Enteritis secundaria a nivolumab, una causa creciente de diarrea

La inmunoterapia es una herramienta cada vez más utilizada en el campo de la oncología. Conviene conocerla debido a sus crecientes usos, entre los que se incluye el tratamiento de tumores del aparato digestivo (hepatocarcinoma1, adenocarcinoma colorrectal con alta inestabilidad en microsatelites2) así como por las reacciones adversas que con elevada frecuencia afectan al tubo digestivo. Presentamos el caso de un varón de 74 años, con antecedentes personales de enfermedad pulmonar obstructiva crónica (EPOC) y melanoma con metástasis pulmonares. Debido a estas patologías tomaba de manera habitual inhaladores de salbutamol y había estado en tratamiento con nivolumab, suspendido hacía cuatro meses tras conseguir una respuesta radiológica completa de las metástasis pulmonares. El paciente refería cuadro diarreico de un mes de evolución, consistente en tres a cuadro deposiciones (Bristol 5-6) sin productos patológicos, que afectaban el descanso nocturno, asociaban molestias centroabdominales intermitentes y pérdida de peso de unos 3-4 kg. No había ingerido alimentos crudos, antibióticos o nuevas medicaciones. Tampoco había convivientes con la misma sintomatología ni había realizado viajes al extranjero. Negaba cualquier otra sintomatología y antecedentes familiares de interés. La exploración física era anodina a excepción de unas ligeras molestias a la palpación profunda en mesogastrio..

Aproximación al manejo de la disección del tronco celíaco

El dolor abdominal constituye uno de los motivos de consulta más frecuentes en los servicios de Urgencias y de Aparato Digestivo. Además, el diagnóstico diferencial supone un importante reto, dado el amplio abanico de entidades clínicas que pueden provocarlo, algunas de ellas con un pronóstico desfavorable. En este sentido, en algunas cohortes no se ha llegado a un diagnóstico específico en más de un 30% de los casos1, 2. Se presenta el caso de un varón de 40 años, fumador activo desde hace más de 20 años, sin otros antecedentes personales ni familiares de interés, excepto traumatismo cerrado abdominal hace cuatro años, que no seguía tratamiento farmacológico habitual. Presentaba dolor abdominal epigástrico continuo e irradiado hacia ambos hipocondrios, de ocho horas de evolución. No asociaba ictericia mucocutánea ni coluria o acolia, tampoco náuseas ni vómitos ni alteraciones en el ritmo y características de las deposiciones. No presentaba fiebre, síndrome constitucional ni otra sintomatología asociada. A la exploración física destacaba dolor a la palpación de epigastrio, sin signos de irritación peritoneal, con peristaltismo y pulsos distales conservados. Asimismo, no presentaba signos de colagenopatía. Para una primera aproximación diagnóstica se realizó analítica de sangre, destacando como únicos hallazgos ligera alteración del perfil hepático (AST 66 U/L, ALT 58 U/L, GGT 106 U/L, FA 76 U/L) con amilasemia, ..

Verification and Control of Turn-Based Probabilistic Real-Time Games

Quantitative verification techniques have been developed for the formal analysis of a variety of probabilistic models, such as Markov chains, Markov decision process and their variants. They can be used to produce guarantees on quantitative aspects of system behaviour, for example safety, reliability and performance, or to help synthesise controllers that ensure such guarantees are met. We propose the model of turn-based probabilistic timed multi-player games, which incorporates probabilistic choice, real-time clocks and nondeterministic behaviour across multiple players. Building on the digital clocks approach for the simpler model of probabilistic timed automata, we show how to compute the key measures that underlie quantitative verification, namely the probability and expected cumulative price to reach a target. We illustrate this on case studies from computer security and task scheduling

The ALHAMBRA survey: An empirical estimation of the cosmic variance for merger fraction studies based on close pairs

Aims. Our goal is to estimate empirically the cosmic variance that affects merger fraction studies based on close pairs for the first time. Methods. We compute the merger fraction from photometric redshift close pairs with 10 h-1 kpc ≤ rp ≤ 50 h-1 kpc and Δv ≤ 500 km s-1 and measure it in the 48 sub-fields of the ALHAMBRA survey. We study the distribution of the measured merger fractions that follow a log-normal function and estimate the cosmic variance σv as the intrinsic dispersion of the observed distribution. We develop a maximum likelihood estimator to measure a reliable σv and avoid the dispersion due to the observational errors (including the Poisson shot noise term). Results. The cosmic variance σv of the merger fraction depends mainly on (i) the number density of the populations under study for both the principal (n1) and the companion (n2) galaxy in the close pair and (ii) the probed cosmic volume Vc. We do not find a significant dependence on either the search radius used to define close companions, the redshift, or the physical selection (luminosity or stellar mass) of the samples. Conclusions. We have estimated the cosmic variance that affects the measurement of the merger fraction by close pairs from observations. We provide a parametrisation of the cosmic variance with n1, n2, and Vc, σv ∝ n1-0.54Vc-0.48 (n_2/n_1)-0.37 . Thanks to this prescription, future merger fraction studies based on close pairs could properly account for the cosmic variance on their results

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL

Objetivos: estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL

Seguimiento de las guías españolas para el manejo del asma por el médico de atención primaria: un estudio observacional ambispectivo

Objetivo Evaluar el grado de seguimiento de las recomendaciones de las versiones de la Guía española para el manejo del asma (GEMA 2009 y 2015) y su repercusión en el control de la enfermedad. Material y métodos Estudio observacional y ambispectivo realizado entre septiembre del 2015 y abril del 2016, en el que participaron 314 médicos de atención primaria y 2.864 pacientes. Resultados Utilizando datos retrospectivos, 81 de los 314 médicos (25, 8% [IC del 95%, 21, 3 a 30, 9]) comunicaron seguir las recomendaciones de la GEMA 2009. Al inicio del estudio, 88 de los 314 médicos (28, 0% [IC del 95%, 23, 4 a 33, 2]) seguían las recomendaciones de la GEMA 2015. El tener un asma mal controlada (OR 0, 19, IC del 95%, 0, 13 a 0, 28) y presentar un asma persistente grave al inicio del estudio (OR 0, 20, IC del 95%, 0, 12 a 0, 34) se asociaron negativamente con tener un asma bien controlada al final del seguimiento. Por el contrario, el seguimiento de las recomendaciones de la GEMA 2015 se asoció de manera positiva con una mayor posibilidad de que el paciente tuviera un asma bien controlada al final del periodo de seguimiento (OR 1, 70, IC del 95%, 1, 40 a 2, 06). Conclusiones El escaso seguimiento de las guías clínicas para el manejo del asma constituye un problema común entre los médicos de atención primaria. Un seguimiento de estas guías se asocia con un control mejor del asma. Existe la necesidad de actuaciones que puedan mejorar el seguimiento por parte de los médicos de atención primaria de las guías para el manejo del asma. Objective: To assess the degree of compliance with the recommendations of the 2009 and 2015 versions of the Spanish guidelines for managing asthma (Guía Española para el Manejo del Asma [GEMA]) and the effect of this compliance on controlling the disease. Material and methods: We conducted an observational ambispective study between September 2015 and April 2016 in which 314 primary care physicians and 2864 patients participated. Results: Using retrospective data, we found that 81 of the 314 physicians (25.8%; 95% CI 21.3–30.9) stated that they complied with the GEMA2009 recommendations. At the start of the study, 88 of the 314 physicians (28.0%; 95% CI 23.4–33.2) complied with the GEMA2015 recommendations. Poorly controlled asthma (OR, 0.19; 95% CI 0.13–0.28) and persistent severe asthma at the start of the study (OR, 0.20; 95% CI 0.12–0.34) were negatively associated with having well-controlled asthma by the end of the follow-up. In contrast, compliance with the GEMA2015 recommendations was positively associated with a greater likelihood that the patient would have well-controlled asthma by the end of the follow-up (OR, 1.70; 95% CI 1.40–2.06). Conclusions: Low compliance with the clinical guidelines for managing asthma is a common problem among primary care physicians. Compliance with these guidelines is associated with better asthma control. Actions need to be taken to improve primary care physician compliance with the asthma management guidelines

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570