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1.
Proc Natl Acad Sci U S A ; 121(39): e2411428121, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39284068

RESUMO

Long COVID occurs in a small but important minority of patients following COVID-19, reducing quality of life and contributing to healthcare burden. Although research into underlying mechanisms is evolving, immunity is understudied. SARS-CoV-2-specific T cell responses are of key importance for viral clearance and COVID-19 recovery. However, in long COVID, the establishment and persistence of SARS-CoV-2-specific T cells are far from clear, especially beyond 12 mo postinfection and postvaccination. We defined ex vivo antigen-specific B cell and T cell responses and their T cell receptors (TCR) repertoires across 2 y postinfection in people with long COVID. Using 13 SARS-CoV-2 peptide-HLA tetramers, spanning 11 HLA allotypes, as well as spike and nucleocapsid probes, we tracked SARS-CoV-2-specific CD8+ and CD4+ T cells and B-cells in individuals from their first SARS-CoV-2 infection through primary vaccination over 24 mo. The frequencies of ORF1a- and nucleocapsid-specific T cells and B cells remained stable over 24 mo. Spike-specific CD8+ and CD4+ T cells and B cells were boosted by SARS-CoV-2 vaccination, indicating immunization, in fully recovered and people with long COVID, altered the immunodominance hierarchy of SARS-CoV-2 T cell epitopes. Meanwhile, influenza-specific CD8+ T cells were stable across 24 mo, suggesting no bystander-activation. Compared to total T cell populations, SARS-CoV-2-specific T cells were enriched for central memory phenotype, although the proportion of central memory T cells decreased following acute illness. Importantly, TCR repertoire composition was maintained throughout long COVID, including postvaccination, to 2 y postinfection. Overall, we defined ex vivo SARS-CoV-2-specific B cells and T cells to understand primary and recall responses, providing key insights into antigen-specific responses in people with long COVID.


Assuntos
Linfócitos T CD8-Positivos , COVID-19 , Receptores de Antígenos de Linfócitos T , SARS-CoV-2 , Humanos , Linfócitos T CD8-Positivos/imunologia , SARS-CoV-2/imunologia , COVID-19/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Epitopos de Linfócito T/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Pessoa de Meia-Idade , Masculino , Feminino , Síndrome de COVID-19 Pós-Aguda , Fenótipo , Linfócitos B/imunologia , Memória Imunológica/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Idoso
2.
J Med Virol ; 95(7): e28895, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37403902

RESUMO

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.


Assuntos
COVID-19 , Convulsões Febris , Masculino , Feminino , Humanos , Criança , COVID-19/complicações , SARS-CoV-2 , Convulsões Febris/etiologia , Interleucina-6 , Interleucina-8 , RNA Viral , Convulsões/etiologia
3.
Vox Sang ; 118(9): 763-774, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37608544

RESUMO

BACKGROUND AND OBJECTIVES: Human neutrophil antigens (HNAs) are categorized into five systems: HNA-1 to HNA-5. Given the importance of neutrophils in immunity, we sought to create awareness of the role of HNA diagnostic services in managing immune neutropenia and transfusion-related acute lung injury. To provide health communities all around the world with access to these services, we conducted a survey to create a directory of these HNA diagnostic services. MATERIALS AND METHODS: An Excel table-based survey was created to capture information on the laboratory's location and was emailed to 55 individuals with known or possible HNA investigation activity. The collected data were then summarized and analysed. RESULTS: Of contacted laboratories, the surveys were returned from 23 (38.2%) laboratories; 17 have already established HNA diagnostic (of them 12 were regular participants of the International Granulocyte Immunobiology Workshop [ISBT-IGIW]), 4 laboratories were in the process of establishing their HNA investigation and the remaining 2 responder laboratories, did not conduct HNA investigations. In established laboratories, investigation for autoimmune neutropenia (infancies and adults) was the most frequently requested, and antibodies against HNA-1a and HNA-1b were the most commonly detected. CONCLUSION: The directory of survey respondents provides a resource for health professionals wanting to access HNA diagnostic services. The present study offers a comprehensive picture of HNA diagnostics (typing and serology), identifying weak points and areas for improvement for the first time. Identifying more laboratories involved in HNA diagnostics with limited access to international societies in the field will globally improve HNA diagnostics.


Assuntos
Neutropenia , Neutrófilos , Adulto , Humanos , Granulócitos , Anticorpos , Inquéritos e Questionários
4.
Clin Infect Dis ; 75(4): 673-681, 2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34849657

RESUMO

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Miocardite , Pericardite , Adolescente , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Criança , Estudos de Coortes , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Miocardite/complicações , Miocardite/etiologia , Pericardite/epidemiologia , Pericardite/etiologia , Vacinação/efeitos adversos
5.
Pediatr Transplant ; 25(5): e13945, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33314508

RESUMO

Allogeneic hematopoietic stem cell transplantation is curative for transfusion-dependent thalassemia, but mixed chimerism (MC) may herald graft rejection. We report a child who failed bone marrow transplant (BMT) from matched unrelated donor (MUD) successfully salvaged with haploidentical peripheral blood stem cell transplant (PBSCT), but had MC in T-lymphocyte compartment despite near-complete donor chimerism in myeloid compartment. MC was successfully improved by repeated CD45RA-depleted donor lymphocyte infusion (DLI). A 2-year-old Chinese girl with beta-thalassemia major underwent 12/12-MUD BMT with HU/AZA/Cy/Flu/Bu/TT conditioning resulted in graft rejection. As donor refused second donation, rescue haploidentical PBSCT was performed with alemtuzumab/fludarabine/treosulfan conditioning. Harvest product was CD3/CD45RA depleted with extra products cryopreserved. Split cell chimerism performed 1-month after haplo-transplant showed 97% mother, 3% MUD, and 0% host for granulocytes but 38% mother, 62% MUD, and 0% host for CD3 + T cells. In view of low haploidentical donor chimerism in T-lymphocyte compartment, CD45RA-depleted DLI using cryopreserved product was performed on day + 38, after thymoglobulin 3 mg/kg given as T-cell depletion 3 days beforehand. T-cell chimerism improved to 51% mother and 49% MUD post-DLI. Second cryopreserved CD45RA-depleted DLI was given 17 days after the first DLI (day + 55), and 100% full chimerism of mother's T cells was gradually established without significant graft-versus-host disease (GVHD) or viral reactivation. To conclude, split lineage chimerism determination is beneficial to guide management strategy. For MC in T-cell compartment, CD45RA-depleted DLI is a potential alternative to unselected T cells as it carries lower risk of GVHD and infection.


Assuntos
Quimerismo , Transplante de Células-Tronco Hematopoéticas/métodos , Antígenos Comuns de Leucócito , Terapia de Salvação/métodos , Linfócitos T/transplante , Transplante Haploidêntico/métodos , Talassemia beta/terapia , Transplante de Medula Óssea , Pré-Escolar , Feminino , Rejeição de Enxerto , Humanos , Talassemia beta/genética , Talassemia beta/imunologia
6.
Biol Blood Marrow Transplant ; 25(3): 424-435, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30412784

RESUMO

Cord blood (CB) is an alternative stem cell source for allogeneic hematopoietic stem cell transplantation (HSCT). The unique advantages of using CB as a stem cell source are a degree of permissibility for HLA mismatch, rapid availability, and relatively risk-free cell collection. Because HLA is highly polymorphic and population-specific, optimal HLA-matched unrelated donors or cord blood units (CBUs) might not be available. In view of the possibility that matched CBUs that include noninherited maternal antigens (NIMAs) might contain acceptable HLA mismatches, we attempted to determine the degree of alloreactivity of CB mononuclear cells (MNCs) on stimulation by the maternal, paternal, and unrelated stimulator cells. Suppression of T cell proliferation, cytotoxicity, and a cytokine profile indicating suppressed Th1 and elevated IL-10 and TGF-ß1 responses were observed in the mixed lymphocyte reaction in response to NIMAs. The increases in IL-10 and TGF-ß1 production may be due to the Th2 response and/or regulatory T cells (Tregs). The reduced IL-10 and TGF-ß1 production after CD25 depletion could have been due to removal of Tregs from the CB cells. Thus, Tregs appear to play an important role in the CB MNC response to NIMAs, possibly due to the induction of IL-10 and TGF-ß1. We hope that our work can provide some evidence of the beneficial effect of NIMAs.


Assuntos
Sangue Fetal/imunologia , Histocompatibilidade/imunologia , Tolerância Imunológica , Linfócitos T Reguladores/imunologia , Adulto , Feminino , Antígenos HLA/imunologia , Humanos , Interleucina-10/metabolismo , Teste de Cultura Mista de Linfócitos , Mães , Fator de Crescimento Transformador beta1/metabolismo
7.
Pediatr Transplant ; : e13240, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921011

RESUMO

Relapsed/refractory NB carries a bleak outcome, warranting novel treatment options. HaploHSCT induces a graft-versus-NB effect via natural killer cell alloreactivity. Review of patients with relapsed/refractory NB who underwent haploHSCT with ex vivo T-cell depletion in our unit from 2013 through 2018. Ten patients were identified (male=5; median age at haploHSCT=6.45 y, range: 3.49-11.02 y). Indications were relapsed in 7 and refractoriness in 3; disease status at haploHSCT was CR in 2, PR in 6, and PD in 2. All patients received peripheral blood stem cell grafts after ex vivo T-cell depletion (CD3/CD19-depletion=1; TCR-αß/CD19-depletion=4; CD3/CD45RA-depletion=4; and TCR-αß/CD45RA-depletion=1). Conditioning regimens were fludarabine-based. Neutrophils engrafted on median D + 10 (range: D + 9 to +13), and platelets engrafted (≥20 × 109 /L) on median D + 8 (range: D + 5 to D + 14). Early T- and NK-cell recovery were evident. Of the 10 patients, acute rejection developed in 1 (who died of PD despite rescue HSCT), and 1 died of sepsis before engraftment; 8 experienced full donor-chimerism post-HSCT. Among the 8, 6 experienced CR, 1 died of PD, and 1 died of pulmonary hypertensive crisis before evaluation. At publication, 4 were in remission (2.8, 7.4, 28.5, and 58.9 months). No significant GvHD occurred. HaploHSCT with selective ex vivo T-cell depletion may be a safe and useful salvage strategy for relapsed/refractory NB.

8.
Transpl Int ; 30(12): 1234-1242, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28777478

RESUMO

Calculated panel reactive antibody (cPRA) represents possibility of encountering an incompatible donor for organ transplant candidates and has gradually replaced traditional PRA as a measurement of sensitization level. We tested two cPRA calculation methods on a cohort of renal candidate (n = 613). HLA typing of 563 Chinese deceased renal donors was used to estimate allele and haplotype frequencies of Hong Kong donor pool. The OPTN formula was adopted to generate cPRA (cPRA (freq)). We also incorporated a computer script to compare unacceptable antigens of patients against HLA phenotype of donors. The cPRA based on historical donor filtering was the percentage of filter out count over total number of donors (cPRA (filter)). Values of cPRA (freq) and cPRA (filter) showed almost perfect agreement with Lin's correlation coefficient equal to 1.000. SD of bias was 0.6 cPRA point. Limit of agreement was 0.9 to -1.5 points difference. Furthermore, the poor agreement between our in-house cPRA and values from other online calculators indicated the necessity to use local population data for accurate cPRA calculation. Built-in donor filtering method was more practicable for Hong Kong due to factors such as cost and flexibility. An on-going donor pool can reflect population allele frequencies and permits efficient periodic update of cPRA.


Assuntos
Seleção do Doador/métodos , Antígenos HLA/imunologia , Isoanticorpos/sangue , Transplante de Rim/mortalidade , Sistema de Registros , Obtenção de Tecidos e Órgãos/métodos , Estudos de Coortes , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Teste de Histocompatibilidade/métodos , Hong Kong , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Masculino , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Imunologia de Transplantes
9.
Nephrology (Carlton) ; 22(12): 985-992, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27587222

RESUMO

AIM: Accumulating literature indicates that late acute rejection (LAR) after kidney transplantation portends an unfavourable prognosis. There are no data on the incidence of LAR in Asian subjects, or its risk factors and associated clinical outcomes. METHODS: We conducted a retrospective single-centre case-+control study to investigate the incidence, risk factors and prognosis of LAR in Chinese kidney transplant recipients. Subjects with or without LAR were matched for age, gender, era of transplantation, allograft type, and maintenance immunosuppression regimen. RESULTS: Thirty-two episodes of LAR occurred within an observation period of 12 years giving an incidence rate of 0.46 episodes per 1000 patient-years. Acute rejection within the first year after transplantation was associated with an increased risk of LAR (OR 3.59, P = 0.041). In patients receiving maintenance immunosuppression regimen with steroid, cyclosporin A (CsA) and mycophenolate or an m-TOR inhibitor, patients with LAR showed lower trough CsA levels prior to and at the time of rejection compared to Controls (86.0 ± 26.1 vs. 105.6 ± 13.3 µg/L, P = 0.049; and 75.7 ± 35.7 vs. 106.0 ± 20.5 µg/L, P = 0.032, respectively). Trough CsA level below 80 µg/L was associated with the development of LAR (OR 10.82, P = 0.032). Patients with LAR showed an inferior allograft survival (P < 0.001) while patient survival rates were similar (P = 0.122). CONCLUSIONS: Late acute rejection is uncommon in Chinese kidney transplant recipients but is associated with reduced allograft survival. Risk factors include acute rejection in the first post-transplant year and trough CsA level below 80 µg/L in patients on CsA-based maintenance immunosuppression. Minimization of immunosuppression in apparently stable kidney transplant recipients must be exercised with caution.


Assuntos
Rejeição de Enxerto/etiologia , Transplante de Rim/efeitos adversos , Doença Aguda , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Rim/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
11.
HLA ; 103(1): e15229, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37728213

RESUMO

Recent studies showed that ABO-adjusted calculated panel reactive antibody (ABO-cPRA) may better reflect the histocompatibility level in a multi-ethnic population, but such data in Asians is not available. We developed an ABO-adjusted cPRA metric on a cohort of waitlist kidney transplant patients (n = 647, 99% Chinese) in Hong Kong, based on HLA alleles and ABO frequencies of local donors. The concordance between the web-based ABO-cPRA calculator and the impact on kidney allocation were evaluated. The blood group distribution for A, B, O and AB among waitlist kidney candidates were 26.2%, 27.5%, 40.1%, and 6.1%, and their chances of encountering incompatible blood group donors were 32.6%, 32.4%, 57.6%, and 0%, respectively. There is poor agreement between web-based ABO-cPRA calculator and our locally developed metrics. Over 90% of patients showed an increase in cPRA after ABO adjustment, most notably in those with cPRA between 70% and 79%. Blood group O patients had a much greater increase in cPRA scores after adjustment while patients of blood group A and B had similar increment. 10.6% of non-AB blood group waitlist patients had ABO-cPRA elevated to ≥80%. A local ABO-adjusted cPRA metric is required for Asian populations and may improve equity in kidney distribution for patients with disadvantageous blood groups. The result from the current study potentially helps other countries/localities in establishing their own unified ABO-cPRA metrics and predict the impact on kidney allocation.


Assuntos
Antígenos de Grupos Sanguíneos , Obtenção de Tecidos e Órgãos , Humanos , Isoanticorpos , Teste de Histocompatibilidade , Alelos , Doadores de Tecidos , Antígenos HLA , Rim
12.
Respir Med Case Rep ; 45: 101909, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37635731

RESUMO

In this report, we describe a case of a 5-year-old girl with poor growth and unresolving pneumonia. Bronchoscopy showed numerous endobronchial mucosal nodules, consisting of dense lymphoid infiltrates. Bacterial culture of the nodule biopsy suggested endobronchial actinomycosis. Genetic test confirmed the diagnosis of APDS.

13.
HLA ; 102(3): 343-347, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37376846

RESUMO

HLA genes are the most polymorphic in the human genome. High resolution HLA typing from 13,870 bone marrow donors in Hong Kong was obtained using Next-generation sequencing (NGS) technology. Among the 67 novel alleles identified, official HLA allele names of 50 novel class I alleles (HLA-A, -B, -C) and 8 novel class II alleles (HLA-DRB1, -DQB1) were assigned by the World Health Organization (WHO) Nomenclature Committee for Factors of the HLA System.


Assuntos
População do Leste Asiático , Antígenos de Histocompatibilidade , Humanos , Alelos , População do Leste Asiático/genética , Frequência do Gene , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos de Histocompatibilidade/genética
14.
HLA ; 102(6): 690-706, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37452528

RESUMO

The primary goal of the HLA-DPA1 ~ promoter ~ HLA-DPB1 haplotype component of the 18th IHIWS was to characterise the extended haplotypes within the HLA-DP region and survey the extent of genetic diversity in this region across human populations. In this report, we analysed single-nucleotide polymorphisms (SNPs) in 255 subjects from 6 different cohorts. The results from the HLA-DP haplotype component have validated findings from the initial pilot study. SNPs in this region were inherited in strong linkage, particularly HLA-DPA1, SNP-linked promoter haplotypes and motifs in exon 2 of HLA-DPB1. We reported 17 SNP-linked haplotypes in the promoter region. Together with HLA-DPA1 and HLA-DPB1 alleles, they formed 74 distinct extended HLA-DP haplotypes in 438 sequences. We also observed the presence of region-specific alleles and promoter haplotypes. Our approach involved phasing extended SNPs including promoter SNPs, HLA-DPA1 and HLA-DPB1 alleles, in a 22 kb region, GRCh38/hg38 (chr6:33,064,111-33,086,679), followed by clustering of these SNPs as one extended haplotype. This hierarchical clustering revealed four major clades, suggesting that haplotypes within each clade may have diverged from a common ancestral haplotype and undergone similar evolutionary processes. The correlation between HLA-DPA1 and the promoter region raises questions about the role of HLA-DPA1 antigen in the heterodimer. This finding requires validation on a larger sample size specifically designed for anthropological analysis. Nevertheless, the results from this study highlight the clinical potential of selecting better-matched donors for patients awaiting haematopoietic stem cell transplants from genetically overlapping groups that share common ancestral haplotypes.


Assuntos
Imunogenética , Humanos , Haplótipos , Frequência do Gene , Projetos Piloto , Alelos , Cadeias beta de HLA-DP/genética , Regiões Promotoras Genéticas
15.
Transplant Cell Ther ; 29(11): 709.e1-709.e11, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37482244

RESUMO

Racial/ethnic minorities have demonstrated worse survival after allogeneic hematopoietic cell transplantation (HCT) compared to whites. Whether the racial disparity in HCT outcomes persists in long-term survivors and possibly may be even exacerbated in this population, which frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study, we compared long-term outcomes among 1-year allogeneic HCT survivors by race/ethnicity and socioeconomic status (SES). The Center for International Blood and Marrow Transplant Research database was used to identify 5473 patients with acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, or myelodysplastic syndromes who underwent their first allogeneic HCT between 2007 and 2017 and were alive and in remission for at least 1 year after transplantation. The study was restricted to patients who underwent HCT in the United States. SES was defined using patient neighborhood poverty level estimated from the recipient's ZIP code of residence; a ZIP code with ≥20% of persons below the federal poverty level was considered a high poverty area. The primary outcome was to evaluate the associations of race/ethnicity and neighborhood poverty level with overall survival (OS), relapse, and nonrelapse mortality (NRM). Cox regression models were used to determine associations of ethnicity/race and SES with OS, relapse, and NRM. Standardized mortality ratios were calculated to compare mortality rates of the study patients and their general population peers matched on race/ethnicity, age, and sex. The study cohort was predominately non-Hispanic white (n = 4385) and also included non-Hispanic black (n = 338), Hispanic (n = 516), and Asian (n = 234) patients. Overall, 729 patients (13%) resided in high-poverty areas. Significantly larger proportions of non-Hispanic black (37%) and Hispanic (26%) patients lived in high-poverty areas compared to non-Hispanic whites (10%) and Asians (10%) (P < .01). Multivariable analysis revealed no significant associations between OS, PFS, relapse, or NRM and race/ethnicity or poverty level when adjusted for patient-, disease- and transplantation-related covariates. Our retrospective cohort registry study shows that among adult allogeneic HCT recipients who survived at least 1 year in remission, there were no associations between race/ethnicity, neighborhood poverty level, and long-term outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Disparidades Socioeconômicas em Saúde , Adulto , Humanos , Estados Unidos , Estudos Retrospectivos , Transplante Homólogo , Recidiva , Doença Crônica , Sobreviventes
18.
Int J Dermatol ; 61(2): 184-190, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34553372

RESUMO

BACKGROUND: HLA-B*15:11 is associated with carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions (SCARs) in Japanese and some Asian populations, but such data remains relatively limited in Chinese. Routine HLA-B*15:02 screening is mandatory before CBZ commencement, however, SCARs related to CBZ were still observed in non-HLA*B-15:02 carriers. OBJECTIVE: We aimed to find out the prevalence of HLA-B*15:11 in Chinese patients and its associations with CBZ-induced SCARs. METHOD: We screened 8,328 blood samples collected for HLA allele typing before CBZ commencement during the period of January 2014 to December 2019. In HLA-B*15:02 negative Chinese patients, HLA-B*15:11 status were further screened, and the incidence of SCARs in the CBZ group was compared with the control group without CBZ use. RESULT: In this cohort, 1416 out of 8328 patients (17%) tested HLA-B*15:02 positive and were advised to avoid CBZ, while 80 (0.96%) were found to be HLA-B*15:11 positive. In 6911 (83%) patients who tested HLA-B*15:02 negative, 70 (1.01%) were HLA-B*15:11 positive. Five out of 70 (7.14%) patients had SCARs. The incidence of SCARs in HLA-B*15:11 carriers who received CBZ was significantly higher than those without CBZ (17.4% [4/23] vs. 2.13% [1/47], P = 0.037*). The odds ratio was 9.68 (95% CI 1.02-92.4, P = 0.048*). These included: one Stevens-Johnson syndrome (SJS), two DRESS, and one MPE after CBZ use, while one developed MPE after phenytoin use in control. CONCLUSION: HLA-B*15:11 is a potential risk factor of CBZ-induced SCARs in HLA-B*15:02 negative Chinese patients. Further screening of HLA-B*15:11 status in those HLA-B*15:02 negative patients is recommended to avoid undesirable SCARs.


Assuntos
Anticonvulsivantes , Síndrome de Stevens-Johnson , Carbamazepina , China , Predisposição Genética para Doença , Antígenos HLA-B/genética , Antígeno HLA-B15/genética , Humanos
19.
Arch Dermatol Res ; 314(7): 651-659, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34213582

RESUMO

Human leukocyte antigen (HLA)-B*58:01 allele is a significant risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs) which is potentially fatal. In some studies, chronic kidney disease (CKD) was also implicated to compound the risk of SCARs. We aim to investigate if pre-treatment HLA-B*58:01 screening can prevent allopurinol-induced SCARs in Chinese patients with CKD and its cost-effectiveness. We prospectively recruited Chinese CKD patients who required allopurinol during 2011-2015 and performed pre-treatment HLA testing (HLA screening group). Patients tested positive for HLA-B*58:01 were refrained from allopurinol while those tested negative were prescribed allopurinol. The incidence of SCARs in the HLA screening group was compared with the historical control in previous 5 years and the cost-effectiveness of HLA testing was analyzed. In the historical control (2006-2010), 3605 patients on allopurinol were screened, 22 out of 1027 (2.14%) CKD Chinese patients newly started on allopurinol developed SCARs, including 6 SJS/TEN. In the HLA screening group, 28 out of 192 patients (14.6%) tested HLA-B*58:01 positive were advised to avoid allopurinol; 156 out of 164 HLA-B*58:01-negative patients received allopurinol and none developed SCARs. The incidence rate of SCARs was significantly lower in the HLA screening group compared with controls (0% vs 2.14% respectively, p = 0.037*). The targeted HLA screening approach was associated with lower healthcare costs compared with no HLA screening (US$ 92,430 vs US$ 281,226). Pre-treatment HLA-B*58:01 screening is cost-effective to target on patients with CKD in Chinese to prevent allopurinol-induced SCARs.


Assuntos
Alopurinol , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Antígenos HLA-B , Insuficiência Renal Crônica , Síndrome de Stevens-Johnson , Alopurinol/efeitos adversos , China/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Antígenos HLA-B/genética , Humanos , Insuficiência Renal Crônica/complicações , Síndrome de Stevens-Johnson/etiologia
20.
Emerg Microbes Infect ; 11(1): 2466-2473, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36149830

RESUMO

In this study, we examined the clinical and electrophysiological outcomes of adolescents in Hong Kong who developed myocarditis or pericarditis following BNT162b2 vaccination for COVID-19, and followed-up for 60-180 days after their initial diagnosis. Clinical assessments included electrocardiogram (ECG) and echocardiogram at the initial admission and follow-up were compared. Treadmill testing was also performed in some cases. Between 14 June 2021 and 16 February 2022, 53 subjects were approached to participate in this follow-up study, of which 28 patients were followed up for >60 days with a median follow-up period of 100 days (range, 61-178 days) and were included in this study. On admission, 23 patients had ECG abnormalities but no high-grade atrioventricular block. Six patients had echocardiogram abnormalities, including reduced contractility, small rim pericardial effusions, and hyperechoic ventricular walls. All patients achieved complete recovery on follow-up. After discharge, 10 patients (35.7%) reported symptoms, including occasional chest pain, shortness of breath, reduced exercise tolerance, and recurrent vasovagal near-syncope. At follow-up, assessments, including ECGs, were almost all normal. Among the three patients with possible ECG abnormalities, all their echocardiograms or treadmill testings were normal. Sixteen patients (57.1%) underwent treadmill testing at a median of 117 days post-admission, which were also normal. However, at follow-up, there was a significant mean bodyweight increase of 1.81 kg (95%CI 0.47-3.1 kg, p = 0.01), possibly due to exercise restriction. In conclusion, most adolescents experiencing myocarditis and pericarditis following BNT162b2 vaccination achieved complete recovery. Some patients developed non-specific persistent symptoms, and bodyweight changes shall be monitored.


Assuntos
Vacina BNT162 , COVID-19 , Miocardite , Pericardite , Adolescente , Humanos , Vacina BNT162/efeitos adversos , COVID-19/prevenção & controle , Seguimentos , Hong Kong/epidemiologia , Miocardite/diagnóstico , Miocardite/etiologia , Pericardite/diagnóstico , Pericardite/etiologia , Vacinação/efeitos adversos
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