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Conflicto de intereses: NC y GL son empleados de Sanofi y pueden tener acciones u opciones sobre acciones. FG ha recibido subvenciones o ayudas a la investigación de Abbvie, Takeda, AB-Biotics, y honorarios por servicios de consulta prestados a Danone, Biocodex, Sanofi, Actial, Menarini. La redacción médica fue realizada por Javier Moran de Food consulting y fue financiada por Sanofi España., Introducción: El estreñimiento tiene una prevalencia del 14-30% en España, su causa es multifactorial y afecta negativamente al bienestar y a la calidad de vida de las personas. Entre los tratamientos para el estreñimiento funcional se encuentran los laxantes osmóticos como Macrogol 4000. El grado de satisfacción con los laxantes es proporcional a la efectividad y mejora de la calidad de vida percibidas. Método: se realizó una encuesta en farmacias españolas a 100 consumidores que adquirían Macrogol 4000 como producto sanitario, con objeto de tratar los síntomas del estreñimiento. Se midieron los cambios en la calidad de vida y la percepción subjetiva de la efectividad a los 4, 8 y 14 días de tratamiento empleando la metodología CATI, basada en encuestas telefónicas. Resultados: Tras 14 días de consumo se observó una reducción significativa (p, Introduction: Constipation has a prevalence of 14-30% in Spain, its cause is multifactorial and negatively affects people’s well-being and quality of life. Treatments for functional constipation include osmotic laxatives such as Macrogol 4000. The degree of satisfaction with laxatives is proportional to the perceived effectiveness and improvement in quality of life. Method: a survey was conducted in Spanish pharmacies among 100 consumers who purchased Macrogol 4000 as a medical device, in order to treat the symptoms of constipation. Changes in quality of life and subjective perception of effectiveness were measured after 4, 8 and 14 days of treatment using CATI methodology, based on telephone surveys. Results: After 14 days of consumption, a significant reduction (p, Este trabajo ha sido financiado por Sanofi España.

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

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 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.

Correlation of the three urinary biomarkers and plasma CA19.9 (CA19.9p). A, Correlation plots (Navy blue: Healthy; Turquoise: chronic pancreatitis (CP); Purple: pancreatic adenocarcinoma (PDAC). B, Pearson correlation coefficients and corresponding significance (NS: non-significant, *: p

Diagnostic performance of urine biomarkers in discriminating pancreatic adenocarcinoma all stages (A-C) and stage I-II (D-F) from chronic pancreatitis patients. A, ROC curves of PDAC (n=143) versus CP (n=62) patients for individual urine biomarkers in the training set (70% of the data). B, ROC curves of PDAC versus CP patients for the panel in the training set and in the independent validation set (30% of the data, PDAC n=49, CP n=30). C, Summary table. D, ROC curves of individual urine biomarkers in training dataset (70%, PDAC stage I-II n= 56, CP=66). E, ROC curves of the panel in training and validation (PDAC stage I-II n=15, CP n=26) dataset. F, Summary table. Cnorm, creatinine-normalised, creat, creatinine, AUC: area under the curve SN: sensitivity, SP: specificity with 95% Confidence Interval (CI). SN and SP in the validation set were derived for optimal cutpoint determined in the training dataset.

Expression of the protein biomarkers in pancreatic cancer tissues. A, Immunohistochemical analysis of REG1A: i) REG1A in poorly differentiated PDAC, ii) luminal REG1A in malignant glands. B, TFF1: i) heterogenous expression in cancer,, ii) luminal TFF1 in malignant gland. C, LYVE1 expression in the scattered lymphatic vessels i) in the muscle layer and ii) in the stroma surrounding malignant gland. D, The biomarker levels during monitoring of pancreatic adenocarcinoma patients: LYVE1, REG1A and TFF1 were measured using ELISA in urine samples collected before surgery and during the patient's follow up. Each point represents log-transformed ELISA values at a particular time point (x-axis).

Exploratory comparison of plasma CA19.9 and the urine biomarker panel in discriminating early pancreatic adenocarcinoma from chronic pancreatitis patients. A, ROC curves of the biomarker panel with corresponding plasma CA19.9 alone and in combination comparing CP urine (n=50), and urines from PDAC stages I-II (n=71) and, I-IIA (n=16) (B). C, Summary table. AUC: area under the curve, SN: sensitivity, SP: specificity with 95% Confidence Interval (CI). SN and SP in the validation set were derived for optimal cutpoint determined in the training dataset.

Supplementary Figure Legends from Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma

Urine biomarker concentrations in different tumours. Scatter dot plots of urine LYVE1, REG1A and plasma CA19.9 in different hepatobiliary pathologies and early stages of pancreatic adenocarcinoma (I-IIA, n=16) and I-II (n=71). The level of TFF1 protein was not measured in these samples due to substantial modifications made to the original ELISA assay by the source company at the moment of this analysis. IPMN (n=33): intraductal papillary mucinous neoplasm, AMP (n=26): ampullary cancer, NET (n=18): neuroendocrine tumour, CHL (n=24): cholangiocarcinoma, DuCA (n=16): duodenal cancer. Bars indicate median and IQR values. Upper bars: Kruskal-Wallis/Dunn's post test, *: p0.05 (no adjustment for multiplicity was made).

Expression of non-redundant proteins identified by GeLC-MS/MS from males and females in healthy controls, chronic pancreatitis and pancreatic adenocarcinoma patients.

Urine proteome analysis. A, schematic outline of the study. B, classification of total identified proteins according to sub-cellular localisation and C, functional activity determined by Ingenuity Pathway Analysis. H: healthy, CP: chronic pancreatitis, PDAC: pancreatic ductal adenocarcinoma, GeLC/MS/MS: SDS-PAGE-Liquid Chromatography-Tandem Mass Spectrometry.

Previous studies have shown that a resistant dextrin soluble fibre has prebiotic properties with related health benefits on blood glucose management and satiety. Our aim was to demonstrate the effects of continuous administration of resistant dextrin on intestinal gas production, digestive sensations, and gut microbiota metabolism and composition. Healthy subjects (n = 20) were given resistant dextrin (14 g/d NUTRIOSE®, Roquette Frères, Lestrem, France) for four weeks. Outcomes were measured before, at the beginning, end, and two weeks after administration: anal evacuations of gas during daytime; digestive perception, girth, and gas production in response to a standard meal; sensory and digestive responses to a comfort meal; volume of colonic biomass by magnetic resonance; taxonomy and metabolic functions of fecal microbiota by shotgun sequencing; metabolomics in urine. Dextrin administration produced an initial increase in intestinal gas production and gas-related sensations, followed by a subsequent decrease, which magnified after discontinuation. Dextrin enlarged the volume of colonic biomass, inducing changes in microbial metabolism and composition with an increase in short chain fatty acids-producing species and modulation of bile acids and biotin metabolism. These data indicate that consumption of a soluble fibre induces an adaptative response of gut microbiota towards fermentative pathways with lower gas production., This work was supported by a grant from Roquette. The research activities were supported in part by the projects PID2021-122295OB-I00 (Ministerio de Ciencia e Innovación, Spain), PID2019-103914RB-I00 (Ministerio de Ciencia e Innovación, Spain), AGL2016-78311-R (Ministerio de Ciencia e Innovación, Spain) and FJC2019-042125-I (Ministerio de Ciencia e Innovación, Spain). Ciberehd is funded by the Instituto de Salud Carlos III.

20 p.-5 fig., Bacterial β-glucans are exopolysaccharides (EPSs), which can protect bacteria or cooperate in biofilm formation or in bacterial cell adhesion. Pediococcus parvulus 2.6 is a lactic acid bacterium that produces an O-2-substituted (1-3)-β-D-glucan. The structural similarity of this EPS to active compounds such as laminarin, together with its ability to modulate the immune system and to adhere in vitro to human enterocytes, led us to investigate, in comparison with laminarin, its potential as an immunomodulator of in vitro co-cultured Caco-2 and PMA-THP-1 cells. O-2-substituted (1-3)-β-D-glucan synthesized by the GTF glycosyl transferase of Pediococcus parvulus 2.6 or that by Lactococcus lactis NZ9000[pGTF] were purified and used in this study. The XTT tests revealed that all β-glucans were non-toxic for both cell lines and activated PMA-THP-1 cells’ metabolisms. The O-2-substituted (1-3)-β-D-glucan modulated production and expression of IL-8 and the IL-10 in Caco-2 and PMA-THP-1 cells. Laminarin also modulated cytokine production by diminishing TNF-α in Caco-2 cells and IL-8 in PMA-THP-1. All these features could be considered with the aim to produce function foods, supplemented with laminarin or with another novel β-glucan-producing strain, in order to ameliorate an individual’s immune system response toward pathogens or to control mild side effects in remission patients affected by inflammatory bowel diseases, This work was supported by the Spanish Ministry of Science, Innovation and Universities (grant RTI2018-097114-B-I00), by the Fondo de Investigación Sanitaria, grant number PI12/00263 and by CIBERehd.

Bacillus clausii; Microbiota; Dysbiosis Bacillus clausii; Microbiota; Disbiosis Bacillus clausii; Microbiota; Disbiosi The gut microbiota is intrinsically linked to human health; disturbances in microbial homeostasis are implicated in both intestinal and extraintestinal disorders. Probiotics are “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host,” and many commercial preparations comprising a diverse range of species are available. While probiotics have been much researched, better understanding of the probiotic effects and applications of species such as Bacillus clausii is warranted. In this narrative literature review, we review the characteristics and mechanisms of action supporting B. clausii as a probiotic and discuss the evidence from clinical studies evaluating B. clausii probiotics for the management of a variety of gastrointestinal disorders and symptoms in children and adults. Finally, we highlight the challenges of future research and the need for more robust and diverse clinical evidence to guide physicians in the clinical application of probiotics for gastrointestinal disorders and other conditions. This study and the journal’s Rapid Service and Open Access Fees were funded by Sanofi.

Objectives Navajo Nation is disproportionately affected by hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease that can quickly progress to respiratory failure and cardiogenic shock. The initial signs and symptoms of HCPS are indistinguishable from coronavirus disease 2019 (COVID-19). However, this distinction is critical, as the disease course differs greatly, with most patients with COVID-19 experiencing mild to moderate illness. We set out to determine if the evaluation of peripheral blood smears for five hematopathologic criteria previously identified as hallmarks of hantavirus infection, or “the hantavirus 5-point screen,” could distinguish between COVID-19 and HCPS. Methods The hantavirus 5-point screen was performed on peripheral blood smears from 139 patients positive for COVID-19 seeking treatment from Tséhootsooí Medical Center and two Emory University hospitals. Results Of these 139 individuals, 136 (98%) received a score of 3/5 or below, indicating low suspicion for HCPS. While thrombocytopenia, one of the key signs of HCPS, was seen in the patients with COVID-19, it was generally mild and remained stable on repeat specimens collected 12 to 24 hours later. Conclusions Given these findings, the 5-point screen remains a useful rapid screening tool for potential HCPS cases and may be useful to distinguish early HCPS from COVID-19 in HCPS endemic regions.

Mycobacterial infections, including those caused by members of the mycobacterium tuberculosis complex [MTC] and Nontuberculous mycobacteria [NTM], can induce widespread morbidity and mortality in people. Mycobacterial infections cause both a delayed immune response, which limits rate of bacterial clearance, and formation of granulomas, which contain bacterial spread, but also contribute to lung damage, fibrosis, and morbidity. Granulomas also limit access of antibiotics to bacteria, which may facilitate development of resistance. MTC members resistant to some or all antibiotics are estimated to account for a third of deaths from tuberculosis [TB], and newly developed antibiotics have already engendered resistance, pointing to the need for new therapeutic approaches. Imatinib mesylate, a cancer drug used to treat chronic myelogenous leukemia [CML] that targets Abl and related tyrosine kinases, is a possible host-directed therapeutic [HDT] for mycobacterial infections, including TB. Here, we use the murineMycobacterium marinum[Mm] infection model, which forms quantifiable granulomas on the tails, in conjunction with transcriptomic analysis of the tail lesions. The data indicate that imatinib induces gene signatures indicative of immune activation at early time points post infection that resemble those seen at later ones, suggesting that imatinib accelerates but does not substantially alter anti-mycobacterial immune responses. Moreover, focusing on the TNFα pathway, which is induced by imatinib, we show that imatinib promotes cell survival in infected bone marrow-derived macrophages [BMDMs] in a manner that depends on caspase 8. Moreover, imatinib limits formation and growth of granulomas, an effect abrogated in mice lacking caspase 8. These data provide evidence for the utility of imatinib as an HDT for mycobacterial infections in accelerating immune responses, and limiting pathology associated with granulomas, and thus mitigating post-treatment morbidity.Author SummaryMycobacterial infections remain an important cause of morbidity and mortality in humans; for example,Mycobacterium tuberculosis[Mtb], the cause of tuberculosis [TB], kills ∼1.5 million and newly infects ∼10 million each year. Although most people effectively combat mycobacterial infections, treatment is compromised in at-risk individuals by an indolent immune response and chronic inflammation, which results in granulomas that encase the bacteria and limit spread. Granulomas also contribute to tissue damage and limit access of antibiotics to bacteria, which engenders resistance. We proposed using imatinib mesylate, a host directed therapeutic [HDT], against mycobacteria. Imatinib, a cancer therapeutic that inhibits Abl and related tyrosine kinases, alters intracellular transit of bacteria during infection. Using systems biology approaches in conjunction with murine infections withMycobacterium marinum, a close genetic relative of Mtb that forms tail granulomas, we report that imatinib does not fundamentally alter the anti-mycobacteria immune response, but rather accelerates it. In addition, imatinib limits granuloma formation and growth, an effect abrogated in mice lacking caspase 8. These data highlight imatinib as a possible HDT for mycobacterial infections including TB with the capacity to augment the immune response in at-risk individuals, and limit granuloma growth, thereby limiting tissue damage.

There is no consensus on how to evaluate inflammatory activity in Takayasu's arteritis (TAK). Here we compare biochemical tests and three clinical scores, which evaluate inflammatory activity (IA) in TAK, versus quantitative 18F-FDG PET/CT as the gold standard.This prospective study included patients with TA diagnosed according to the American College of Rheumatology (ACR) criteria. IA was assessed through laboratory tests, clinical scores of the National Institute of Health (NIH), Dabague-Reyes (DR) and the Indian Takayasu Clinical Activity Score 2010 (ITAS2010), and the result of these assessments was compared against 18F-FDG PET/CT Standardised Uptake Values (SUVmax).A total of 35 patients were studied, 86% were women. SUVmax had positive correlations with acute phase reactants and DR and NIH. Agreement of 18F-FDG PET/CT was significant with erythrocyte sedimentation rate (ESR) and DR score. Receiver Operating Characteristic (ROC) curve analysis showed diagnostic value for inflammatory activity in ESR, DR and NIH scores, which had higher specificity when they were estimated with new cut-off points for the Mexican population.ESR and other phase reactants have good sensitivity but low specificity to evaluate IA in TAK when compared against 18F-FDG PET/CT. Among all the clinical scores, DR had the best diagnostic value, with strong potential as a clinical tool to define the inflammatory status in TAK patients when the study image is not available. However, in complex TAK cases with doubtful diagnosis after assessment by clinical scores or laboratory, 18F-FDG PET/CT remains mandatory.

The potential transient vanilloid receptor type 1 (TRPV1) plays important functional roles in the vascular system. In the present study, we explored the role of the TRPV1 in the production of nitric oxide (NO), biopterines (BH4 and BH2), cyclic guanosine monophosphate (cGMP), malondialdehyde (MDA), phosphodiesterase-3 (PDE-3), total antioxidant capacity (TAC), and calcitonin gene-related peptide (CGRP) in the rat aorta. Wistar rats were divided into four groups: (1) control, (2) capsaicin (CS, 20 mg/kg), (3) capsazepine (CZ, 24 mg/kg), and (4) CZ + CS. Treatments were applied daily for 4 days before removing the thoracic aortas for testing of aortic tissue and endothelial cells. TRPV1 activation produced increases in BH4 14%, cGMP 25%, NO 29%, and TAC 59.2% in comparison to the controls. BH2 and MDA increased with CZ. CGRP shows a tendency to decrease with CZ. The analysis by immunocytochemistry confirmed that the TRPV1 is present in aortic endothelial cells. Aortic endothelial cells were obtained from healthy rats and cultured to directly explore the effects of CS and CZ. The activation of the TRPV1 (CS 30 μM) produced increases in BH4 17%, NO 36.6%, TAC 56.3%, and CGRP 65%, when compared to controls. BH2 decreased with CZ + CS. CS effects were diminished by CZ in cells and in the tissue. We conclude that the TRPV1 is a structure present in the membrane of aortic endothelial cells and that it participates in the production of NO. The importance of the TRPV1 should be considered in vascular reactivity studies.

El papel del modelado estadistico en la gestion de emergencias es fundamental para perfilar o apoyar las decisiones en torno a la atencion de los eventos. En 2020 con el surgimiento de la pandemia por coronavirus, los paises rapidamente se prepararon para la atencion del comportamiento de contagio y el impacto que tendria en la salud publica. En Costa Rica, un equipo de especialistas preparo estudios sobre el comportamiento de la curva de contagio y su efecto en la ocupacion de camas hospitalarias durante los primeros tres meses de la presencia de la epidemia. Los estudios se basaron en la estimacion de modelos estadisticos de crecimiento exponencial y logistico, los cuales proporcionaron los pronosticos del numero de casos diarios y acumulados. La prediccion de casos permitio alimentar un modelo de simulacion para la proyeccion de demanda de camas hospitalarias por pacientes de la COVID-19. Los analisis se basaron en los datos aportados por el Ministerio de Salud en torno a los casos confirmados por coronavirus desde la aparicion del primer caso en Costa Rica. Se estimaron cuatro modelos: logistico, Richards, Gompertz y exponencial, los cuales generaron la prediccion de casos diarios. Tambien se estimo el numero de reproducibilidad mediante estadistica bayesiana para cuantificar la transmisibilidad del virus. Los resultados permitieron anticipar el comportamiento inicial del virus en Costa Rica y el potencial efecto de las medidas de contencion que se adopta-ron a partir de la declaratoria de emergencia nacional. JEL: C15 Metodos de simulacion estadisticaAlternate abstract: The role of statistical modeling in emergency management is essential to shape or sup-port decisions regarding the care of events. In 2020 with coronavirus pandemic, countries quickly braced themselves for attention to contagious behavior and the impact it would have on public health. In Costa Rica, a team of specialists prepared studies on the behavior of the contagion curve and its effect on the occupation of hospital beds during the first three months of the epidemic. The studies were based on statistical model estimation of exponential and logistic growth, which provided forecasts of the daily and accumulated case numbers. The prediction of cases allowed feeding a simulation model for the projection of demand for hospital beds by patients with COVID-19. The analysis were based on data provided by the Ministry of Health regarding confirmed cases of coronavirus since the appearance of the first case in Costa Rica. Four models were estimated: logistic, Richards, Gompertz and Exponential, which generated daily case predictions. The reproducibility number was also estimated using Bayesian statistics to quantify the virus transmissibility. The results made it possible to anticipate the initial behavior of the virus in Costa Rica and the potential effect of the containment measures adopted after the declaration of national emergency. JEL: C15 Statistical simulation methods: general.Alternate abstract: O papel da modelagem estatistica na gestao de emergencias e fundamental para delinear ou apoiar as decisoes em torno da resposta aos eventos. Em 2020, com o surgimento da pandemia do coronavirus, os paises rapidamente se prepararam para responder ao com-portamento de contagio e para o impacto que provocaria sobre a saude publica. Na Costa Rica, uma equipe de especialistas preparou estudos sobre o comportamento da curva de contagio e seu efeito sobre a ocupacao de leitos hospitalares durante os primeiros tres meses da epidemia. Os estudos se basearam na estimativa de modelos estatisticos de crescimento exponencial e logistico, os quais proporcionaram prognosticos quanto ao numero de casos diarios e acumulados. A predicao de casos permitiu alimentar um modelo de simulacao para a projecao da demanda de leitos hospitalares por pacientes com COVID-19. As analises se basearam em dados fornecidos pelo Ministerio de Saude em relacao aos casos confirmados de coronavirus a partir do aparecimento do primeiro caso na Costa Rica. Estimaram-se quatro modelos: logistico, Richards, Gompertz e exponencial, os quais geraram a estimativa de casos diarios. Estimou-se tambem o numero de reprodutibilidade por meio da estatistica bayesiana de forma a quantificar a transmissibi-lidade do virus. Os resultados permitiram antecipar o comportamento inicial do virus na Costa Rica e o potencial efeito das medidas de contencao adotadas a partir da declaracao de emergencia nacional. JEL: C15 Metodos de simulacao estatistica.

While amoebic infection is widely known as a cause of gastroenteritis, keratitis, and meningoencephalitis, amoebae are challenging to recognize at unexpected sites. Despite multiple case reports of sinonasal amoebiasis, amoebic infection is not regularly considered in the differential diagnosis of sinonasal necroinflammatory disease. Here, we aim to characterize the pathologic features of sinonasal amoebiasis to facilitate better recognition. We identified sinonasal amoebiasis in 4 men, median age of 67 years (range: 37 to 71 y). All were immunocompromised, including 2 with chronic lymphocytic leukemia, 1 with human immunodeficiency virus, and 1 with human immunodeficiency virus and kidney transplant. Patients presented with nasal mucosal necrosis or polypoid masses, with facial ulceration in 1 patient and distant dermal nodules in another. Biopsies displayed extensive necrotic debris and inflammation. Although amoebic cysts were abundant in 3 cases, they were mistaken for yeast at frozen section in 1 case; 1 case showed only rare trophozoites that were not recognized on initial biopsy. Periodic acid Schiff and Grocott Methenamine Silver stains highlighted the organisms, and polymerase chain reaction confirmed Acanthamoeba species in 3 cases tested. 2 patients responded well to antiprotozoal medications, but 2 died of disease. Overall, sinonasal amoebiasis presents as a necroinflammatory process in patients immunocompromised for various reasons. Amoebae can mimic other organisms or be incredibly scarce, requiring active consideration to recognize amoebiasis and differentiate it from overlapping conditions like invasive fungal sinusitis, granulomatosis with polyangiitis, and natural killer/T-cell lymphoma. Because sinonasal amoebiasis is highly treatable when diagnosed promptly, pathologists play a critical role in the recognition of this rare necroinflammatory disease.

Reductive stress (RS) increases the reducing equivalents and components of the antioxidant system that can disturb redox homeostasis. Hibiscus Sabdariffa Linnaeus (HSL) has antioxidant properties and provides compounds that favor the functioning of the antioxidant systems, and excess in its consumption could lead to RS. The goal was to evaluate the vascular reactivity modulation by RS associated to the HSL infusions consumption of different percentages. 40 male Wistar rats were divided into 4 groups. Group 1; Control, Groups 2, 3 and 4; were supplemented with 15, 30 and 60 g/L of HSL calyxes respectively. Vascular reactivity, morphological changes, and different components of antioxidant systems were evaluated in the thoracic aorta including glucose-6-phosphate dehydrogenase, glutathione-S-transferase, thioredoxin-reductase, glutathione, selenium, thiols, lipoperoxidation, and 3-nitrityrosine. Vasoconstriction was increased and vasorelaxation decreased. These alterations were reversed by O2− and H2O2. The wall thickness and elastic fibers (p = 0.004 and p = 0.02, respectively), the glucose-6-phosphate dehydrogenase (p = 0.02), thioredoxin-reductase, lipoperoxidation, glutathione (p = 0.01), and selenium (p = 0.04) were increased but decreased thiols (p

13 p.-4 fig-3 tab., 1,3-β-glucans are extracellular polysaccharides synthesized by microorganisms and plants, with therapeutic potential. Among them, the O2-substituted-(1–3)-β-D-glucan, synthesized by some lactic acid bacteria (LAB), has a prebiotic effect on probiotic strains, an immunomodulatory effect on monocyte-derived macrophages, and potentiates the ability of the producer strain to adhere to Caco-2 cells differentiated to enterocytes. In this work, the O2-substituted-(1–3)-β-D-glucan polymers produced by GTF glycoyltransferase in the natural host Pediococcus parvulus 2.6 and in the recombinant strain Lactococcus lactis NZ9000[pNGTF] were tested. Their immunomodulatory activity was investigated in an ex vivo model using human biopsies from patients affected by Crohn’s disease (CD). Both polymers had an anti-inflammatory effect including, a reduction of Interleukine 8 both at the level of its gene expression and its secreted levels. The overall data indicate that the O2-substituted-(1–3)-β-D-glucan have a potential role in ameliorating inflammation via the gut immune system cell modulation., This work was supported by the Spanish Ministry of Science, Innovation, and Universities (grant RTI2018-097114-B-I00), by the Fondo de Investigación Sanitaria, grant number PI12/00263, and by CIBERehd.

Background and aims In patients undergoing peroral endoscopic myotomy (POEM) who are receiving antithrombotic therapy, the risk of bleeding and thromboembolic events is unknown. Our primary aim was to assess the safety of POEM in this patient subset. Secondary outcomes assessed were rates of clinical success, gastroesophageal reflux disease (GERD) and procedure-related outcomes. Methods This was an international, 1:1, case-control study performed at ten centers using prospectively maintained databases. All consecutive patients who underwent POEM before November 2019 were considered for inclusion. Cases were patients on antiplatelet and/or anticoagulant therapy. Controls not receiving antithrombotics were matched for age and esophageal motility disorder. Primary outcomes were major bleeding and thromboembolic events on postprocedural day 30. Results Of 2,895 patients undergoing POEM identified, 126 cases (103 on antiplatelets, 35 anticoagulants, 12 both) and 126 controls were enrolled. Major bleeding rate was higher in the antithrombotics users (5.6% vs 0.8%, P = .03). Anticoagulants and clopidogrel were temporarily interrupted in all cases. Aspirin was continued in 40.5% of users without increasing the bleeding risk. One thromboembolic event occurred in each group (0.79%; P = 1.00). No POEM-related deaths were noted. Rates of clinical success (91.7% vs 96% in controls, P = .20), postprocedural GERD and technical-related outcomes were similar in both groups. Antithrombotic management was heterogeneous and guidelines were not adhered to in 23.8% of cases. Conclusions POEM is safe and effective in patients receiving antithrombotic therapy although it is associated with a greater risk of major bleeding.

There are uncertainties concerning the possible benefits derived from the insertion of double-pigtail plastic stents (DPS) within lumen-apposing metal stents (LAMS) in EUS-guided choledochoduodenostomy (CDS). The aim of this study was to determine whether a DPS within a biliary LAMS offers a potential benefit in EUS-guided CDS for the palliative management of malignant biliary obstruction. This was a multicentre retrospective study at three tertiary institutions. Period: May 2015 to August 2020. Two interventional strategies (LAMS alone and LAMS plus DPS) were compared. The choice was the endoscopist’s discretion. Inclusion: unresectable/inoperable biliopancreatic tumours with previous failed ERCP. Clinical success: bilirubin decrease > 30% at 4 weeks. Forty-one consecutive cases of EUS-CDS using biliary LAMS were treated (22 women; mean age, 72.3 years) during the study period. The procedure was technically successful in 39 (95.1%), who were managed using the two strategies (22 LAMS alone; 17 LAMS plus DPS). No differences between the groups, in terms of clinical success (77.3 vs 87.5%, p = 0.67), adverse events (AEs, 13.6 vs 11.8%, p = 0.99), recurrent biliary obstruction (RBO, 13.6 vs 23.5%, p = 0.67), or survival rate (p = 0.67) were encountered. The LAMS alone group had a shorter length of procedure (50 min vs 66 min, p = 0.102). No risk factors related to clinical success, AEs, RBO, or survival were detected. The technical variant of adding a coaxial DPS within LAMS in EUS-CDS seems not to be enough to prevent biliary morbidities, and it is a time-consuming strategy. Although prospective studies are needed, these results do not support its routine use.

Endoscopic necrosectomy through lumen apposition metal stents (LAMS) is increasingly being used for complicated walled-off pancreatic necrosis (WOPN), but the need for necrosectomy after stent placement is not well understood. The aim of this study was to evaluate clinical, endoscopic, and radiologic predictors of the need for necrosectomy in patients treated with LAMS. We retrospectively reviewed patients with WOPN treated with LAMS from 2014 to 2017. Necrosectomy was performed only in patients who had recurrent fever or hemodynamic instability during follow-up. Univariate and multivariate analyses were performed. We included 15 patients, 67% men and median age was 75 (54–76) years. Two (13%) presented adverse events, one immediate and one delayed. In the first case, the stent migrated to the gastric cavity during deployment but was relocated in the same procedure. In the second case, the patient presented bleeding on day 36 due to a pseudoaneurysm that was successfully treated with embolization. Clinical success was 100%, but five patients (33%) required endoscopic necrosectomy (4 mechanical and 1 irrigation) and one (7%) required surgical necrosectomy of distant collections. The percentage of necrosis in the collection detected in a previous CT scan (45 [35–66]% vs 10 [5–17]%) was the only factor to predict the need for necrosectomy in the multivariate analysis (OR 1.18 [1.01–1.39]). LAMS is efficient to treat WOPN but more than a third will need necrosectomy. The percentage of necrosis in the collection detected in the CT scan seems to predict the need for necrosectomy.

Infections caused by members of the mycobacterium tuberculosis complex [MTC] and nontuberculous mycobacteria [NTM] can induce widespread morbidity and mortality in people. Mycobacterial infections cause both a delayed immune response, which limits rate of bacterial clearance, and formation of granulomas, which contain bacterial spread, but also contribute to lung damage, fibrosis, and morbidity. Granulomas also limit access of antibiotics to bacteria, which may facilitate development of resistance. Bacteria resistant to some or all antibiotics cause significant morbidity and mortality, and newly developed antibiotics readily engender resistance, highlighting the need for new therapeutic approaches. Imatinib mesylate, a cancer drug used to treat chronic myelogenous leukemia [CML] that targets Abl and related tyrosine kinases, is a possible host-directed therapeutic [HDT] for mycobacterial infections, including those causing TB. Here, we use the murine Mycobacterium marinum [Mm] infection model, which induces granulomatous tail lesions. Based on histological measurements, imatinib reduces both lesion size and inflammation of surrounding tissue. Transcriptomic analysis of tail lesions indicates that imatinib induces gene signatures indicative of immune activation and regulation at early time points post infection that resemble those seen at later ones, suggesting that imatinib accelerates but does not substantially alter anti-mycobacterial immune responses. Imatinib likewise induces signatures associated with cell death and promotes survival of bone marrow-derived macrophages [BMDMs] in culture following infection with Mm. Notably, the capacity of imatinib to limit formation and growth of granulomas in vivo and to promote survival of BMDMs in vitro depends upon caspase 8, a key regulator of cell survival and death. These data provide evidence for the utility of imatinib as an HDT for mycobacterial infections in accelerating and regulating immune responses, and limiting pathology associated with granulomas, which may mitigate post-treatment morbidity.

SARS-CoV-2 infects type II pneumocytes and disrupts redox homeostasis by overproducing reactive oxygen species (ROS). N-acetyl cysteine (NAC) is a precursor of the synthesis of glutathione (GSH) and it restores the loss of redox homeostasis associated to viral infections. The aim of the study is to evaluate the effect of the treatment with NAC on the enzymatic antioxidant system in serum from patients infected by SARS-CoV-2. We evaluated the enzymatic activities of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), -S-transferase (GST), and reductase (GR) by spectrophotometry and the concentrations of the glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2–), and lipid peroxidation (LPO) in serum. The activity of the extracellular super oxide dismutase (ecSOD) was determined by native polyacrylamide gels, and 3-nitrotyrosine (3-NT) was measured by ELISA. A decrease in the activities of the ecSOD, TrxR, GPx, GST GR, (p = 0 ≤ 0.1), and the GSH, TAC, thiols, and NO2– (p ≤ 0.001) concentrations and an increase in LPO and 3-NT (p = 0.001) concentrations were found in COVID-19 patients vs. healthy subjects. The treatment with NAC as an adjuvant therapy may contribute to a reduction in the OS associated to the infection by SARS-CoV-2 through the generation of GSH. GSH promotes the metabolic pathways that depend on it, thus contributing to an increase in TAC and to restore redox homeostasis.

Death is medically described as the irreversible loss of essential characteristics and requires irreversible loss of capacity for consciousness and capacity to breathe. Death certification has legal, ethical, philosophical, biological, cultural, and religious characteristics and consequences. Its diagnosis is based on the best available scientific evidence: somatic, circulatory and/or neurological criteria. Even if we accept the determination of death is “scientific” and a set of criteria for its diagnosis have been established, death diagnosis still differs among countries. It is for this reason and sporadic cases like the one occurred recently in Spain, that “artistic” aspects of medicine and the mystery of the extensively described condition catalepsy revive. Catalepsy is a medical condition characterized by inactivity, decreased responsiveness to external stimuli, and a tendency to maintain an immobile posture (muscular rigidity). This condition may be associated with psychotic disorders, nervous system drug toxicity, and other conditions. Moreover, its influence in artistic literature and mass media have led to the consideration of catalepsy as a cornerstone in the confluence of medicine, art, mystery, science and society.

Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (

Hay una corrección posterior a este artículo: http://hdl.handle.net/10486/701800, Este artículo tiene una primera parte: http://hdl.handle.net/10486/701802, El tratamiento de la reservoritis es un escenario complejo que requiere una estrecha colaboración médico-quirúrgica. El tratamiento de elección de la reservoritis aguda es el ciprofloxacino o el metronidazol. Ante un primer episodio de reservoritis se recomienda la profilaxis de recidiva con una mezcla de probióticos; sin embargo, no está tan clara su utilidad como profilaxis primaria para prevenir un primer episodio de reservoritis tras la cirugía. El tratamiento de la reservoritis crónica refractaria debe iniciarse con una combinación de antibióticos, y si esta fracasa el siguiente escalón terapéutico es la budesonida oral. Algunas formas refractarias necesitarán terapias biológicas, siendo los anti-TNF α la primera opción, reservándose otros biológicos para pacientes refractarios. La ileostomía definitiva puede ser una opción final en los pacientes más graves, Pouchitis treatment is a complex entity that requires a close medical and surgical relationship. The elective treatment for acute pouchitis is antibiotics. After a first episode of pouchitis it is recommended prophylaxis therapy with a probiotic mix, nevertheless it is not clear the use of this formulation for preventing a first episode of pouchitis after surgery. First-line treatment for chronic pouchitis is an antibiotic combination. The next step in treatment should be oral budesonide. Selected cases of severe, chronic refractory pouchitis may benefit from biologic agents, and anti-TNF α should be recommended as the first option, leaving the new biologicals for multi-refractory patients. Permanent ileostomy may be an option in severe refractory cases to medical treatment

Pouchitis treatment is a complex entity that requires a close medical and surgical relationship. The elective treatment for acute pouchitis is antibiotics. After a first episode of pouchitis it is recommended prophylaxis therapy with a probiotic mix, nevertheless it is not clear the use of this formulation for preventing a first episode of pouchitis after surgery. First-line treatment for chronic pouchitis is an antibiotic combination. The next step in treatment should be oral budesonide. Selected cases of severe, chronic refractory pouchitis may benefit from biologic agents, and anti-TNF α should be recommended as the first option, leaving the new biologicals for multi-refractory patients. Permanent ileostomy may be an option in severe refractory cases to medical treatment.