Rationale and study design for an Individualized PeriopeRative Open lung VEntilatory approach in Emergency Abdominal Laparotomy/scopy: study protocol for a prospective international randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPC) are the most frequent postoperative complications, with an estimated prevalence in elective surgery ranging from 20% in observational cohort studies to 40% in randomized clinical trials. However, the prevalence of PPCs in patients undergoing emergency abdominal surgery is not well defined. Lung-protective ventilation aims to minimize ventilator-induced lung injury and reduce PPCs. The open lung approach (OLA), which combines recruitment manoeuvres (RM) and positive end-expiratory pressure (PEEP) titration, aims to minimize areas of atelectasis and the development of PPCs; however, there is no conclusive evidence in the literature that OLA can prevent PPCs. The purpose of this study is to compare an individualized perioperative OLA with conventional standardized lung-protective ventilation in patients undergoing emergency abdominal surgery with clinical signs of intraoperative lung collapse. METHODS: Randomized international clinical trial to compare an individualized perioperative OLA (RM plus individualized PEEP and individualized postoperative respiratory support) with conventional lung-protective ventilation (standard PEEP of 5 cmH2O and conventional postoperative oxygen therapy) in patients undergoing emergency abdominal surgery with clinical signs of lung collapse. Patients will be randomised to open-label parallel groups. The primary outcome is any severe PPC during the first 7 postoperative days, including: acute respiratory failure, pneumothorax, weaning failure, acute respiratory distress syndrome, and pulmonary infection. The estimated sample size is 732 patients (366 per group). The final sample size will be readjusted during the interim analysis. DISCUSSION: The Individualized Perioperative Open-lung Ventilatory Strategy in emergency abdominal laparotomy (iPROVE-EAL) is the first multicentre, randomized, controlled trial to investigate whether an individualized perioperative approach prevents PPCs in patients undergoing emergency surgery.

Metastasis Models: Thermodynamics and Complexity.

The thermodynamic formalism of nonequilibrium systems together with the theory of complex systems and systems biology offer an appropriate theoretical framework to explain the complexity observed at the macroscopic level in physiological phenomena. In turn, they allow the establishment of an appropriate conceptual and operational framework to address the study of phenomena such as the emergence and evolution of cancer.This chapter is organized as follows: In Subheading 1, an integrated vision of these disciplines is offered for the characterization of the emergence and evolution of cancer, seen as a nonlinear dynamic system, temporally and spatially self-organized out of thermodynamic equilibrium. The development of the various mathematical models and different techniques and approaches used in the characterization of cancer metastasis is presented in Subheading 2. Subheading 3 is devoted to the time course of cancer metastasis, with particular emphasis on the epithelial-mesenchymal transition (EMT henceforth) as well as chronotherapeutic treatments. In Subheading 4, models of the spatial evolution of cancer metastasis are presented. Finally, in Subheading 5, some conclusions and remarks are presented.

Efectividad y seguridad de los nuevos anticuerpos monoclonales en la profilaxis de la migraña / Effectiveness and safety of new monoclonal antibodies in migraine prophylaxis

Objetivos: Analizar la efectividad y seguridad en vida real de los nuevos anticuerpos monoclonales subcutáneos para la profilaxis de la migraña. Métodos: Estudio observacional retrospectivo llevado a cabo desde enero de 2020 hasta abril de 2021 con pacientes diagnosticados de migraña crónica o episódica. Las variables de interés se analizaron por el personal facultativo farmacéutico en una base de datos anonimizada. Esta base se completa como práctica clínica habitual durante la entrevista clínica en la consulta de pacientes externos. Resultados: Se analizaron 53 pacientes. Se observó una reducción del número de crisis respecto al valor basal a los 3, a los 6 y a los 12 meses de tratamiento, así como de otros fármacos para el tratamiento de la migraña. La mayoría de reacciones adversas descritas fueron de tipo leve, obligando a la suspensión del tratamiento de solo uno de los pacientes. Se describió un aumento de la tensión arterial en varios pacientes, así como una incidencia de estreñimiento superior a los ensayos pivotales. Conclusiones: Este estudio muestra una disminución del número de crisis de migraña y del uso de otros fármacos antimigrañosos tras el uso de anticuerpos monoclonales. Los tratamientos se pueden considerar seguros, observándose una baja incidencia de reacciones adversas graves. La mayoría de pacientes fueron tratados con erenumab. Se dispone de menos datos a medida que avanza del tiempo de estudio, por lo que resulta necesario recopilar más información para conocer el perfil de efectividad y seguridad de estos fármacos a largo plazo.(AU)

Objectives: To analyse the effectiveness and safety in real life of new subcutaneous monoclonal antibodies for the prophylaxis of migraine. Methods: Retrospective observational study conducted from January 2020 to April 2021 with patients diagnosed with chronic or episodic migraine. The variables of interest were collected by the pharmacist in an anonymised database during the clinical interview in the outpatient clinic. This databased is completed as standard clinical practice during the clinical interview in the outpatient clinic. Results: 53 patients were analysed. A reduction in the number of attacks from baseline was observed at 3, 6 and 12 months of treatment, as well as for other migraine treatment drugs. Most of the adverse reactions described were mild, leading to discontinuation of treatment in only one patient. An increase in blood pressure was reported in several patients, as well as a higher incidence of constipation than in pivotal trials. Conclusions: This study shows a decrease in the number of migraine attacks and in the use of other anti-migraine drugs after the use of monoclonal antibodies. The treatments can be considered safe, with a low incidence of serious adverse reactions. Most patients were treated with erenumab. Less information is available as the study time progresses, so more information needs to be collected to understand the long-term effectiveness and safety profile of these drugs.(AU)

NMR-based metabolomics to determine the fluctuation of metabolites in hydroponic purslane crops at different harvesting times.

Purslane (Portulaca oleracea L.) has a high content of nutrients and medicinal effects that depend on the genotype, harvesting time, and production system. The objective of the present research work was to elucidate the NMR-based metabolomics profiling of three native purslane cultivars from Mexico (Xochimilco, Mixquic, and Cuautla) grown under hydroponic conditions and harvested in three different times (32, 39, and 46 days after emergence). Thirty-nine metabolites identified in the 1H NMR spectra of aerial parts of purslane, 5 sugars, 15 amino acids, 8 organic acids, 3 caffeoylquinic acids, as well as 2 alcohols and 3 nucleosides, choline, O-phosphocholine and trigonelline were also detected. A total of 37 compounds were detected in native purslane from Xochimilco and Cuautla, whereas 39 compounds were detected in purslane from Mixquic. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) separated the cultivars into three clusters. Mixquic cultivar had the highest number of differential compounds (amino acids and carbohydrates), followed by Xochimilco and Cuautla cultivars, respectively. Changes in the metabolome were observed in latest times of harvest for all the cultivars studied. The differential compounds were glucose, fructose, galactose, pyruvate, choline, and 2-hydroxysobutyrate. The results obtained in this investigation may contribute to selecting the best cultivar of purslane and the best time in which the levels of nutrients are optimal.

SARS-CoV-2 seroprevalence in workers from a Colombian University Hospital.

BACKGROUND: Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection. AIMS: To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia. METHODS: In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT-PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT-PCR/antigen test (<3 months, 3-6 months, >6 months). RESULTS: We included 1021 workers (80% women, median age 34 years (interquartile range 28-42), 73% medical personnel, 23% with previous positive RT-PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6-37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT-PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3-6 months) and 48% (>6 months). In participants with a previous negative RT-PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3-6 months) and 29% (>6 months). CONCLUSIONS: High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT-PCR/antigen status and time elapsed since the diagnostic test.

Tratamiento quirúrgico de los leiomiosarcomas de vena cava. Serie de casos en un hospital de tercer nivel y revisión de la literatura / Surgical treatment of vena cava leiomyosarcomas: Series of cases in a referral center and literature review

Introducción Los tumores primarios de vena cava inferior son tumores raros de origen mesenquimal que surgen de la musculatura lisa de la pared. Debido a su escasa prevalencia, existen pocos datos definitivos sobre su tratamiento y pronóstico. Su tratamiento se basa en principios oncológicos generales. Métodos Se ha analizado una serie de 6 casos intervenidos desde 2010 a 2020, evaluando distintos parámetros relacionados con las características demográficas del tumor, del tratamiento recibido y de los resultados obtenidos en supervivencia y morbilidad. Además, se ha llevado a cabo una revisión bibliográfica de la evidencia disponible actualmente. Resultados En todos los pacientes se llevó a cabo una resección quirúrgica óptima con R0 en 4/6 y R1 en 2/6. La mayor morbilidad sucedió en un paciente fallecido en periodo intraoperatorio. Se realizó cavorrafia en un paciente y cavoplastia en 5/6 utilizando injerto criopreservado en 3/6 y prótesis en 2/6. Al final del seguimiento de nuestra serie (con una media de seguimiento de 10,7 meses), el 50% de los pacientes continúan vivos. La media de supervivencia fue de 11,3±9,07 meses. De los 6 pacientes, 3 presentaron recidivas hematógenas con un intervalo libre de enfermedad de 9±2 meses. Conclusión El diagnóstico y tratamiento del leiomiosarcoma de vena cava inferior continúa siendo un reto. Debido a su baja prevalencia, resultará difícil establecer un tratamiento totalmente estandarizado, y se recomienda su abordaje en centros especializados. Por otra parte, se deberían intentar aunar los casos intervenidos de cara a avanzar en el conocimiento del abordaje de esta enfermedad (AU)

Introduction Primary tumors of the inferior vena cava are rare tumors of mesenchymal origin. They arise from the smooth muscles of the vena cava wall. Due to its low prevalence, there are few definitive data on its treatment and prognosis. Its treatment is based on general oncological principles. Methods A series of six cases operated from 2010 to 2020 were analyzed. Different parameters related to the demographic characteristics, the tumor, the treatment received, and the results obtained in survival and morbidity were analyzed. In addition, a bibliographical review of the currently available evidence was carried out. Results Optimal surgical resection was accomplished in all patients with R0 in 4/6 and R1 in 2/6. The greatest morbidity occurred in a patient who died in the intraoperative period. Cavography was performed in one patient and cavoplasty in 5/6 using cryopreserved graft in 3/6 and prothesis in 2/6. The 50% were still alive at the end of the follow-up (with a mean follow-up of 10.7 months). The mean survival was 11.3±9.07 months. 3/6 patients presented hematogenous recurrences with a disease-free interval of 9±2 months. Conclusion The diagnosis and treatment of inferior vena cava leiomyosarcoma is still a challenge. Due to its low prevalence, it will be difficult to establish a totally standardized treatment and its approach is recommended in specialized centers. On the other hand, a multicentric study should be made to collect the most cases as possible in order to advance in the understanding of the approach to this disease (AU)

Effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir and combinations thereof in hospitalized patients with COVID-19: a pragmatic, open-label randomized trial.

BACKGROUND: The use of rosuvastatin plus colchicine and emtricitabine/tenofovir in hospitalized patients with SARS-CoV-2 disease (COVID-19) has not been assessed. The objective of this study was to assess the effectiveness and safety of rosuvastatin plus colchicine, emtricitabine/tenofovir, and their combined use in these patients. METHODS: This was a randomized, controlled, open-label, multicentre, parallel, pragmatic study conducted in six referral hospitals in Bogotá, Colombia. The study enrolled hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 complicated with pneumonia, not on chronic treatment with the study medications, and with no contraindications for their use. Patients were assigned 1:1:1:1. 1) emtricitabine with tenofovir disoproxil fumarate (FTC/TDF, 200/300 mg given orally for 10 days); 2) colchicine plus rosuvastatin (COLCH+ROSU, 0.5 mg and 40 mg given orally for 14 days); 3) emtricitabine with tenofovir disoproxil plus colchicine and rosuvastatin at the same doses and for the same period of time (FTC/TDF+COLCH+ROSU); or 4) the Colombian consensus standard of care, including a corticosteroid (SOC). The primary endpoint was 28-day all-cause mortality. A modified intention-to-treat analysis was used together with a usefulness analysis to determine which could be the best treatment. The trial was registered at ClinicalTrials.gov: NCT04359095. FINDINGS: Out of 994 candidates considered between August 2020 and March 2021, 649 (65.3%) patients agreed to participate and were enrolled in this study; among them, 633 (97.5%) were included in the analysis. The mean age was 55.4 years (SD ± 12.8 years), and 428 (68%) were men; 28-day mortality was significantly lower in the FTC/TDF+COLCH+ROSUV group than in the SOC group, 10.7% (17/159) vs. 17.4% (28/161) (hazard ratio [HR] 0.53; 95% CI 0.29 to 0.96). Mortality in the FTC/TDF group was 13.8% (22/160, HR 0.68, 95% CI 0.39 to 1.20) and 14.4% in the COLCH+ROSU group (22/153) (HR 0.78, 95% CI 0.44 to 1.36). A lower need for invasive mechanical ventilation was observed in the FTC/TDF+COLCH+ROSUV group than in the SOC group (risk difference [RD] - 0.08, 95% CI 0.11 to 0.04). Three patients presented severe adverse events, one severe diarrhoea in the COLCH+ROSU and one in the FTC/TDF+COLCH+ROSU group and one general exanthema in the FTC/TDF group. INTERPRETATION: The combined use of FTC/TDF+COLCH+ROSU reduces the risk of 28-day mortality and the need for invasive mechanical ventilation in hospitalized patients with pulmonary compromise from COVID-19. More randomized controlled trials are needed to compare the effectiveness and cost of treatment with this combination versus other drugs that have been shown to reduce mortality from SARS-CoV-2 infection and its usefulness in patients with chronic statin use.

Clinical phenotypes for risk stratification in small-for-gestational-age fetuses.

OBJECTIVE: To evaluate whether clinical phenotypes of small-for-gestational-age (SGA) fetuses can be identified and used for adverse perinatal outcome risk stratification to facilitate clinical decision-making. METHODS: This was a multicenter observational cohort study conducted in two tertiary care university hospitals. SGA fetuses were classified according to maternal, fetal and placental conditions using a two-step cluster algorithm, in which fetuses with more than one condition were assigned to the cluster associated with the highest mortality risk. Delivery and perinatal outcomes were compared using chi-square test among SGA clusters, and the associations between outcomes and each cluster were evaluated by calculating odds ratios (OR), adjusted for gestational age. RESULTS: The study included 17 631 consecutive singleton pregnancies, of which 1274 (7.2%) were defined as SGA at birth according to INTERGROWTH-21st standards. Nine SGA clinical phenotypes were identified using a predefined conceptual framework. All delivery and perinatal outcomes analyzed were significantly different among the nine phenotypes. The whole SGA cohort had a three-times higher risk of perinatal mortality compared with non-SGA fetuses (1.4% vs 0.4%; P < 0.001). SGA clinical phenotypes exhibited three patterns of perinatal mortality risk: the highest risk was associated with congenital anomaly (8.3%; OR, 17.17 (95% CI, 2.17-136.12)) and second- or third-trimester hemorrhage (8.3%; OR, 9.94 (95% CI, 1.23-80.02)) clusters; medium risk was associated with gestational diabetes (3.8%; OR, 9.59 (95% CI, 1.27-72.57)), preterm birth (3.2%; OR, 4.65 (95% CI, 0.62-35.01)) and intrauterine growth restriction (3.1%; OR, 5.93 (95% CI, 3.21-10.95)) clusters; and the lowest risk was associated with the remaining clusters. Perinatal mortality rate did not differ between SGA fetuses without other clinical conditions (54.1% of SGA fetuses) and appropriate-for-gestational-age fetuses (0.1% vs 0.4%; OR, 0.41 (95% CI, 0.06-2.94); P = 0.27). SGA combined with other obstetric pathologies increased significantly the risk of perinatal mortality, as demonstrated by the increased odds of perinatal death in SGA cases with gestational diabetes compared to non-SGA cases with the same condition (OR, 24.40 (95% CI, 1.31-453.91)). CONCLUSIONS: We identified nine SGA clinical phenotypes associated with different patterns of risk for adverse perinatal outcome. Our findings suggest that considering clinical characteristics in addition to ultrasound findings could improve risk stratification and decision-making for management of SGA fetuses. Future clinical trials investigating management of fetuses with SGA should take into account clinical information in addition to Doppler parameters and estimated fetal weight. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Fetal cerebellar growth and Sylvian fissure maturation: international standards from Fetal Growth Longitudinal Study of INTERGROWTH-21st Project.

OBJECTIVE: To construct international ultrasound-based standards for fetal cerebellar growth and Sylvian fissure maturation. METHODS: Healthy, well nourished pregnant women, enrolled at < 14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of INTERGROWTH-21st , an international multicenter, population-based project, underwent serial three-dimensional (3D) fetal ultrasound scans every 5 ± 1 weeks until delivery in study sites located in Brazil, India, Italy, Kenya and the UK. In the present analysis, only those fetuses that underwent developmental assessment at 2 years of age were included. We measured the transcerebellar diameter and assessed Sylvian fissure maturation using two-dimensional ultrasound images extracted from available 3D fetal head volumes. The appropriateness of pooling data from the five sites was assessed using variance component analysis and standardized site differences. For each Sylvian fissure maturation score (left or right side), mean gestational age and 95% CI were calculated. Transcerebellar diameter was modeled using fractional polynomial regression, and goodness of fit was assessed. RESULTS: Of those children in the original FGLS cohort who had developmental assessment at 2 years of age, 1130 also had an available 3D ultrasound fetal head volume. The sociodemographic characteristics and pregnancy/perinatal outcomes of the study sample confirmed the health and low-risk status of the population studied. In addition, the fetuses had low morbidity and adequate growth and development at 2 years of age. In total, 3016 and 2359 individual volumes were available for transcerebellar-diameter and Sylvian-fissure analysis, respectively. Variance component analysis and standardized site differences showed that the five study populations were sufficiently similar on the basis of predefined criteria for the data to be pooled to produce international standards. A second-degree fractional polynomial provided the best fit for modeling transcerebellar diameter; we then estimated gestational-age-specific 3rd , 50th and 97th smoothed centiles. Goodness-of-fit analysis comparing empirical centiles with smoothed centile curves showed good agreement. The Sylvian fissure increased in maturation with advancing gestation, with complete overlap of the mean gestational age and 95% CIs between the sexes for each development score. No differences in Sylvian fissure maturation between the right and left hemispheres were observed. CONCLUSION: We present, for the first time, international standards for fetal cerebellar growth and Sylvian fissure maturation throughout pregnancy based on a healthy fetal population that exhibited adequate growth and development at 2 years of age. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Efectividad y seguridad en vida real de nivolumab en el tratamiento del cáncer de pulmón no microcítico en segunda línea / Real-life efficacy and safety of nivolumab in the treatment of second-line non-small cell lung cáncer

Objetivo: Evaluar la efectividad y el perfil de seguridad de nivolumab utilizado en segunda línea en el tratamiento del cáncer de pulmón no microcítico en la práctica clínica real. Material y métodos: Estudio observacional retrospectivo en pacientes con cáncer de pulmón no microcítico en tratamiento con nivolumab en segunda línea entre diciembre-2015 y noviembre-2019. Se evaluó la respuesta mediante criterios RECIST v1.1 (Response Evaluation Criteria in Solid Tumors). Variables principales de efectividad: tasa de respuesta objetiva (TRO) y supervivencia global (SG); variables secundarias: supervivencia libre de progresión (SLP). Los posibles factores predictores de respuesta (edad, sexo, histología y ECOG-PS -Eastern Cooperative Oncology Gropup-Performance status-) se analizaron mediante un modelo de riesgos proporcionales de Cox para la SG Y SLP, y odds ratio para TRO. La seguridad se evaluó mediante la aparición de eventos adversos (EAs) y su grado según CTCEA v5.0 (Criterios Comunes de Terminología para Eventos Adversos).Resultados: Se incluyeron 48 pacientes, con una mediana de edad de 65,5 años (rango 46-83), mayoritariamente hombres (85,5%), ECOG-PS 0-1 (85%). En cuanto a la efectividad, TRO=27% (IC95% 14,04-40,12), mediana SG 13,01 meses (IC95% 7,67-18,36) y SLP 5,29 meses (IC95% 3,53-7,05). El sexo se identificó como factor predictor de mejor respuesta en términos de TRO. Un 10% de los pacientes presentaron al menos un EA G3-G4.Conclusiones: Nivolumab tuvo una efectividad ligeramente superior a la demostrada en ensayos clínicos. La seguridad del tratamiento fue aceptable, posicionando nivolumab como una alternativa válida en el tratamiento de cáncer de pulmón no microcítico en segunda línea. (AU)

Objective: To evaluate the effectiveness and safety profile of nivolumab used in second line for the treatment of non-small cell lung cancer in real clinical practice. Material and methods: Retrospective observational study was carried off in patients with non-small cell lung cancer treated with nivolumab in the second line between December 2015 and November 2019. The response was evaluated using RECIST v1.1 criteria. Main survival variables: objective response rate (ORR) and overall survival (OS); secondary variables: progression-free survival (PFS). The possible predictive response factors (age, sex, histology and ECOG-PS) were analyzed using a Cox proportional hazard model for survival, and odds ratio for the objective response rate. The safety was evaluated through the occurrence of adverse events (AD) and their degree according to CTCEA v5.Results: 48 patients were included, median age of 65.5 years (range 46-83), mostly men (85.5%), ECOG-PS 0-1 (85%). Regarding effectiveness, ORR=27% (95% CI 14.04-40.12), median SG 13.01 months (95% CI 7.67-18.36) and SLP 5.29 months (95% CI 3.53-7.05). Sex was identified as a predictor of better response in terms of ORR. EA G3-G4 appeared in 10% of patients.Conclusions: Nivolumab had a slightly higher effectiveness than demonstrated in clinical trials. The safety of the treatment was acceptable, positioning nivolumab as a valid alternative in the treatment of non-small cell lung cancer in second line. (AU)

Resultados en vida real de los antivirales de acción directa en el tratamiento de la hepatitis C crónica / Real life results of direct acting antiviral in hepatitis C treatment

Objetivo: Los antivirales de acción directa han logrado tasas de respuesta viral sostenida muy elevadas desde su comercialización. El objetivo de este trabajo fue el análisis de la efectividad y seguridad de los antivirales de acción directa en pacientes infectados por el virus de la hepatitis C crónica.Métodos: Se incluyeron pacientes infectados con el virus de la hepatitis C (VHC) y coinfectados por VHC y virus de la inmunodeficiencia humana (VIH) que iniciaron tratamiento con antivirales de acción directa entre 2015-2019. Como variable de efectividad se midió la respuesta viral sostenida.Resultados: Se incluyeron 303 pacientes, 235 (77,56%) monoinfectados y 68 (22,44%) coinfectados. El genotipo de virus más prevalente fue el 1 en ambos grupos. La proporción de cirróticos fue superior en la población monoinfectada 38,3% vs. 20,6%; p=0,047). De los 303 pacientes, a 279 se le analizó la carga viral a las 12 semanas de tratamiento; un 97,8% (273/279) alcanzaron respuesta viral sostenida, confirmándose 6 fracasos virológicos. En un análisis de subgrupos, en la mayoría de grupos según la presencia o no de cirrosis, la coinfección VIH y el genotipo, la efectividad se situó próxima o por encima del 90%. El tratamiento fue seguro, con toxicidad leve y sólo una suspensión de tratamiento. Se detectaron interacciones medicamentosas potenciales en un 20% de los pacientes.Conclusiones: Los antivirales de acción directa presentaron una efectividad elevada, igual e incluso superior a la descrita en los ensayos clínicos, e incluso en subpoblaciones difíciles de tratar. (AU)

Objetive: Direct-acting antivirals have achieved high sustained viral response rates since their commercialization. The main objective of this study was the analysis of the efficacy and safety of direct-acting antivirals in patients infected with the chronic hepatitis C virus.Methods: Patients infected with hepatitis C virus (HCV) and co-infected with HCV and human immunodeficiency virus (HIV) who started treatment with direct-acting antiviral drugs between 2015-2019 were included. The sustained viral response was measured as the effectivity variable.Results: 303 patients were included, 235 (77.56%) were monoinfected and 68 (22.44%) were co-infected. Genotype 1 virus was the most prevalent 1 in both groups. The proportion of cirrhotic was higher in the monoinfected population (38.3% vs. 20.6%; p=0.047). Of the 303 patients, 279 pacients had viral load analysis at 12 weeks of treatment, 97.8% (273/279) achieved sustained viral response and 6 virological failures were confirmed. In a subgroup analysis, the majority of the groups, regardless of the presence or not of cirrhosis, HIV coinfection or genotype, the efficacy was close to or above 90%. The treatment was safe, with mild toxicity and only one treatment suspension. Potential drug interactions were detected in 20% of patients.Conclusions: Direct-acting antivirals with a high efficacy, equal to or greater than that described in clinical trials, and even with subpopulations difficult to treat. (AU)

Popularidad de Neurología en España: análisis de la elección de la especialidad / The popularity of neurology in Spain: An analysis of specialty selection

INTRODUCCIÓN: Neurología es una de las especialidades ofertadas a los opositores que acceden a la formación sanitaria especializada cada año. Este proyecto analiza los datos de elección de Neurología en los últimos años. MATERIAL Y MÉTODOS: Los datos de la elección se han obtenido de la publicación oficial del Ministerio de Sanidad, Servicios Sociales e Igualdad. Se ha recabado información de los distintos centros docentes con relación a la disponibilidad de unidad de ictus, intervencionismo endovascular, consultas de referencia nacional relacionadas con Neurología, guardias específicas para residentes y vinculación con facultades de medicina o redes de investigación nacional. RESULTADOS: La mediana de elección de número de orden para Neurología ha descendido anualmente, situando la especialidad en la convocatoria 2016 entre las cuatro más populares. Los electores son mayoritariamente mujeres de nacionalidad española y baremo académico alto. La mediana de los hospitales con mayor número de camas, intervencionismo vascular, unidad de ictus o consultas de referencia nacional es significativamente menor. Lo mismo sucede al analizar los centros según guardias específicas de Neurología para residentes o vinculación con facultades de medicina o redes de investigación nacionales. Los centros con menor mediana de número de orden para el periodo 2012-2016 fueron los hospitales universitarios Clínico San Carlos, 12 de Octubre y Vall d'Hebron. CONCLUSIONES: Neurología ha ido mejorando de manera progresiva en la elección de plazas de especialización, situándose entre las cuatro más populares. Los electores se decantan por centros grandes, de mayor complejidad asistencial y con intensa actividad investigadora

INTRODUCTION: Neurology is one of the medical specialties offered each year to residency training candidates. This project analyses the data associated with candidates choosing neurology residency programmes in recent years. METHODS: Data related to specialty selection were obtained from official reports by the Spanish Ministry of Health, Social Services, and Equality. Information was collected on several characteristics of teaching centres: availability of stroke units, endovascular intervention, national reference clinics for neurology, specific on-call shifts for neurology residents, and links with medical schools or national research networks. RESULTS: The median selection list position of candidates selecting neurology training has been higher year on year; neurology was among the 4 most popular residency programmes in 2016. Potential residents were mainly female, Spanish, and had good academic results. The median number of hospitals with higher numbers of beds, endovascular intervention, stroke units, and national reference clinics for neurology is significantly lower. This is also true when centers are analysed by presence of specific on-call shifts for neurology residents and association with medical schools or national research networks. The centres selected by candidates with the highest median selection list position in 2012-2016 were the Clínico San Carlos, 12 de Octubre, and Vall d'Hebron university hospitals. CONCLUSIONS: Neurology has gradually improved in residency selection choices and is now one of the 4 most popular options. Potential residents prefer larger centres which are more demanding in terms of patient care and which perform more research activity

Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: A proposal for a multi-centric prospective trial.

BACKGROUND: COVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19. STUDY DESIGN AND METHODS: This multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function.This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48-72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators.Trial registration: ClinicalTrial.gov NCT-04380818 https://clinicaltrials.gov/ct2/show/NCT04380818?term=RADIOTHERAPY&cond=COVID&draw=2&rank=4.

Ammonia volatilisation from pig slurry and ANS with DMPP applied to Westerwold ryegrass (Lolium multiflorum Lam., cv. Trinova) under Mediterranean conditions.

Ammonia volatilisation from agriculture represents an important nitrogen (N) loss which has both environmental and economic impacts. In regions where large amounts of manures are available, there is a need to find appropriate management strategies that help to reuse them without increasing ammonia volatilisation. A study was made of the effect on ammonia volatilisation and yield of fertilising ryegrass with pig slurry (PS) and ammonium nitrosulphate (ANS-26) alone and with the 3,4-dimethylpyrazol phosphate (DMPP) nitrification inhibitor added to them. The study was conducted under Mediterranean conditions at two different sites. The treatments (control, PS, PS + DMPP, ANS-26 and ENTEC®) were established in a randomised block design with three replicates. Ammonia was sampled daily after each fertilisation using semi-static volatilisation chambers. We hypothesised that PS could replace mineral fertiliser without substantially increasing ammonia volatilisation in the studied systems. Temperature positively correlated with ammonia emissions. On the whole, during the two years of the study, the PS treatments presented higher average cumulative ammonia volatilisation (25% of total ammonium nitrogen (TAN) applied at Site 1; 21% of TAN applied at Site 2) than the mineral ones (11% of TAN applied at Site 1; 10% of TAN applied at Site 2). At pre-sowing, ammonia volatilisation was significantly (p < .05) lower (51% at Site 1; 55% at Site 2) than after ryegrass cuts due to burying PS immediately after application. Overall, applying DMPP had no effect on ammonia volatilisation. There were no significant differences in average yield (from 13.7 to 15.8 kg ha-1 at Site 1; from 11.6 to 13.5 kg ha-1 at Site 2) between the fertilised treatments, though ENTEC® tended to increase it. Applying PS (pre-sowing fertilisation) in combination with mineral N or processed PS fractions after ryegrass cuts could be an interesting option for the recycling of this livestock by-product without increasing ammonia volatilisation while maintaining yields.

Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): study protocol for a multicenter randomized Phase II non-inferiority clinical trial.

BACKGROUND: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. METHODS/DESIGN: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. CONCLUSION: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.