A high concentration of TGF-β correlates with opportunistic infection in liver and kidney transplantation

Transforming growth factor-β (TGF-β) has been associated with numerous human infections, but its role in the occurrence of opportunistic infection (OI) after solid organ transplantation remains unexplored. This study aimed to assess the utility of the TGF-β following in vitro stimulation of whole peripheral blood (WPB) as a surrogate biomarker of post-transplant OI in a cohort of liver and kidney recipients. Thirty liver and thirty-one kidney transplant recipients were recruited to be prospectively monitored for one-year post-transplantation. Enzyme-linked immunosorbent assay (ELISA) was performed to calculate IFN-γ, IL-17, IL-10 and TGF-β concentration in the supernatant from the activated WPB. Recipients showed higher TGF-β concentrations compared to IFN-γ, IL-17, IL-10 at baseline, although these differences were not significant between INF and NoINF. However, recipients who developed an OI within the first sixth months had a higher concentration of TGF-β than those without OI. A concentration of TGF-β > 363.25 pg/ml in liver and TGF-β > 808.51 pg/ml in kidney recipients were able to stratify patients at high risk of OI with a sensitivity and specificity above 70% in both types of solid organ transplantations. TGF-β could provide valuable information for the management of liver and kidney recipients at risk of post-transplant infection.Our work was possible thanks to the support and funding obtained from the “Instituto de Salud Carlos III (ISCIII)”, Spanish Ministry of Health (Grant Number PI15/01370 and P19/01194); and co-funding by the European Union from the European Regional Development Fund (ERDF) with the principle of “A manner to build Europe”

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

El grupu neandertal de la Cueva d'El Sidrón (Borines, Piloña)

Na monografía clásica de Puig y Larraz (1896: 250-252) amiéntense delles cavidaes del Conceyu de Piloña, pero non la Cueva d’El Sidrón (Fig. 1). Esta conocíase, ensin dulda, dende la Guerra Civil y el maquis al servir d’abellugu a persiguíos políticos, y guarda una alcordanza imborrable nuna de les sos múltiples entraes, yá qu’ellí ta enterrada Olvido Otero González (1908-1938). Per El Sidrón pasaron munches persones a lo llargo de los años, pero en 1994 prodúxose’l descubrimientu per parte d’unos espeleólogos xixoneses d’unos güesos humanos que dieron un importante xiru a la conocencia de los nuesos antepasaos neandertales.Peer Reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Algoritmo clínico-patológico para establecer el diagnóstico diferencial entre rechazo celular agudo y hepatitis C recurrente en el trasplante hepático

Objetivo: El objetivo de nuestro estudio fue el desarrollar y validar un sistema de algoritmo diagnóstico basado en características clínicas y morfológicas con el fin de encontrar las diferencias entre hepatitis C recurrente (VHC) y rechazo celular agudo (RCA) en las biopsias de los pacientes trasplantados por VHC. Metodología: Se analizaron 288 biopsias hepáticas de 121 pacientes trasplantados por VHC. Se alcanzó un consenso diagnóstico para VHC recurrente y RCA entre clínicos y patólogos en 214 biopsias. Se tomó una muestra al azar de 114 biopsias hepáticas (cohorte de derivación), para formar el árbol de decisión diagnóstica, formado por las variables morfológicas obtenidas en el modelo de regresión logística y el tiempo desde el trasplante. Posteriormente se evaluó usando una muestra de 100 biopsias hepáticas (cohorte de validación). Resultados: La presencia de endotelitis junto con un tiempo desde el trasplante hepático de menos de 6 semanas excluyen definitivamente la presencia de VHC recurrente. Después de obtener el árbol de regresión, la precisión diagnóstica fue del 96% y 93% respectivamente para la cohorte de derivación y validación. Ambos casos superaron la precisión diagnóstica original del patólogo que fue del 91% (P < 0.05, para ambas situaciones) Conclusiones: Un modelo de regresión logística de las características morfológicas y clínicas en las biopsias hepáticas de los pacientes trasplantados por VHC puede ser útil para distinguir entre VHC recurrente y RCA. Aim: The aim of our study was develop and validate an algorithm system based on clinical and morphological features for finding the differences between recurrent hepatitis C virus (HCV) and acute cellular rejection (ACR) in liver biopsies of HCV transplanted patients. Methods: Two hundred and eighty-eight liver biopsies were analyzed from 121 patients transplanted for HCV. A diagnostic consensus was reached between clinicians and pathologists in 214 biopsies for the diagnosis of recurrent HCV or ACR. A random sample of 114 liver biopsies (derivation cohort) was taken to generate the diagnostic tree and was subsequently evaluated using the validation cohort in 100 liver biopsies by recursive partitioning analysis of morphological variables and time since transplantation. Results: The presence of endotheliitis together with a time of less than 6 weeks since LT definitely excluded recurrent HCV. After obtaining the regression tree, diagnostic accuracy was 96% and 93% in the derivation and validation cohort, respectively. Both cases surpassed the pathologist’s original diagnosis, which had a diagnostic accuracy of 91% (P < 0.05, for both comparisons). Conclusion: A recursive partitioning analysis of the morphological and clinical features in liver biopsies from HCV-transplanted patients may be useful for easily distinguishing between recurrent HCV and ACR

Evaluating the Link between BAFF System Gene Expression and Acute Rejection Development in Kidney Transplantation

B-cell activating factor (BAFF) system signaling is critical for B-cell homeostasis, effector functions, and tolerance maintenance in transplants, but it has not been studied in kidney transplant recipients (KTRs). The aim was to analyze the changes in BAFF system expression in KTRs with/without acute rejection (AR/NAR). The BAFF system expression was analyzed by qPCR in 40 KTRs. A meta-analysis of BAFF system expression and histological renal damage was identified by the Chronic Allograft Damage Index (CADI) and performed from the GEO database. Proliferation-inducing ligand (APRIL) expression increased at three- and six-months post-KT (p = 0.014 and p p = 0.038). BAFF expression remained stable in NAR-KTRs, but was increased in CADI concerning the No-CADI group at one year (p = 0.008). BCMA expression increased in the CADI group at one- (p = 0.001) and six-years post-KT (p = 0.024). At three months, the transmembrane activator and calcium modulator interactor (TACI) gene significantly elevated KTRs with DSAs (donor-specific antibody; p = 0.034). KTRs with DSAs significantly increase the B-cell activating factor receptor (R-BAFF; p = 0.021) and TACI (p = 0.018) between pre- and three-month post-KT. Changes in the expression of the BAFF system increase during post-KTR in the development of AR and chronic allograft damage, and could be an important pathological tool to detect and prevent kidney graft outcomes

GHEN, Grupo de Historia del Español Norteño

Sitio web del Grupo de Historia del Español Norteño. Consultado el 22/04/2019.El grupo de investigación GHEN, Grupo de Historia del Español Norteño, está formado por investigadores de diferentes centros y universidades, especializados en el estudio filológico del castellano medieval. La creación de dicho grupo responde a la ambición de desarrollar una línea común de investigación: las variedades castellanas septentrionales desde sus primeros testimonios escritos.Para ello, el grupo GHEN trabaja en la confección de un amplio corpus de representación del español norteño, el corpus CORHEN, Corpus Histórico del Español Norteño, así como en el análisis lingüístico de dichos testimonios, a fin de establecer una cronología y diatopía de los fenómenos lingüísticos del castellano en la etapa medieval.Peer reviewe