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ACE2 expression; COVID-19; Cancer Expresión ACE2; COVID-19; Cáncer Expressió ACE2; COVID-19; Càncer Background: SARS-CoV-2 (COVID-19) elicits a T-cell antigen-mediated immune response of variable efficacy. To understand this variability, we explored transcriptomic expression of angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) and of immunoregulatory genes in normal lung tissues from patients with non-small cell lung cancer (NSCLC). Methods: This study used the transcriptomic and the clinical data for NSCLC patients generated during the CHEMORES study [n = 123 primary resected (early-stage) NSCLC] and the WINTHER clinical trial (n = 32 metastatic NSCLC). Results: We identified patient subgroups with high and low ACE2 expression (p = 1.55 × 10−19) in normal lung tissue, presumed to be at higher and lower risk, respectively, of developing severe COVID-19 should they become infected. ACE2 transcript expression in normal lung tissues (but not in tumor tissue) of patients with NSCLC was higher in individuals with more advanced disease. High-ACE2 expressors had significantly higher levels of CD8+ cytotoxic T lymphocytes and natural killer cells but with presumably impaired function by high Thymocyte Selection-Associated High Mobility Group Box Protein TOX (TOX) expression. In addition, immune checkpoint-related molecules – PD-L1, CTLA-4, PD-1, and TIGIT – are more highly expressed in normal (but not tumor) lung tissues; these molecules might dampen immune response to either viruses or cancer. Importantly, however, high inducible T-cell co-stimulator (ICOS), which can amplify immune and cytokine reactivity, significantly correlated with high ACE2 expression in univariable analysis of normal lung (but not lung tumor tissue). Conclusions: We report a normal lung immune-tolerant state that may explain a potential comorbidity risk between two diseases – NSCLC and susceptibility to COVID-19 pneumonia. Further, a NSCLC patient subgroup has normal lung tissue expressing high ACE2 and high ICOS transcripts, the latter potentially promoting a hyperimmune response, and possibly leading to severe COVID-19 pulmonary compromise. FundingThe authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research leading to these results on the CHEMORES study data, an initiative from the Chemotherapy resistance consortium, has received funding from the European Union Sixth Framework (FP6) Integrated Project. The research on the WINTHER trial data leading to these results has received funding from the European Union Seventh Framework Program (FP7) (WINTHER: FP7/2007-2013 under grant agreement n°306125). WINTHER, an initiative from the WIN Consortium, was funded in part by ARC Foundation for cancer research (France), Pfizer Oncology, Lilly France SAS, and Novartis Pharmaceuticals Corporation. Funded in part by The FERO/J.P. Morgan Private Bank Clinical Oncology Research Grant, National Cancer Institute grant P30 P30-CA023100 (RK), Israeli Science Foundation grant 1188/16 (ER), Instituto Salud Carlos III – Programa Rio Hortega Contract grant CM15/00255 (EF) and Canadian Institutes for Health Research (grant MOP-142281, GB) and the Canadian Cancer Society (grant 703811, GB).

Background/aims The aim of our study is to evaluate the association between meals and perceived gastrointestinal symptoms in real life in a French cohort of irritable bowel syndrome (IBS) patients. Methods This prospective cross-sectional observational study included patients from the French association (association des patients souffrant du syndrome de l'intestin irritable [APSSII]) of IBS. Data were collected on demographics, IBS subtype, dietary food, and meal-induced gastrointestinal symptoms from patient filled self-questionnaires or questionnaires. Results Eighty-four patients with IBS were included; 82.3% female with a mean age of 46.9 ± 15.7 years. Each transit pattern subtype represented one-third of the population. Forty-five percent of patients had severe IBS according to IBS-Severity Scoring System; mean IBS Quality of Life score was 53.9 ± 18.3. Patients believed that food could trigger or exacerbate gastrointestinal symptoms in 73.3% and 93.4%, respectively. Eighty-nine percent had already tried diets, mostly lactose free diet and low fermentable, oligosaccharides, disaccharides, monosaccharides, and polyols diet in 61.3% and 53.6% of cases. Thirty-nine percent of meals induced gastrointestinal symptoms. Meal-induced gastrointestinal symptoms were associated with severity and subtype but not with quality of life. Conclusions This study has confirmed the important link between gastrointestinal symptoms and food. Gastrointestinal symptoms induced by meals are frequent and associated with severity and IBS-diarrhea subtype. Our study also underlines patients' interest in food and diet. More knowledge is needed on food that triggers IBS symptoms but also on diet conditions in order to improve this condition.

Summary Background While all resources have been mobilized to fight COVID-19, this study aimed to analyze the consequences of lockdown and pandemic stress in participants with and without Irritable Bowel Syndrome (IBS). Methodology An online survey was proposed to people with or without IBS during the exponential phase of the pandemic in France. The questionnaire included questions about socio-demographic data, conditions of confinement , activities carried out, IBS characteristics, measurement of stress level, consequences on sleep, fatigue, anxiety and depression, and quality of life (both perceived non-specific and specific for IBS). Results/Discussion From March 31 to April 15, 2020, 304 participants, 232 with IBS and 72 without were included in the survey (mean age: 46.8 ± 16.8 years, female gender: 75.3%). Age, level of education, financial resources, living space per person and activities performed during confinement were identical in both groups. Stress linked to fear of COVID-19, lockdown and financial worries was at the same level in both groups, but the psychological consequences and deterioration of quality of life (QOL) were both higher in IBS participants. In a univariate analysis , teleworking, solitary confinement, and low household resources had a variable impact on the scores of depression, anxiety, fatigue and non-specific perceived QOL, but in a multivariate analysis , the only factor explaining a deterioration of non-specific QOL was the fact of suffering from IBS. Conclusion/Perspectives Stress linked to the COVID-19 pandemic and confinement is high and equivalent in both IBS and non-IBS participants, with higher psychological and QOL consequences in IBS patients who have altered coping capacities.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) in patients with a preexisting duodenal stent is particularly challenging and has a low success rate. Endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) has been increasingly used as an alternative to percutaneous transhepatic biliary drainage after failed ERCP. EUS-guided choledochoduodenostomy (EUS-CD) and EUS-guided hepaticogastrostomy (EUS-HGS) have been reported to have similar efficacity. Recently, a novel dedicated fully-covered lumen-apposing metal stent (LAMS) has been developed for EUS-CD (Hot AXIOS; Boston Scientific, Massachusetts, United States). It seems that this new device decreases the morbidity of EUS-CD. We present a case in which EUS-CD with LAMS through an uncovered metal duodenal stent was used successfully.

The originality of this retrospective study relies on the evaluation of the effectiveness of the endoscopic internal drainage (EID) according to the type of fistula. METHODS: The type of fistula was classified initially according to a CT scan with oral opacification: fistula without a communicating abscess (type I), fistula with a communicating abscess (type II), and fistula with an abscessed sub- and sus-diaphragmatic communicating collection (type III). Treatment algorithm consisted of the insertion of a nasojejunal feeding tube (NJFT) for type I fistulas and the placement of a NJFT with EID with or without surgical drainage for types II and III. RESULTS: Forty-nine patients were included. The clinical success rate with fistula healing was 100% in group I, 96% in group II, and 12% for group III (p = 0.001). Mean time for diagnosis of the fistula was significantly higher in type III (p = 0.04). The mean estimated size of the defect was higher in type II, 11.2 mm and III, 10 mm versus type I, 2.8 mm (p = 0.001). The average number of scheduled endoscopic sessions were 2, 2.7, and 5.2 for types I, II, and III, respectively (p = 0.001). The number of unscheduled reinterventions was also significantly higher in type III (p = 0.03). The NJFT was left in place for a significantly longer duration in type III (136 days) compared to types I (3, 13) and II (49) p = 0.001. CONCLUSION: This study shows that proper characterization of the type of fistula before the endoscopic treatment of post-sleeve fistulas improves the efficacy of the endoscopic treatment.

Summary Background & aims Pancreatic exocrine insufficiency (PEI) impairs fat absorption, but few data are available on protein absorption. We investigated this question in patients with chronic pancreatitis, both in the absence and presence of enzyme therapy, using a stable isotope sensitive method. Methods Eleven patients with sustained PEI and regular enzyme substitution were investigated at hospital, after a washout period without enzyme substitution, and later after reintroduction of substitution. The digestibility and postprandial metabolism of dietary protein were characterized after the ingestion of a semi-synthetic single meal containing 20 g 15 N-labeled casein. Results At baseline, 20 ± 8% of dietary nitrogen was transferred to the metabolic pools vs. 24.5 ± 7% under enzyme treatment ( P = 0.04). After treatment, the transfer of dietary nitrogen tended to increase in plasma amino acids, and increased significantly in plasma proteins and the deamination pool. In contrast, the fecal excretion of dietary nitrogen did not demonstrate any treatment effect. In patients not receiving insulin for diabetes, the treatment stimulated insulin secretion. Conclusions Protein malabsorption was mostly undetectable using standard fecal tests. The study of the postprandial fate of dietary protein revealed a moderate increase of its transfer to metabolic pools after enzyme substitution.