depressive episodes and suicidal thoughts during depression were identified as independent risk factors for SAs. Additionally, significant sociodemographic and clinical differences were found between individuals misdiagnosed with MDD in BD and patients with MDD who have attempted suicide.

    CONCLUSIONS: This study highlights the importance of accurate diagnosis in individuals with BD and provide valuable insights for the targeted identification and intervention of individuals with BD misdiagnosed as having MDD and those with genuine MDD, particularly in relation to suicidal behavior.

  7. Tan YK, Siau CS, Chan LF, Kõlves K, Zhang J, Ho MC, et al.
    Asian J Psychiatr, 2023 Nov;89:103772.
    PMID: 37748229 DOI: 10.1016/j.ajp.2023.103772
    This cross-sectional study aimed to validate the Life Events Checklist for DSM-5 (LEC-5) among Malaysian undergraduates (N = 500; mean age = 21.66 ± 1.57), of which 90.4% had ever experienced a lifetime traumatic event. Cronbach's alpha of .87 (95% CI [.86, .89]) and McDonald's omega of .89 (95% CI [.89, .93]) indicated good reliability. Confirmatory factor analysis based on a six-factor structure showed the best fit. The measurement invariance showed that the six-factor structure was similar across sexes. Therefore, the Malay LEC-5 is a valid and reliable instrument to screen for traumatic events among Malaysian undergraduates.
  8. Cheng AL, Li J, Vaid AK, Ma BB, Teh C, Ahn JB, et al.
    Clin Colorectal Cancer, 2014 Sep;13(3):145-55.
    PMID: 25209093 DOI: 10.1016/j.clcc.2014.06.004
    Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.
  9. Cheng J, Wang Y, Hou J, Luo D, Xie Q, Ning Q, et al.
    J Clin Virol, 2014 Dec;61(4):509-16.
    PMID: 25200354 DOI: 10.1016/j.jcv.2014.08.008
    In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B.
  10. Singh R, Jayanna M, Wong J, Lim LG, Zhang J, Lv J, et al.
    Endosc Int Open, 2015 Feb;3(1):E14-8.
    PMID: 26134765 DOI: 10.1055/s-0034-1377610
    The advent and utility of new endoscopic imaging modalities for predicting the histology of Barrett's esophagus (BE) in real time with high accuracy appear promising and could potentially obviate the need to perform random biopsies where guidelines are poorly adhered to. We embarked on evaluating the performance characteristics of white-light endoscopy with magnification (WLE-z), narrow-band imaging with magnification (NBI-z) and a combination of both modalities.
  11. Tan JWC, Sim D, Ako J, Almahmeed W, Cooper ME, Dalal JJ, et al.
    Eur Cardiol, 2021 Feb;16:e14.
    PMID: 33976709 DOI: 10.15420/ecr.2020.52
    The Asian Pacific Society of Cardiology convened a consensus statement panel for optimising cardiovascular (CV) outcomes in type 2 diabetes, and reviewed the current literature. Relevant articles were appraised using the Grading of Recommendations, Assessment, Development and Evaluation system, and consensus statements were developed in two meetings and were confirmed through online voting. The consensus statements indicated that lifestyle interventions must be emphasised for patients with prediabetes, and optimal glucose control should be encouraged when possible. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are recommended for patients with chronic kidney disease with adequate renal function, and for patients with heart failure with reduced ejection fraction. In addition to SGLT2i, glucagon-like peptide-1 receptor agonists are recommended for patients at high risk of CV events. A blood pressure target below 140/90 mmHg is generally recommended for patients with type 2 diabetes. Antiplatelet therapy is recommended for secondary prevention in patients with atherosclerotic CV disease.
  12. Searchfield GD, Zhang J, Biswas R, De Ridder D, Deutsch B, Hall DA, et al.
    PMID: 34291436 DOI: 10.1007/7854_2021_230
  13. Searchfield GD, Zhang J, Biswas R, De Ridder D, Deutsch B, Hall DA, et al.
    Curr Top Behav Neurosci, 2021;51:461-483.
    PMID: 33665781 DOI: 10.1007/7854_2020_217
    This volume has highlighted the many recent advances in tinnitus theory, models, diagnostics, therapies, and therapeutics. But tinnitus knowledge is far from complete. In this chapter, contributors to the Behavioral Neuroscience of Tinnitus consider emerging topics and areas of research needed in light of recent findings. New research avenues and methods to explore are discussed. Issues pertaining to current assessment, treatment, and research methods are outlined, along with recommendations on new avenues to explore with research.
  14. Maspero J, De Paula Motta Rubini N, Zhang J, Sanclemente G, Amador JR, El Sayed MH, et al.
    World Allergy Organ J, 2023 Mar;16(3):100724.
    PMID: 37033301 DOI: 10.1016/j.waojou.2022.100724
    BACKGROUND: There are gaps in our understanding of the epidemiology of atopic dermatitis (AD) in adults.

    OBJECTIVE: To evaluate the prevalence and severity of AD in adults from countries/regions within Asia, Eurasia, Latin America, Middle East, and Russia.

    METHODS: This international, web-based survey was performed in Argentina, Brazil, China, Colombia, Egypt, Hong Kong, Israel, Malaysia, Mexico, Russia, Kingdom of Saudi Arabia (KSA), Singapore, Taiwan, Thailand, Turkey, and United Arab Emirates. Questionnaires were sent to adult members of online respondent panels for determination of AD and assessment of severity. A diagnosis of AD required respondents to meet the modified United Kingdom (UK) Working Party criteria and to self-report they had a physician diagnosis of AD. Severity of AD was determined using Patient-Oriented Scoring of Atopic Dermatitis (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), and Patient Global Assessment (PGA).

    RESULTS: Among respondents by country/region the prevalence of AD ranged from 3.4% in Israel to 33.7% in Thailand. The prevalence was generally higher in females versus males. Severity varied by scale, although regardless of scale the proportion of respondents with mild and moderate disease was higher than severe disease. PGA consistently resulted in the lowest proportion of severe AD (range 2.4% China - 10.8% Turkey) relative to PO-SCORAD (range 13.4% China - 41.6% KSA) and POEM (range 5.1% China - 16.6% Israel).

    CONCLUSIONS: This survey highlights the importance of AD in adults, with high prevalence and high morbidity among respondents and emphasizes that AD is not just a disease of childhood-there is disease persistence and chronicity in adults.

  15. Maspero J, De Paula Motta Rubini N, Zhang J, Sanclemente G, Amador JR, El Sayed MH, et al.
    World Allergy Organ J, 2024 Nov;17(11):100966.
    PMID: 39568731 DOI: 10.1016/j.waojou.2024.100966
    [This corrects the article DOI: 10.1016/j.waojou.2022.100724.].
  16. Karupaiah T, Rahman SMM, Zhang J, Kumar N, Jamiyan B, Pokharel RK, et al.
    JMIR Pediatr Parent, 2024 Dec 04;7:e63410.
    PMID: 39630493 DOI: 10.2196/63410
    BACKGROUND: Rising childhood obesity rates in Asia are adding risk for the future adult burden of obesity and noncommunicable diseases. Weak policies across most Asian countries enable unrestricted marketing of obesogenic foods and beverages to children. Television is the common medium for food marketing to reach this audience.

    OBJECTIVE: This study aimed to assess the extent and nature of television food and nonalcoholic beverage marketing in 9 Asian countries (Bangladesh, China, India, Malaysia, Mongolia, Nepal, the Philippines, Sri Lanka, and Vietnam) with capacity building support from the International Network for Food and Obesity/Non-Communicable Disease Research, Monitoring and Action Support, who enabled harmonization of data collection method and content analyses.

    METHODS: Advertised foods were categorized as permitted or not permitted based on the nutrient profile models established by the World Health Organization regional offices for South-East Asia (SEARO) and the World Health Organization regional offices for Western Pacific (WPRO). Overall rates of food advertisements (advertisements per hour per channel) and persuasive strategy use were analyzed along with comparisons between children's peak viewing time (PVT) and non-PVT.

    RESULTS: Cross-country comparisons, irrespective of country income level, indicated that not permitted food advertising dominated children's popular television channels, especially during PVT with rates as per WPRO or SEARO criteria ranging from 2.40/2.29 (Malaysia) to 9.70/9.41 advertisements per hour per channel (the Philippines). Persuasive strategy rates were also comparatively higher during PVT. Sugar-sweetened beverages, sugar-containing solid foods, and high salt- and fat-containing snacks and fast foods were frequently advertised. Evaluation of the application of WPRO and SEARO nutrient profile models identified inconsistencies due to regional taste and cuisine variations across Asia.

    CONCLUSIONS: This study clearly showed that unhealthy food marketing through popular children's television channels is widely occurring in Asia and is a clear breach of child rights. Evidence outcomes will benefit advocacy toward stronger policy regulations to control unhealthy food marketing and strengthen strategies to promote a healthier food environment for Asia's children.

  17. Yu N, Lee T, Tassone D, Vogrin S, Phan S, Wu DM, et al.
    Intern Med J, 2024 Nov;54(11):1856-1866.
    PMID: 39234975 DOI: 10.1111/imj.16504
    BACKGROUND: Thiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNFα) agents is associated with higher anti-TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD).

    AIMS: We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy.

    METHODS: We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels.

    RESULTS: The study included 743 paired 6-TGN and anti-TNFα levels (640 infliximab and 103 adalimumab). 6-TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6-TGN cut-off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6-TGN cut-off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing.

    CONCLUSION: 6-TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6-TGN levels in the lower end of the therapeutic range (230-260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing.

  18. Khan KS, Fawzy M, Chien P, Geary M, Bueno-Cavanillas A, Nunez-Nunez M, et al.
    Int J Gynaecol Obstet, 2025 Jan 31.
    PMID: 39887735 DOI: 10.1002/ijgo.16118
    The number of retractions of randomized clinical trials (RCTs) following post-publication allegations of misconduct is increasing. To address this issue, we aimed to establish an international multistakeholder consensus on post-publication integrity concerns related to RCTs. After prospective registration (https://osf.io/njksm), we assembled a multidisciplinary stakeholder group comprising 48 participants from 18 countries across six continents, recruited using a curated list of journal editors and snowballing. An underpinning evidence synthesis collated 89 articles related to post-publication integrity concerns. Integrity statements related to RCTs created were subjected to anonymized two-round Delphi survey. A hybrid face-to-face-online consensus development meeting was convened to consolidate the consensus. The response rates of the two Delphi survey rounds were 65% (31/48) and 67% (32/ 48), respectively. There were 101 and 41 statements in the first and second Delphi rounds, respectively. After the two Delphi rounds and the consensus development meeting, consensus was achieved on 104 statements consolidated to 84 after merging, editing, and removing duplicates. This set of statements included general aspects (n = 9), journal instructions (n = 14), editorial and peer review (n = 7), correspondence and complaints (n = 4), investigations for integrity concerns (n = 16), decisions and sanctions (n = 9), critical appraisal guidance (n = 1), systematic reviews of RCTs (n = 8), and research recommendations (n = 16). In conclusion, this international multistakeholder consensus statement aimed to underpin policies for preventing post-publication integrity concerns in RCT publications and assist in improving investigations of misconduct allegations.
  19. Cappellini MD, Viprakasit V, Taher AT, Georgiev P, Kuo KHM, Coates T, et al.
    N Engl J Med, 2020 03 26;382(13):1219-1231.
    PMID: 32212518 DOI: 10.1056/NEJMoa1910182
    BACKGROUND: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients.

    METHODS: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies.

    RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 μg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo.

    CONCLUSIONS: The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.).

Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links