COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Endoscopic papillectomy for ampullary lesions of minor papilla.

BACKGROUND AND AIMS: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied. METHODS: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test. RESULTS: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months). CONCLUSIONS: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.

Pan-intestinal capsule endoscopy as first-line procedure in patients with suspected mid or lower gastrointestinal bleeding.

BACKGROUND: Pan-intestinal capsule endoscopy (PCE) evaluates the small bowel and colon noninvasively. This study evaluated diagnostic accuracy and safety of PCE vs. colonoscopy as first-line examination in suspected mid-lower gastrointestinal bleeding (MLGIB). METHODS: In this prospective, single-center, single-blinded cohort study, consecutive patients with suspected MLGIB underwent PCE followed by same-day colonoscopy. Diagnostic accuracy for potentially hemorrhagic lesions (PHLs; combined diagnosis by PCE + colonoscopy) and incidence of adverse events were assessed. RESULTS: 100 patients were included (median age 70 [range 18-92] years; 65% female). PHLs were diagnosed in 46 patients, including small-bowel and/or colon angioectasias in 32. PCE correctly identified 54 individuals without PHLs, and 95.7% (44/46) of those with PHLs vs. 50.0% (23/46) for colonoscopy (P<0.01). PHLs were detected by PCE alone in 65.2% (30/46), both examinations in 28.3% (13/46), and colonoscopy alone in 6.5% (3/46). PHLs were diagnosed at the ileocolonic region in 28% of patients, with PCE diagnosing 25/28 cases (89.3%) and colonoscopy diagnosing 23/28 (82.1%; P=0.13). Interventional procedures were performed at colonoscopy in 13/81 patients with iron-deficiency anemia (16.0%) vs. 6/19 patients with overt bleeding (31.6%; P<0.01). No significant adverse events occurred with PCE vs. 2% with colonoscopy. CONCLUSIONS: In patients with MLGIB, PCE avoided further invasive procedures in >50% of patients. PCE was safe and more effective than colonoscopy in identifying PHL both in the small bowel and colon. These results support the potential use of PCE as first-line examination in patients with suspected MLGIB.

Training in basic gastrointestinal endoscopic procedures: a European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) Position Statement.

This ESGE Position Statement provides structured and evidence-based guidance on the essential requirements and processes involved in training in basic gastrointestinal (GI) endoscopic procedures. The document outlines definitions; competencies required, and means to their assessment and maintenance; the structure and requirements of training programs; patient safety and medicolegal issues. 1: ESGE and ESGENA define basic endoscopic procedures as those procedures that are commonly indicated, generally accessible, and expected to be mastered (technically and cognitively) by the end of any core training program in gastrointestinal endoscopy. 2: ESGE and ESGENA consider the following as basic endoscopic procedures: diagnostic upper and lower GI endoscopy, as well as a limited range of interventions such as: tissue acquisition via cold biopsy forceps, polypectomy for lesions ≤ 10 mm, hemostasis techniques, enteral feeding tube placement, foreign body retrieval, dilation of simple esophageal strictures, and India ink tattooing of lesion location. 3: ESGE and ESGENA recommend that training in GI endoscopy should be subject to stringent formal requirements that ensure all ESGE key performance indicators (KPIs) are met. 4: Training in basic endoscopic procedures is a complex process and includes the development and acquisition of cognitive, technical/motor, and integrative skills. Therefore, ESGE and ESGENA recommend the use of validated tools to track the development of skills and assess competence. 5: ESGE and ESGENA recommend incorporating a multimodal approach to evaluating competence in basic GI endoscopic procedures, including procedural thresholds and the measurement and documentation of established ESGE KPIs. 7: ESGE and ESGENA recommend the continuous monitoring of ESGE KPIs during GI endoscopy training to ensure the trainee's maintenance of competence. 9: ESGE and ESGENA recommend that GI endoscopy training units fulfil the ESGE KPIs for endoscopy units and, furthermore, be capable of providing the dedicated personnel, infrastructure, and sufficient case volume required for successful training within a structured training program. 10: ESGE and ESGENA recommend that trainers in basic GI endoscopic procedures should be endoscopists with formal educational training in the teaching of endoscopy, which allows them to successfully and safely teach trainees.

Recurrence rate after piecemeal endoscopic mucosal resection of <20 mm non-pedunculated colorectal lesions: should we worry about the risk?

INTRODUCTION: There is scarce data focused on recurrence neoplasia rate (RR) after piecemeal endoscopic mucosal resection (pEMR) of 10-19 mm non-pedunculated colorectal lesions (NPL). We aimed to analyze the RR after pEMR of 10-19 mm NPL, identify risk factors for its development and compare it with RR after pEMR of ≥ 20 mm NPL. METHODS: Retrospective cohort-study including all ≥10 mm NPL resected by pEMR in our center between 2018-2022 with an early repeat colonoscopy (ERC). RR was defined as recurrence neoplasia identified in the ERC EMR scar with virtual chromoendoscopy or histological confirmation. RESULTS: A total of 444 NPL were assessed, 124 (27.9%) with 10-19 mm. In the ERC, performed a median of 6 months after pEMR, RR was significantly lower for 10-19 mm NPL compared to ≥ 20 mm NPL (13/124 vs 68/320, p = 0.005). In subgroup analysis, RR after pEMR of 15-19 mm NPL was significantly higher compared to 10-14 mm NPL (13/98 vs 0, p = 0.041) but not significantly different compared to ≥ 20 mm NPL (13/98 vs 68/320, p = 0.073). In multivariable analysis, size of NPL (HR 1.501, 95% CI 1.012-2.227, p = 0.044) was the only independent risk factor identified for RR for 10-19 mm NPL. CONCLUSION: Although the early RR after pEMR of 10-19 mm NPL is significantly lower compared to ≥ 20 mm NPL, it is non-negligible (10.5%) and appears to be the highest among 15-19 mm NPL. The size of the lesion was the only independent risk factor for RR. Our findings should be accounted in the selection of the most appropriate post-polypectomy endoscopic surveillance.

Acute Nonvariceal Upper Gastrointestinal Bleeding in Patients Using Anticoagulants: Does the Timing of Endoscopy Affect Outcomes?

BACKGROUND: In patients with acute nonvariceal upper gastrointestinal bleeding (NVUGIB), early (≤ 24 h) endoscopy is recommended following hemodynamic resuscitation. Nevertheless, scarce data exist on the optimal timing of endoscopy in patients with NVUGIB receiving anticoagulants. OBJECTIVE: To analyze how the timing of endoscopy may influence outcomes in anticoagulants users admitted with NVUGIB. METHODS: Retrospective cohort study which consecutively included all adult patients using anticoagulants presenting with NVUGIB between January 2011 and June 2020. Time from presentation to endoscopy was assessed and defined as early (≤ 24 h) and delayed (> 24 h). The outcomes considered were endoscopic or surgical treatment, length of hospital stay, intermediate/intensive care unit admission, recurrent bleeding, and 30-day mortality. RESULTS: From 636 patients presenting with NVUGIB, 138 (21.7%) were taking anticoagulants. Vitamin K antagonists were the most frequent anticoagulants used (63.8%, n = 88). After adjusting for confounders, patients who underwent early endoscopy (59.4%, n = 82) received endoscopic therapy more frequently (OR 2.4; 95% CI 1.1-5.4; P = 0.034), had shorter length of hospital stay [7 (IQR 6) vs 9 (IQR 7) days, P = 0.042] and higher rate of intermediate/intensive care unit admission (OR 2.7; 95% CI 1.3 - 5.9; P = 0.010) than patients having delayed endoscopy. Surgical treatment, recurrent bleeding, and 30-day mortality did not differ significantly between groups. CONCLUSION: Early endoscopy (≤ 24 h) in anticoagulant users admitted with acute nonvariceal upper gastrointestinal bleeding is associated with higher rate of endoscopic treatment, shorter hospital stay, and higher intermediate/intensive care unit admission. The timing of endoscopy did not influence the need for surgical intervention, recurrent bleeding, and 30-day mortality.

Comorbidities, acute kidney injury and long-term mortality in elderly patients hospitalized because of hip fracture: a moderation analysis.

INTRODUCTION: Femoral fractures in elderly individuals present significant health challenges, often leading to increased morbidity and mortality. Acute kidney injury (AKI) during hospitalization further complicates outcomes, yet the interaction between AKI severity and comorbidities, as quantified by the Charlson Comorbidity Index (CCI), remains poorly understood in this population. This study aimed to assess the associations between AKI severity and the CCI and between AKI severity and one-year mortality postfemoral fracture in elderly patients. METHODOLOGY: This study utilized data from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database and focused on elderly patients (> 65 years) admitted with hip fractures. Patients were categorized based on AKI stage according to the KDIGO criteria and CCI scores. The primary outcome assessed was all-cause mortality one year after hospital discharge. The statistical analyses included logistic regression, Cox proportional hazards regression and moderation analysis with the Johnson-Neyman technique to evaluate associations between AKI and long-term mortality and between the CCI and long-term mortality. RESULTS: The analysis included 1,955 patients and revealed that severe AKI (stages 2 and 3) was independently associated with increased one-year mortality. Notably, the CCI moderated these associations significantly. A lower CCI score was significantly correlated with greater mortality in patients with severe AKI. The impact of severe AKI was greater for those with a CCI as low as 3, more than doubling the observed one-year mortality rate. In contrast, higher CCI scores (≥8) did not significantly impact mortality. Sensitivity analyses supported these findings, underscoring the robustness of the observed associations. CONCLUSION: This study elucidates the complex interplay between AKI severity and comorbidities and long-term mortality in elderly hip fracture patients. These findings underscore the importance of considering both AKI severity and comorbidity burden in prognostic assessments and intervention strategies for this vulnerable population. Targeted interventions tailored to individual risk profiles may help mitigate the impact of AKI on mortality outcomes, ultimately improving patient care and outcomes. Further research is warranted to explore the underlying mechanisms involved and refine risk stratification approaches in this population.

Why copper catalyzes electrochemical reduction of nitrate to ammonia.

Electrochemical reduction of nitrate (NO3RR) has drawn significant attention in the scientific community as an attractive route for ammonia synthesis as well as alleviating environmental concerns for nitrate pollution. To improve the efficiency of this process, the development of catalyst materials that exhibit high activity and selectivity is of paramount importance. Copper and copper-based catalysts have been widely investigated as potential catalyst materials for this reaction both computationally and experimentally. However, less attention has been paid to understanding the reasons behind such high activity and selectivity. Herein, we use Density Functional Theory (DFT) to identify reactivity descriptors guiding the identification of active catalysts for the NO3RR, establish trends in activity, and explain why copper is the most active and selective transition metal for the NO3RR to ammonia among ten different transition metals, namely Au, Ag, Cu, Pt, Pd, Ni, Ir, Rh, Ru, and Co. Furthermore, we assess NO3RR selectivity by taking into account the competition between the NO3RR and the hydrogen evolution reaction. Finally, we propose various approaches for developing highly active catalyst materials for the NO3RR.

Real-life patency of plastic biliary stents in the pandemic era: is stent removal after 6 months safe and effective?

BACKGROUND: The SARS-CoV-2 pandemic conditioned the optimal timing of some endoscopic procedures. ESGE guidelines recommend replacement or removal of the plastic biliary stents within 3-6 months to reduce the risk of complications. Our aim was to analyse the outcomes of patients who had delayed plastic biliary stent removal following endoscopic retrograde cholangiopancreatography (ERCP) in the pandemic era. METHODS: Retrospective study including consecutive ERCPs with plastic biliary stent placement between January 2019 and December 2021. Delayed removal was defined as presence of biliary stent >6 months after ERCP. The evaluated outcomes were stent migration, stent dysfunction, obstructive jaundice, cholangitis, acute pancreatitis, hospitalization, and biliary pathology-related mortality. RESULTS: One-hundred and twenty ERCPs were included, 56.7% male patients, with a mean age of 69.4 ± 15.7 years. Indications for plastic biliary stent insertion were choledocholithiasis (72.5%), benign biliary stricture (20.0%), and post-cholecystectomy fistula (7.5%). Delayed stent removal occurred in 32.5% of the cases. The median time to stent removal was 3.5 ± 1.3 months for early removal and 8.6 ± 3.1 months for delayed removal. Patients who had delayed stent removal did not have a significantly higher frequency of stent migration (20.5 vs 11.1%, p = 0.17), stent dysfunction (17.9 vs 13.6%, p = 0.53), hospitalization (17.9 vs 14.8%, p = 0.66), obstructive jaundice (2.6 vs 0.0%, p = 0.33), cholangitis (10.3 vs 13.6%, p = 0.77), acute pancreatitis (0.0 vs 1.2%, p = 1.0), or biliary pathology-related mortality (2.6 vs 1.2%, p = 0.55). CONCLUSIONS: Delayed plastic biliary stent removal does not seem to have a negative impact on patients' outcomes. In the current pandemic situation, while scheduled endoscopic procedures may have to be postponed, elective removal of plastic biliary stents can be safely deferred.

Identifying inflammatory bowel disease patients at risk of metabolic dysfunction-associated fatty liver disease: usefulness of non-invasive steatosis predictive scores.

BACKGROUND: Inflammatory bowel disease (IBD) patients have a higher risk of metabolic dysfunction-associated fatty liver disease (MAFLD) compared with the general population. However, it is not known whether available non-invasive hepatic steatosis scores are useful in predicting MAFLD in IBD patients. We aimed to analyze the performances of MAFLD screening score (MAFLD-S), Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Clinical Prediction Tool for NAFLD in Crohn's Disease (CPN-CD), in identifying MAFLD in IBD patients. METHODS: A cross-sectional study was carried out including consecutive adult IBD outpatients submitted to transient elastography (TE). MAFLD criteria were assessed, and hepatic steatosis (HS) was defined by a controlled attenuation parameter (CAP) >248 dB/m using TE. MAFLD-S, FLI, HSI, and CPN-CD were calculated and their accuracy for the prediction of MAFLD was evaluated through their areas under the receiver-operating characteristic (AUROC) curves. RESULTS: Of 168 patients, body mass index ≥25, type 2 diabetes mellitus, dyslipidemia and arterial hypertension were present in 76 (45.2%), 10 (6.0%), 53 (31.5%), 20 (11.9%), respectively. HS was identified in 77 (45.8%) patients, of which 65 (84.4%) fulfilled MAFLD criteria. MAFLD-S (AUROC, 0.929 [95% CI, 0.888-0.971]) had outstanding and FLI (AUROC, 0.882 [95% CI, 0.830-0.934]), HSI (AUROC, 0.803 [95% CI, 0.736-0.871]), and CPN-CD (AUROC, 0.822 [95% CI, 0.753-0.890) had excellent discrimination in predicting MAFLD. CONCLUSIONS: MAFLD-S, FLI, HSI and CPN-CD scores can accurately identify MAFLD in IBD patients, allowing the selection of those in whom hepatic steatosis and metabolic risk factors assessment may be particularly beneficial.

Reply to comment on "Ultrasonographic scores for ileal Crohn's disease assessment: better, worse or the same as contrast­enhanced ultrasound?

We read the comments by Nylund K et al. regarding our paper "Ultrasonographic scores for ileal Crohn's disease assessment: Better, worse or the same as contrast­enhanced ultrasound?". Intestinal ultrasound has become one of the most valuable developments in the past decade, a non-invasive, well-tolerated exam, with an easy repeatability, and absence of sedation, ionizing radiation, or preparation. Particularly for inflammatory bowel disease, where there is a lack of agreement of patient's symptoms with disease activity, in an era where the paradigm of mucosal healing is changing to transmural healing, and with the emergence of several therapies leading to repeated imaging surveillance, it is essential to highlight the role of intestinal ultrasound. Although intestinal ultrasound is an increasingly used tool to monitor inflammatory bowel disease activity, there is no widely accepted reproducible activity index, since the methodology for the development of the scores was shown to be insufficient in most studies and none have been adequately validated (Bots et al., J Crohns Colitis 12:920-9, 2018). In our study, we showed that the contrast-enhanced ultrasound (CEUS) peak enhancement derived from the time-intensity curve (TIC) is a promising non-invasive emerging method with a good accuracy to correlate clinical and endoscopic activity in the terminal ileum, superior to intestinal ultrasound scores relying on bowel wall thickness and colour Doppler.

Gastrostomy Button Diameter and Length Variations after Percutaneous Endoscopic Gastrostomy: One Size Does Not Fit All.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a useful option for long-term enteral nutrition. Low-profile gastrostomy tubes ("buttons") may afterward be placed in the stomach through the abdominal wall following maturation of the preexisting ostomy. Regular verification is essential since inadequate sizing is associated with accidental exteriorization or food leakage. We aimed to evaluate gastrostomy buttons diameter or length variations on the first year after their placement and possible factors associated with these variations. METHODS: We analyzed consecutive PEGs between 2016 and 2018. A minimum follow-up of 12 after gastrostomy button placement was required. Diameter or length variations were assessed in a specialized PEG appointment during the follow-up period. RESULTS: Final sample included 94 patients, from which 65 (69.1%) were women, and 29 (30.9%) were men, with a mean age of 76.9 ± 13.3 years. Measurements variations occurred in 44 (46.8%) patients. Diameter variation was significantly more frequent in patients living in a nursing home (OR = 5.43; 95% CI = 1.32-22.27; p = 0.019), patients with previous PEG tube dislodgement (OR = 3.84; 95% CI = 1.21-12.20; p = 0.023), and male patients (OR = 3.50; 95% CI = 1.06-11.49, p = 0.039). Length variation occurred more frequently in patients with a weight change during the follow-up period greater than 5 kg (OR = 3.71; 95% CI = 1.14-12.05; p = 0.029). CONCLUSIONS: A significant proportion of patients with gastrostomy buttons required a change in their measurements, especially if male, living in nursing homes, having significant weight changes, or accidental tube exteriorization. This emphasizes the importance of having a specialized PEG appointment to regularly assure the best fitted button for each patient and ultimately guarantee an adequate nutritional intake.

Decision-To-Scope Score: A novel tool with excellent accuracy in predicting foreign bodies in the esophagus.

INTRODUCTION: Foreign body (FB) ingestion is a common indication for urgent esophagogastroduodenoscopy (EGD). Nevertheless, most pass spontaneously through the gastrointestinal (GI) tract. Differently from GI bleeding, there is no validated score aiming to identify "low-risk" patients in suspected FB ingestion. We aimed to create a score able to discriminate patients who are candidates to emergent EGD in this scenario. METHODS: Retrospective study of consecutive patients admitted for suspected FB in the upper GI tract between 2016 and 2021. The evaluated outcome was endoscopic confirmation of FB in the esophagus. Variables significantly associated with the outcome on multivariate analysis were computed into a score predicting endoscopic confirmation. RESULTS: We included 228 patients. From these, 97 (42.5%) had a confirmed FB in EGD. Time since ingestion <6 h (OR = 4.0; P = 0.042), absence of any meal after FB ingestion (OR = 7.1; P = 0.005), dysphagia (OR = 11.8; P < 0.001), odynophagia (OR = 4.6; P = 0.004), and drooling (OR = 15.1; P < 0.001) were independent predictors of confirmed FB. These variables were used to compute a FB predicting score-the Decision-To-Scope (DTS) Score: time since ingestion <6 h (+1 point), absence of meals (+2 points), dysphagia (+3 points), odynophagia (+1 point), and drooling (+4 points). DTS-Score had excellent accuracy to predict the outcome (AUC = 0.953; 95%CI = 0.928-0.977; P < 0.001). The optimal cutoff to identify low-risk patients was a score ≤5 (sensitivity 85.0% and specificity 94.7%). CONCLUSIONS: More than half of the suspected FB were not confirmed by EGD. The DTS-Score presented excellent accuracy at stratifying patients' risk and may contribute to the decision to perform emergent EGD in suspected FB ingestion.

What Is the Optimal Bowel Preparation for Capsule Colonoscopy and Pan-intestinal Capsule Endoscopy? A Systematic Review and Meta-Analysis.

BACKGROUND: The rate of adequate cleansing (ACR) and complete examinations (CR) are key quality indicators in capsule colonoscopy (CC) and pan-intestinal capsule endoscopy (PCE). AIMS: To evaluate the efficacy of bowel preparation protocols regarding ACR and CR. METHODS: We conducted a systematic review and meta-analysis, search terms regarding colon capsule preparation, publication date from 2006/01, and date of search 2021/12, in six bibliographic databases. Multiple steps of the cleansing protocol were assessed: diet, adjunctive laxatives, purgative solution, use of prokinetic agents, and "booster". The meta-analytical frequency of ACR and CR was estimated, and subgroup analyses performed. Strategies associated with higher ACR and CR were explored using meta-analytical univariable and multivariable regression models. RESULTS: Twenty-six observational studies and five RCTs included (n = 4072 patients). The pooled rate of ACR was 72.5% (95% C.I. 67.8-77.5%; I2 = 92.4%), and the pooled rate of CR was 83.0% (95% C.I. 78.7-87.7%; I2 = 96.5%). The highest ACR were obtained using a low-fibre diet [78.5% (95% C.I. 72.0-85.6%); I2 = 57.0%], adjunctive laxatives [74.7% (95% C.I. 69.8-80.1%); I2 = 85.3%], and split dose < 4L polyethylene glycol (PEG) as purgative [77.5% (95% C.I. 68.4-87.8%); I2 = 47.3%]. The highest CR were observed using routine prokinetics prior to capsule ingestion [84.4% (95% C.I. 79.9-89.2%); I2 = 89.8%], and sodium phosphate (NaP) as "booster" [86.2% (95% C.I. 82.3-90.2%); I2 = 86.8%]. In univariable models, adjunctive laxatives were associated with higher ACR [OR 1.81 (95% C.I. 1.13; 2.90); p = 0.014]. CR was higher with routine prokinetics [OR 1.86 (95% C.I. 1.13; 3.05); p = 0.015] and split-dose PEG purgative [OR 2.03 (95% C.I. 1.01; 4.09), p = 0.048]. CONCLUSIONS: Main quality outcomes (ACR, CR) remain suboptimal for CC and PCE. Despite considerable heterogeneity, our results support low-fibre diet, use of adjunctive sennosides, split dose < 4L PEG, and routine prokinetics, while NaP remains the most consistent option as booster.

The role of ethical leadership and social networks in the promotion of workplace happiness and quality of care: A cross-sectional study.

This study examines the sequential effects of perceived ethical leaders and the strength of social networks among healthcare professionals on the perceived workplace happiness of healthcare professionals and its impacts on the quality of provided care. We conduct a partial least squares (PLS) analysis to estimate the relationship between the variables. Data comes from a survey conducted to 321 healthcare professionals with primary/direct contact with patients working at Portuguese hospitals. We use previously validated scales in the literature for measuring the variables; ethical leadership, social network in the context of the workplace; satisfaction, engagement, and commitment as proxies of workplace happiness, and, quality of care provided to patients (the outcome of the research model). Results show that ethical leadership positively influences social networks, workplace happiness, and quality of provided care. Social networks also have a positive relationship with workplace happiness and quality of provided care. Additionally, the workplace happiness of healthcare professionals positively influences the quality of provided care to patients. Our work addresses a diverse research gap regarding hospitals' ethical and social environment and hospital performance. Specifically, the empirical operationalisation of ethical leadership fights a literature gap in healthcare management. Moreover, we report evidence on the influence of antecedents, but also the performance consequences, of workplace happiness in healthcare environments. Our findings contribute to the literature while providing managerial implications for healthcare settings.

Two-Stage Framework for Faster Semantic Segmentation.

Semantic segmentation consists of classifying each pixel according to a set of classes. Conventional models spend as much effort classifying easy-to-segment pixels as they do classifying hard-to-segment pixels. This is inefficient, especially when deploying to situations with computational constraints. In this work, we propose a framework wherein the model first produces a rough segmentation of the image, and then patches of the image estimated as hard to segment are refined. The framework is evaluated in four datasets (autonomous driving and biomedical), across four state-of-the-art architectures. Our method accelerates inference time by four, with additional gains for training time, at the cost of some output quality.

Gasdermin-D activation by SARS-CoV-2 triggers NET and mediate COVID-19 immunopathology.

BACKGROUND: The release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear. OBJECTIVES: We aim to investigate the role of the Gasdermin-D (GSDMD) pathway on NETs release and the development of organ damage during COVID-19. METHODS: We performed a single-cell transcriptome analysis in public data of bronchoalveolar lavage. Then, we enrolled 63 hospitalized patients with moderate and severe COVID-19. We analyze in blood and lung tissue samples the expression of GSDMD, presence of NETs, and signaling pathways upstreaming. Furthermore, we analyzed the treatment with disulfiram in a mouse model of SARS-CoV-2 infection. RESULTS: We found that the SARS-CoV-2 virus directly activates the pore-forming protein GSDMD that triggers NET production and organ damage in COVID-19. Single-cell transcriptome analysis revealed that the expression of GSDMD and inflammasome-related genes were increased in COVID-19 patients. High expression of active GSDMD associated with NETs structures was found in the lung tissue of COVID-19 patients. Furthermore, we showed that activation of GSDMD in neutrophils requires active caspase1/4 and live SARS-CoV-2, which infects neutrophils. In a mouse model of SARS-CoV-2 infection, the treatment with disulfiram inhibited NETs release and reduced organ damage. CONCLUSION: These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy.

Apex Score: Predicting Flares in Small-Bowel Crohn's Disease After Mucosal Healing.

BACKGROUND: Optimal strategies for using small-bowel capsule endoscopy (SBCE) in established small-bowel Crohn's disease (CD) remain uncertain. Mucosal healing (MH) has emerged as a valuable predictor of a flare-free disease. We aimed to evaluate the occurrence of disease flare on patients with small-bowel CD and MH, as well as to create a score identifying patients in higher risk for this outcome. METHODS: We analyzed consecutive patients submitted to SBCE for assessment of MH and included those where MH was confirmed. The incidence of disease flare was assessed during follow-up (minimum 12 months). A score predicting disease flare was created from several analyzed variables. RESULTS: From 47 patients with MH, 12 (25.5%) had a flare (versus 48.3% in excluded patients without MH; p = 0.01). Age ≤ 30 years (OR  = 70; p  = 0.048), platelet count ≥ 280 × 103/L (OR  = 12.24; p  =  0.045) and extra-intestinal manifestations (OR  =  11.76; p  =  0.033) were associated with increased risk of CD flare during the first year after SBCE with MH. These variables were used to compute a risk-predicting score-the APEX score-which assigned the patients to having low (0-3 points) or high-risk (4-7 points) of disease flare and had excellent accuracy toward predicting disease relapse (AUC  =  0.82; 95%CI 0.64-0.99). CONCLUSION: Patients with small-bowel CD and MH were not free of disease flares on the subsequent year, despite presenting lower rates when compared to those without MH. The APEX score demonstrated excellent accuracy at stratifying patients relapse risk and guiding further therapeutic options for patients achieving MH.

Liposomal Delivery of Newly Identified Prophage Lysins in a Pseudomonas aeruginosa Model.

Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium that presents resistance to several antibiotics, thus, representing a major threat to human and animal health. Phage-derived products, namely lysins, or peptidoglycan-hydrolyzing enzymes, can be an effective weapon against antibiotic-resistant bacteria. Whereas in Gram-positive bacteria, lysis from without is facilitated by the exposed peptidoglycan layer, this is not possible in the outer membrane-protected peptidoglycan of Gram-negative bacteria. Here, we suggest the encapsulation of lysins in liposomes as a delivery system against Gram-negative bacteria, using the model of P. aeruginosa. Bioinformatic analysis allowed for the identification of 38 distinct complete prophages within 66 P. aeruginosa genomes (16 of which newly sequenced) and led to the identification of 19 lysins of diverse sequence and function, 5 of which proceeded to wet lab analysis. The four purifiable lysins showed hydrolytic activity against Gram-positive bacterial lawns and, on zymogram assays, constituted of autoclaved P. aeruginosa cells. Additionally, lysins Pa7 and Pa119 combined with an outer membrane permeabilizer showed activity against P. aeruginosa cells. These two lysins were successfully encapsulated in DPPC:DOPE:CHEMS (molar ratio 4:4:2) liposomes with an average encapsulation efficiency of 33.33% and 32.30%, respectively. The application of the encapsulated lysins to the model P. aeruginosa led to a reduction in cell viability and resulted in cell lysis as observed in MTT cell viability assays and electron microscopy. In sum, we report here that prophages may be important sources of new enzybiotics, with prophage lysins showing high diversity and activity. In addition, these enzybiotics following their incorporation in liposomes were able to potentiate their antibacterial effect against the Gram-negative bacteria P. aeruginosa, used as the model.

P020 Proton Pump Inhibitor Therapy: Providing "Acid" Outcomes in Patients With Inflammatory Bowel Disease Under Infliximab Treatment.

BACKGROUND: A recent meta-analysis has suggested that proton pump inhibitor (PPI) therapy is associated with lower clinical remission rates and a higher number of hospitalizations in patients with inflammatory bowel disease (IBD) under infliximab therapy. We aimed to assess if these differences kept their significance when adjusted for other possible confounders. METHODS: Cohort study of consecutive patients with Crohn's disease (CD) and Ulcerative Colitis (UC) under infliximab therapy. A minimum follow-up of 54 weeks after introduction of infliximab treatment was required. The analyzed outcomes were deep remission at week 54 and the need of IBD-related hospitalization, corticosteroid treatment or abdominal surgery under infliximab treatment. Collected possible confounders were age, gender, smoking habits, perianal disease, extra-intestinal manifestations, familiar history of IBD and concomitant use of immunomodulators. RESULTS: Our final sample included 104 patients, 56 (53.8%) of them females, with a mean age of 38.2±13.1 years. From these, 77 (74.0%) had CD and 27 (26.0%) had UC. PPI therapy was described in 21 (20.2%) of the patients under infliximab treatment. On univariate analysis, PPI users were found to have significantly lower rates of deep remission at week 54 (7.7 vs 28.3%; p = 0.034) and higher IBD-related hospitalization rates (47.6 vs 21.7%; p = 0.034). No differences were found regarding the need of corticosteroid therapy (4.8 vs 10.8%; p = 0.398) or abdominal surgery (33.7 vs 21.7; p = 0.201). When adjusted for the collected confounders by multivariate analysis, while not significantly influencing deep remission at week 54 (OR = 0.16; 95%CI = 0.02-1.63; p = 0.121), concomitant PPI therapy was a significant independent risk factor for IBD-related hospitalization (OR = 3.22; 95%CI = 1.11-9.34; p = 0.04). CONCLUSION: Despite not conducting to significantly different deep remission rates, concomitant PPI therapy was associated with a three-fold increase in hospitalization rates in IBD patients under infliximab treatment, even when adjusted for classical risk factors for adverse outcomes in IBD. These findings emphasize the importance of restricting PPI treatment to those with a clear clinical indication, especially in this set of patients.