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Background & Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identifying ideal candidates remains a challenge. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating marker of immune activation that has previously been associated with liver inflammation, but its prognostic value in patients receiving TIPS is unknown. In the present study, we evaluated the potential clinical relevance of suPAR levels in patients undergoing TIPS insertion. Methods: suPAR concentrations were measured by ELISA in hepatic vein (HV) and portal vein (PV) blood samples from 99 patients (training cohort) as well as peripheral venous blood samples from an additional 150 patients (validation cohort) undergoing TIPS placement. The association between suPAR levels and patient outcomes was assessed using Kaplan-Meier methods and Cox-regression analyses. Results: suPAR concentrations were significantly higher in HV samples compared to PV samples and correlated with PV concentration, the presence of ascites, renal injury, and consequently with the Child-Pugh and MELD scores. Patients with lower suPAR levels had significantly better short- and long-term survival after TIPS insertion, which remained robust after adjustment for confounders in multivariate Cox-regression analyses. Sensitivity analysis showed an improvement in risk prediction in patients stratified by Child-Pugh or MELD scores. In an independent validation cohort, higher levels of suPAR predicted poor transplant-free survival after TIPS, particularly in patients with Child-Pugh A/B cirrhosis. Conclusion: suPAR is largely derived from the injured liver and its levels are predictive of outcome in patients undergoing TIPS. suPAR, as a surrogate of hepatic inflammation, may be used to stratify care in patients following TIPS insertion. Impact and implications: Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective therapy for complications of portal hypertension. However, clinical outcomes following TIPS placement vary widely between patients and identification of the ideal candidates remains challenging. We show that soluble urokinase plasminogen activator receptor (suPAR), a circulating marker of immune activation that can easily be measured in routine clinical practice, is a novel marker to identify patients who will benefit from TIPS and those who will not.
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Oro- and nasopharyngeal swab specimens by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) to detect SARS-CoV-2 is currently the main diagnostic tool during the ongoing COVID-19 pandemia. Accurate performance of the procedure to avoid false negative results, adequate personal protective equipment and material sparing algorithms are mandatory while obtaining swab specimens. In the current stey-by-step review a feasible approach will be presented.
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COVID-19/diagnóstico , Nasofaringe/virología , Orofaringe/virología , Manejo de Especímenes , COVID-19/prevención & control , Prueba de Ácido Nucleico para COVID-19 , Humanos , Equipo de Protección Personal , SARS-CoV-2/genética , Manejo de Especímenes/instrumentación , Manejo de Especímenes/métodos , Manejo de Especímenes/normasRESUMEN
BACKGROUND: Cancer is the second leading cause of death worldwide and incidence rates for several tumor entities are rising. In addition to a high cancer-specific mortality rate, many cancer patients also suffer from additional comorbidities. Among these, several psychological morbidities have been extensively studied in the past, but findings on the association between cancer and dementia have remained conflicting. In the present study, we evaluated the possibility of an association between cancer and dementia. METHODS: Based on data from the IQVIA Disease Analyzer database, a total of 92,868 cancer outpatients initially diagnosed between 2000 and 2018 were matched by age, gender, index year, and yearly consultation frequency to 92,868 individuals without cancer. Ten-year incidence rates of dementia were compared for the two cohorts. RESULTS: The overall cumulative incidence of dementia was significantly higher in cancer patients (19.7%) than in non-cancer patients (16.7%, p < 0.001). Cox regression models confirmed that this association was significant for both male (HR: 1.35 [1.30-1.41], p < 0.001) and female (HR: 1.26 [1.21-1.31], p < 0.001) patients and was consistent among all age groups analyzed (65-70, 71-75, 76-80, 81-85, and >85 years). In addition, the association between cancer and dementia was significant for all cancer entities analyzed (skin, digestive organs, prostate, breast, urinary tract, lymphoid and hematopoietic tissue, and lung cancer) and most pronounced in patients with lung cancer (HR: 1.44 [1.28-1.62], p < 0.001). CONCLUSIONS: Our data provide strong evidence for an increased incidence of dementia in a large cohort of patients with different cancer entities, which should raise awareness of this important comorbidity in cancer patients.
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INTRODUCTION: Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) show a rapidly increasing incidence worldwide. Although both diseases often occur in the same patient population, their mutual influence is not fully understood. We therefore aimed at analyzing the impact of T2D on the incidence of NAFLD in a large cohort of outpatients in Germany. RESEARCH DESIGN AND METHODS: 32 201 patients with T2D diagnosed between 2012 and 2018 were identified in the IQVIA Disease Analyzer database. Probability of NAFLD was analyzed using Cox regression models. RESULTS: The cumulative incidence of NAFLD within the 7-year observation period was 4.3%. The probability of NAFLD was significantly higher among patients with T2D with increased body mass index but not hemoglobin A1c. Prescriptions of sodium-glucose cotransporter-2 inhibitors (HR: 0.54, 95% CI 0.45 to 0.64), glucagon-like peptide-1 receptor antagonists (HR: 0.65, 95% CI 0.52 to 0.81), and insulin (HR: 0.72, 95% CI 0.62 to 0.8) were significantly associated with lower incidence of NAFLD. CONCLUSION: Our data from a large population-based cohort of patients with T2D identified sociodemographic and therapeutic parameters associated with NAFLD incidence in patients with T2D which should be taken into account for novel therapeutic concepts.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Alemania , Humanos , Incidencia , Enfermedad del Hígado Graso no Alcohólico/epidemiologíaRESUMEN
We describe the unique disease course and cure of SARS-CoV-2 infection in a patient with SCID and graft failure. In absence of a humoral immune response, viral clearance was only achieved after transfusion of convalescent plasma. This observation underscores the necessity of the humoral immune response for SARS-CoV-2 clearance.
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COVID-19/terapia , SARS-CoV-2/fisiología , Inmunodeficiencia Combinada Grave/complicaciones , Adulto , Anticuerpos Antivirales/sangre , COVID-19/complicaciones , COVID-19/inmunología , COVID-19/virología , Femenino , Rechazo de Injerto/complicaciones , Rechazo de Injerto/inmunología , Rechazo de Injerto/virología , Humanos , Inmunización Pasiva , Inmunodeficiencia Combinada Grave/inmunología , Inmunodeficiencia Combinada Grave/virología , Respuesta Virológica Sostenida , Carga Viral , Replicación Viral , Sueroterapia para COVID-19RESUMEN
Objective: The affection of both the peripheral (PNS) and central nervous system (CNS) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been assumed to play a direct role in the respiratory failure of patients with Corona virus disease 2019 (COVID-19) through affection of medullary cardiorespiratory centers resulting in neurological complications and sequelae. Methods: We used a multimodal electrophysiological approach combined with neuropsychological investigations to study functional alteration of both the PNS and CNS in four patients with severe COVID-19. Results: We found electrophysiological evidence for affection of both the PNS and CNS, and particularly affection of brain stem function. Furthermore, our neuropsychological investigations provide evidence of marked impairment of cognition independent of delirium, and outlasting the duration of acute infection with SARS-CoV-2. Conclusion: This case series provides first direct electrophysiological evidence for functional brain stem involvement in COVID-19 patients without evident morphological changes supporting the notion of the brain stem contributing to respiratory failure and thus promoting severe courses of the disease. Moreover, sustained neuropsychological sequelae in these patients may be of particular psychosocial and possibly also economic relevance for society.