Genetic and Molecular Factors in Drug-Induced Liver Injury: A Review

The diagnosis of drug-induced liver injury (DILI) is challenging and based on complex diagnostic criteria. DILI falls into two main categories i) intrinsic 'dose-dependent' Type A reactions ii) 'idiosyncratic' or Type B reactions (which are usually not predictable). Idiosyncratic reactions can be immunoallergic (hypersensitivity), or metabolic, although overlap between categories can occur. The aim of this review is to summarise the general view of underlying mechanisms in DILI and to highlight individual risk factors for developing hepatotoxicity. Polymorphisms of bioactivation/ toxification pathways through CYP450 enzymes (Phase I), detoxification reactions (Phase II) and excretion/transport (Phase III) are explored together with immunological factors that might determine DILI. The importance of establishing a multidisciplinary and multi-centric network to promote the understanding and research in hepatotoxicity is underlined. Challenges such as genetic analyses for association studies and whole genome studies, pharmacogenetic testing and future approaches to study DILI are considered. Knowledge regarding these operational mechanisms could provide further insight for the prospective identification of susceptible patients at risk of developing drug-induced hepatotoxicity.

Programa de vigilància de les infeccions nosocomials als hospitals de Catalunya (Programa VINCat)

Infeccions nosocomials; Hospitals; Vigilància epidemiològicaNosocomial infections; Hospitals; Epidemiological surveillanceInfecciones nosocomiales; Hospitales; Vigilancia epidemiológicaVINCat és un programa del Servei Català de la Salut que estableix un sistema de vigilància unificat de les infeccions nosocomials als hospitals de Catalunya. La seva missió és contribuir a reduir les taxes d’aquestes infeccions mitjançant la vigilància epidemiològica activa i continuada. El programa es fonamenta en la tasca que porten a terme els professionals dels equips multidisciplinaris de control d’infecció dels hospitals catalans.VINCat is a program of the Catalan Health Service that establishes a unified surveillance system for nosocomial infections in hospitals in Catalonia. Its mission is to help reduce the rates of these infections through active and ongoing epidemiological surveillance. The program is based on the work carried out by the multidisciplinary teams of infection control of Catalan hospitals.VINCat es un programa del Servicio Catalán de la Salud que establece un sistema de vigilancia unificado de las infecciones nosocomiales en los hospitales de Cataluña. Su misión es contribuir a reducir las tasas de estas infecciones mediante la vigilancia epidemiológica activa y continuada. El programa se fundamenta en la tarea que llevan a cabo los profesionales de los equipos multidisciplinares de control de infección de los hospitales catalanes

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

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

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

Estudio de mezclas de disolventes orgánicos y trigliceridos de aceite de linaza o los ácidos grasos libres. II.- Aplicación a la viscosidad de las ecuaciones de Andrade, Krone, McAllister e Hildebrand

A regression study of Andrade, Krone, McAllister and Hildebrand equations with experimental data of viscosity of mixtures of triglycerides or free fatty acids and trichloroethylene, tetrachloroethylene and hexane was carried out. Temperature range studied was 278-313 K in steps of 5K.&lt;br /&gt; The results showed that the Hildebrand equation presents the best fit for all the viscosity data of the mixtures studied, tending towards a lineal or parabolic function of its parameters.&lt;br /&gt; Andrade and Krone equations presented acceptable fits for all mixtures studied except the fatty acids and hexane mixture. The McAllister equation was applicable only to mixtures with tetrachloroethylene.&lt;br&gt;&lt;br&gt;Se ha realizado el estudio de regresión de las ecuaciones de Andrade, Krone, McAllister e Hildebrand con datos experimentales de viscosidad de mezclas de triglicéridos o ácidos grasos libres con tricloroetileno, tetracloroetileno y hexano en el intervalo de temperaturas de 278 a 313 K cada 5 K.&lt;br /&gt; Los resultados obtenidos indican que el mejor ajuste de los datos experimentales de viscosidad lo presenta la ecuación de Hildebrand, buscándose una función lineal o parabólica con la fracción molar de sus dos parámetros.&lt;br /&gt; Las ecuaciones de Andrade y Krone presentan un ajuste aceptable para todas las mezclas estudiadas excepto para las de ácidos grasos en hexano y la ecuación de McAllister es únicamente aplicable a las mezclas con tetracloroetileno

Estudio de mezclas de disolventes orgánicos y triglicéridos de aceite de linaza o los ácidos grasos libres. I.- Volumen molar, refracción molar y viscosidad dinámica

Measurements of molar volume, refraction index and dynamic viscosity in mixtures of fatty acids or triglycerides and trichloroethylene, tetrachloroethylene and hexane were realized. Temperature range studied was 278-313 K each 5 K. The relationship between molar volume and molar fraction show high correlation coefficient In fatty acids with trichloroethylene and tetrachloroethylene mixtures. On the other hand, hexane mixtures show little contractions of molar volume at low molar fractions. Triglyceride mixtures present important deviations with regard to the ideality of the molar volume. The adjusts obtained for the molar volume values versus temperature are acceptable, calculating the coefficients of thermal expansion of the studied mixtures. Equally, the adjust of the experimental results of viscosity for two prediction equations are studied: one of additive type and the other of parabolic type.Se han realizado medidas del volumen molar, índice de refracción y viscosidad dinámica en el intervalo de temperatura de 278 K a 313 K cada 5 K, a mezclas de ácidos grasos o triglicéridos con tricloroetileno, tetracloroetileno y hexano. Las mezclas de ácidos grasos con tricloroetileno y tetracloroetileno, presentan unos altos coeficientes de correlación para los valores del volumen molar frente a la fracción molar, mientras que las mezclas con hexano, a fracciones molares bajas, manifiestan una pequeña contracción del volumen molar. Las mezclas de triglicéridos presentan importantes desviaciones con respecto a la Idealidad del volumen molar. Los ajustes obtenidos para los valores del volumen molar frente a la temperatura son aceptables, determinándose los valores del coeficiente de dilatación volumétrica a presión constante de las mezclas estudiadas. Igualmente se ha estudiado el ajuste de los resultados experimentales de viscosidad a dos ecuaciones de predicción: una del tipo aditiva y otra del tipo parabólico

A Provegetarian Food Pattern Emphasizing Preference for Healthy Plant-Derived Foods Reduces the Risk of Overweight/Obesity in the SUN Cohort

Provegetarian diets (i.e., preference for plant-derived foods but not exclusion of animal foods) have been associated with a reduced risk of long-term weight gain and could be more easily embraced than strict vegetarian diets. However, not all plant-derived foods are equally healthy. In the "Seguimiento Universidad de Navarra" (SUN) cohort, we prospectively evaluated the association between different provegetarian food patterns and the incidence of overweight/obesity in 11,554 participants with initial body mass index <25 kg/m2. A provegetarian food pattern (FP) was built by assigning positive scores to plant foods and reverse scores to animal foods. A healthful and an unhealthful provegetarian FP, which distinguished between healthy (fruits/vegetables/whole grains/nuts/legumes/olive oil/coffee) and less-healthy plant foods (fruit juices/potatoes/refined grains/pastries/sugary beverages), were also built. A total of 2320 new cases of overweight or obesity were identified after a median follow-up of 10.3 years. Higher baseline conformity with the overall provegetarian FP was inversely associated with overweight/obesity (HR comparing extreme quintiles: 0.85; 95% CI: 0.75 to 0.96; p-trend: 0.014). This association was stronger for the healthful FP (HR: 0.78; 95% CI: 0.67 to 0.90; p-trend: <0.001) and was not apparent for the unhealthful FP (HR: 1.07; 95% CI: 0.92 to 1.23; p-trend: 0.551). In a large prospective cohort of relatively young adults, better conformity with a healthy provegetarian diet was associated with a reduced long-term risk of overweight/obesity, whereas no consistent trend was found for a FP that emphasized less-healthy plant foods