mTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels) / Los inhibidores de mTOR como potencial factor predisponente para la hepatitis crónica E: resultados del estudio prospectivo colaborativo CHES (Chronic Hepatitis E Screening in patients with immune impairment and increased transaminases levels)

Background: Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. Patients and methods: CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. Results: Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. Conclusions: Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E. (AU)

Introducción: La infección crónica por el virus de la hepatitis E (VHE) en personas con disfunción inmunitaria tiene un curso progresivo conllevando una rápida progresión a cirrosis hepática. Sin embargo, los datos prospectivos a este respecto son escasos. El objetivo de este estudio fue determinar la prevalencia y factores de riesgo para la infección crónica VHE en sujetos con disfunción inmunitaria y elevación de enzimas hepáticos. Pacientes y métodos: CHES es un estudio prospectivo multicéntrico que incluyó adultos con transaminasas elevadas durante al menos 6 meses y alguno de estos factores: receptores de trasplante, infección por VIH, hemodiálisis, cirrosis hepática o tratamiento inmunosupresor. En todos los sujetos se realizaron IgG/IgM anti-VHE (Wantai Elisa) y ARN-VHE por una técnica super sensible (Roche Diagnostics). Además, todos los participantes contestaron una encuesta epidemiológica. Resultados: 381 pacientes fueron incluidos: 131 trasplantados, 115 cirróticos, 51 infectados por VIH, 87 bajo inmunosupresores, 4 hemodiálisis. En total, 210 sujetos recibían inmunosupresores. La IgG anti-VHE fue positiva en 94 (25,6%) sujetos, con tasas similares en todas la causas de disfunción inmunitaria. El ARN-VHE fue positivo en 6 (1,6%) pacientes, todos ellos trasplantados, siendo la tasa de infección crónica VHE en receptores de órgano sólido del 5,8%. En la población de trasplantados, solo el tratamiento con inhibidores de mTOR se asoció de forma independiente a la hepatitis crónica VHE, mientras que los niveles de ALT impactaron en el modelo general. Conclusiones: A pesar de los niveles anormales de transaminasas, solo se objetivó hepatitis crónica VHE en trasplantados de órgano sólido. En esta población, la tasa de hepatitis crónica VHE fue del 5,8% y solo el tratamiento con inhibidores de mTOR se asoció de forma independiente a la hepatitis crónica E. (AU)

Chronic Functional Adaptations Induced by the Application of Transcranial Direct Current Stimulation Combined with Exercise Programs: A Systematic Review of Randomized Controlled Trials.

The present systematic review aimed to determine the chronic effects of the combination of transcranial direct current stimulation (tDCS) and exercise on motor function and performance outcomes. We performed a systematic literature review in the databases MEDLINE and Web of Science. Only randomized control trials that measured the chronic effect of combining exercise (comprising gross motor tasks) with tDCS during at least five sessions and measured any type of motor function or performance outcome were included. A total of 22 interventions met the inclusion criteria. Only outcomes related to motor function or performance were collected. Studies were divided into three groups: (a) healthy population (n = 4), (b) neurological disorder population (n = 14), and (c) musculoskeletal disorder population (n = 4). The studies exhibited considerable variability in terms of tDCS protocols, exercise programs, and outcome measures. Chronic use of tDCS in combination with strength training does not enhance motor function in healthy adults. In neurological disorders, the results suggest no additive effect if the exercise program includes the movements pretending to be improved (i.e., tested). However, although evidence is scarce, tDCS may enhance exercise-induced adaptations in musculoskeletal conditions characterized by pain as a limiting factor of motor function.

Gut Microbiota Composition in Long-Remission Ulcerative Colitis is Close to a Healthy Gut Microbiota.

BACKGROUND: Microbiome studies report low gut microbial richness and diversity in ulcerative colitis (UC) patients. We explored whether UC patients who reach long-term clinical, endoscopic, and histological remission show a gut microbial ecosystem that is similar to healthy individuals. METHODS: We collected 184 stool samples from 111 individuals (UC patients in long remission, short remission, flare, and healthy control subjects). Microbiota was analyzed by amplicon sequencing (16S ribosomal RNA) and quantitative polymerase chain reaction for specific taxa. All UC remission patients were followed-up for 2 years. FINDINGS: A drop in species diversity and richness, underrepresentation of butyrate producers, and gain of potentially harmful bacteria were significantly detected in samples from disease-flare and short-remission patients. In contrast, Chao1 and Shannon indexes of diversity did not differ among patients in long remission and healthy control subjects. Long-remission patients also presented fecal bacterial composition closer to that in healthy control subjects. There was a positive correlation between Akkermansia muciniphila abundance and time in remission (rs = 0.53, P < .001). Logistic regression analysis showed that a high Shannon index (odds ratio, 4.83; 95% confidence interval, 1.5-20.6) or presence of A. muciniphila (odds ratio, 4.9; 95% confidence interval, 1.12-29.08) in fecal samples at entry was independently associated with clinical remission over a follow-up period of 24 months. INTERPRETATION: UC patients who achieve long-term remission show evidence of substantial recovery of the gut microbial ecosystem in terms of diversity and composition. Recovery may just reflect adequate control of inflammatory activity, but higher bacterial diversity or the presence of A. muciniphila in fecal samples predicts flare-free outcomes.

Microbiome studies have shown low gut microbial richness and diversity in ulcerative colitis patients. Patients who achieve long-term remission show evidence of substantial recovery of the gut microbial ecosystem in terms of diversity and composition.

Severe and refractory gastrointestinal toxicity due to immune checkpoint inhibitors: clinical experience in a tertiary referral hospital.

INTRODUCTION: immune checkpoint inhibitors (ICI) are increasingly used to treat several types of cancer. These drugs lead to a wide range of toxicities. Immune-related gastrointestinal adverse events are common and potentially severe. In this manuscript, we recount the real clinical experience in a tertiary center. METHODS: a retrospective and observational study was conducted in adult patients under ICI treatment. Included patients had been referred to the Gastrointestinal Service of Hospital Universitario Vall d'Hebron for evaluation of severe toxicities, from January 2017 to January 2020, for whom the clinical, epidemiological and evolutive data were collected. RESULTS: a total of 18 patients were included. Fifty-five percent received anti-programmed cell death protein 1 (PD-1)/anti-programmed death-ligand 1 (anti PD-L1), 11 % received anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and 33 % received both treatments. The toxicities were manifested as enterocolitis, microscopic colitis and gastritis. Upper gastrointestinal endoscopy was performed in seven patients; all were proved to have histological changes on duodenum biopsies. Treatment was stopped in all patients and steroids were initiated. Sixty-six per cent achieved clinical remission with steroids. Five patients received anti-TNF treatment (infliximab). Only one of the five had responded. Two anti-TNF refractory patients received ustekinumab, with an appropriate clinical response. One patient received apheresis granulocyte as concomitant treatment. A patient with a steroid-dependent course started vedolizumab. Three patients had other immune-related adverse events. CONCLUSION: gastrointestinal immune-related adverse events are acquiring a higher profile in daily practice and gastroenterologists play an even greater role in the management of these patients.

Influencia de la obesidad, los factores sociodemográficos y las características del parto en la aparición de la hemorragia posparto / Influence of obesity, sociodemograpgical factors and characteristitcs of delivery on the development of post-partum hemorrhage

Objetivo: analizar la asociación de las características sociodemográficas, la obesidad pregestacional, la ganancia ponderal excesiva durante la gestación y las características del parto, con el riesgo de sufrir una hemorragia posparto (HPP).Método: estudio descriptivo, transversal, retrospectivo realizado con mujeres cuyos partos acontecieron en el año 2018 en un hospital de segundo nivel. Se incluyeron mujeres gestantes con parto único, con un recién nacido vivo, a término, con parto vaginal y con un completo control gestacional en el hospital. Se recogió información de la historia clínica acerca de la edad y el origen de la mujer, el índice de masa corporal pregestacional, la ganancia ponderal durante la gestación y diferentes variables relacionadas con el parto. La variable resultado fue la HPP (> 500mL).Resultados: se incluyeron N= 831 mujeres. La edad media fue de 31,8 años (DE:5,38), el 62,7% era española; el 64,6%, multípara; el 41,7% presentaba sobrepeso/obesidad pregestacional; el 26,2%, una ganancia ponderal excesiva durante la gestación; el 89,3% tuvo un parto eutócico y el 70,4% de los alumbramientos fue dirigido. Veinte mujeres presentaron HPP (2,4%). No se halló asociación con ninguna característica de las estudiadas a excepción del tipo de alumbramiento (p= 0,039). Las pacientes con alumbramiento no-espontáneo presentaron mayor riesgo de sufrir HPP: 5,39 veces más (1,13-25,75; p= 0,022) cuando el alumbramiento era dirigido y 5,29 (1,3-21,69; p= 0,013) cuando era manual.Conclusiones: ni los factores sociodemográficos ni las características antropométricas pre y posgestacionales influyen en la aparición de HPP. Un alumbramiento no-espontáneo aumenta el riesgo de HPP hasta cinco veces más. Estos datos deben ser interpretados con cautela.(AU)

Objective: to analyse the association of sociodemographic characteristics, pre-pregnancy obesity, excessive weight gain during pregnancy and characteristics of delivery with the risk of suffering a post-partum haemorrhage (PPH).Method: a retrospective, cross-sectional, descriptive study conducted with women who gave birth during 2018 in a second level hospital. The study included pregnant women with single birth of a live newborn at term, with vaginal delivery and complete pregnancy monitoring at hospital. The following information was collected from the clinical record: age and origin of the mother, pre-pregnancy body mass index, weight gain during pregnancy, and different variables associated with delivery. The outcome variable was PPH (> 500mL).Results: the study included N= 831 women; their mean age was 31.8 years (SD:5.38), 62.7% were Spanish; 64.6% were multiparous; 41.7% presented pre-pregnancy overweight / obesity; 26.2% had an excessive weight gain during pregnancy; 89,3% had natural deliveries and 70,4% of deliveries were directed. Twenty women presented PPH (2.4%). No association was found with any of the characteristics studied, except for type of delivery (p= 0.039). Patients with non-spontaneous delivery presented higher risk of suffering PPH; 5.39 times more (1.13-25.75; p= 0.022) when delivery was directed and 5.29 (1.3-21.69; p= 0.013) when it was manual.Conclusions: neither sociodemographic factors nor pre and post-pregnancy anthropometric characteristics have influence on the development of PPH. Non-spontaneous delivery increases the risk of PPH up to five times more. These data must be interpreted cautiously.(AU)

mTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels).

BACKGROUND: Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. PATIENTS AND METHODS: CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. RESULTS: Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. CONCLUSIONS: Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.

Health-related quality of life decline in clinically stable inflammatory bowel disease patients during the COVID-19 outbreak.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) affects many aspects of a patient's life and impairs their health-related quality of life (HRQoL). The COVID-19 outbreak has led to important mobility restrictions and a dramatic re-adjustment of social habits and health systems. This study aimed to assess the influence of the outbreak and mobility restrictions on the HRQoL of IBD patients with stable clinical remission on biologic treatment. Their self-perceived stress scores during the outbreak were also assessed. METHODS: A prospective, observational study was performed in IBD patients on biologic treatment with stable clinical remission. Patients with both Crohn's disease and Ulcerative Colitis patients were included. Patients filled in the IBDQ9 and the Perceived stress scale (PSS) electronically. To determine any changes, the results of the IBDQ9 during the outbreak were compared with the last IBDQ9 before the outbreak. RESULTS: 106 patients in clinical remission were included, with a median age of 42 year, 42% were female and 77% had CD. Median preCOVID-19 IBDQ9 was 72.1[66.5-80.12] and decreased to 69.2 [63.1-77.10] during the outbreak (p<0.001). The median PSS score was 12 [9-19]. There was a significant negative correlation between the PSS and the outbreak IBDQ9 (r=-0.66, p< 0.001). Regression analysis showed that the PSS score was associated with a lower IBDQ-9 during the outbreak(p<0.001) Conclusion: There was a negative impact of the COVID19 outbreak on the HRQoL of IBD patients in remission, with higher self-perceived stress scores associated with a lower QoL. The COVID-19 outbreak may have long-term implications for the HRQoL in these patients.

Health-related quality of life decline in clinically stable inflammatory bowel disease patients during the COVID-19 outbreak

Background and aims: Inflammatory bowel disease (IBD) affects many aspects of a patient’s life and impairs their health-related quality of life (HRQoL). The COVID-19 outbreak has led to important mobility restrictions and a dramatic re-adjustment of social habits and health systems. This study aimed to assess the influence of the outbreak and mobility restrictions on the HRQoL of IBD patients with stable clinical remission on biologic treatment. Their self-perceived stress scores during the outbreak were also assessed. Methods: A prospective, observational study was performed in IBD patients on biologic treatment with stable clinical remission. Patients with both Crohn’s disease and Ulcerative Colitis patients were included. Patients filled in the IBDQ9 and the Perceived stress scale (PSS) electronically. To determine any changes, the results of the IBDQ9 during the outbreak were compared with the last IBDQ9 before the outbreak. Results: 106 patients in clinical remission were included, with a median age of 42 year, 42% were female and 77% had CD. Median preCOVID-19 IBDQ9 was 72.1[66.5-80.12] and decreased to 69.2 [63.1-77.10] during the outbreak (p<0.001). The median PSS score was 12 [9-19]. There was a significant negative correlation between the PSS and the outbreak IBDQ9 (r=-0.66, p< 0.001). Regression analysis showed that the PSS score was associated with a lower IBDQ-9 during the outbreak(p<0.001) Conclusion: There was a negative impact of the COVID19 outbreak on the HRQoL of IBD patients in remission, with higher self-perceived stress scores associated with a lower QoL. The COVID-19 outbreak may have long-term implications for the HRQoL in these patients (AU)

Severe and refractory gastrointestinal toxicity due to immune checkpoint inhibitors: clinical experience in a tertiary referral hospital

Introduction: immune checkpoint inhibitors (ICI) are increasingly used to treat several types of cancer. These drugs lead to a wide range of toxicities. Immune-related gastrointestinal adverse events are common and potentially severe. In this manuscript, we recount the real clinical experience in a tertiary center. Methods: a retrospective and observational study was conducted in adult patients under ICI treatment. Included patients had been referred to the Gastrointestinal Service of Hospital Universitario Vall d’Hebron for evaluation of severe toxicities, from January 2017 to January 2020, for whom the clinical, epidemiological and evolutive data were collected. Results: a total of 18 patients were included. Fifty-five percent received anti-programmed cell death protein 1 (PD-1)/ anti-programmed death-ligand 1 (anti PD-L1), 11 % received anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and 33 % received both treatments. The toxicities were manifested as enterocolitis, microscopic colitis and gastritis. Upper gastrointestinal endoscopy was performed in seven patients; all were proved to have histological changes on duodenum biopsies. Treatment was stopped in all patients and steroids were initiated. Sixty-six per cent achieved clinical remission with steroids. Five patients received anti-TNF treatment (infliximab). Only one of the five had responded. Two anti-TNF refractory patients received ustekinumab, with an appropriate clinical response. One patient received apheresis granulocyte as concomitant treatment. A patient with a steroid-dependent course started vedolizumab. Three patients had other immune-related adverse events. Conclusion: gastrointestinal immune-related adverse events are acquiring a higher profile in daily practice and gastroenterologists play an even greater role in the management of these patients. (AU)

Co Treatment With Biologic Agents and Immunotherapy in the Setting of irAEs of Difficult Management.

In recent years, immunotherapy has become an important pillar of cancer treatment, with high response rates regardless of tumor histology or baseline mutations, sometime in patients without any alternative of treatment. Moreover, these treatments are moving from later line therapies to front-line therapies in the metastasic setting. However, immune activation associated with immune check-point inhibitors (ICI) is not selective and a large variety of immune-related adverse events, with an increasing frequency, have been associated with anti-PD1, anti-PD-1/L-1 and anti-CTLA-4 agents. In clinical trials, and sometimes also in real life practice, patients who develop severe toxicities on ICI-based therapies are usually not allowed to resume ICI once their disease progresses, because of the chance of developing severe irAEs on rechallenge with immunotherapies. Moreover, patients with irAEs suffer important side effects due to the high dose corticosteroids that are used to treat them. Therapy with ICI is sometimes the only alternative for certain patients, and for this reason co treatment with classic (DMARDS) or biologic immunosuppression therapy and ICI must be considered. Co-treatment with this type of immunosuppressant drugs, apart from allowing the maintenance of ICI therapy, drive to a lesser use of corticosteroids, with an improvement of the safety and quality of life of the patients. Such a tailored scheme of treatment is mostly an expert opinion based on recommendation and currently there is scarce evidence supporting it. Herein we present comprehensive, current recommendations and real-world data on the use of co-treatment with ICI and DMARDS and biologic immunosuppression.

Impacto de la infección por COVID-19 durante la gestación / Impact of COVID-19 infection during pregnancy

Objetivo: analizar el impacto de la infección por SARS-CoV-2 en mujeres gestantes sobre las consecuencias obstétricas y perinatales. Método: estudio descriptivo, longitudinal, observacional y retrospectivo realizado en el Hospital Infanta Cristina (Parla, Madrid) en mujeres gestantes con infección por COVID-19 durante la segunda mitad del embarazo y/o parto, desde el inicio de la pandemia en España en marzo hasta diciembre de 2020. Se analizó la asociación entre la necesidad de ingreso hospitalario y las variables sociodemográficas, antropométricas y de la gestación con la prueba T de Student, U de Mann-Whitney. Chi cuadrado de Pearson y prueba exacta de Fisher con una significación p< 0,05. Resultados: se incluyeron 46 mujeres. De estas un 37% era española y su edad media fue de 31,3 años. El índice de masa corporal (IMC) medio de las mujeres gestantes fue de 25,9 kg/m2, mayoritariamente fueron multíparas con una media gestacional en el momento del diagnóstico de 33,8 semanas y predominando las gestantes asintomáticas (54,23%) seguido de los síntomas como tos y disnea (13%) y fiebre (13%). Precisaron ingreso hospitalario cuatro mujeres de las cuales una requirió cuidados intensivos. No se hallaron diferencias significativas según el ingreso hospitalario, aunque la edad gestacional en el momento del parto fue más baja entre las mujeres hospitalizadas (38 vs. 39,5 semanas; p= 0,095) y su IMC fue superior (29,7 vs. 25 kg/m2; p= 0,559). No se produjo ninguna muerte perinatal. Conclusiones: la infección por COVID-19 no parece influir en la evolución de la gestación ni en la supervivencia perinatal, aunque se precisa más investigación al respecto.(AU)

Objective: to analyse the impact of the infection by SARS-CoV-2 in pregnant women, in terms of obstetric and perinatal consequences. Method: a descriptive, longitudinal, observational and retrospective study conducted in the Hospital Infanta Cristina (Parla, Madrid) with pregnant women infected with COVID-19 during the second half of their pregnancy and/or labour, since the start of the pandemic in Spain in March until December 2020. The association between the need for hospital admission and sociodemographic, anthropometric and pregnancy variables was analysed with the Student’s T test, Mann Whitney U test, Pearson’s Chi Squared and Fisher’s Exact Test, with a p< 0.05 significance. Results: the study included 46 women; 37% of them were Spanish, and their mean age was 31.3 years. The mean Body Mass Index (BMI) of the pregnant women was of 25.9 kg/m2, the majority were multiparous, and there was a predominance of asymptomatic pregnancies (54.23%) followed by symptoms such as cough and dyspnea (13%) and fever (13%). Four women required hospital admission, and one of them required Intensive Care. No significant differences were found according to hospital admission, although the gestational age at the time of delivery was lower among hospitalized women (38 vs. 39.5 weeks; p= 0.095) and their BMI was higher (29.7 vs. 25 kg/m2; p= 0.559). There were no perinatal deaths. Conclusions: infection by COVID19 does not seem to have any impact on pregnancy evolution or perinatal survival, although further research is required.(AU)

Effectiveness of a Telephone-Based Motivational Intervention for Smoking Cessation in Patients With Crohn Disease: A Randomized, Open-Label, Controlled Clinical Trial.

A randomized, open-label, controlled clinical trial was designed to assess the effectiveness of a motivational intervention based on the 5 R's model (relevance, risks, rewards, roadblocks, and repetition) delivered by specialized inflammatory bowel disease nurses every 3 months over a 1-year period as compared with patients who were followed regularly. Patients diagnosed with Crohn disease, aged 18 years or older, who reported being active smokers with Internet access at home and an e-mail address were eligible. A total of 144 patients (72 per group) were included (50% women, median age 40 years). They smoked a median of 10 cigarettes per day (range = 1-40) and had been smoking for a median of 22 years (range = 1-51). Motivation to quit (Richmond test) was low in 73 patients, moderate in 39 patients, and high in 32 patients. Statistically significant differences between the study groups in the predisposition to change, motivation to quit, and tobacco withdrawal were not found. However, 14 patients (20.9%) in the intervention group and 9 patients (13.2%) among controls stopped smoking at the end of the study. These findings support a higher trend toward smoking cessation associated with the motivational intervention 5 R's. This behavioral strategy can aid patients with Crohn disease to quit smoking.

Normalization of long-term quality of life in Crohn's disease patients receiving ustekinumab.

BACKGROUND AND AIM: ustekinumab is a fully human monoclonal antibody against IL-12/23, approved for induction and maintenance treatment of Crohn's disease (CD). Real-life data shows its true effectiveness in terms of clinical and endoscopic response. However, there is little information regarding health-related quality of life (HRQoL) in CD patients receiving ustekinumab. The main aim of this study was to define long-term clinical remission and HRQoL normalization. The clinical predictive factors of clinical remission were investigated as a secondary aim. METHODS: a retrospective, observational study was performed in CD patients under ustekinumab treatment in the Hospital Vall d'Hebron, between January 2009 and January 2019. Clinical remission was defined using the Crohn's Disease Activity Index (CDAI) and HRQoL normalization was defined by the 36-item Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: thirty-three patients were included. The average disease evolution was eleven years (standard deviation [SD]: 8), perianal disease was present in 13 patients (39 %), 30 patients (91 %) had previously been treated with alfa tumor necrosis factor antagonists (anti-TNF) agents and 22 patients (67 %) had a history of intestinal resection. Twenty-four patients (73 %) had undergone one year of treatment. Seventeen patients (51 %) reached clinical remission and six (18 %) restored the HRQoL. No predictors of clinical remission were identified. CONCLUSIONS: ustekinumab shows clinical effectiveness in real-life conditions similar to previous data. Normalization of HRQoL is low compared to clinical remission, which may be due to the inaccuracy of the indicator and the severe disease course. Such normalization is a challenge for physicians dealing with inflammatory bowel diseases.

Características de los partos de inicio espontáneo en fase de luna llena y fase de luna nueva / Characteristics of births with spontaneous onset on full moon phase and new moon phase

OBJETIVO: conocer el número de partos y las características de los partos de inicio espontáneo en fase de luna llena y fase de luna nueva. MÉTODO: estudio retrospectivo realizado en el Hospital Infanta Cristina (Parla, Madrid) en el periodo 2009-2015, en el que se atendieron un total de 11.948 partos. Criterios inclusión: mujeres gestantes que iniciaron el parto de forma espontánea durante las fases de luna llena y luna nueva (según las fases lunares establecidas por el Instituto Geográfico Nacional); parto eutócico, instrumental o cesárea urgente; gestaciones a término (≥ a 37 semanas y ≤ a 42 semanas). Los datos se obtuvieron de los libros de partos. Se efectuó un análisis descriptivo de las variables. RESULTADOS: 4.086 partos se iniciaron de forma espontánea en las dos fases lunares estudiadas: 2.035 (49,8%) en fase de luna llena y 2.051 (50,2%) en fase de luna nueva. Los partos durante la fase de luna llena, 1.002 (49,23%), fueron primíparas y 1.033 (50,77%) multíparas. Durante la fase de luna nueva, 1.005 (49,02%) fueron primíparas y 1.046 (50,98%) multíparas. La media (DE) de semanas de gestación en la muestra de luna llena fue de 39,31 (1,12) y en la fase de luna nueva fue de 39,27 semanas (1,10). No se detectaron diferencias significativas entre los partos en fase de luna llena y luna nueva. CONCLUSIONES: el número de partos y las características de los partos de inicio espontáneo son similares en las fases de luna llena y luna nueva

OBJECTIVE: to understand the number of births and the characteristics of labours with spontaneous onset on full moon phase and new moon phase. METHOD: a retrospective study conducted in the Hospital Infanta Cristina (Parla, Madrid) in the 2009-2015 period, where 11,948 labours were managed in total. Inclusion criteria: pregnant women with spontaneous-onset labour during the full moon and new moon phases (according to the moon phases determined by the National Geographic Institute); natural or instrumental delivery, or urgent caesarean section; full-term gestation (≥ 37 weeks and ≤ 42 weeks). Data were collected from the Register of Births. There was a descriptive analysis of variables. RESULTS: in total, 4,086 labours were spontaneously initiated in the two moon phases studied: 2,035 (49.8%) in full moon phase and 2,051 (50.2%) in new moon phase. During the new moon phase, 1,005 (49.02%) were primiparous and 1,046 (50.98%) were multiparous. The mean (SD) weeks of gestation in the full moon sample were 39,31 (1.12), and in the new moon phase, 39,27 weeks. (1.10). No significant differences were detected between labours in the full moon and new moon phases. CONCLUSIONS: the number of births and the characteristics of labours with spontaneous onset are similar in the full moon and the new moon phases

Postural Stability and Cognitive Performance of Subjects With Parkinson's Disease During a Dual-Task in an Upright Stance.

BACKGROUND: The reviewed studies on center of pressure (COP) displacement in Parkinson's disease (PD) subjects show important methodological differences and contradictory results with regard to healthy subjects. The dual-task paradigm method has been used to examine cognitive prioritization strategies to control concurrent postural and cognitive tasks. The motor requirements, such as pronouncing words, involved in the cognitive tasks used in double-task conditions could be related to the heterogeneity of the results. RESEARCH OBJECTIVE: To compare postural sway and cognitive performance in subjects with PD and controls using a dual-task paradigm with a cognitive task free of motor demands. We tried to examine the prioritization strategy of PD patients regarding healthy adults to control for concurrent postural and cognitive tasks. MATERIALS AND METHODS: 25 subjects with PD and 20 healthy controls carried out a postural task under both single-task and dual-task conditions. The postural task was to stand as still as possible, with eyes first open and then closed. The dual-task condition added a concurrent cognitive task based on phoneme monitoring. COP displacement variables and cognitive performance were compared between the groups and within-subject factors were also examined. RESULTS: PD participants showed higher COP displacement results than the controls. All participants shortened the mean sway radius in dual-task conditions compared with single-task conditions; only healthy subjects presented less transversal COP sway in dual-task conditions than in single-task conditions. The cognitive performance of PD patients on a phoneme monitoring task worsened when they carried it out while maintaining balance in a standing position compared to sitting. The opposite effect occurred in control subjects. CONCLUSION: This study confirms the negative influence of Parkinson's disease on the control of standing stability, increasing the COP sway amplitude. The attentional demands of a postural task, such as standing balance, may be greater in PD patients than in healthy subjects. This would affect the performance of patients during dual-task conditions to be able to control a postural task while performing other cognitive tasks. In these conditions, cognitive performance would be negatively affected. These results suggest that subjects with PD, at least during initial disease stages, prioritize postural control over other concurrent tasks, as is also seen in healthy subjects.

Variability in non-invasive brain stimulation studies: Reasons and results.

Non-invasive brain stimulation techniques (NIBS), such as Theta Burst Stimulation (TBS), Paired Associative Stimulation (PAS) and transcranial Direct Current Stimulation (tDCS), are widely used to probe plasticity in the human motor cortex (M1). Although TBS, PAS and tDCS differ in terms of physiological mechanisms responsible for experimentally-induced cortical plasticity, they all share the ability to elicit long-term potentiation (LTP) and depression (LTD) in M1. However, NIBS techniques are all affected by relevant variability in intra- and inter-subject responses. A growing number of factors contributing to NIBS variability have been recently identified and reported. In this review, we have readdressed the issue of variability in human NIBS studies. We have first briefly discussed the physiological mechanisms responsible for TBS, PAS and tDCS-induced cortical plasticity. Then, we have provided statistical measures of intra- and inter-subject variability, as calculated in previous studies. Finally, we have reported in detail known sources of variability by categorizing them into physiological, technical and statistical factors. Improving knowledge about sources of variability could lead to relevant advances in designing new tailored NIBS protocols in physiological and pathological conditions.

Solutions for managing variability in non-invasive brain stimulation studies.

In the last three decades, a number of non-invasive brain stimulation (NIBS) protocols, capable of assessing and modulating plasticity in the human motor cortex (M1), have been described. For almost as long, NIBS has delivered the tantalising prospect of non-invasive neuromodulation as a therapeutic intervention for neurorehabilitation, psychiatry, chronic pain and other disease states. Apart from modest effects in depression, this early promise has not been realised since the symptomatic improvements produced by NIBS are generally weak. One key factor explaining this lack of clinical translation concerns variability in response to NIBS. Several studies have demonstrated a number of physiological, technical and statistical factors accounting for intra- and inter-subject variability. However, solutions to overcome this problem are still under debate. In the present review, we have provided a detailed description of methodological and technical solutions to control known factors influencing variability. We have also suggested potential strategies to strengthen and stabilize NIBS-induced after-effects. Finally, we propose new possible outcome variables which better reflect intrinsic cortical activity, allowing a more sensitive measurement and valid interpretation of responses to NIBS.

Rectal Aberrant Crypt Foci in Humans Are Not Surrogate Markers for Colorectal Cancer Risk.

INTRODUCTION: Over the past 20 years, aberrant crypt foci (ACF) have emerged as potential precursors and biomarkers for colorectal cancer (CRC). However, data regarding their molecular pathogenesis, as well as their endoscopic and histological identification, remain inconsistent. METHODS: A wide cohort of ACF from 100 control subjects and 100 case patients, including patients with adenoma and CRC, were characterized for endoscopic, morphologic, and molecular features. RESULTS: We observed that among all the endoscopic features evaluated, only the number of large ACF correlated with CRC risk (P = 0.003), whereas the histological classification, as assessed by 2 different pathologists, was inconsistent and did not differ between control and case patients. Moreover, only a few APC and BRAF mutations and no microsatellite instability were detected in our samples. KRAS mutations were detected in 16.3% of ACF samples, which also exhibited increased MGMT hypermethylation. However, none of those events were found to be predictive of CRC risk. DISCUSSION: Although ACF might be preneoplastic lesions of the colon, they are not suitable biomarkers for assessing CRC progression.

Distributed cortical structural properties contribute to motor cortical excitability and inhibition.

The link between the local structure of the primary motor cortex and motor function has been well documented. However, motor function relies on a network of interconnected brain regions and the link between the structural properties characterizing these distributed brain networks and motor function remains poorly understood. Here, we examined whether distributed patterns of brain structure, extending beyond the primary motor cortex can help classify two forms of motor function: corticospinal excitability and intracortical inhibition. To this effect, we recorded high-resolution structural magnetic resonance imaging scans in 25 healthy volunteers. To measure corticospinal excitability and inhibition in the same volunteers, we recorded motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation and short-interval intracortical inhibition (SICI) in a separate session. Support vector machine (SVM) pattern classification was used to identify distributed multi-voxel gray-matter areas, which distinguished subjects who had lower and higher MEPs and SICIs. We found that MEP and SICI classification could be predicted based on a widely distributed, largely non-overlapping pattern of voxels in frontal, parietal, temporal, occipital, and cerebellar regions. Thus, structural properties distributed over the brain beyond the primary motor cortex relate to motor function.

A Preliminary Comparison of Motor Learning Across Different Non-invasive Brain Stimulation Paradigms Shows No Consistent Modulations.

Non-invasive brain stimulation (NIBS) has been widely explored as a way to safely modulate brain activity and alter human performance for nearly three decades. Research using NIBS has grown exponentially within the last decade with promising results across a variety of clinical and healthy populations. However, recent work has shown high inter-individual variability and a lack of reproducibility of previous results. Here, we conducted a small preliminary study to explore the effects of three of the most commonly used excitatory NIBS paradigms over the primary motor cortex (M1) on motor learning (Sequential Visuomotor Isometric Pinch Force Tracking Task) and secondarily relate changes in motor learning to changes in cortical excitability (MEP amplitude and SICI). We compared anodal transcranial direct current stimulation (tDCS), paired associative stimulation (PAS25), and intermittent theta burst stimulation (iTBS), along with a sham tDCS control condition. Stimulation was applied prior to motor learning. Participants (n = 28) were randomized into one of the four groups and were trained on a skilled motor task. Motor learning was measured immediately after training (online), 1 day after training (consolidation), and 1 week after training (retention). We did not find consistent differential effects on motor learning or cortical excitability across groups. Within the boundaries of our small sample sizes, we then assessed effect sizes across the NIBS groups that could help power future studies. These results, which require replication with larger samples, are consistent with previous reports of small and variable effect sizes of these interventions on motor learning.