Miocarditis como expresión de lupus eritematoso sistémico. Presentación de un caso

El lupus eritematoso sistémico es una enfermedad autoinmune de etiología desconocida, cuyo cuadro clínico incluye diversas manifestaciones cardiovasculares, que se pueden presentar entre el 50 y 60 % de los pacientes. La miocarditis es infrecuente (10 %) y puede evolucionar tanto a miocardiopatía dilatada como a la mejoría. Por tales razones se presenta el caso de una paciente femenina de 24 años, de color de piel negra, ingresada en el Hospital José Ramón Martínez del municipio de Guanajay, Artemisa, por disnea y palpitaciones ante moderados esfuerzos. Tenía historia previa de infección respiratoria durante el periodo epidémico de la influenza H1N1, diagnosticada por neumonía con derrame cuya evolución fue tórpida. Los elementos clínicos claves en la sospecha y diagnóstico de lupus eritematoso sistémico fueron la presencia de úlceras en el paladar blando y signos de artritis de las articulaciones interfalángicas de ambos pies, así como la historia previa de derrame pleural y manifestaciones de insuficiencia cardíaca, es decir participación multisistémica. Los exámenes de laboratorio mostraron el cribado de anticuerpos antinucleares positivo, disminución de los niveles de complemento CH50 y C3. Actualmente está controlada con esteroides e inmunosupresores

Retrospective study of 149 cases of salivary gland carcinoma in a Spanish hospital population

The clinical and histological characteristics of salivary gland tumors vary widely, complicating their diagnosis and management, and major differences have been recorded in the distribution of histopathological diagnoses among different countries. This retrospective study reviewed the demographic (age, sex) and clinicopathological (pathology diagnosis and localization) characteristics of cases diagnosed with primary SGC between June 1992 and May 2014 in the Pathology Department of the 12 de Octubre Hospital of Madrid. Diagnoses were recorded according to the 2005 WHO classification. The study included 149 SCG patients, aged between 11 and 94 yrs, with mean age at onset of 55.56 yrs and peak incidence in the eighth decade of life. The male:female ratio was 1.01. The parotid gland was the most frequently involved (75.2%). The most frequent carcinoma was mucoepidermoid carcinoma (24.2%), followed by acinic cell carcinoma (15.4%). The demographic and histopathological characteristics of patients with salivary gland carcinomas in Spain, reported here for the first time, are broadly similar to those found in other countries

HIV-Infected Subjects With Poor CD4 T-Cell Recovery Despite Effective Therapy Express High Levels of OX40 and α4β7 on CD4 T-Cells Prior Therapy Initiation

Background HIV-infected subjects with suboptimal CD4 restoration despite suppressive combined antiretroviral treatment (cART) (immunodiscordant subjects) have been classically characterized after a variable period of time under cART. Recently, we have reported that an increased frequency of proliferating CD4 T-cells in these subjects is already present before the cART onset. The potential contribution of peripheral compensatory homeostatic proliferation (HP) is yet unknown. We aimed to analyze the expression of HP-related cellular markers on CD4 T-cells of immunodiscordant subjects before cART. Go to: Methods We analyzed the expression of OX40 and α4β7 on peripheral CD4 T-cells from immunodiscordant and control subjects (n = 21 each group) before cART initiation, and also on available follow-up samples (after 24 month of suppressive cART). Additionally, we tested the expression of these markers in an in vitro system for the study of human HP processes. Go to: Results Immunodiscordant subjects showed increased levels of OX40 and α4β7 on CD4 T-cells before cART initiation. While the cART tended to reduce these levels, immunodiscordant subjects still maintained comparatively higher levels of OX40 and α4β7 after 24 months under suppressive cART. These HP-related markers were upregulated in vitro during the human HP, especially during the fast HP. Go to: Conclusion Our results are compatible with exacerbated HP processes in immunodiscordant subjects, already before the cART onset.Fondo de Investigación Sanitaria FIS PI14/01693 PI13/0796 PI16/0503Fondos Europeos para el Desarrollo Regional (FEDER) CTS2593Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo CTS2593AGAUR 2017SGR948GILEAD GLD14/293The Spanish AIDS Research Network of Excellence RD12/0017/0029 RD16/0025/0019 RD16/0025/0006Junta de Andalucía. Consejería de Salud y Bienestar Social C-0013-201

HIV-Infected Subjects With Poor CD4 T-Cell Recovery Despite Effective Therapy Express High Levels of OX40 and α4β7 on CD4 T-Cells Prior Therapy Initiation

BackgroundHIV-infected subjects with suboptimal CD4 restoration despite suppressive combined antiretroviral treatment (cART) (immunodiscordant subjects) have been classically characterized after a variable period of time under cART. Recently, we have reported that an increased frequency of proliferating CD4 T-cells in these subjects is already present before the cART onset. The potential contribution of peripheral compensatory homeostatic proliferation (HP) is yet unknown. We aimed to analyze the expression of HP-related cellular markers on CD4 T-cells of immunodiscordant subjects before cART.MethodsWe analyzed the expression of OX40 and α4β7 on peripheral CD4 T-cells from immunodiscordant and control subjects (n = 21 each group) before cART initiation, and also on available follow-up samples (after 24 month of suppressive cART). Additionally, we tested the expression of these markers in an in vitro system for the study of human HP processes.ResultsImmunodiscordant subjects showed increased levels of OX40 and α4β7 on CD4 T-cells before cART initiation. While the cART tended to reduce these levels, immunodiscordant subjects still maintained comparatively higher levels of OX40 and α4β7 after 24 months under suppressive cART. These HP-related markers were upregulated in vitro during the human HP, especially during the fast HP.ConclusionOur results are compatible with exacerbated HP processes in immunodiscordant subjects, already before the cART onset

Real-world experience with bezlotoxumab for prevention of recurrence of Clostridioides difficile infection

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period

Early high-titer plasma therapy to prevent severe Covid-19 in older adults

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).Fil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pérez Marc, Gonzalo. Hospital Militar Central, Buenos Aires; ArgentinaFil: Wappner, Diego. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bianchi, Alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Braem, Virginia. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Esteban, Ignacio. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wood, Cristian. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Berrueta, Mabel. Hospital Militar Central; ArgentinaFil: Rondan, Aníbal. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Lescano, Gabriela Mariel. Hospital Dr. Carlos Bocalandro; ArgentinaFil: Cruz, Pablo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Ritou, Yvonne. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Fernández Viña, Valeria Silvina. Hospital Simplemente Evita; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Esperante, Sebastian. 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: Ferreti, Adrián. Hospital Dr. Carlos Bocalandro; ArgentinaFil: Ofman, Gaston. University of Oklahoma; Estados UnidosFil: Ciganda, Álvaro. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal Especializado de Agudos y Cronicos San Juan de Dios.; ArgentinaFil: Rodriguez, Rocío. Hospital Simplemente Evita; ArgentinaFil: Lantos, Jorge. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Valentini, Ricardo. No especifíca;Fil: Itcovici, Nicolás. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Hintze, Alejandra. No especifíca;Fil: Oyarvide, M. Laura. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Etchegaray, Candela. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Neira, Alejandra. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Name, Ivonne. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Alfonso, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Swiss Medical Group; ArgentinaFil: López Castelo, Rocío. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Caruso, Gisela. Hospital Militar Central; ArgentinaFil: Rapelius, Sofía. Hospital Militar Central; ArgentinaFil: Alvez, Fernando. Hospital Militar Central; ArgentinaFil: Etchenique, Federico. Hospital Militar Central; ArgentinaFil: Dimase, Federico. Hospital Militar Central; ArgentinaFil: Alvarez, Darío. Hospital Militar Central; ArgentinaFil: Aranda, Sofía S.. Hospital Militar Central; ArgentinaFil: Sánchez Yanotti, Clara Inés. Hospital Militar Central; ArgentinaFil: De Luca, Julián. Hospital Militar Central; ArgentinaFil: Jares Baglivo, Sofía. Hospital Militar Central; ArgentinaFil: Laudanno, Sofía. Fundación Hematológica Sarmiento; ArgentinaFil: Nowogrodzki, Florencia. Swiss Medical Group; ArgentinaFil: Larrea, Ramiro. Hospital Municipal San Isidro; ArgentinaFil: Silveyra, María. Hospital Militar Central; ArgentinaFil: Leberzstein, Gabriel. No especifíca;Fil: Debonis, Alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Molinos, Juan. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: González, Miguel. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Perez, Eduardo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Kreplak, Nicolás. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pastor Argüello, Susana. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Gibbons, Luz. Hospital Municipal de San Isidro; ArgentinaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Bergel, Eduardo. Sanatorio Sagrado Corazón; ArgentinaFil: Polack, Fernando Pedro. Provincia de Buenos Aires. Ministerio de Salud; Argentin

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality