Influence of ethnicity on the distribution of genetic polymorphisms associated with risk of chronic liver disease in South American populations

BACKGROUND: The global burden of chronic liver disease is rising. Besides environmental, behavioral, viral and metabolic factors, genetic polymorphisms in patatin-like phospholipase-3 (PNPLA3) and vitamin D receptor (VDR) genes have been related to the development of chronic liver disease and progression towards liver cancer. Although their prevalence differs remarkably among ethnic groups, the frequency of these polymorphisms in South American populations -whose genetic background is highly admixed- has been poorly studied. Hence, the aim of this study was to characterize polymorphisms related to chronic liver disease and their association with the genetic ancestry of South American populations. RESULTS: DNA samples from 258 healthy unrelated male volunteers were analyzed. The frequencies of G and C alleles of rs738409 polymorphism (PNPLA3 gene) were 74 % and 26 %, respectively; whereas the bAt (CCA) haplotype (VDR gene) was observed in 32.5 % of the samples. The GG genotype of PNPLA3 rs738409 and the bAt (CCA) haplotype -associated with an increased risk of chronic liver disease and progression towards liver cancer- were significantly more frequent among samples exhibiting maternal and paternal Native American haplogroups (63.7 % and 64.6 %), intermediate among admixed samples (45.1 % and 44.9 %; p = 0.03) and the lowest for Non-native American ancestry (30.1 % and 29.6 %; p = 0.001 and p = 0.0008). CONCLUSIONS: These results suggest that individuals with Native American ancestry might have a high risk of chronic liver disorders and cancer. Furthermore, these data not only support the molecular evaluation of ancestry in multi-ethnic population studies, but also suggest that the characterization of these variants in South American populations may be useful for establishing public health policies aimed at high risk ethnic communities.Fil: Pontoriero, Ana Cecilia. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trinks, Julieta. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hulaniuk, María Laura. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fortuny, Lisandro. Hospital Italiano; ArgentinaFil: Burgos Pratx, Leandro. Hospital Italiano; ArgentinaFil: Frías, Analía. Hospital Materno Infantil “Ramón Sardá”; ArgentinaFil: Torres, Oscar. Hospital Materno Infantil “Ramón Sardá”; ArgentinaFil: Nuñez, Félix. Hospital Italiano; ArgentinaFil: Gadano, Adrián. Hospital Italiano; ArgentinaFil: Argibay, Pab lo. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentin

A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia

BACKGROUND:Convalescent plasma is frequently administered to patients with Covid-19 and hasbeen reported, largely on the basis of observational data, to improve clinical outcomes.Minimal data are available from adequately powered randomized, controlled trials. METHODS:We randomly assigned hospitalized adult patients with severe Covid-19 pneumoniain a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome wasthe patient?s clinical status 30 days after the intervention, as measured on a six-pointordinal scale ranging from total recovery to death. RESULTS:A total of 228 patients were assigned to receive convalescent plasma and 105 toreceive placebo. The median time from the onset of symptoms to enrollment inthe trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the mostfrequent severity criterion for enrollment. The infused convalescent plasma had amedian titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to1:3200]. No patients were lost to follow-up. At day 30 day, no significant differencewas noted between the convalescent plasma group and the placebo group in thedistribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83(95% confidence interval [CI], 0.52 to 1.35; P=0.46). Overall mortality was 10.96%in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of −0.46 percentage points (95% CI, −7.8 to 6.8). Total SARS-CoV-2 antibodytiters tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS:no significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo.(PlasmAr ClinicalTrials.gov number, NCT04383535.)Fil: Simonovich, Ventura A.. Hospital Italiano. Departamento de Medicina. Servicio de Clinica Medica.; ArgentinaFil: Burgos Pratx, Leandro D.. Hospital Italiano. Departamento de Medicina. Servicio de Clinica Medica.; ArgentinaFil: Scibona, Paula. Hospital Italiano. Departamento de Medicina. Servicio de Clinica Medica.; ArgentinaFil: Beruto, Maria Valeria. No especifíca;Fil: Vallone, Miguel Gabriel. No especifíca;Fil: Vázquez, C.. No especifíca;Fil: Savoy, N.. No especifíca;Fil: Giunta, Diego Hernan. No especifíca;Fil: Pérez, L.G.. No especifíca;Fil: Sánchez, M.L.. No especifíca;Fil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ojeda, D.S.. No especifíca;Fil: Santoro, D.M.. No especifíca;Fil: Camino, P. J.. No especifíca;Fil: Antelo, S.. No especifíca;Fil: Rainero, K.. No especifíca;Fil: Vidiella, G. P.. No especifíca;Fil: Miyazaki, E. A.. No especifíca;Fil: Cornistein, W.. No especifíca;Fil: Trabadelo, O. A.. No especifíca;Fil: Ross, F. M.. No especifíca;Fil: Spotti, M.. No especifíca;Fil: Funtowicz, G.. No especifíca;Fil: Scordo, W. E.. No especifíca;Fil: Losso, M. H.. No especifíca;Fil: Ferniot, I.. No especifíca;Fil: Pardo, P. E.. No especifíca;Fil: Rodriguez, E.. No especifíca;Fil: Rucci, P.. No especifíca;Fil: Pasquali, J.. No especifíca;Fil: Fuentes, N. A.. No especifíca;Fil: Esperatti, M.. No especifíca;Fil: Speroni, G. A.. No especifíca;Fil: Nannini, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Matteaccio, A.. No especifíca;Fil: Michelangelo, H.G.. No especifíca;Fil: Follmann, D.. No especifíca;Fil: Lane, H. Clifford. No especifíca;Fil: Belloso, Waldo Horacio. Hospital Italiano. Departamento de Medicina. Servicio de Clinica Medica.; Argentin

Distribution of genetic polymorphisms associated to hepatitis c virus (HCV) antiviral response in a multiethnic and admixed population

2 p.Single-nucleotide polymorphisms (SNPs) near IL28B and ITPA genes have been described as predictors of response to antiviral treatment and ribavirin induced-hemolytic anemia in HCV patients, respectively. The prevalence of these polymorphisms differs among ethnic groups; however, there is a paucity of information about South American populations. Hence, the aim of this study was to determine the prevalence of these SNPs in the healthy population of different ethnic groups residing in Argentina.http://www.viral-hep.org/default.aspxFil: Thinks, Julieta. Hospital Italiano de Buenos Aires. Instituto de Ciencias Básicas y Medicina Experimental; Argentina.Fil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina.Fil: Hulaniuk, María Laura. Hospital Italiano de Buenos Aires. Instituto de Ciencias Básicas y Medicina Experimental; Argentina.Fil: Burgos Pratx, Leandro. Servicio de Medicina Transfusional; Argentina.Fil: Ré, Viviana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Virología Dr. José María Vanella; Argentina.Fil: Fortuny, Lisandro. Servicio de Medicina Transfusional; Argentina.Fil: Frías, Analía. Servicio de Medicina Transfusional; Argentina.Fil: Torres, Oscar. Servicio de Medicina Transfusional; Argentina.Fil: Nuñez, Félix. Servicio de Medicina Transfusional; Argentina.Fil: Gadano, Adrián. Servicio de Hepatología; Argentina.Fil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina.Fil: Flichman, Diego Martín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina.Otras Ciencias de la Salu

Recomendaciones para el descarte de productos de CPH/linfocitos criopreservados: consenso del Grupo Argentino de Trasplante de Médula Ósea (GATMO)

The cryopreservation and storage of hematopoietic stem cells (HSCs) is usually required in the autologous stem cells transplant setting and, in some cases, for allogenic products. The storage of these products has a validity defined by the storage characteristics, clinical utility and security conditions of the product. Here, we present recommendations elaborated by the Argentinian Group of Bone Marrow Transplantation (GATMO).El procedimiento de criopreservación y almacenamiento (CyA) de las células progenitoras hematopoyéticas (CPH) es requerido con frecuencia para la realización de un trasplante CPH autólogo y en algunas ocasiones se requiere la CyA de productos celulares alogénicos (CPH o linfocitos). El almacenamiento de estos productos celulares tiene una validez definida por el medio en el que se almacena, la utilidad clínica del producto y las condiciones de seguridad del producto que fue almacenado. Se presentan recomendaciones emitidas por el Grupo Argentino de Trasplante sobre el descarte de productos criopreservados y almacenados.

Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome

Nucleotide excision repair pathway (NER) is an essential mechanism for single-strand breaks (SSB) repair while xeroderma pigmentosum family (XPA to XPG) is the most important system to NER. Myelodysplastic syndrome (MDS) is a heterogeneous hematological cancer characterized by cytopenias and risk of acute myeloid leukemia (AML) transformation. MDS pathogenesis has been associated with problems of DNA repair system. This report aimed to evaluate NER polymorphisms (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) in 269 MDS patients of different populations in Latin America (173 Brazilian and 96 Argentinean). Genotypes were identified in DNA samples by RT-qPCR using TaqMan SNP Genotyping Assay. Regarding rs1799793 polymorphism of XPD for Brazilian population, the heterozygous genotype AG presented a high odds ratio (OR) to have a normal karyotype (p = 0.012, OR=3.000) and the mutant homozygous genotype AA was associated to a high OR of AML transformation (p = 0.034, OR=7.4). In Argentine population, the homozygous mutant AA genotype of rs1800975 polymorphism of XPA was associated with an increased odd to have hemoglobin levels below 8g/dL (p = 0.013, OR=10.000) while for the rs1799793 polymorphism of XPD, the heterozygous AG genotype decreased OR to be classified as good (p < 0.001, OR=9.05 × 10−10), and intermediate (p < 0.001, OR=3.08 × 10−10), according to Revised-International Prognostic Scoring System. Regarding the rs1800067 polymorphisms of XPF, the homozygous mutant AA genotype showed a decreased OR to be classified as good (p < 0.001, OR=4.03 × 10−13) and intermediate (p < 0.001, OR=2.54 × 10−13). Our report reinforces the heterogeneity of MDS and demonstrates the importance of ethnic differences and regional influences in pathogenesis and prognosis of MDS

Development and Validation of a Treatment Benefit Index to Identify Hospitalized Patients With COVID-19 Who May Benefit From Convalescent Plasma

Importance: Identifying which patients with COVID-19 are likely to benefit from COVID-19 convalescent plasma (CCP) treatment may have a large public health impact.   Objective: To develop an index for predicting the expected relative treatment benefit from CCP compared with treatment without CCP for patients hospitalized for COVID-19 using patients' baseline characteristics.   Design, Setting, and Participants: This prognostic study used data from the COMPILE study, ie, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) evaluating CCP vs control in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. A combination of baseline characteristics, termed the treatment benefit index (TBI), was developed based on 2287 patients in COMPILE using a proportional odds model, with baseline characteristics selected via cross-validation. The TBI was externally validated on 4 external data sets: the Expanded Access Program (1896 participants), a study conducted under Emergency Use Authorization (210 participants), and 2 RCTs (with 80 and 309 participants).   Exposure: Receipt of CCP.   Main Outcomes and Measures: World Health Organization (WHO) 11-point ordinal COVID-19 clinical status scale and 2 derivatives of it (ie, WHO score of 7-10, indicating mechanical ventilation to death, and WHO score of 10, indicating death) at day 14 and day 28 after randomization. Day 14 WHO 11-point ordinal scale was used as the primary outcome to develop the TBI.   Results: A total of 2287 patients were included in the derivation cohort, with a mean (SD) age of 60.3 (15.2) years and 815 (35.6%) women. The TBI provided a continuous gradation of benefit, and, for clinical utility, it was operationalized into groups of expected large clinical benefit (B1; 629 participants in the derivation cohort [27.5%]), moderate benefit (B2; 953 [41.7%]), and potential harm or no benefit (B3; 705 [30.8%]). Patients with preexisting conditions (diabetes, cardiovascular and pulmonary diseases), with blood type A or AB, and at an early COVID-19 stage (low baseline WHO scores) were expected to benefit most, while those without preexisting conditions and at more advanced stages of COVID-19 could potentially be harmed. In the derivation cohort, odds ratios for worse outcome, where smaller odds ratios indicate larger benefit from CCP, were 0.69 (95% credible interval [CrI], 0.48-1.06) for B1, 0.82 (95% CrI, 0.61-1.11) for B2, and 1.58 (95% CrI, 1.14-2.17) for B3. Testing on 4 external datasets supported the validation of the derived TBIs.   Conclusions and Relevance: The findings of this study suggest that the CCP TBI is a simple tool that can quantify the relative benefit from CCP treatment for an individual patient hospitalized with COVID-19 that can be used to guide treatment recommendations. The TBI precision medicine approach could be especially helpful in a pandemic