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Background: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. Methods: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. Conclusion: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Resumen Introduccion La reconstruccion esofagica es un proceso quirurgico tecnicamente muy complejo, gravado por una importante morbilidad. Clasicamente se han utilizado la gastroplastia y la coloplastia, aunque la yeyunoplastia ya fue descrita por Roux en 1907. Parece demostrado que la plastia de yeyuno libre es una muy buena opcion en el tratamiento de la enfermedad del esofago cervical, pero no esta tan claro el papel de la yeyunoplastia supercharged en la reconstruccion del esofago toracico. El objetivo de este estudio es el analisis de las reconstrucciones esofagicas realizadas en nuestra unidad y que precisaron de un injerto de yeyuno. Metodos Estudio retrospectivo de las reconstrucciones esofagicas realizadas con yeyunoplastias en nuestra unidad entre enero de 2011 y diciembre de 2019. Se analizan datos epidemiologicos, indicaciones, tecnica quirurgica y morbimortalidad. Resultados Se realizaron 67 procedimientos quirurgicos de reconstruccion esofagica compleja de los que 10 fueron yeyunoplastias: 5 yeyunos libres en esofago cervical y 5 supercharged en esofago toracico con abordaje transesternal. La morbilidad, mortalidad, estancia media y tiempo de retirada de la alimentacion enteral fueron menores en los yeyunos libres que en los supercharged. Conclusiones En nuestro grupo la yeyunoplastia supercharged es la ultima opcion para la reconstruccion del esofago toracico; el acceso por esternotomia media nos permite un excelente abordaje del mediastino anterior y los vasos mamarios internos. El yeyuno libre seria la primera eleccion —con indemnidad del resto de esofago— en la reconstruccion del esofago cervical.

Statement of problem. Polyetheretherketone (PEEK) has been advocated to replace metal components in dentistry. Although PEEK is a high-performance polymer with a white color, adequate biological response, and resistance to fracture, data to support PEEK as an alternative material for implant abutments are lacking. Purpose. The purpose of this in vitro study was to assess the mechanical and functional properties of PEEK implant abutments as a nonmetallic alternative to titanium abutments, which presents esthetic limitations and greater difficulty to customize clinically. Material and methods. Implant abutments manufactured by using PEEK (n=24) or titanium grade 5 (n=24) were attached to MIS Implants type M4 3.75×16 mm with an internal screw tightened to 25 Ncm. Screw loosening and microleakage was assessed by submersion in a 2% methylene blue solution for 48 hours at 37 C. Both groups were compared with and without applying dynamic loading; fatigue testing was performed following the International Organization for Standardization (ISO) 14801:2016 standard. All specimens were observed under a stereomicroscope at ×8 magnification. Statistically significant differences among the PEEK and titanium implant abutments were tested with 2-factor ANOVA and the chi-square analysis for nonpaired and paired data, respectively (a=.05). Results. The implant abutments made of titanium were better in all mechanical tests. The torque loss of titanium abutments was approximately 10%, while PEEK showed a significantly higher (P

Background and Purpose: Mechanical thrombectomy (MT) in ischemic stroke patients with poor prestroke conditions remains controversial. We aimed to analyze the frequency of previously disabled patients treated with MT in clinical practice, the safety and clinical response to MT of patients with preexisting disability, and the disabled patient characteristics associated with a better response to MT. Methods: We studied all consecutive patients with anterior circulation occlusion treated with MT from January 2017 to December 2019 included in the Codi Ictus Catalunya registry—a government-mandated, prospective, hospital-based data set. Prestroke disability was defined as modified Rankin Scale score 2 or 3. Functional outcome at 90 days was centrally assessed by a blinded evaluator of the Catalan Stroke Program. Favorable outcome (to return at least to prestroke modified Rankin Scale at 90 days) and safety and secondary outcomes were compared with patients without previous disability. Logistic regression analysis was used to assess the association between prestroke disability and outcomes and to identify a disabled patient profile with favorable outcome after MT. Results: Of 2487 patients included in the study, 409 (17.1%) had prestroke disability (313 modified Rankin Scale score 2 and 96 modified Rankin Scale score 3). After adjustment for covariates, prestroke disability was not associated with a lower chance of achieving favorable outcome at 90 days (24% versus 30%; odds ratio, 0.79 [0.57–1.08]), whereas it was independently associated with a higher risk of symptomatic intracranial hemorrhage (5% versus 3%; odds ratio, 2.04 [1.11–3.72]) and long-term mortality (31% versus 18%; odds ratio, 1.74 [1.27–2.39]) compared with patients without disability. Prestroke disabled patients without diabetes, Alberta Stroke Program Early CT Score >8 and National Institutes of Health Stroke Scale score Conclusions: Despite a higher mortality and risk of symptomatic intracranial hemorrhage, prestroke-disabled patients return as often as independent patients to their prestroke level of function, especially those nondiabetic patients with favorable early ischemic signs profile. These data support a potential benefit of MT in patients with previous mild or moderate disability after large anterior vessel occlusion stroke.

The purpose of this article is to bring attention to the potential importance of extracellular vesicles (EVs) of microbial origin in the production of fermented foods. We anticipate that understanding the role of the EVs in these processes will contribute to the development of new tools in food biotechnology. The reasons that lead us to make such claim are given as: (i) the production of EVs is a widespread feature in all domains of life; (ii) a growing number of functions are being identified for EVs, the most prominent one being biological communication; (iii) the study of EVs has become important for the understanding of biological processes and as a diagnostic and therapeutic tool in the biomedical sciences; (iv) many fermented foods require the activity of microbial consortia involving multiple species; (v) an increasing number of studies are showing that interactions between microorganisms may be relevant in the development of fermentation processes and would therefore be of biotechnological interest (Curiel et al., 2017; Tronchoni et al., 2017; Conacher et al., 2019)., Author’s work on EVs is funded by the Spanish Government through grants PID2019‐105159RB‐I00 and BES‐2016‐077557 (training contract for AM). JT was funded by FGCSIC by the COMFUTURO program.

Central nervous system (CNS) infections such as meningitis and encephalitis are medical emergencies that require rapid diagnosis of the causative pathogen to guide early and adequate treatment since a delay in implementing an adequate antimicrobial therapy can lead to death. The current microbiological diagnostic methods based on culture or antigen detection have important limitations in their capacity to accurately identify the different potential pathogens causing CNS and, in the time, to obtaining results. Rapid syndromic molecular arrays have been developed. The main advantage of using a meningoencephalitis panel based in a multiplex test is that includes bacteria, viruses and fungi, covering the most prevalent microorganisms causing meningitis and encephalitis and the turn-around time is circa 1h. The use of these multiplex-PCR based tools is reviewed and the advantages and disadvantages of this technique are discussed.

Aims TASK-1 (K2P3.1) two-pore domain potassium channels are atrial-specific and significantly upregulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In the present study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF. Methods and results Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 d of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 d of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram. Conclusions Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients. Translational perspective Pharmacological suppression of atrial TASK 1 potassium currents prolongs atrial refractoriness with no effects on ventricular repolarization, resulting in atrial-specific class III antiarrhythmic effects. In our preclinical pilot study the respiratory stimulant doxapram was successfully administered for cardioversion of acute AF as well as rhythm control of persistent AF in a clinically relevant porcine animal model.

Introduction Classic cardiovascular risk factors do not explain all the cardiovascular events. Obstructive sleep apnoea (OSA) has been proposed as a potential and prevalent cardiovascular risk factor. Our study aimed to describe the prevalence of OSA in a middle-aged cohort with mild–moderate cardiovascular risk and evaluate its association with atherosclerotic disease. Methods This is an observational cross-sectional ancillary study of the ILERVAS project which was aimed to study subclinical arterial disease in a cohort with mild–moderate cardiovascular risk. In a sample of consecutive subjects, we performed a sleep study and evaluate OSA prevalence and its association with carotid and femoral atheroma plaques and atherosclerotic burden. Results Overall, 966 subjects with a median age of 57 years (25–75th percentile; 52–62) and a body mass index (BMI) of 28.5 kg/m2 (25.6–31.6) were included. Of these, 72.6% (69.7%–75.3%) had OSA (apnoea–hypopnoea index (AHI) ≥ 5/h); 35.7% (32.8%–38.8%) had mild OSA (AHI 5–14.9/h) and 36.9% (33.9%–39.9%) had moderate/severe OSA (AHI ≥ 15/h). Mean oxygen saturation and the percentage of time with oxygen saturation Conclusions This study confirms a high prevalence of OSA in patients with mild–moderate cardiovascular risk and shows an association between atherosclerotic burden, total and femoral plaque with CT90 and mean oxygen saturation, suggesting the importance of OSA-related hypoxaemia in the induction of atherosclerotic disease.

Background and study aims Data from Japanese series show that surface morphology of laterally spreading tumors (LST) in the colon identifies lesions with different incidence and pattern of submucosal invasion. Such data from western countries are scarce. We compared clinical and histological features of LST in a western country and an eastern country, with special interest on mucosal invasiveness of LST, and investigated the effect of clinical factors on invasiveness in both countries. Patients and methods Patients with LST lesions ≥20 mm were included from a multicenter prospective registry in Spain and from a retrospective registry from the National Cancer Center Hospital East, Japan. The primary outcome was the presence of submucosal invasion in LST. The secondary outcome was the presence of high-risk histology, defined as high-grade dysplasia or submucosal invasion. Results We evaluated 1102 patients in Spain and 663 in Japan. Morphological and histological characteristics differed. The prevalence of submucosal invasion in Japan was six-fold the prevalence in Spain (Prevalence Ratio PR = 5.66; 95%CI: 3.96, 8.08), and the prevalence of high-risk histology was 1.5 higher (PR = 1.44; 95%CI: 1.31, 1.58). Compared to the granular homogeneous type and adjusted by clinical features, granular mixed, flat elevated, and pseudo-depressed types were associated with higher odds of submucosal invasion in Japan, whereas only the pseudo-depressed type showed higher risk in Spain. Regarding high-risk histology, both granular mixed and pseudo-depressed were associated with higher odds in Japan, compared with only the granular mixed type in Spain. Conclusion This study reveals differences in location, morphology and invasiveness of LST in an eastern and a western cohort.

INTRODUCTION The aim of this study is to analyze the expression of the main oxidant scavenger superoxide dismutase (EC-SOD), its main binding protein Fibulin-5 and several oxidative and nitrosative-derived products in the lung of COPD patients and controls. MATERIALS AND METHODS Lung tissue samples from 19 COPD patients and 20 control subjects were analyzed. The architecture of elastic fibres was assessed by light and electron microscope histochemical techniques, and levels of EC-SOD and fibulin-5 were analyzed by immunohistochemistry and RT-PCR. The impact of oxidative stress on the extracellular matrix was estimated by immunolocalization of 4-hydroxynonenal (4-HNE), malondialdehyde (MDA) and 3-nitrotyrosine (3-NYT) adducts. RESULTS Alveolar walls of COPD patients exhibited abnormal accumulations of collapsing elastic fibres, showing a pierced pattern in the amorphous component. The semiquantitative analysis revealed that COPD patients have a significantly reduced expression of both EC-SOD and fibulin-5 (0.59±0.64 and 0.62±0.61, respectively) in alveolar, bronchiolar and arteriolar walls compared to control subjects (1.39±0.63 and 1.55±0.52, respectively, p

Background and objective Axial spondyloarthritis is an immune-mediated disease with a high cost, diagnostic delay and associated complications that makes it a particularly important condition. This work aims to establish a certification standard (SpACE Project) for monographic consultations in its diagnosis and treatment. Materials and methods Qualitative study of consensus, through the technique of the nominal group. First, a pragmatic review of the literature was carried out. Second, professionals involved throughout the care process (rheumatology, ophthalmology, gastroenterology, traumatology, family medicine, physical therapy, and nursing) were included. Results Thirty-seven possible standards were extracted from the pragmatic review of the literature. During the consensus phase only those standards with high feasibility and importance in the care process were prioritized. Finally, the group of 26 experts agreed on the inclusion of 14 standards. Discussion and conclusions SpACE is a consensus-based certification standard that seeks to improve health outcomes and more integrated care.

Background Current scientific evidence on the effect of Extracorporeal Shock Wave Therapy (ESWT) as adjunctive treatment for postburn scars is scarce. However preliminary evidence, indicates it might prove a useful tool. Materials and methods A prospective, randomized, controlled study was conducted from February 2017 to February 2019. Patients with postburn scars were divided into two groups with twenty patients per group. The control group received the standard treatment for postburn scars. The ESWT group received the standard treatment and treatment of postburn scars with ESWT 512 impulses of 0.15 mJ/mm2 in each session, twice per week for 4 weeks. We assessed the appearance of scar with the Vancouver Scar Scale (VSS), pruritus and pain with Visual Analog Scale (VAS) before the start of the treatment and at 2 weeks and 5 months after the treatment. Results Both groups showed improvements in all variables through the study. However, these improvements were only statistically significant for the VSS at the 6th month for the control group and VSS and VAS pain and pruritus for the ESWT group. Nonetheless the results failed to show statistically significant differences between the ESWT and the control group neither at two weeks after treatment nor at 5 months after treatment. Conclusion Our study questions the relevance of ESWT as adjunctive treatment for postburn scars as far as outward appearance, pain and pruritus as end-results are concern. Nonetheless, further studies are required to accurately assess the potential benefits of ESWT as an adjunctive treatment for postburn scars.

Introduction and objectives Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. Methods This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire , adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses. Results Total polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale. Conclusions An inverse association was found between consumption of the ‘other polyphenols’ class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case.

Este artículo de investigación se encuentra disponible en la siguiente URL: https://www.revistanefrologia.com/es-pdf-S0211699521001612 En este artículo de investigación también participan: Lorenzo Fácila Rubio, Javier Gamarra Ortiz, Jose A. García-Donaire, Lisardo García-Matarín, Sílvia Gràcia Garcia, María Isabel Gutiérrez Pérez, Julio Hernández Moreno, Pilar Mazón Ramos, Rosario Montañés Bermudez, Manuel Muñoz Torres, Pedro de Pablos-Velasco, Manuel Pérez-Maraver, Carmen Suárez Fernández, Salvador Tranche Iparraguirre y José Luis Górriz. La enfermedad renal crónica (ERC) es un importante problema de salud pública a nivel mun-dial afectando a más del 10% de la población espa˜nola. Se asocia a elevada comorbilidad,mal pronóstico, así como a un gran consumo de recursos en el sistema sanitario. Desde lapublicación del último documento de consenso sobre ERC publicado hace siete a˜nos, hansido escasas las evidencias y los ensayos clínicos que hayan mostrado nuevas estrategiasen el diagnóstico y tratamiento de la ERC, con excepción de los nuevos ensayos en la enfer-medad renal diabética. Esta situación ha condicionado que no se hayan actualizado lasguías internacionales específicas de ERC. Esta rigidez y actitud conservadora de las guíasno debe impedir la publicación de actualizaciones en el conocimiento en algunos aspectos, que pueden ser clave en la detección y manejo del paciente con ERC. En este documento, elaborado en conjunto por diez sociedades científicas, se muestra una actualización sobre conceptos, aclaraciones, criterios diagnósticos, estrategias de remisión y nuevas opciones terapéuticas. Se han revisado las evidencias y los principales estudios publicados en estos aspectos de la ERC, considerándose más bien un documento de información sobre esta patología. El documento incluye una actualización sobre la detección de la ERC, factores de riesgo, cribado, definición de progresión renal, actualización en los criterios de remisión con nuevas sugerencias en la población anciana, monitorización y estrategias de prevención de la ERC, manejo de comorbilidades asociadas, especialmente en diabetes mellitus, funciones del médico de Atención Primaria en el manejo de la ERC y qué no hacer en Nefrología. El objetivo del documento es que sirva de ayuda en el manejo multidisciplinar del paciente con ERC basado en las recomendaciones y conocimientos actuales. Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific societies, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options. The evidence and the main studies published on these aspects of CKD have been revie- wed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabe- tes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology. The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge.

Objective To identify the prevalence of pre-pregnancy overweight/obesity in pregnant women and its relationship with socio-demographic factors and to describe the maternal and perinatal outcomes in a Barcelona hospital (Spain). Method A descriptive cross-association study, with retrospective data collection, was performed Barcelona Hospital. The data of 5447 pregnant women who delivered at >=23 weeks of gestation were included. Body Mass Index (BMI) data were categorised into World Health Organization classifications. p values Results The prevalence of pre-pregnancy obesity was 8.4% and 18.9% for overweight. Gestational diabetes was more frequent in pre-pregnancy overweight/obesity (OR 1.92: 95% CI 1.54–2.40 and OR 3.34: 95% CI 2.57–4.33), as were preeclampsia (OR 2.08: 95% CI 1.55–2.79 and OR 3.35: 95% CI 2.38–4.71), induction of labour (OR 1.19: 95% CI 1.02–1.38 and OR 1.94: 95% CI 1.57–2.10), caesarean section (OR 1.41: 95% CI 1.21–1.65 and OR 2.68: 95% CI 2.18–3.29), prematurity (OR 1.28: 95% CI 1–1.65 and OR 1.79: 95% CI 1.32–2.44) and macrosomia (OR 1.87: 95% CI 1.43–2.46 and OR 2.03: 95% CI 1.40–2.93). Conclusions One in four pregnant women had pre-pregnancy overweight or obesity. This study shows the relationship between pre-pregnancy overweight or obesity with adverse maternal and perinatal outcomes.

Background -- The definition of population-specific outcomes is an essential precondition for the implementation of value-based health care. We developed a minimum standard outcome set for overall adult health (OAH) to facilitate the implementation of value-based health care in tracking, comparing, and improving overall health care outcomes of adults across multiple conditions, which would be of particular relevance for primary care and public health populations. Methods -- The International Consortium for Health Outcomes Measurement (ICHOM) convened an international panel (patients, clinicians, and topic experts). Following the development of a conceptual framework, a modified Delphi method (supported by public consultations) was implemented to identify, in sequence, the relevant domains, the best instruments for measuring them, the timing of measurement, and the relevant adjustment variables. Findings -- Outcomes were identified in relation to overall health status and the domains of physical, mental, and social health. Three instruments covering these domains were identified: PROMIS Scale v1.2—Global Health (10 items), WHO Wellbeing Index (5 items), and the WHO Disability Assessment Schedule 2.0 (12 items). Case-mix variables included a range of sociodemographic and biometric measures. Yearly measurement was proposed for all outcomes and most case-mix variables. Interpretation -- The ICHOM OAH Standard Set has been developed through consensus-based methods based on predefined criteria following high standards for the identification and selection of high-quality measures The involvements of a wide range of stakeholders supports the acceptability of the set, which is readily available for use and feasibility testing in clinical settings.

Background: Attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are child-onset neurodevelopmental disorders frequently accompanied by cognitive difficulties. In the current study, we aim to examine the genetic overlap between ADHD and ASD and cognitive measures of working memory (WM) and attention performance among schoolchildren using a polygenic risk approach. Methods: A total of 1667 children from a population-based cohort aged 7-11 years with data available on genetics and cognition were included in the analyses. Polygenic risk scores (PRS) were calculated for ADHD and ASD using results from the largest GWAS to date (N = 55 374 and N = 46 351, respectively). The cognitive outcomes included verbal and numerical WM and the standard error of hit reaction time (HRTSE) as a measure of attention performance. These outcomes were repeatedly assessed over 1-year period using computerized version of the Attention Network Test and n-back task. Associations were estimated using linear mixed-effects models. Results: Higher polygenic risk for ADHD was associated with lower WM performance at baseline time but not over time. These findings remained significant after adjusting by multiple testing and excluding individuals with an ADHD diagnosis but were limited to boys. PRS for ASD was only nominally associated with an increased improvement on verbal WM over time, although this association did not survive multiple testing correction. No associations were observed for HRTSE. Conclusions: Common genetic variants related to ADHD may contribute to worse WM performance among schoolchildren from the general population but not to the subsequent cognitive-developmental trajectory assessed over 1-year period. This work was supported by the European Research Council under the Grant Agreement number 268479 - the BREATHE project. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the ‘Centro de Excelencia Severo Ochoa 2019-2023’ Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. S.Alemany and N.Vilor-Tejedor are funded by Juan de la Cierva Programme (Ministry of Science, Innovation and Universities - Spanish State Research Agency, ref. IJCI-2017-34068, and ref. FJC-2018-038085-I).

International audience; Thymic epithelial tumors are rare neoplastic proliferations of thymic epithelial cells. The aggressiveness of these malignancies increases as higher is the histologic subtype, being thymic carcinoma the most aggressive subtype, with a greater tendency to metastatic spread. In metastatic setting, there is no standard treatment after progression on platinum-based chemotherapy. In this scenario, monotherapy treatment either with lenvatinib, a multi-tyrosine kinase inhibitor with antiangiogenic properties, or pembrolizumab, an immune-checkpoint inhibitor, has reported clinical activity. Potential combination of both agents may have synergistic activity as reported in other cancer types. PECATI trial is a single-arm, investigator-initiated phase II study aiming to assess the activity and safety of the combination of lenvatinib and pembrolizumab in 43 patients with advanced B3-thymoma or thymic carcinoma who progressed on or after at least one previous line of platinum-based chemotherapy. The primary endpoint of the trial is 5-month progression-free survival rate and the secondary endpoints include overall response rate, duration of response, and overall survival.

Este artículo de investigación se encuentra disponible en la siguiente URL: https://www.revistanefrologia.com/es-pdf-S0211699521001570 En este artículo de investigación también participan: Ramón A. García-Trabanino, Miguel Hueso, Pedro Trinidad, Aquiles Jara, Mónica Furlano, Rosana Gelpi, Ana Vila-Santandreu, César A. Restrepo, Maya Sánchez-Baya, Carolt Arana, Marián Goicoechea, Verónica Coll, Julián Segura, Orlando Gutiérrez, Kamyar Kalantar-Zadeh, Emilio Sánchez y Alejandro Ferreiro.

Resumen Introduccion El cruce duodenal (CD) se considera una de las tecnicas mas efectivas para lograr la perdida de peso y disminuir las comorbilidades en pacientes con obesidad morbida. Material y metodos Estudio descriptivo unicentrico en el que se analizaron 224 pacientes intervenidos de CD directo con ligadura de la arteria gastrica derecha laparoscopico. El objetivo fue describir los resultados ponderales, resolucion de comorbilidades, suplementacion nutricional y complicaciones postquirurgicas a dos, cinco y 10 anos. Resultados La edad media de la cohorte fue de 49,3 (23-65) anos, el peso e indice de masa corporal (IMC) medio fueron de 131,8(20)kg y 49,8(5)kg/m2. El porcentaje de exceso de peso perdido a dos, cinco y 10 anos fue de 80,6(15)%, 69,3(18)%, 67,4(18)%, respectivamente. La remision completa de la diabetes a dos y cinco anos se evidencio en 35 (85,4%) y 27 (70,4%) pacientes. En el postoperatorio inmediato, la tasa de complicaciones Clavien-Dindo ≥ III fue en 15 pacientes (6,7%) y la mortalidad a 30 y 90 dias fue de uno (0,4%) y dos (0,9%) pacientes. La necesidad de cirugia revisional se realizo en dos pacientes (0,9%). El 80% de los pacientes requirio en algun momento suplementacion nutricional extra a partir de los dos anos de la cirugia. Conclusiones El CD directo es una tecnica con un bajo indice de complicaciones quirurgicas en pacientes con un IMC entre 45 y 55 kg/m2. El control metabolico y la perdida ponderal es sostenida con un bajo indice de cirugia revisional. Aun asi, conlleva la necesidad de un seguimiento postquirurgico estrecho para la valoracion de suplementacion nutricional.

Atrial fibrillation; Oral anticoagulants; Adherence; Persistence; Electronic health records Fibrilación auricular; Tratamiento anticoagulante oral; Adherencia; Persistencia; Registros electrónicos de salud Fibril·lació auricular; Tractament anticoagulant oral; Adherència; Persistència; Registres electrònics de salut Objective: We aimed to describe sociodemographic, comorbidities, co-medication and risk of thromboembolic events and bleeding in patients with NVAF initiating oral anticoagulants (OAC) for stroke prevention, and to estimate adherence and persistence to OAC. Setting: Primary Health Care (PHC) in the Catalan Health Institute (ICS), Catalunya, Spain. Participants: All NVAF adult patients initiating OAC for stroke prevention in August 2013---December 2015. Methods: Population-based cohort study. Persistence was measured in patients initiating OAC in August 2013---December 2014. Data source: SIDIAP, which captures electronic health records from PHC in the (ICS), covering approximately 5.8 million people. Results: 51,690 NVAF patients initiated OAC; 47,197 (91.3%) were naive to OAC and 32,404 (62.7%) initiated acenocoumarol. Mean age was 72.8 years (SD 12.3) and 49.4% were women. Platelet-aggregation inhibitors were taken by 9105 (17.6%) of the patients. Persistence and adherence were estimated up to the end of follow-up. For 22,075 patients, persistence was higher among the non-naive patients [n = 258 (61.7%)] than among the naive [n = 11,502 (53.1%)]. Adherence was estimated for patients initiating DOAC and it was similar in naive and non-naive patients. Among the naive to DOAC treatment, those starting rivaroxaban showed a highest proportion [(n = 360 (80.1%)] of good adherence at implementation (MPR > 80%) while patients starting dabigatran were less adherent [n = 203 (47.8%)]. Conclusions: Acenocoumarol was the most frequently prescribed OAC as first therapy in NVAF patients. Non-naive to DOAC showed better persistence than naive. Rivaroxaban showed higher proportion of adherent patients during the implementation phase than apixaban and dabigatran the lowest. Objetivo: Describir datos sociodemográficos, comorbilidades, comedicaciones y riesgo de eventos tromboembólicos y hemorrágicos de los pacientes con fibrilación auricular no valvular (FANV) que inician tratamiento anticoagulante por vía oral (TAO) para prevención del ictus. Estimar adherencia y persistencia al TAO. Emplazamiento: Atención primaria (AP) del Instituto Catalán de Salud (ICS), Cataluña, España. Participantes: Adultos con FANV que inician TAO para prevención de ictus entre agosto del 2013 y diciembre del 2015. Métodos: Estudio de cohortes de base poblacional. Adherencia y persistencia se midieron en pacientes que iniciaban TAO entre agosto del 2013 y diciembre del 2014. Fuente de datos: SIDIAP, base de datos procedentes de registros electrónicos de AP del ICS, que cubre aproximadamente una población de 5,8 millones de personas. Resultados: Cincuenta y un mil seiscientos noventa pacientes con FANV iniciaron TAO, 47.197 (91,3%) eran naïve al TAO y 32.404 (62,7%) iniciaron acenocumarol. Su edad media era 72,8 años (DE 12,3) y el 49,4% eran mujeres; 90105 (17,6%) recibían tratamiento antiagregante plaquetario. Persistencia y adherencia se estimaron hasta el final del seguimiento. La persistencia a anticoagulantes orales directos (ACOD) fue mayor en no naïve que en naïve (61,7% vs. 53,1%). La adherencia a ACOD fue similar en los 2 grupos. Entre los naïve, los pacientes que iniciaban rivaroxabán (80,1%) mostraron mayor adherencia en la implementación (MPR > 80%), mientras que los que iniciaban dabigatrán fueron menos adherentes (47,8%). Conclusiones: Acenocumarol fue el anticoagulante más prescrito. Los pacientes no naïve mostraron mejor persistencia al tratamiento que los naïve. Rivaroxabán mostró mayores tasas de adherencia que apixabán y dabigatrán, las menores.

Background & Aims To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). Methods We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. Results One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. Conclusions A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. Lay summary Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.

Background More than 20% of hospitalized patients with COVID-19 demonstrate ARDS requiring ICU admission. The long-term respiratory sequelae in such patients remain unclear. Research Question What are the major long-term pulmonary sequelae in critical patients who survive COVID-19? Study Design and Methods Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated 3 months after hospitalization discharge. The follow-up comprised symptom and quality of life, anxiety and depression questionnaires, pulmonary function tests, exercise test (6-min walking test [6MWT]), and chest CT imaging. Results One hundred twenty-five patients admitted to the ICU with ARDS secondary to COVID-19 were recruited between March and June 2020. At the 3-month follow-up, 62 patients were available for pulmonary evaluation. The most frequent symptoms were dyspnea (46.7%) and cough (34.4%). Eighty-two percent of patients showed a lung diffusing capacity of less than 80%. The median distance in the 6MWT was 400 m (interquartile range, 362-440 m). CT scans showed abnormal results in 70.2% of patients, demonstrating reticular lesions in 49.1% and fibrotic patterns in 21.1%. Patients with more severe alterations on chest CT scan showed worse pulmonary function and presented more degrees of desaturation in the 6MWT. Factors associated with the severity of lung damage on chest CT scan were age and length of invasive mechanical ventilation during the ICU stay. Interpretation Three months after hospital discharge, pulmonary structural abnormalities and functional impairment are highly prevalent in patients with ARDS secondary to COVID-19 who required an ICU stay. Pulmonary evaluation should be considered for all critical COVID-19 survivors 3 months after discharge.

Background Despite atezolizumab and bevacizumab (A + B) is currently the first‐line treatment for hepatocellular carcinoma (HCC) patients, some patients will not be adequate for this combination. In the setting of sorafenib some adverse events have been proposed as prognostic factors. Objective To characterize the early diarrhoea development as prognostic factor in 344 HCC patients. Methods The development of early diarrhoea in sorafenib treatment defined as patients who developed diarrhoea and needed dose modification within the first 60 days of treatment (e‐diarrhoea) and 3‐grouping variables were analysed: Patients with e‐diarrhoea, patients who developed diarrhoea after the first 60 days of treatment (L‐diarrhoea) and patients that never developed diarrhoea (never diarrhoea). Results The median overall survival in sorafenib treated patients was significantly different across groups (6.8 months for e‐diarrhoea, 26.7 months for L‐diarrhoea and 13.3 months for never‐diarrhoea). The emergence of e‐diarrhoea was associated with poor outcomes (hazard ratio [HR] 1.84 [95%CI 1.15–2.95]), while there was no increased/decreased risk of dismal evolution in patients with L‐diarrhoea (HR 0.66 [95%CI 0.42–1.03]). Conclusion The emergence of e‐diarrhoea in HCC patients treated with sorafenib is an early predictor of dismal evolution under this therapy. Thus, prompt identification of these non‐responders may be useful for an early switch to second‐line therapies., Key Summary Established knowledge on this subject Diarrhoea is a frequent adverse event of sorafenib and its emergence has been associated to better outcomes. What are the significant and/or new findings of this study? Early diarrhoea (e‐diarrhoea) in hepatocellular carcinoma patients treated with sorafenib is an early predictor of dismal evolution.Diarrhoea under sorafenib should not be taken as a predictive parameter of lack of benefit.E‐diarrhoea could be used as clinical biomarker for switching to second‐line therapies.

Background A description of individuals with SARS-CoV-2 infection comparing the first and second waves could help adapt health services to manage this highly transmissible infection. Objective We aimed to describe the epidemiology of individuals with suspected SARS-CoV-2 infection, and the characteristics of patients with a positive test comparing the first and second waves in Catalonia, Spain. Methods This study had 2 stages. First, we analyzed daily updated data on SARS-CoV-2 infection in individuals from Girona (Catalonia). Second, we compared 2 retrospective cohorts of patients with a positive reverse-transcription polymerase chain reaction or rapid antigen test for SARS-CoV-2. The severity of patients with a positive test was defined by their admission to hospital, admission to intermediate respiratory care, admission to the intensive care unit, or death. The first wave was from March 1, 2020, to June 24, 2020, and the second wave was from June 25, 2020, to December 8, 2020. Results The numbers of tests and cases were lower in the first wave than in the second wave (26,096 tests and 3140 cases in the first wave versus 140,332 tests and 11,800 cases in the second wave), but the percentage of positive results was higher in the first wave than in the second wave (12.0% versus 8.4%). Among individuals with a positive diagnostic test, 818 needed hospitalization in the first wave and 680 in the second; however, the percentage of hospitalized individuals was higher in the first wave than in the second wave (26.1% versus 5.8%). The group that was not admitted to hospital included older people and those with a higher percentage of comorbidities in the first wave, whereas the characteristics of the groups admitted to hospital were more alike. Conclusions Screening systems for SARS-CoV-2 infection were scarce during the first wave, but were more adequate during the second wave, reflecting the usefulness of surveillance systems to detect a high number of asymptomatic infected individuals and their contacts, to help control this pandemic. The characteristics of individuals with SARS-CoV-2 infection in the first and second waves differed substantially; individuals in the first wave were older and had a worse health condition.

Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimize the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluna with the aim of establishing recommendations for the selection of the fecal microbiota donor.

Resumen Introduccion La cirugia robotica ha demostrado su eficacia en ciertos procedimientos quirurgicos. Sin embargo, en cirugia hepatica y pancreatica (HBP) su uso es todavia poco frecuente. Se presenta la experiencia inicial en cirugia robotica HBP de una unidad especializada en un hospital de tercer nivel. Metodo Se han estudiado en forma prospectiva los resultados de los pacientes intervenidos de cirugia HBP robotica entre abril de 2018 y octubre de 2020. Los datos analizados corresponden a datos demograficos, tecnicas quirurgicas realizadas y morbimortalidad asociada. Resultados Se intervinieron 64 pacientes, sometidos a 35 hepatectomias (mayores [6,7%], anatomicas [52,9%], limitadas [34,4%], quistectomias [3%] y marsupializaciones [3%]) y 29 pancreatectomias/resecciones duodenales (distales [48,2%], centrales [6,9%], cefalicas [13,8%], enucleaciones [24,1%], ampulectomias [3,5%] y resecciones duodenales [3,5%]). En cirugia hepatica el tiempo operatorio medio fue de 204,4 minutos (100-265 min), la mediana de complicaciones postoperatorias segun la escala de Clavien-Dindo fue de uno (1-4), las perdidas hematicas medias de 166,7 mL (100-300 mL), no existio conversion y la estancia postoperatoria media de cuatro dias (2-14 dias). En cirugia pancreatica el tiempo operatorio medio fue de 243,8 minutos (125-460 min), la mediana de complicaciones postoperatorias de dos (1-4), las perdidas hematicas de 202,3 mL (100-500 mL) asociadas a una tasa de conversion del 17,8% y una estancia media de siete dias (3-23 dias). Conclusiones La cirugia robotica HBP es segura y factible. Se sugiere que su uso facilita la cirugia conservadora de parenquima, el acceso a segmentos posteriores hepaticos y la realizacion de anastomosis en la reconstruccion pancreatica respecto a la cirugia laparoscopica.

Resumen Antecedentes y objetivos Los dispositivos auditivos osteointegrados utilizan la transmision del sonido por via osea para producir una mejoria auditiva. Los mecanismos y factores que intervienen en esta transmision han sido ampliamente estudiados, sin embargo, existen otros aspectos que no conocemos, por ejemplo, la influencia que tiene la potencia de salida del procesador. El objetivo principal de este estudio fue conocer si existe alguna relacion entre la potencia que emiten estos dispositivos y la mejoria auditiva que producen. Materiales y metodos Hemos realizado un estudio en 44 pacientes portadores de un Baha® 5 percutaneo. De cada paciente se obtuvieron los umbrales de via aerea y osea en audiometria tonal liminar, en audiometria en campo libre, y en audiometria verbal en silencio y con ruido de fondo, tanto previa como posteriormente a la implantacion. Tambien se recogieron los umbrales de conduccion osea directa a traves del procesador y los valores de ganancia en la potencia de salida del procesador. Resultados El umbral tonal medio en campo libre fue de 39,29 dB (DE 9,15), obteniendo una ganancia media de 29,18 dB (DE 10,13) con el uso del dispositivo. Esto supuso el cierre del gap entre via aerea y osea en el 63,64% de los pacientes. El umbral tonal medio de la conduccion osea directa fue de 27,6 dB (DE 10,91), lo que supone 8,4 dB menos que el umbral tonal medio de la via osea. La ganancia media en inteligibilidad fue del 39,15% (DE 23,98) para intensidades de 40 dB y del 36,66% (DE 26,76) para intensidades de 60 dB. La ganancia media en la relacion senal-ruido fue de −5,9 dB (DE 4,32). Por otro lado, los valores medios de potencia de salida fueron de 27,95 dB μN (DE 6,51) para G40 y de 26,22 dB μN (DE 6,49) para G60. Al analizar la relacion entre los umbrales de via osea y los valores de G40 y G60 observamos una correlacion en frecuencias a partir de 1.000 Hz. Sin embargo, no se encontro una asociacion estadisticamente significativa entre las potencias de salida y la ganancia auditiva tonal o la ganancia en inteligibilidad. Conclusiones Los dispositivos auditivos osteointegrados producen una mejoria auditiva en los pacientes tanto a nivel tonal como en inteligibilidad, incluso con ruido de fondo. La mayoria de los pacientes consiguieron cerrar el gap previo existente entre via aerea y osea con el dispositivo. Existe una relacion directa entre los umbrales tonales en la via osea y los valores de potencia de salida que emite el procesador, aunque solo en frecuencias medias y agudas. Sin embargo, la relacion entre la potencia de salida y la mejoria en inteligibilidad en silencio y con ruido de fondo es mucho menor. Mas investigaciones en cuanto a factores que puedan influir en estas variables serian necesarias.

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by the BBSRC (BBI025751/1 and BB/I025263/1). GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. DCa is funded by the MRC (MC_UU_00011/1 and MC_UU_00011/5). GS is financially supported by the MRC [New Investigator Research Grant, MR/S009310/1] and the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1]. AH is supported by the South-Eastern Norway Regional Health Authority (2020022) and the Research Council of Norway (274611 and 288083). The POSEIDON work was supported by the German Research Foundation [DFG; grant FOR2107; RI908/11-2 and WI3429/3-2], the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent, under the auspices of the e:Med Programme [01ZX1314G; 01ZX1614G] through grants 01EE1406C, 01EE1409C and through ERA-NET NEURON, “SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation” [01EW1810], through ERA-NET NEURON “Impact of Early life MetaBolic and psychosocial strEss on susceptibility to mental Disorders; from converging epigenetic signatures to novel targets for therapeutic intervention” [01EW1904] and by a grant of the Dietmar-Hopp Foundation. The general design of the Generation R Study is made possible by financial support from Erasmus Medical Center, Rotterdam, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw) and the Ministry of Health, Welfare and Sport. The EWAS data were funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project nr. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by a grant from the National Institute of Child and Human Development (R01HD068437). AN and HT are supported by a grant of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development). AN is also supported by a Canadian Institutes of Health Research team grant. The work of HT is further supported by a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). JFF has received funding from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no. 529051022) and the European Union’s Horizon 2020 research and innovation programme (733206, LifeCycle; 633595, DynaHEALTH). The work of CAMC, JF and RM has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 848158 (EarlyCause Project). Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, CP18/00018), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615) Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. SA is funded by a Juan de la Cierva—Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness (IJCI-2017-34068). The Project Viva work was supported by the US National Institutes of Health grants R01 HD034568, UH3 OD023286 and R01 ES031259. The CHAMACOS project was supported by grants from the Environmental Protection Agency [R82670901 and RD83451301], the National Institute of Environmental Health Science (NIEHS) [P01 ES009605, R01ES021369, R01ES023067, R24ES028529, F31ES027751], the National Institute on Drug Abuse (NIDA) [R01DA035300], the National Institutes of Health (NIH) [UG3OD023356] and the National Institute of Mental Health (NIMH) [T32MH112510]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the EPA, NIEHS, or NIH. We thank all funding sources for the EDEN study (not allocated for the present study but for the cohort): Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris–Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programs (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (in collaboration with the French Association of Diabetic Patients (AFD), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale complementary health insurance (MGEN), French national agency for food security, French speaking association for the study of diabetes and metabolism (ALFEDIAM), grant # 2012/51290-6 Sao Paulo Research Foundation (FAPESP), EU funded MeDALL project. PREDO: The PREDO Study has been funded by the Academy of Finland (JL: 311617 and 269925, KR: 1312670 ja 128789 1287891), EraNet Neuron, EVO (a special state subsidy for health science research), University of Helsinki Research Funds, the Signe and Ane Gyllenberg foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Jane and Aatos Erkko Foundation, the Novo Nordisk Foundation, the Päivikki and Sakari Sohlberg Foundation, Juho Vainio foundation, Yrjö Jahnsson foundation, Jalmari and Rauha Ahokas foundation, Sigrid Juselius Foundation granted to members of the Predo study board. Methylation assays were funded by the Academy of Finland (269925). SJL is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

Resumen Objetivo Examinar el patron de prescripcion de los distintos inhibidores de la dipeptidil-peptidasa 4 (iDPP4) en funcion del filtrado glomerular estimado (FGe) en condiciones de practica clinica real. Metodologia Estudio descriptivo observacional con base de datos poblacional (SIDIAP Catalunya). Se incluyeron sujetos diagnosticados de diabetes mellitus tipo 2 (DM2) con evaluacion de su funcion renal y tratamiento activo con iDPP4. Se incluyeron pacientes en el momento de la determinacion del FGe (CKD-EPI), con un periodo de observacion de 6 meses posterior a su inclusion. Para cada sujeto se estimo la dosis diaria prescrita (DDP) de iDPP4, su dosis teorica segun su nivel de insuficiencia renal que establecen las recomendaciones de la ficha tecnica (DDD-aj) y el ratio RDP (DDP/DDD-aj). Se considero que un sujeto estaba sobretratado si su RDP era superior a 1,2 (> 20%). Resultados La muestra estudiada fue de 72.135 sujetos con una edad media de 69,7 (± 11,6) anos y un 55,9% de varones. El porcentaje de pacientes con sobretratamiento varia segun el tipo de farmaco iDPP4 y el estadio de la funcion renal. Globalmente la sobredosificacion se registro en el 7,15% de todos los tratamientos con iDPP4. En estadios avanzados (IIIb, IV y V) la sobredosificacion fue muy superior (del 36,8% para todos los iDPP4 y si excluimos la linagliptina del 58,7%). Discusion En condiciones de practica clinica real, mas de un tercio de los pacientes con DM2 con insuficiencia renal avanzada presentaban una sobredosificacion de los iDPP4, puesto que no se ajustan correctamente las dosis al filtrado glomerular de cada paciente.

Objective To assess whether a sustained optimal haemoglobin value in the 3 months after admission for heart failure (HF) decompensation reduces morbidity and mortality during the 12 months after admission for acute HF. Patients and method Retrospective study of the 1408 patients older than 65 years included in the RICA registry divided into 3 groups: no anaemia (group A), recovered anaemia (group B), and persistent anaemia (group C), according to haemoglobin levels on admission, and 3 months after discharge. Kaplan-Meier curves were constructed, comparing the groups using the log-rank test and a Cox regression model was performed to analyse survival. Results 578 (41.1%), 299 (21.2%) and 531 (37.7%) were included in groups A, B and C, respectively. We recorded a total of 768 deaths and readmissions. There were 23 (4%), 12 (4%) and 49 (9.2%), (p=.001) individuals who died due to HF and 154 (27%), 73 (24%) and 193 (36%) (P Conclusions Persistent anaemia in the months after admission for HF increases morbidity and mortality in the subsequent year.

Machine learning; Mechanical ventilation; Prognostic model Aprenentatge automàtic; Ventilació mecànica; Model pronòstic Aprendizaje automático; Ventilacion mecanica; Modelo pronóstico Purpose Existing expert systems have not improved the diagnostic accuracy of ventilator-associated pneumonia (VAP). The aim of this systematic literature review was to review and summarize state-of-the-art prediction models detecting or predicting VAP from exhaled breath, patient reports and demographic and clinical characteristics. Methods Both diagnostic and prognostic prediction models were searched from a representative list of multidisciplinary databases. An extensive list of validated search terms was added to the search to cover papers failing to mention predictive research in their title or abstract. Two authors independently selected studies, while three authors extracted data using predefined criteria and data extraction forms. The Prediction Model Risk of Bias Assessment Tool was used to assess both the risk of bias and the applicability of the prediction modelling studies. Technology readiness was also assessed. Results Out of 2052 identified studies, 20 were included. Fourteen (70%) studies reported the predictive performance of diagnostic models to detect VAP from exhaled human breath with a high degree of sensitivity and a moderate specificity. In addition, the majority of them were validated on a realistic dataset. The rest of the studies reported the predictive performance of diagnostic and prognostic prediction models to detect VAP from unstructured narratives [2 (10%)] as well as baseline demographics and clinical characteristics [4 (20%)]. All studies, however, had either a high or unclear risk of bias without significant improvements in applicability. Conclusions The development and deployment of prediction modelling studies are limited in VAP and related outcomes. More computational, translational, and clinical research is needed to bring these tools from the bench to the bedside. The project is supported by the Academy of Finland (project number 326291) and the University of Oulu.

Introduction The aim of this article is to summarize published information on systemic infective complications of tattoos to gain an update of the current picture. Methods A literature search was performed in PubMed database (2009–2019), and compared with a search without year restriction. Eligibility criteria were studies on systemic tattoo-related infections, including case reports, case series, outbreak investigations, reviews, and systematic reviews. Results We identified 17 manuscripts with systemic infections between 2009 and 2019, with one reported fatality. In contrast to the historical records, no reports of systemic tuberculosis, syphilis or viral (hepatitis or HIV) infections were reported within the study period. A few sporadic cases or Mycobacterium leprae (India) or regional lymphadenopathy associated with skin lesions in non-tuberculosis mycobacteria were identified. Persistent fever with rigour was common in bacterial bloodstream infections. One episode of staphylococcal toxic shock syndrome and several episodes of septic shock were reported, associated with cellulitis or necrotizing fasciitis within two weeks of the procedure, predominantly caused by pyogenic bacteria (S. aureus or streptococcus). Identification of lung or systemic embolisms in the absence of local symptoms, was indicative of (right or left) infective endocarditis. Conclusions Bacterial bloodstream infections should be considered in subjects developing fever and rigour after tattoos, regardless of local symptoms. A shift in causative organisms has been documented, when comparing with historical reports. NTM are emerging organisms causing lymphadenopathy. Strict hygiene conditions are essential when performing a tattoo.

Purpose:FGFR1 amplification (FGFR1amp) is recurrent in metastatic breast cancer (MBC) and is associated with resistance to endocrine therapy and CDK4/6 inhibitors (CDK4/6is). Multi-tyrosine kinase inhibitors (MTKIs) and selective pan-FGFR inhibitors (FGFRis) are being developed for FGFR1amp breast cancer. High-level FGFR amplification and protein expression by IHC have identified breast cancer responders to FGFRis or MTKIs, respectively.Experimental Design:Here, we used preclinical models and patient samples to identify predictive biomarkers to these drugs. We evaluated the antitumor activity of an FGFRi and an MTKI in a collection of 17 breast cancer patient–derived xenografts (PDXs) harboring amplification in FGFR1/2/3/4 and in 10 patients receiving either an FGFRi/MTKI. mRNA levels were measured on FFPE tumor samples using two commercial strategies. Proliferation and angiogenesis were evaluated by detecting Ki-67 and CD31 in viable areas by immunofluorescence.Results:High FGFR1–4 mRNA levels but not copy-number alteration (CNA) is associated with FGFRi response. Treatment with MTKIs showed higher response rates than with FGFRis (86% vs. 53%), regardless of the FGFR1–4 mRNA levels. FGFR-addicted PDXs exhibited an antiproliferative response to either FGFRis or MTKIs, and PDXs exclusively sensitive to MTKI exhibited an additional antiangiogenic response. Consistently, the clinical benefit of MTKIs was not associated with high FGFR1–4 mRNA levels and was observed in patients previously treated with antiangiogenic drugs.Conclusions:Tailored therapy with FGFRis in molecularly selected MBC based on high FGFR1–4 mRNA levels warrants prospective validation in patients with CDK4/6i-resistant luminal breast cancer and in patients with TNBC without targeted therapeutic options.

Resumen Introduccion Los quistes de coledoco son una rara entidad en la que se forman dilataciones quisticas del arbol biliar, con mayor prevalencia en poblaciones asiaticas. El objetivo principal del estudio fue el analisis de los resultados clinicos y quirurgicos en el manejo de los quistes biliares. De forma secundaria, se realizo un analisis comparativo de las principales series historicas publicadas. Metodos Estudio observacional retrospectivo en un unico centro de tercer nivel. Se incluyeron pacientes intervenidos quirurgicamente entre enero de 1988 y diciembre de 2019. Los datos demograficos, clinicos y analiticos de los pacientes, tipos de quiste, metodos diagnosticos, tecnica quirurgica empleada, asi como los resultados del seguimiento y complicaciones a corto y largo plazo fueron analizados. Se realizo un estudio descriptivo comparativo con las principales series historicas. Resultados Se identificaron 17 pacientes con edad media de 39,9 anos (DE: 20,54); el 58,8% eran varones. La mediana de seguimiento fue de 5 anos (1-15). Los quistes tipo I fueron los mas frecuentes (41,2%); la manifestacion clinica mas frecuente fue el dolor abdominal (58,8%). La escision quistica con derivacion biliodigestiva fue el principal procedimiento realizado en quistes tipo I (85,7%). Un 29,4% presento complicaciones posquirurgicas. No hubo hallazgos de malignidad en el estudio anatomopatologico. Conclusiones Los quistes de coledocos constituyen una patologia de baja incidencia que requiere un alto nivel de sospecha para su diagnostico. El tratamiento quirurgico se ajusta al tipo de quiste, siendo la escision del quiste y la derivacion biliodigestiva el tratamiento quirurgico mas comunmente empleado.

Research in advanced industrialized democracies on social attitudes toward same-sex marriage suggests that intergroup social contact and positive media coverage play an important role in promoting tolerance and support for same-sex marriage. Using AmericasBarometer survey data for eighteen countries in 2010, 2012, and 2014, this article examines the ways in which individual-level Internet use interacts with news exposure, country-level quality of democracy, Internet penetration, and their association with support for same-sex marriage. The results suggest that not only is Internet use associated with greater support for same-sex marriage, but that among those who both use the Internet and pay more attention to the news, the positive effects are amplified. In addition, national level of democracy, economic development, and Internet use are also associated with overall higher probabilities of supporting same-sex marriage. We find that Internet use has a strong positive association with the probability of supporting same-sex marriage as the percentage of the national population on the Internet increases. These findings extend our understanding of social and political tolerance of same-sex marriage in Latin America. Investigacion en paises industrializados sugiere que el contacto entre grupos sociales y la cobertura positiva de los mismos en medios de comunicacion juegan un papel importante en la promocion de tolerancia y en aumentar apoyo al matrimonio entre personas del mismo sexo. Basandonos en las encuestas del AmericasBarometer de 2010, 2012 y 2014, este articulo examina como el uso de la Internet interactua con el consumo de noticias, la calidad de la democracia en el pais, el grado nacional de penetracion de la Internet, y su asociacion con mayor apoyo al matrimonio igualitario. Estos resultados sugieren que no solamente existe una asociacion entre el uso de la Internet y apoyo al matrimonio igualitario, pero que esta asociacion amplifica los efectos positivos entre las personas que usan la Internet y prestan atencion a las noticias. Ademas, la calidad de la democracia al nivel nacional, niveles de desarrollo economico, asi como el uso de la Internet estan tambien asociados con probabilidades mayores de apoyo. Encontramos que existe una fuerte asociacion positiva entre el uso de la Internet y probabilidades de mayor apoyo conforme aumenta el porcentaje de la poblacion con acceso a la Internet.

Resumen Desde hace anos y de manera progresiva, la ecografia se ha incorporado en las diferentes especialidades medicas como una herramienta necesaria e indispensable. En patologia digestiva la ecografia abdominal a pie de cama o inmediata permite el diagnostico rapido y/o el seguimiento de distintas patologias intraabdominales. Por otro lado, la ecografia es muy util como guia en determinados procedimientos intervencionistas dado que comporta una mayor seguridad. A pesar de ser una tecnica no invasiva, la ecografia tiene el inconveniente de ser muy operador dependiente, por lo que es necesario garantizar que aquellos profesionales que realicen ecografias dispongan del suficiente nivel de capacitacion tecnica. En Catalunya, tradicionalmente la ecografia digestiva es una tecnica que es llevada a cabo por el servicio de radiologia y, todavia no se ha incorporado como herramienta en la especialidad en Ap. Digestivo. En este contexto, la Societat Catalana de Radiologia y la Societat Catalana de Digestologia han considerado necesaria la redaccion de un documento marco, consensuado, sobre la utilizacion y aprendizaje de la ecografia por especialistas en el aparato digestivo. El documento establece: como deberia ser la formacion, en que indicaciones, que requerimientos minimos de material y como debe documentarse la exploracion para que la ecografia realizada por el especialista de digestivo sea util y segura.

In the last decades, microbiology laboratories have undergone unprecedented technological changes which have revolutionized the diagnosis of infectious diseases. They have last generation technology which allows precise, rapid and effective diagnosis of a wide range of infectious diseases, while also providing valuable information on the antibiotic sensitivity/resistance of the causal microorganism, thereby notably reducing the morbidity and mortality of the patients and at the same time improving in-hospital patient management. Several studies have shown that with the increase in the use of rapid diagnostic techniques this technological advancement has a greater impact when accessibility to the microbiology laboratory is possible beyond the usual 7 h workday. This document discusses the need for clinical microbiology services to work 24 h a day, 7 days a week (24/7).

Objectives Berzosertib (formerly M6620, VX-970) is an intravenous, highly potent and selective, first-in-class ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. We assessed the safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of berzosertib plus gemcitabine in an expansion cohort of patients with advanced non–small cell lung cancer (NSCLC). The association of efficacy with TP53 status and other tumor markers was also explored. Materials and Methods Adult patients with advanced histologically confirmed NSCLC received berzosertib 210 mg/m2 (days 2 and 9) and gemcitabine 1000 mg/m2 (days 1 and 8) at the recommended phase 2 dose established in the dose escalation part of the study. Results Thirty-eight patients received at least one dose of study treatment. The most common treatment–emergent adverse events were fatigue (55.3%), anemia (52.6%), and nausea (39.5%). Gemcitabine had no apparent effect on the PK of berzosertib. The objective response rate (ORR) was 10.5% (4/38, 90% confidence interval [CI] 3.7–22.5). In the exploratory analysis, the ORR was 30.0% (3/10, CI: 9.0–61.0%) in patients with high loss of heterozygosity (LOH) and 11.0% (1/9, 90% CI: 1.0–43.0%) in patients with low LOH. The ORR was 33.0% (2/6, CI: 6.0–73.0%) in patients with high tumor mutational burden (TMB), 12.5% (2/16, 90% CI: 2.0–34.0%) in patients with intermediate TMB, and 0% (0/3, 90% CI: 0.0–53.6%) in patients with low TMB. Conclusions Berzosertib plus gemcitabine was well tolerated in patients with advanced, pre-treated NSCLC. Based on the observed clinical efficacy, future clinical trials should involve genomically selected patients.

Among others, expression levels of programmed cell death 1 ligand 1 (PD‐L1) have been explored as biomarkers of the response to immune checkpoint inhibitors in cancer therapy. Here, we present the results of a chemical screen that interrogated how medically approved drugs influence PD‐L1 expression. As expected, corticosteroids and inhibitors of Janus kinases were among the top PD‐L1 downregulators. In addition, we identified that PD‐L1 expression is induced by antiestrogenic compounds. Transcriptomic analyses indicate that chronic estrogen receptor alpha (ERα) inhibition triggers a broad immunosuppressive program in ER‐positive breast cancer cells, which is subsequent to their growth arrest and involves the activation of multiple immune checkpoints together with the silencing of the antigen‐presenting machinery. Accordingly, estrogen‐deprived MCF7 cells are resistant to T‐cell‐mediated cell killing, in a manner that is independent of PD‐L1, but which is reverted by estradiol. Our study reveals that while antiestrogen therapies efficiently limit the growth of ER‐positive breast cancer cells, they concomitantly trigger a transcriptional program that favors their immune evasion., Under prolonged hormone therapy, ER+ breast cancer cells activate an inflammatory transcriptional program, which includes a generalized upregulation of immune checkpoint mediators together with the downregulation of the antigen‐presenting machinery. These findings reveal that, while hormone therapies efficiently arrest the growth of ER+ breast cancer cells, they also promote a phenotype switch that favors their immune evasion.

BackgroundThe most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.MethodsFace-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.Results3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.ConclusionADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.