Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Trasplantament de ronyó; RemdesivirCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Trasplante de riñón; RemdesivirCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Kidney transplantation; RemdesivirIntroduction Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients. Methods We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed. Results Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug. Conclusion In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy

Anti-trbc1 antibody-based flow cytometric detection of t-cell clonality: Standardization of sample preparation and diagnostic implementation

© 2021 by the authors.A single antibody (anti-TRBC1; JOVI-1 antibody clone) against one of the two mutually exclusive T-cell receptor β-chain constant domains was identified as a potentially useful flow-cytometry (FCM) marker to assess Tαβ-cell clonality. We optimized the TRBC1-FCM approach for detecting clonal Tαβ-cells and validated the method in 211 normal, reactive and pathological samples. TRBC1 labeling significantly improved in the presence of CD3. Purified TRBC1+ and TRBC1− monoclonal and polyclonal Tαβ-cells rearranged TRBJ1 in 44/47 (94%) and TRBJ1+TRBJ2 in 48 of 48 (100%) populations, respectively, which confirmed the high specificity of this assay. Additionally, TRBC1+/TRBC1− ratios within different Tαβ-cell subsets are provided as reference for polyclonal cells, among which a bimodal pattern of TRBC1-expression profile was found for all TCRVβ families, whereas highly-variable TRBC1+/TRBC1− ratios were observed in more mature vs. naïve Tαβ-cell subsets (vs. total T-cells). In 112/117 (96%) samples containing clonal Tαβ-cells in which the approach was validated, monotypic expression of TRBC1 was confirmed. Dilutional experiments showed a level of detection for detecting clonal Tαβ-cells of ≤10−4 in seven out of eight pathological samples. These results support implementation of the optimized TRBC1-FCM approach as a fast, specific and accurate method for assessing T-cell clonality in diagnostic-FCM panels, and for minimal (residual) disease detection in mature Tαβ+ leukemia/lymphoma patients.This work was supported by the CB16/12/00400 (CIBERONC) and PI20-01346 grants, from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (Madrid, Spain) and FONDOS FEDER, and by the EuroFlow Foundation (Leiden, The Netherlands). N. Muñoz-García is supported by a pre-doctoral grant (Ref. IBPredoc17/00012) from IBSAL (Salamanca, Spain). M. Lima, N. Villamor, A.W. Langerak, J.J.M. van Dongen, A. Orfao, and J. Almeida are members of the EuroFlow Consortiu

Seroprevalence of IgG and IgM anti-SARS-CoV-2 among voluntary blood donors in Rio de Janeiro, Brazil

Background: In Brazil, mathematical models for deriving estimates and projections of COVID-19 cases have been developed without data on asymptomatic SARS-CoV-2 infection. We estimated the seroprevalence of antibodies to SARS-CoV-2 among blood donors in the State of Rio de Janeiro. Methods: Data were collected on 2,857 blood donors from April 14 to 27, 2020. We report the crude prevalence of antibodies to SARS-CoV-2, the weighted prevalence by the total state population, and adjusted prevalence estimates for test sensitivity and specificity. To establish the correlates of SARS-CoV-2 prevalence, we used logistic regression models. The analysis included period and site of blood collection, sociodemographic characteristics, and place of residence. Results: The proportion of SARS-Cov-2 positive tests without any adjustment was 4.0% (95% CI 3.3-4.7%), and the weighted prevalence was 3.8% (95% CI 3.1-4.5%). Further adjustment by test sensitivity and specificity produced lower estimates, 3.6% (95% CI 2.7-4.4%) and 3.3% (95% CI 2.6-4.1%), respectively. The variable most significantly associated with the crude prevalence was the period of blood collection: the later the period, the higher the prevalence. Regarding socio-demographic characteristics, the younger the blood donors, the higher the prevalence, and the lower the educational level, the higher the odds of a positive SARS-Cov-2 antibody. Similar results were found for the weighted prevalence. Discussion: Although our findings resulted from a convenience sample, they match some basic premises: the increasing trend over time, since the epidemic curve in the state is still on the rise; the higher prevalence among the youngest who are more likely to circulate; and the higher prevalence among the less educated as they have more difficulties in following the social distancing recommendations. Despite the study limitations, it is possible to infer that protective levels of natural herd immunity to SARS-CoV-2 are far from being reached in Rio de Janeiro

Dynamic Intracellular Metabolic Cell Signaling Profiles During Ag-Dependent B-Cell Differentiation

© 2021 Díez, Pérez-Andrés, Bøgsted, Azkargorta, García-Valiente, Dégano, Blanco, Mateos-Gomez, Bárcena, Santa Cruz, Góngora, Elortza, Landeira-Viñuela, Juanes-Velasco, Segura, Manzano-Román, Almeida, Dybkaer, Orfao and Fuentes.Human B-cell differentiation has been extensively investigated on genomic and transcriptomic grounds; however, no studies have accomplished so far detailed analysis of antigen-dependent maturation-associated human B-cell populations from a proteomic perspective. Here, we investigate for the first time the quantitative proteomic profiles of B-cells undergoing antigen-dependent maturation using a label-free LC-MS/MS approach applied on 5 purified B-cell subpopulations (naive, centroblasts, centrocytes, memory and plasma B-cells) from human tonsils (data are available via ProteomeXchange with identifier PXD006191). Our results revealed that the actual differences among these B-cell subpopulations are a combination of expression of a few maturation stage-specific proteins within each B-cell subset and maturation-associated changes in relative protein expression levels, which are related with metabolic regulation. The considerable overlap of the proteome of the 5 studied B-cell subsets strengthens the key role of the regulation of the stoichiometry of molecules associated with metabolic regulation and programming, among other signaling cascades (such as antigen recognition and presentation and cell survival) crucial for the transition between each B-cell maturation stage.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) and Junta Castilla-León (COVID19 grant COV20EDU/00187). Fundación Solórzano FS/38-2017.The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. AL-V is supported by VIII Centenario-USAL PhD Program. PJ-V is supported by JCYL PhD Program and scholarship JCYL-EDU/601/2020. PD and EB are supported by a JCYL-EDU/346/2013 Ph.D. scholarship

Enteric Budesonide in Transplant and Native IgA Nephropathy: Real-World Clinical Practice

Budesonide; Transplant; NephropathyBudesonida; Trasplante; NefropatíaBudesonida; Trasplantament; Nefropati

10-year analysis of human immunodeficiency virus incidence in first-time and repeat donors in Brazil

INTRODUÇÃO: A incidência em doadores de sangue de primeira vez e de repetição é uma medida importante do risco de infecção por HIV transmitido por transfusão. Entretanto, no Brasil pouco se sabe sobre a tendência da incidência do HIV em doadores de sangue ao longo do tempo, e sobre o risco residual nas doações de sangue. Ao mesmo tempo, o entendimento e o monitoramento da incidência é de grande relevância, pois os fatores de risco para uma unidade doada estar em janela infecciosa ou imunológica são desconhecidos e, principalmente, os dados de tendências de incidência do HIV não estão disponíveis em relação à população geral do Brasil. Para tentar ajudar a preencher essa lacuna, este estudo avaliou a incidência do HIV ao longo do tempo em quatro grandes hemocentros no Brasil. MÉTODOS: As doações foram testadas e os resultados confirmados por meio de testes sorológicos para HIV de 2007 a 2016 e, adicionalmente, foram realizados testes para a detecção de ácido nucleico a partir de 2011. O teste de avidez do antígeno limitante (LAg) foi realizado em amostras positivas para HIV em doadores de primeira vez para classificar se uma infecção foi adquirida recentemente. Foi calculada a incidência em doadores de primeira vez usando a duração média da infecção recente, e em doadores de repetição usando métodos clássicos. As tendências temporais e demográficas foram avaliadas por meio da regressão de Poisson. RESULTADOS: No período de 10 anos compreendido pelo estudo, a incidência estimada de HIV em doadores de primeira vez se mostrou maior em Recife (45,1 casos por 100.000 pessoas-ano), seguido por São Paulo (32,2 casos por 100.000 pessoas-ano) e por Belo Horizonte (23,3 casos por 100.000 pessoasano). Em doadores de repetição a incidência também foi maior em Recife (33,2 casos novos de HIV por 100.000 pessoas-ano), seguido por Belo Horizonte (27,5 casos novos de HIV por 100.000 pessoas-ano) e por São Paulo (17,0 casos novos por 100.000 pessoas-ano). Já no Rio de Janeiro os resultados entre doadores de primeira vez foram estimados em 35,9 casos por 100.000 pessoasano de 2013 a 2016; e entre os doadores de repetição a incidência foi estimada em 29,2 casos por 100.000 pessoas-ano de 2011 a 2016. A incidência de HIV foi maior em doadores espontâneos do que em doadores de reposição, e entre os doadores mais jovens que comparecem ao hemocentro mais vezes para doar. O risco residual de transmissão de HIV por transfusão foi de 5,46 e 7,41 por milhão de unidades de concentrado de hemácias e de plasma fresco congelado transfundidas, respectivamente. CONCLUSÃO: Não foram evidenciadas alterações no padrão da incidência de HIV ao longo dos 10 anos de estudo. Reduzir a doação feita por indivíduos com infecção por HIV recentemente adquirida é a forma mais segura de reduzir o risco de infecção transmitida por transfusão, e atenção especial é necessária para os doadores de repetição, para determinados grupos etários e para as regiões com maior incidência de HIVBACKGROUND: Incidence in first-time and repeat blood donors is an important measure of transfusion-transmitted HIV infection risk. In Brazil, little is known about the trend in the incidence of HIV in blood donors over time and about the residual risk in blood donations. Understanding and monitoring incidence is of great importance, as the risk factors related to transfusion transmission are unknown and, mainly, data on incidence trends are not available in relation to the general population of Brazil. To try to help fill this gap, this study assessed HIV incidence over time at four large blood centers in Brazil. MATERIALS AND METHODS: Donations were screened and confirmed using serological assays for HIV from 2007 to 2016, and additionally screened by nucleic acid testing from 2011 forward. Limiting antigen (LAg) avidity testing was conducted on HIV seroreactive samples from first-time donors to classify whether an infection was recently acquired. We calculated incidence in first-time donors using the mean duration of recent infection and in repeat donors using classical methods. Time and demographic trends were assessed using Poisson regression. RESULTS: Over the 10-year period, HIV incidence in first-time donors was highest in Recife (45.1/100.000 person-years (105 py)) followed by São Paulo (32.2/105 py) and then Belo Horizonte (23.3/105 py), and in repeat donors was highest in Recife (33.2/105 py), Belo Horizonte (27.5/105 py) and São Paulo (17.0/105 py). Results from Rio de Janeiro were available from 2013 to 2016 with incidence in first-time donors of 35.9/105 py, and from 2011 to 2016 with incidence of 29.2/105 py in repeat donors. The incidence of HIV was higher in community donors than in replacement donors, and among younger donors who attend the blood center more often to donate. Incidence varied by other donor demographics. When incidence was considered in 2-year intervals, no significant trend was evident. Overall residual risk of transfusion-transmitted HIV infection was 5.46 and 7.41 per million units of packed red blood cell (pRBC) and fresh frozen plasma (FFP) transfused, respectively. CONCLUSION: HIV incidence in both first time and repeat donors varied by region in Brazil. Clear secular trends were not evident. Reducing donation among donors with newly acquired HIV infection is the safest way to reduce the risk of transfusiontransmitted infection, and special attention is needed for repeat donors, age groups and regions with the highest HIV incidenc

Comparison of Two Methods of Capillary Sampling in Blood Pre-Donation Anemia Screening in Brazil

Background: The laboratory tests most used by blood banks to diagnose anemia are the hemoglobin (Hb) and microhematocrit (Hct) tests, measured from capillary samples. Objective: To analyze the two capillary screening methods for pre-donation anemia by comparing their agreement in diagnosing anemia. Method: A cross-sectional study in a population of 15,521 blood donation candidates for whom information was available on Hb and Hct, performed from capillary blood samples. Hb was determined using the HemoCue® test and Hct by the centrifugation method. The Kappa coefficient was calculated to assess the agreement between the methods. Pearson’s correlation tests and gender-adjusted linear regression were used to assess the change in the response variable (Hb) as a function of the explanatory variable (Hct). Results: The majority of the study population were men (70.4%), aged between 18 and 44 years (72.1%), who declared themselves white or mixed skin color (85.6%), and had undergone at least 11 years of complete education (72.4%). The Kappa coefficient found was 92.7 and 99.2 for women and men, respectively. Pearson’s correlation showed a correlation coefficient of 0.98 and the linear regression graph showed an adequate relationship between the tests with R2 = 0.97. Conclusions: Comparing the Hb and Hct capillary tests, it was found that Hct can be safely used to screen for anemia in pre-blood donation

High-Sensitive TRBC1-Based Flow Cytometric Assessment of T-Cell Clonality in Tαβ-Large Granular Lymphocytic Leukemia

Flow cytometric (FCM) analysis of the constant region 1 of the T-cell receptor β chain (TRBC1) expression for assessing Tαβ-cell clonality has been recently validated. However, its utility for the diagnosis of clonality of T-large granular lymphocytic leukemia (T-LGLL) needs to be confirmed, since more mature Tαβ cells (i.e., T-LGL normal-counterpart) show broader TRBC1+/TRBC1− ratios vs. total Tαβ cells. We compared the distribution and absolute counts of TRBC1+ and TRBC1− Tαβ-LGL in blood containing polyclonal (n = 25) vs. clonal (n = 29) LGL. Overall, polyclonal TRBC1+ or TRBC1− Tαβ-LGL ranged between 0.36 and 571 cells/μL (3.2–91% TRBC1+ cells), whereas the clonal LGL cases showed between 51 and 11,678 cells/μL (96% TRBC1+ cells). Among the distinct TCRVβ families, the CD28− effector-memory and terminal-effector polyclonal Tαβ cells ranged between 0 and 25 TRBC1+ or TRBC1− cells/μL and between 0 and 100% TRBC1+ cells, while clonal LGL ranged between 32 and 5515 TRBC1+ or TRBC1− cells/μL, representing 98% TRBC1+ cells. Our data support the utility of the TRBC1-FCM assay for detecting T-cell clonality in expansions of Tαβ-LGL suspected of T-LGLL based on altered percentages of TRBC1+ Tαβ cells. However, in the absence of lymphocytosis or in the case of TαβCD4-LGL expansion, the detection of increased absolute cell counts by the TRBC1-FCM assay for more accurately defined subpopulations of Tαβ-LGL-expressing individual TCRVβ families, allows the detection of T-cell clonality, even in the absence of phenotypic aberrations.This work was supported by the CB16/12/00400 (CIBERONC) and PI20-01346 grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (Madrid, Spain) and FONDOS FEDER; the 0639-IDIAL-NET-3-3 grant (INTERREG POCTEP Spain-Portugal) from Fondo Europeo de Desarrollo Regional, and by the EuroFlow Foundation (Leiden, The Netherlands). N.M.-G. was supported by a pre-doctoral grant (Ref. IBPredoc17/00012) from IBSAL (Salamanca, Spain). M.L.,N.V., J.J.M.v.D., A.O. and J.A. are members of the EuroFlow Consortiu

Economy, environment and resources in prehistoric Malta

This project has received funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7-2007-2013) (Grant agreement No. 323727)

Economy, environment and resources in prehistoric Malta

Reconstruction of the changing environmental context of the human settlement of the Maltese Islands has been a major focus of the FRAGSUS Project and readers are referred to the first publication in this series for the full details, against which the evidence presented here can be read (Volume 1, Chapters 2-5 & 11). It is important to note from the outset that much evidence confirms that certain aspects of the environment - particularly soil properties, levels of vegetation cover and surface water - changed considerably during prehistory and indeed subsequently (Fig. 9.1)