Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Dapagliflozin – derribando barreras en el tratamiento actual de la diabetes mellitus

La diabetes mellitus (DM) se asocia con un altogrado de morbilidad y mortalidad prematura,un acortamiento sustancioso de la esperanzade vida, un deterioro marcado de la calidad de vida ycostos financieros exorbitantes. Gran parte de estos problemaspueden atribuirse a fallas importantes en los tratamientosantidiab&eacute;ticos vigentes, considerando que engeneral el control metab&oacute;lico tiende a ser pobre en lospacientes con DM. Estas deficiencias han sido el motor deuna revigorizaci&oacute;n en el estudio molecular y cl&iacute;nico de estaenfermedad. En este escenario, los inhibidores del SGLT2(SGLT2i) han alcanzado un gran nivel de aceptaci&oacute;n en lapr&aacute;ctica cl&iacute;nica en virtud de su eficacia robusta, su perfil detolerabilidad benigno, su versatilidad para la implementaci&oacute;ny una multitud de efectos pleiotr&oacute;picos beneficiososen varios sistemas org&aacute;nicos. Entre los distintos SGLT2i, elDAP se destaca en este aspecto, en tanto parece ofrecerefectos nefroprotectores y cardioprotectores especialmentepoderosos, con un riesgo marcadamente bajo de hipoglicemia.En la DM tipo 2, se ha documentado la utilidaddel DAP tanto en monoterapia como en combinaci&oacute;n coninsulinoterapia y otros f&aacute;rmacos antidiab&eacute;ticos orales. Porotro lado, en la DM tipo 1, aunque se dispone de menosdatos cl&iacute;nicos, la evidencia preliminar sugiere buena eficacia.En esta revisi&oacute;n se discuten las caracter&iacute;sticas farmacol&oacute;gicasb&aacute;sicas y cl&iacute;nicas diferenciales del DAP

Lesión pancreática causada por Covid-19: ¿es la diabetes una secuela de la infección?

Durante la pandemia por COVID-19, se ha observado que comorbilidades como la hipertensi&oacute;n arterial, enfermedades cardiovasculares y la diabetes mellitus (DM) parecen ser m&aacute;s frecuentes en estos pacientes. Un cuerpo importante de evidencia se&ntilde;ala entre estas a la DM como la entidad que supone un mayor riesgo a desarrollar complicaciones e incluso la muerte. Gran parte de este peor pron&oacute;stico se ha atribuido al efecto delet&eacute;reo de la DM en la inmunolog&iacute;a humoral y adaptativa. Pero m&aacute;s all&aacute; de esto, la relaci&oacute;n entre la COVID-19 y la DM podr&iacute;a ser bidireccional. Se ha observado que la enzima convertidora de angiotensina 2 sirve como puerta de entrada para el SARS-CoV. Este receptor est&aacute; presente en un gran N&Uacute;MERO de tejidos, incluyendo el p&aacute;ncreas, donde su expresi&oacute;n es muy elevada. Existe suficiente evidencia apoyando la noci&oacute;n de lesi&oacute;n pancre&aacute;tica y pancreatitis en la COVID-19. Sin embargo, en el contexto de los casos severos es dif&iacute;cil determinar si la presencia de pancreatitis se debe al da&ntilde;o directo al tejido pancre&aacute;tico por parte del SARS-CoV-2 o si es el resultado de la respuesta inflamatoria desregulada que forma parte de la enfermedad. Independientemente de la causa, la lesi&oacute;n pancre&aacute;tica supone un factor de riesgo importante para el futuro desarrollo de DM o de prediabetes, as&iacute; como tambi&eacute;n dificulta el correcto tratamiento de los pacientes con DM preestablecida. El objetivo de esta revisi&oacute;n es evaluar los mecanismos moleculares subyacentes a la lesi&oacute;n pancre&aacute;tica en los pacientes infectados con SARS-CoV-2 y revisar la epidemiolog&iacute;a pertinente en este sentido

Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study

Objective To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies.Patients and methods 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model.Results The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i.Conclusion COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation

Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study

International audienceBackground: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects.Conclusion: L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients

Role of age and comorbidities in mortality of patients with infective endocarditis.

The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups: A total of 3120 patients with IE (1327  There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in th