Presence of Epstein-Barr virus (EBV) antigens detected by sensitive methods has no influence on local immune environment in diffuse large B cell lymphoma.

EBV+ diffuse large B cell lymphoma (DLBCL) not otherwise specified (NOS) is a new entity confirmed by the World Health Organization (WHO) in 2017. In this new entity, the virus may contribute to a tolerogenic microenvironment. Traces of the virus have been described in DLBCL with more sensitive methods, in cases that were originally diagnosed as negative. The aim of this study was to analyze the expression of immune response genes in the tumor microenvironment to disclose the role of the virus and its traces in DLBCL. In 48 DLBCL cases, the expression of immune response genes and the presence of molecules that induce tolerance, such as TIM3, LAG3 and PDL1 by immunohistochemistry (IHC), were studied. To broaden the study of the microenvironment, tumor-associated macrophages (TMAs) were also explored. No significant differences were observed in the expression of immune response genes in the EBV+ DLBCL and those cases that were EBV- DLBCL but that exhibited viral traces, assessed by ViewRNA assay. Only the EBV+ DLBCL cases displayed a significantly higher increase in the expression of CD8 and cytotoxic T cells detected by gene expression analysis, and of PDL1 in tumor cells and in the expression of CD68 in the tumor microenvironment detected by IHC, not observed in those cases with viral traces. The increase in CD8 and cytotoxic T cells, PDL1 and CD68 markers only in EBV+ DLBCL may indicate that traces of viral infection might not have influence in immune response markers.

To evaluate the detection rate of local and whole-body recurrence by integrated [18F]F-PSMA-1007 PET/MR assessment of prostate cancer patients treated with prostatectomy with very low biochemical recurrence (<0.5ng/ml). Therapeutic implications.

OBJECTIVE: To analyse the efficacy of integrated assessment of [18F]F-PSMA-1007 PET/MRI on the early detection of local recurrence (LR) for prostate cancer patients with PSA levels <0.5ng/ml after radical prostatectomy. To assess the location of recurrence so that therapy may be tailored to patient. METHODS: Prospective study including 35 patients with prostate cancer (PCa), who were referred for a [18F]F-PSMA-1007 PET/MR after prostatectomy with a very initial PSA value increase (PSA<0,5ng/ml). Simultaneous acquisition in a PET/MRI hybrid equipment (SIGNA-GE), 1h after administration of 370%±10% MBq of [18F]F-PSMA-1007: Prostate selective imaging (20min): multiparametric PET+MRI (MRImp): DIXON, T1, T2, diffusion sequences post-gadolinium administration. Whole body image (30min): PET+MRI: DIXON, T1, T2, diffusion, STIR sequences. A nuclear physician and a radiologist jointly reviewed the studies: In order to assess LR, the "Prostate Imaging for Recurrence Reporting" system was used on MRI, as well as the Likert scale on the PET prostate imaging. The remaining lesions were classified as N1 and M1a. RESULTS: PET/MRI was positive in 25 patients (71,4%) and negative in 10 patients (28,6%). RL was detected in 15 patients (42.9%): in 2 (5.7%) MRI was superior; in 3 (8.6%) PET was superior; integrated PET/MRI showed improved results in 5 patients (14.3%) for the detection of LR. Location of recurrences: LR in 11 patients (44.0%); N1 in 10 (40.0%); LR+N1 (8.0%) in 2; LR+N1+M1a in 2 (8.0%). In 20 patients (80%) the PET/MRI findings allowed radioguided radiotherapy implementation (11 on LR, and 9 on N1), whereas hormonal treatment was decided in 5 patients (20%) due to multimetastases/spread disease. CONCLUSION: [18F]F-PSMA-1007 PET/MRI has a 71.4% recurrence detection rate after prostatectomy with PSA<0.5ng/ml. Its combined PET and MRI study increases the detection of LR by 14.3%, with a high N1+M1a detection rate (56%), allowing radioguided radiotherapy in 80% of patients.

[Two new cases of X-linked intellectual developmental disorder-105 linked to a previously unreported pathogenic variant in the USP27X gene]. / Dos nuevos casos de discapacidad intelectual ligada al cromosoma X tipo 105 por variante patógena en el gen USP27X no descrita previamente.

INTRODUCTION: X-linked intellectual developmental disorder is clinically and genetically heterogeneous. The ubiquitin specific peptidase 27 X-linked gene (USP27X) has been associated with X-linked intellectual developmental disorder, and only 17 affected males have been described in the literature to date. CASE REPORT: A 6-year-old boy was assessed due to intellectual developmental disability, language delay, behavioural disorder, microcephaly and particular features. His mother had learning difficulties and a facial phenotypic overlap. A maternal uncle had an intellectual developmental disorder. Physical examination revealed an unusual phenotype (triangular facies, long palpebral fissures and eyelashes, medially eyebrow loss, prominent auricles), mild brachydactylia and hypoplasia in the distal phalanges. The clinical exome identified the probably pathogenic variant NM_001145073.3: c.692delT in the USP27X gene. The results of the family segregation analysis were positive: the mother and maternal uncle were harbourers, while healthy maternal aunt was not. CONCLUSIONS: We present two new cases of X-linked intellectual developmental disorder due to a previously unreported variant in the USP27X gene. Both patients presented neurological symptoms without any significant involvement at other levels, according to the literature. One of the cases presented microcephaly, particular features and digital anomalies, which broadens the phenotypic spectrum of this disease.

TITLE: Dos nuevos casos de discapacidad intelectual ligada al cromosoma X tipo 105 por variante patógena en el gen USP27X no descrita previamente.Introducción. La discapacidad intelectual ligada al cromosoma X es un trastorno clínica y genéticamente heterogéneo. El gen de la proteasa 27 específica de la ubiquitina ligada al cromosoma X (USP27X) se ha asociado a discapacidad intelectual ligada al cromosoma X, y en la actualidad sólo se ha descrito a 17 varones afectos en la bibliografía. Caso clínico. Niño de 6 años valorado por discapacidad intelectual, retraso del lenguaje, trastorno de la conducta, microcefalia y rasgos particulares. Madre con dificultades de aprendizaje y fenotipo facial solapante. Un tío materno con discapacidad intelectual aislada. En la exploración física destaca un fenotipo peculiar (facies triangular, fisuras palpebrales y pestañas largas, cejas menos pobladas medialmente, pabellones auriculares prominentes), leve braquidactilia e hipoplasia de falanges distales. El exoma clínico identificó la variante probablemente patógena NM_001145073.3: c.692delT en el gen USP27X. El estudio de segregación familiar fue positivo: madre y tío materno portadores, tía materna sana no portadora. Conclusiones. Describimos dos nuevos casos con discapacidad intelectual ligada al cromosoma X por variante no descrita previamente en el gen USP27X. Ambos pacientes presentan clínica neurológica sin afectación significativa a otros niveles de acuerdo con la bibliografía. Uno de los casos asocia microcefalia, rasgos particulares y anomalías digitales, lo que permite ampliar el espectro fenotípico de esta enfermedad.

Characterization of hospitalized patients with acute kidney injury associated with COVID-19 in Spain: renal replacement therapy and mortality. FRA-COVID SEN Registry Data.

BACKGROUND: Acute kidney injury (AKI) is common among hospitalized patients with COVID-19 and associated with worse prognosis. The Spanish Society of Nephrology created the AKI- COVID Registry to characterize the population admitted for COVID-19 that developed AKI in Spanish hospitals. The need of renal replacement therapy (RRT) therapeutic modalities, and mortality in these patients were assessed MATERIAL AND METHOD: In a retrospective study, we analyzed data from the AKI-COVID Registry, which included patients hospitalized in 30 Spanish hospitals from May 2020 to November 2021. Clinical and demographic variables, factors related to the severity of COVID-19 and AKI, and survival data were recorded. A multivariate regression analysis was performed to study factors related to RRT and mortality. RESULTS: Data from 730 patients were recorded. A total of 71.9% were men, with a mean age of 70 years (60-78), 70.1% were hypertensive, 32.9% diabetic, 33.3% with cardiovascular disease and 23.9% had some degree of chronic kidney disease (CKD). Pneumonia was diagnosed in 94.6%, requiring ventilatory support in 54.2% and admission to the ICU in 44.1% of cases. The median time from the onset of COVID-19 symptoms to the appearance of AKI (37.1% KDIGO I, 18.3% KDIGO II, 44.6% KDIGO III) was 6 days (4-10). A total of 235 (33.9%) patients required RRT: 155 patients with continuous renal replacement therapy, 89 alternate-day dialysis, 36 daily dialysis, 24 extended hemodialysis and 17 patients with hemodiafiltration. Smoking habit (OR 3.41), ventilatory support (OR 20.2), maximum creatinine value (OR 2.41), and time to AKI onset (OR 1.13) were predictors of the need for RRT; age was a protective factor (0.95). The group without RRT was characterized by older age, less severe AKI, and shorter kidney injury onset and recovery time (p < 0.05). 38.6% of patients died during hospitalization; serious AKI and RRT were more frequent in the death group. In the multivariate analysis, age (OR 1.03), previous chronic kidney disease (OR 2.21), development of pneumonia (OR 2.89), ventilatory support (OR 3.34) and RRT (OR 2.28) were predictors of mortality while chronic treatment with ARBs was identified as a protective factor (OR 0.55). CONCLUSIONS: Patients with AKI during hospitalization for COVID-19 had a high mean age, comorbidities and severe infection. We defined two different clinical patterns: an AKI of early onset, in older patients that resolves in a few days without the need for RRT; and another more severe pattern, with greater need for RRT, and late onset, which was related to greater severity of the infectious disease. The severity of the infection, age and the presence of CKD prior to admission were identified as a risk factors for mortality in these patients. In addition chronic treatment with ARBs was identified as a protective factor for mortality.

Seroprevalencia y factores de riesgo asociados a infección por Trypanosoma cruzi y Toxoplasma gondii en la comunidad Saimadoyi, Sierra de Perijá, estado Zulia / Seroprevalence and risk factors associated to infection by Trypanosoma cruzi and Toxoplasma gondii in the Saimadoyi community, Sierra de Perija, Zulia state

La enfermedad de Chagas y la toxoplasmosis constituyen problemas de salud característicos de zonas rurales. El objetivo de esta investigación fue determinar la seroprevalencia de Trypanosoma cruzi y Toxoplasma gondii en la comunidad Saimadoyi. Se estudiaron 166 muestras de sueros de individuos de ambos sexos (100 femeninos y 66 masculinos) con edades comprendidas entre 1 a 83 años. La determinación de anticuerpos se realizó a través de la técnica de ELISA, utilizando kits disponibles comercialmente. La seroprevalencia de Trypanosomacruzi fue de 51% (87/166), mientras que para Toxoplasma gondii fue de 57% (95/166). La mayoría de casos positivos se encontraron en los individuos menores de 20 años, sin embargo, no se encontraron diferencias significativas con respecto al género o grupo de edad para ambas parasitosis. Los datos epidemiológicos mostraron que los factores de riesgo estadísticamente significativos (p<0,05) para la infección por T. cruzi fueron el tipo de vivienda, contacto con perros o chipos y contaminación del suelo con heces; mientras que para la infección por T. gondii, el contacto con gatos y la higiene inadecuada fueron los riesgos significativos. El elevado número de casos seropositivos en mujeres en edad reproductiva sugiere la transmisión vertical de ambos parásitos.

Chagas disease and toxoplasmosis are health problems characteristic of rural areas. The aim of this research was to determine the seroprevalence of Trypanosoma cruzi y Toxoplasma gondii. in community Saimadoyi. 166 serum samples from individuals of both sexes (100 female 66 male and) aged 1-83 years were studied. The determination of antibodies was performed by ELISA using a commercial kit. Trypanosoma cruzi seroprevalence was 51% (87/166), while for Toxoplasma gondii was 57% (95/166). Most positive cases were found in people under 20 years old, however no significant differences with regard to gender or age group for both parasites were found. Epidemiological data showed statistically significant risk factors (p <0.05) for T. cruzi infection were the type of housing, contact with dogs or chipos and soil contamination with feces; while for T. gondii infection, contact with cats and poor hygiene were the significant risks. The high number of seropositives cases in women of reproductive age suggests vertical transmission of both parasites.

Detección de virus entéricos en un sistema piloto de tratamiento de aguas residuales municipales / Detection of Enteric Viruses in a Pilot System for Municipal Wastewater Treatment

Se evaluó un sistema piloto de tratamiento de aguas residuales municipales para verificar su capacidad de remoción de patógenos virales. La presencia de Adenovirus, Calicivirus, Enterovirus, Virus de Hepatitis A y Virus de Hepatitis E. Se determinó mediante RT-PCR (Reacción en Cadena de la Polimerasa con Transcriptasa Reversa). Además se examinó la eficacia de los colifagos como indicadores y se verificó la presencia de indicadores bacterianos clásicos. Se obtuvo un 100% de positividad para la presencia de todos los virus en la entrada y salida del sistema, por lo que el sistema no es capaz de eliminarlos. Los colifagos no fueron removidos por este sistema, pero sirvieron como indicadores para la presencia de virus entéricos en el mismo. Los indicadores bacterianos redujeron su número a su paso por el sistema, pero aún al final del sistema, los coliformes se encontraban en números por encima de los límites establecidos por las leyes venezolanas. Por lo tanto, sería necesario agregar otros pasos al sistema, para poder obtener un efluente que cumpla las leyes y que garantice la ausencia de virus entéricos.

A pilot system for treating municipal waste was evaluated to verify its ability to remove viral pathogens. The presence of Adenovirus, Calicivirus, Enterovirus and Hepatitis A and E was determined using RT-PCR. The efficiency of coliphages as indicators and the presence of classic bacterial indicators were also investigated. A 100% positivity was obtained for the presence of all viruses at the entrance and exit of the system; therefore, the system was not able to remove them. Coliphages weren’t removed by the system, but they were effective as indicators of enteric viral presence in it. Bacterial indicators reduced their number going through the system, but even at the end of the system, coliforms had numbers above the limits dictated by Venezuelan law. Therefore, it would be necessary to add additional steps to the system in order to obtain an effluent that meets the laws and to ensure the absence of enteric viruses.

Utilidad de la transcripción reversa-reacción en cadena de la polimerasa (RT-PCR) para la vigilancia proactiva y el diagnóstico clínico del dengue / Utility of everse-reaction transcrptions in chain of polimerase (RT-PCR) to the proactive surveillance and clinical diagnoses of dengue

Un sistema de vigilancia proactiva efectivo para dengue requiere de técnicas de laboratorio rápidas y confiable que puedan detectar tempranamente la transmisión viral para predecir las epidemias con suficiente anticipación. En este sentido, la técnica de reverso transcripción-reacción en cadena de la polimerasa (RT-PCR) es una alternativa que ha sido utilizada exitosamente en sistema de vigilancia proactiva de centro y Sur América. En este estudio comparamos las cualidades del diagnóstico confirmatorio temprano del dengue de las técnicas RT-PCR, aislamiento viral en células C6/36 y serotipificación con anticuerpos con monoclonales antidengue (AIV), ensayo inmunoenzimático de captura de IgM anti-dengue (MAC-ELISA) y la inhibición de la hemaglutinación (IHA). Para el estudio utilizamos 1.019 sueros de pacientes atendidos por el sistema de vigilancia proactiva del estado Aragua, Venezuela. Los resultados desmotraron que la RT_PCR tuvo: a)mayores tasas de positividad que el AIV, el MAC-ELISA y la IHA, b)Alta sensibilidad (100 por ciento) y aceptable especificidad (73,5 por ciento) respecto al AIV y c)buena eficacia y rapidez en obtener resultados en los cuatros días iniciales de la enfermedad. Estas cualidades la convierte en una poderosa herramienta para la vigilancia proactiva del dengue(au)

Determinación de interferón circulante en sueros de pacientes con dengue: estudio preliminar / Determination of circulating interferon in sera of dengue patients

En el presente estudio se muestran los resultados obtenidos al determinar la presencia de interferón (IFN) circulantes en sueros pareados de 37 personas que resultaron enfermas durante la epidemia de dengue que afectó a Nicaragua en 1985. Diecisiete sueros pareados no presentaron anticuerpos inhibidores de la hemaglutinación, detectándose IFN en el 47 % de ellos. En los restantes 20 pares fue posible establecer el diagnóstico de la infección por dengue mediante la seroconversión; en el 60 % de ellos se detectó presencia de IFN, observándose con más frecuencia en el suero correspondiente a la fase aguda de la enfermedad. Además, se discuten aspectos relacionados con la detección de IFN como indicador de la infección viral y su posible utilización para el diagnóstico

Septicemia due to a non-0 1, non-0 139 Vibrio cholerae

We describe a patient with a non-0:1, non-0:139 Vibrio cholerae septicemia associated with ecythema gangrenosa-like skin lesions. The patient acquired the infection in Puerto Rico. Given the high fatality rate, it is important for the medical community to consider the diagnosis in high risk patients with exposures in Puerto Rico tropical waters