Markers of Natural Killer Cell Exhaustion in HIV/HCV Coinfection and Their Dynamics After HCV Clearance Mediated by Direct-Acting Antivirals.

Background: Liver fibrosis is a leading cause of morbimortality in people with HIV/hepatitis C virus (HCV). Natural killer (NK) cells are linked with amelioration of liver fibrosis; however, NK cells from individuals coinfected with HIV/HCV with cirrhosis display impaired functionality and high PD-1 expression. Here, we aimed to study PD-1, TIGIT, and Tim3 as potential exhaustion markers in NK cells from persons coinfected with HIV/HCV with mild and advanced liver fibrosis. We also evaluated the role of PD-1 expression on NK cells after HCV clearance by direct-acting antivirals (DAAs). Methods: Peripheral blood mononuclear cells were isolated from individuals coinfected with HIV/HCV (N = 54; METAVIR F0/F1, n = 27; F4, evaluated by transient elastography, n = 27). In 26 participants, samples were collected before, at the end of, and 12 months after successful DAA treatment. The frequency, immunophenotype (PD-1, TIGIT, and Tim3 expression), and degranulation capacity (CD107a assay) of NK cells were determined by flow cytometry. Results: Unlike PD-1, Tim3 and TIGIT were comparably expressed between persons with mild and advanced fibrosis. Degranulation capacity was diminished in NK/TIGIT+ cells in both fibrosis stages, while NK/PD-1+ cells showed a lower CD107a expression in cirrhotic cases. Twelve months after DAA treatment, those with advanced fibrosis showed an improved NK cell frequency and reduced NK/PD-1+ cell frequency but no changes in CD107a expression. In individuals with mild fibrosis, neither PD-1 nor NK cell frequency was modified, although the percentage of NK/CD107a+ cells was improved at 12 months posttreatment. Conclusions: Although DAA improved exhaustion and frequency of NK cells in cirrhotic cases, functionality was reverted only in mild liver fibrosis, remarking the importance of an early DAA treatment.

Rapid identification of Histoplasma capsulatum directly from cultures by multiplex PCR.

The multiplex PCR developed from a suspension of the yeast fungi correctly identified fifty-one clinical of H. capsulatum var. capsulatum strains isolated from clinical samples and soil specimens. The multiplex PCR was developed by combining two pairs of primers, one of them was specific to the H. capsulatum and the other one, universal for fungi, turned out to be specific to H. capsulatum, regardless of the fungus isolate studied. Primers designed to amplify a region of about 390-bp (Hc I-Hc II) and a region of approximately 600-bp (ITS1-ITS4) were used to identify a yeast isolated as H. capsulatum when both regions could be amplified. Absolute agreement (100 % sensitivity) could be shown between this assay and the cultures of H. capsulatum according to their morphological characteristics. Failure to amplify the target DNA sequence by PCR with primers Hc I-Hc II in the presence of the ITS1-ITS4 amplicon in isolates of P. brasiliensis, Cryptococcus neoformans, Trichosporon spp, Candida glabrata, C. albicans, C. tropicalis, C. parapsilosis, C. krusei, or Penicillium marneffei was an unequivocal sign of the high specificity of this assay. The assay specificity was also found to be 100 %. Incipient yeast forms obtained from clinical samples were identified as H. capsulatum by the PCR assay described before the morphological characteristics were registered shortening the time of diagnosis.

Liver cirrhosis in HIV/HCV-coinfected individuals is related to NK cell dysfunction and exhaustion, but not to an impaired NK cell modulation by CD4+ T-cells.

INTRODUCTION: HIV worsens HCV-related liver disease by accelerating fibrosis progression; however, progression rates are extremely variable among HIV/HCV-coinfected individuals. NK cells are associated with modulation of liver fibrosis and are profoundly altered during HCV and HIV infections. CD4+ T-cells modulate NK cell function, and are also affected by HIV infection. Here, we aim to characterize the association of hepatic fibrosis with both the phenotype and function of peripheral NK cells and their regulation by CD4+ T-cells, in HIV/HCV-coinfected individuals. METHODS: Thirty-four HIV/HCV-coinfected individuals with minimal (n = 16) and advanced (n = 18) fibrosis (METAVIR F0/F1 and F4 scores respectively) and 20 healthy volunteers were enrolled. PBMC were obtained from peripheral blood samples and NK and CD4+ T-cells were isolated and analysed. NK cell phenotype (CD25, CD69, Nkp46, NKG2D, PD-1), degranulation (CD107a) and IFN-γ and TNF-α production, as well as CD4+ T-cell activation (CD69, CD25 and CD38) were measured by flow cytometry. CD4+ T-cell conditioned medium (CM) derived from F0/F1 or F4 individuals was assessed for IL-2 levels by ELISA. Modulation of NK cell functionality by these CMs was also analysed. RESULTS: When comparing to NK cells from individuals with minimal fibrosis, degranulation and cytokine secretion by NK cells from subjects with F4 scores was significantly impaired, while PD-1 expression was augmented. On the one hand, neither the expression of activation markers nor IL-2 secretion was distinctly induced in CD4+ T-cells from subjects with F0/F1 or F4 METAVIR scores. Finally, NK cell degranulation and cytokine secretion were not differentially modulated by CD4+ T-cell CM, whether CD4+ T-cells derived from subjects with minimal or advanced fibrosis. CONCLUSIONS: Low levels of NK and CD4+ T-cells in HIV/HCV-coinfected individuals with advanced liver fibrosis have been previously described. Here, we show that advanced liver fibrosis in coinfected individuals is associated to a defective function of NK cells and an increased expression of the exhaustion/senescence marker PD-1. This NK signature could not be attributed to changes in the ability of CD4+ T-cells to modulate NK cell function.

Características epidemiológicas y clínicas de pacientes internados con COVID-19 en la Ciudad de Buenos Aires / Epidemiological and clinical characteristics of patients hospitalized with COVID-19 in Buenos Aires cityEsta obra está bajo una licencia de CreativeCommons Reconocimiento-NoComercial 4.0Internacionalhttps://creativecommons.org/licenses/by-nc/4.0/i

Introducción: La pandemia de COVID-19 representa un desafío para la salud mundial y continúa en investigación. Objetivo: Describir las características epidemiológicas, demográficas, clínicas y la mortalidad por todas las causas de pacientes internados con COVID-19 en un establecimiento de salud privado de la Ciudad de Buenos Aires. Materiales y métodos: Se realizó un estudio retrospectivo, de corte transversal y descriptivo entre el 3 de marzo y el 8 de julio de 2020. Se incluyeron pacientes adultos con diagnóstico confirmado de COVID-19 por RT-PCR de hisopado nasofaríngeo internados en sala general y unidad de terapia intensiva (UTI) del Sanatorio San José. Se analizaron las características epidemiológicas, demográficas (edad, sexo, ocupación, procedencia, residencia), clínicas y mortalidad por todas las causas. Las variables continuas fueron descriptas con mediana y rango intercuartilo (RIC) y las variables categóricas con número y porcentaje. Se utilizó el programa STATA v 13.0.Resultados: Se incluyeron 118 pacientes. La mediana de edad fue de 50 años, 51% varones. Las comorbilidades más prevalentes fueron hipertensión arterial 31,4%, enfermedad neurológica crónica 27,1%, enfermedad cardiovascular 14,4% y diabetes 13,6%. Los signos y síntomas más frecuentes: fiebre 68,6% y tos 51,7%. Según la severidad inicial: 33,9% neumonía moderada y 27,1% grave. El 75% de las tomografías de tórax reveló vidrio esmerilado; linfopenia presentó el 30%. No se detectó coinfección viral. La mortalidad por todas las causas fue del 20%, y del 57% en UTI con ventilación mecánica. Conclusiones: Nuestro trabajo describe las características y mortalidad de pacientes internados con COVID-19. Es necesario aumentar la evidencia para desarrollar modelos de predicción clínica relacionados con COVID-19.Palabras clave: infecciones por coronavirus, pandemias, epidemiología, COVID-19.

ntroduction: The COVID-19 pandemic represents a global health challenge and continues to be investigated.Objective: To describe the epidemiological, demographic, clinical characteristics and all-cause mortality of patients hospitalized with COVID-19, in a private health care facility in Buenos Aires city.Materials and methods: A retrospective, cross-sectional, and descriptive study was conducted between March 3 and July 8, 2020. Adult patients with a confirmed diagnosis of COVID-19 by nasopharyngeal swab RT-PCR, admitted to the general ward and intensive care unit (ICU) at the San José Sanatorium were included. Epidemiological, demographic (age, sex, occupation, origin, residence), clinical characteristics, and all-cause mortality were analyzed. Continuous variables were described with median and interquartile range (IQR) and categorical variables with number and percentage. The STATA v 13.0 program was used. Results: 118 patients were included. The median age was 50 years, 51% were men. The most prevalent comorbidities: arterial hypertension 31.4%, chronic neurological disease 27.1%, cardiovascular disease 14.4% and diabetes 13.6%. The most frequent signs and symptoms: fever 68.6% and cough 51.7%. According to the initial severity: 33.9% moderate pneumonia and 27.1% severe. Ground glass was reported in 75% of chest scans; lymphopenia presented 30%. Viral coinfection was not detected. Mortality from all causes was 20%, and 57% in ICU with mechanical ventilation.Conclusions: Our work describes the characteristics and mortality of hospitalized patients with COVID-19. Increased evidence is needed to develop clinical predictive models related to COVID-19

Parálisis diafragmática y de cuerda vocal en un paciente cón Síndrome de Churg-Strauss: reporte de un caso / Diaphragmatic and vocal cord paralysis in Churg-Strauss syndrome: a case report

El Síndrome de Churg-Strauss es una vasculitis sistémica que afecta vasos de pequeño y mediano calibre y que suele presentarse con asma, fiebre, hipereosinofilia, insuficiencia cardiaca, daño renal y neuropatía periférica. esta última se observa en el 65 por ciento al 80 por ciento de los casos, siendo el compromiso de nervios craneales en una minoría, y aún más excepcional la parálisis de cuerdas vocales y el diafragma. Las neuropatías por vasculitis sistémicas pueden resultar en morbilidad grave e incluso la muerte, por esto la necesidad de instaurar un tratamiento temprano. Reportamos el caso de un paciente que padeció parálisis diafragmática y de cuerda vocal por síndrome de Churg-Strauss.

Churg-Strauss syndrome is a systemic vasculitis of the small and medium sized vessels that usually occurs with asthma, fever, hypereosinophilia, cardiac failure, renal damage and peripheral neuropathy. The latter affects 65 percent to 80 percent of patients, cranial nerves involvement is rare while vocal cord and diaphragmatic paralysis are exceptional. Neuropathies due to systemic vasculitis may result in significant disability and death, therefore the importance to institute an early treatment. We report here a patient who suffered diaphragmatic and vocal cord paralysis due to Churg-Strauss syndrome.