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Purpose To compare the diagnostic performance of T1 mapping and MR elastography (MRE) for staging of hepatic fibrosis and grading inflammation with histopathology as standard of reference. Methods 68 patients with various liver diseases undergoing liver biopsy for suspected fibrosis or with an established diagnosis of cirrhosis prospectively underwent look-locker inversion recovery T1 mapping and MRE. T1 relaxation time and liver stiffness (LS) were measured by two readers. Hepatic fibrosis and inflammation were histopathologically staged according to a standardized fibrosis (F0–F4) and inflammation (A0–A2) score. For statistical analysis, independent t test, and Mann–Whitney U test and ROC analysis were performed, the latter to determine the performance of T1 mapping and MRE for fibrosis staging and inflammation grading, as compared to histopathology. Results Histopathological analysis diagnosed 9 patients with F0 (13.2%), 21 with F1 (30.9%), 11 with F2 (16.2%), 10 with F3 (14.7%), and 17 with F4 (25.0%). Both T1 mapping and MRE showed significantly higher values for patients with significant fibrosis (F0-1 vs. F2-4; T1 mapping p p p p p = 0.01). T1 mapping showed a tendency toward lower diagnostic performance without statistical significance for significant fibrosis (F2-4) (AUC 0.79 vs. 0.91, p = 0.06) and with a significant difference compared to MRE for severe fibrosis (F3-4) (AUC 0.79 vs. 0.94, p = 0.03). For both T1 mapping and MRE, diagnostic performance for diagnosing hepatic inflammation (A1-2) was low (AUC 0.72 vs. 0.71, respectively). Conclusion T1 mapping is able to diagnose hepatic fibrosis, however, with a tendency toward lower diagnostic performance compared to MRE and thus may be used as an alternative to MRE for diagnosing hepatic fibrosis, whenever MRE is not available or likely to fail due to intrinsic factors of the patient. Both T1 mapping and MRE are probably not sufficient as standalone methods to diagnose hepatic inflammation with relatively low diagnostic accuracy.

BACKGROUND There is limited information on the effects of statins on the outcomes of liver transplantation (LT), regarding either their use by LT recipients or donors. AIM To analyse the association between statin exposure and recipient and graft survival. METHODS We included adult LT recipients with deceased donors in a nationwide prospective database study. Using a multistate modelling approach, we examined the effect of statins on the transition hazard between LT, biliary and vascular complications and death, allowing for recurring events. The observation time was 3 years. RESULTS We included 998 (696 male, 70%, mean age 54.46 ± 11.14 years) LT recipients. 14% of donors and 19% of recipients were exposed to statins during the study period. During follow-up, 141 patients died; there were 40 re-LT and 363 complications, with 66 patients having two or more complications. Treatment with statins in the recipient was modelled as a concurrent covariate and associated with lower mortality after LT (HR = 0.35; 95% CI 0.12-0.98; p = 0.047), as well as a significant reduction of re-LT (p = 0.004). However, it was not associated with lower incidence of complications (HR = 1.25; 95% CI = 0.85-1.83; p = 0.266). Moreover, in patients developing complications, statin use was significantly associated with decreased mortality (HR = 0.10; 95% CI = 0.01-0.81; p = 0.030), and reduced recurrence of complications (HR = 0.43; 95% CI = 0.20-0.93; p = 0.032). CONCLUSIONS Statin use by LT recipients may confer a survival advantage. Statin administration should be encouraged in LT recipients when clinically indicated.

Introduction The goal of this project was to create an up-to-date joint European clinical practice guideline for the diagnosis and treatment of faecal incontinence (FI), using the best available evidence. These guidelines are intended to help guide all medical professionals treating adult patients with FI (e.g., general practitioners, surgeons, gastroenterologists, other healthcare workers) and any patients who are interested in information regarding the diagnosis and management of FI. Methods These guidelines have been created in cooperation with members from the United European Gastroenterology (UEG), European Society of Coloproctology (ESCP), European Society of Neurogastroenterology and Motility (ESNM) and the European Society for Primary Care Gastroenterology (ESPCG). These members made up the guideline development group (GDG). Additionally, a patient advisory board (PAB) was created to reflect and comment on the draft guidelines from a patient perspective. Relevant review questions were established by the GDG along with a set of outcomes most important for decision making. A systematic literature search was performed using these review questions and outcomes as a framework. For each predefined review question, the study or studies with the highest level of study design were included. If evidence of a higher-level study design was available, no lower level of evidence was sought or included. Data from the studies were extracted by two reviewers for each predefined important outcome within each review question. Where possible, forest plots were created. After summarising the results for each review question, a systematic quality assessment using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was performed. For each review question, we assessed the quality of evidence for every predetermined important outcome. After evidence review and quality assessment were completed, recommendations could be formulated. The wording used for each recommendation was dependent on the level of quality of evidence. Lower levels of evidence resulted in weaker recommendations and higher levels of evidence resulted in stronger recommendations. Recommendations were discussed within the GDG to reach consensus. Results These guidelines contain 45 recommendations on the classification, diagnosis and management of FI in adult patients. Conclusion These multidisciplinary European guidelines provide an up-to-date comprehensive evidence-based framework with recommendations on the diagnosis and management of adult patients who suffer from FI.

Zusammenfassung Einleitung Kinder und Jugendliche mit chronischen Magen-, Darm-, Pankreas-, und Lebererkrankungen benötigen eine altersgerechte und qualifizierte Behandlung. Anhand einer repräsentativen Umfrage wird die strukturelle und personelle ambulante und stationäre Versorgung von Kindern mit chronischen Magen-, Darm-, Pankreas- und Lebererkrankungen in Deutschland analysiert. Methodik 319 Kliniken für Kinder- und Jugendmedizin sowie 50 kindergastroenterologische Praxen in Deutschland wurden eingeladen, an der anonymen Online-Umfrage über EFS Survey teilzunehmen. Es wurden die Struktur der Einrichtungen, Weiterbildungsbefugnisse, Kooperationen, Behandlungs- bzw. Betreuungsdaten und eine Einschätzung des Versorgungsbedarfs systematisch erfasst und deskriptiv ausgewertet. Ergebnisse An der Umfrage haben 81 Kliniken und 10 Praxen teilgenommen. Fast zwei Drittel der Kliniken (n=52) erbringen ambulante kindergastroenterologische Leistungen. Meist bis zu 10 (25,4%) oder 20 Stunden/Woche (33,8%). Ein Viertel der Kliniken bietet keine Sprechstunden an. Der ambulante Versorgungsbedarf kann von zwei Dritteln der Institutionen nicht gedeckt werden. Die Hälfte aller Kliniken gab an, dass der stationäre kindergastroenterologische Versorgungsbedarf gedeckt werden kann. Ein Drittel kann diesen jedoch nicht abdecken und nur selten gibt es ungenutzte Kapazitäten. 35 Kliniken (43,2%) verfügen über eine Weiterbildungsbefugnis gemäß Landesärztekammer (n=33) und/oder sind Weiterbildungszentrum der Gesellschaft für pädiatrische Gastroenterologie und Ernährung (GPGE) (n=18). Schlussfolgerung Es besteht sowohl ein ambulantes als auch stationäres Versorgungsdefizit in der Kinder- und Jugendgastroenterologie. Dieses resultiert unter anderem aus den ökonomischen Rahmenbedingungen und Personalmangel. Gut ausgebildete Fachärzt*innen mit Spezialisierung in Kinder- und Jugendgastroenterologie werden für eine flächendeckende qualifizierte Versorgung weiterhin benötigt. Zukünftige Studien sollten auch den kindergastroenterologischen Versorgungsbedarf aus Sicht anderer Gruppen einbeziehen, wie betroffener Patienten*innen, internistischer Gastroenterolog*innen und niedergelassener Kinder- und Jugendärzt*innen.

Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study. We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes. The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 (p = 0.0018), presence of ascites (p = 0.0152), right-sided tumours (p = 0.0002), the presence of portal vein thrombosis (p = 0.0378) and main portal vein thrombosis (p = 0.0028), ALBI grade 2 (p = 0.0043) and 3 (p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events. This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes. Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE. NCT02305459.

Background Motorized spiral enteroscopy (MSE) has been shown to be safe and effective for deep enteroscopy in studies performed at expert centers with limited numbers of patients without previous abdominal surgery. This study aimed to investigate the safety, efficacy, and learning curve associated with MSE in a real-life scenario, with the inclusion of patients after abdominal surgery and with altered anatomy. Methods Patients with indications for deep enteroscopy were enrolled in a prospective observational multicenter study. The primary objective was the serious adverse event (SAE) rate; secondary objectives were the diagnostic and therapeutic yield, procedural success, time, and insertion depth. Data analysis was subdivided into training and core (post-training) study phases at centers with different levels of MSE experience. Results 298 patients (120 women; median age 68, range 19–92) were enrolled. In the post-training phase, 21.5 % (n = 54) had previous abdominal surgery, 10.0 % (n = 25) had surgically altered anatomy. Overall, SAEs occurred in 2.3 % (7/298; 95 %CI 0.9 %–4.8 %). The SAE rate was 2.0 % (5/251) in the core group and 4.3 % (2/47) in the training group, and was not increased after abdominal surgery (1.9 %). Total enteroscopy was achieved in half of the patients (n = 42) undergoing planned total enteroscopy. In 295/337 procedures (87.5 %), the anatomical region of interest could be reached. Conclusions This prospective multicenter study showed that MSE was feasible and safe in a large cohort of patients in a real-life setting, after a short learning curve. MSE was shown to be feasible in postsurgical patients, including those with altered anatomy, without an increase in the SAE rate.

This study explored factors that can predict effectiveness outcomes after transarterial radioembolization in colorectal liver metastases in the liver. In a cohort of 237 patients, among other factors, we found that an Aspartate transaminase to Platelet Ratio Index (APRI) value of > 0.40 was a particularly strong independent predictor of worse overall survival, progression-free survival and hepatic progression-free survival outcomes. Background: Transarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal cancer in the liver (mCRC). A better understanding of the prognostic factors and treat-ment application can improve survival outcomes. Methods: We analysed the safety and effectiveness of 237 mCRC patients included in the prospective observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) for indepen-dent prognostic factors for overall survival (OS), progression-free survival (PFS) and hepatic progression-free survival (hPFS) using the Cox proportional-hazard model. Results: The median OS was 9.8 months, median PFS was 3.4 months and median hPFS was 4.2 months. Independent prognostic factors for an improved overall survival were the absence of extra-hepatic disease ( P = .0391), prior locoregional procedures ( P = .0037), an Aspartate transaminase to Platelet Ratio Index (APRI) value of 0.40 ( P = .0416) and prior ablation ( P = .0323), and for hPFS these were 2 to 5 tumor nodules ( P = .0148), Albumin-bilirubin (ALBI) grade 3 ( P = .0075) and APRI > 0.40 ( P = .0207). During the study, 95 of 237 (40.1%) patients experienced 197 adverse events, with 28 of 237 (11.8%) patients having a grade 3 or higher adverse events. Conclusion: Including easy-to-acquire laboratory markers INR, APRI, ALBI and using partition model dosimetry can identify mCRC patients that may benefit from TARE.

Inflammatory bowel diseases (IBDs) are systemic diseases that manifest not only in the gut and gastrointestinal tract, but also in the extraintestinal organs in many patients. The quality of life for patients with IBD can be substantially affected by these extraintestinal manifestations (EIMs). It is important to have knowledge of the prevalence, pathophysiology, and clinical presentation of EIMs in order to adapt therapeutic options to cover all aspects of IBD. EIMs can occur in up to 24% of patients with IBD before the onset of intestinal symptoms, and need to be recognized to initiate appropriate diagnostic procedures. EIMs most frequently affect joints, skin, or eyes, but can also affect other organs, such as the liver, lung, and pancreas. It is a frequent misconception that a successful therapy of the intestinal inflammation will be sufficient to treat EIMs satisfactorily in most patients with IBD. In general, peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum can be associated with active intestinal inflammation and can improve on standard treatment of the intestinal inflammation. However, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis usually occur independent of disease flares. This review provides a comprehensive overview of epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in IBD.

Enteral feed bezoars are difficult to treat and can lead to serious adverse events. There is no standardized treatment approach and various strategies have been suggested. We herein describe three cases of successful dissolutions of feed bezoars consisting of Promote® Fibre Plus with sodium bicarbonate 8.4% in critically ill patients. To provide the rationale for this approach, the effect of sodium bicarbonate 8.4% on enteral feed concretions was studied in vitro. First, Promote® Fibres Plus was incubated with hydrochloric acid with gradually decreasing pH values to establish a pH at which the solution solidifies. The resulting enteral feed concretion was exposed to sodium bicarbonate 8.4% and Coca Cola®. All patients were successfully treated with sodium bicarbonate 8.4% without the need of lengthy or repeat endoscopies. In vitro, Promote® Fibres Plus solidifies when acidified below a pH of 4.6. The resulting enteral feed concretions dissolved when exposed to sodium bicarbonate 8.4%. Incubation with Coca Cola® had no effect. We provide evidence that enteral feed bezoars consisting of Promote® Fibres Plus can be efficiently and safely treated with sodium bicarbonate 8.4% offering a new approach for daily patient care.

Eosinophilic esophagitis (EoE) is a chronic progressive disease. Diagnostic delay (DD) is associated with increased risk of esophageal strictures and food impactions. We aimed to assess the evolution of DD since the first description of EoE in 1993 until 2021.We analyzed data from patients prospectively included in the Swiss EoE database. DD was calculated as the time interval between the first occurrence of EoE symptoms and the confirmed diagnosis. DD was analyzed annually over time (1989-2021) and according to milestone publications in the field (1993: first description; 2007: first consensus recommendations; and 2011: updated consensus recommendations). In addition, a Cox proportional hazards model has been used to describe the relation between DD and covariates.Complete data of 1,152 patients (857 male [74%]; median age at diagnosis: 38 years, interquartile range: 28-49, range: 1-86) were analyzed. Overall, median DD was 4 years (interquartile range: 1-11, range, 0-56), with DD ≥ 10 years in 32% of the population. Over time, DD did not significantly change, neither annually nor according to release dates of milestone publications with a persistently stable fraction of roughly one-third of all patients with a DD of ≥10 years. Both ages at diagnosis ( P0.001, with an increase in DD up to the age of 31-40 years) and at symptom onset (younger patients had a longer DD; P0.001) were significantly associated with DD.DD has not changed since the first description of EoE almost 30 years ago and remains substantial. Even today, one-third of patients have a persistently high DD of ≥10 years. Substantial efforts are warranted to increase awareness for EoE and its hallmark symptom, solid food dysphagia, as an age-independent red-flag symptom among healthcare professionals and presumably the general population alike to lower risk of long-term complications.

Constipation is a common problem, affects 15% of the population, and is often self-diagnosed and self-managed. Over the past 3 decades, there have been significant advances in our understanding and management of chronic constipation, with the emerging recognition that occasional constipation (OC) is another subtype that falls outside current classifications. The purpose of this review was to describe the process of developing and proposing a new definition for OC based on expert consensus and taking into consideration the multifactorial nature of the problem such as alterations in bowel habit that include stool frequency and difficulty with stool passage, perception of the sufferer, duration of symptoms, and potential responsiveness to treatment. Leading gastroenterologists from 5 countries met virtually on multiple occasions through an online digital platform to discuss the problem of OC and recommended a practical, user-friendly definition: "OC can be defined as intermittent or occasional symptomatic alteration(s) in bowel habit. This includes a bothersome reduction in the frequency of bowel movements and/or difficulty with passage of stools but without alarming features. Bowel symptoms may last for a few days or a few weeks, and episodes may require modification of lifestyle, dietary habits and/or use of over-the-counter laxatives or bulking agents to restore a satisfactory bowel habit." Prospective studies are required to validate this definition and determine OC prevalence in the community. This review highlights current knowledge gaps and could provide impetus for future research to facilitate an improved understanding of OC and development of evidence-based management guidelines.

BACKGROUND AND AIMS Inflammatory bowel disease (IBD) requires long-term drug therapy in most patients, posing a risk for adverse drug events with the need for discontinuation. In this study, we investigated adverse events (AE) necessitating drug discontinuation in pediatric and adolescent IBD patients. METHODS We used data prospectively collected from IBD patients below the age of 18 enrolled in the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), namely demographic variables, medical characteristics, drug treatments and related AE. We analysed the frequency, type, and risk factors for AE necessitating drug discontinuation. RESULTS A total of 509 pediatric IBD patients fulfilled the inclusion criteria of which 262 (51.5%) were diagnosed with Crohn's disease (CD), 206 (40.5%) with ulcerative colitis (UC), and 41 (8%) with IBD-unclassified (IBD-U). In total, 132 (25.9%) presented with at least one drug-related AE that required drug cessation. Immunomodulators (methotrexate 29/120 (24.2%), azathioprine 57/372 (15.3%)) followed by tumor necrosis factor (TNF)-alpha antagonists (adalimumab 8/72 (11.1%), infliximab 22/227 (9.7%)) accounted for the highest proportions of AE necessitating treatment discontinuation. Treatment schemes with at least 3 concomitant drugs significantly amplified the risk for development of drug-related AE (OR = 2.50, 95%CI [1.50-4.17]) in all pediatric IBD patients. CONCLUSIONS Drug-related AE necessitating discontinuation are common in pediatric and adolescent inflammatory bowel disease patients. Caution needs to be taken in the case of concomitant drug use.

INTRODUCTION: 13 C-breath tests are valuable, noninvasive diagnostic tests that can be widely applied for the assessment of gastroenterological symptoms and diseases. Currently, the potential of these tests is compromised by a lack of standardization regarding performance and interpretation among expert centers. METHODS: This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of 13 C-breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 43 experts from 18 European countries. Consensus on individual statements and recommendations was established if ≥ 80% of reviewers agreed and

Background Ischemia–reperfusion injury (IRI) is the pathophysiological hallmark of hepatic dysfunction after orthotopic liver transplantation (OLT). Related to IRI, early allograft dysfunction (EAD) after OLT affects short- and long-term outcome. During inflammatory states, the liver seems to be the main source of procalcitonin (PCT), which has been shown to increase independently of bacterial infection. This study investigates the association of PCT, IRI and EAD as well as the predictive value of PCT during the first postoperative week in terms of short- and long-term outcome after OLT. Methods Patients ≥ 18 years undergoing OLT between January 2016 and April 2020 at the University Hospital of Zurich were eligible for this retrospective study. Patients with incomplete PCT data on postoperative days (POD) 1 + 2 or combined liver-kidney transplantation were excluded. The PCT course during the first postoperative week, its association with EAD, defined by the criteria of Olthoff, and IRI, defined as aminotransferase level > 2000 IU/L within 2 PODs, were analysed. Finally, 90-day as well as 12-month graft and patient survival were assessed. Results Of 234 patients undergoing OLT, 110 patients were included. Overall, EAD and IRI patients had significantly higher median PCT values on POD 2 [31.3 (9.7–53.8) mcg/l vs. 11.1 (5.3–25.0) mcg/l; p p p = 0.01 and 80.4% vs. 93.8%; p = 0.033). IRI patients with PCT p = 0.001 and 68.4% vs. 93.8%; p = 0.008) as well as impaired 12-month graft and patient survival (57.9% vs. 96.3%; p = 0.001 and 68.4% vs. 96.3%; p = 0.008), while the outcome of IRI patients with PCT > 15 mcg/l on POD 2 was comparable to that of patients without IRI/EAD. Conclusion Generally, PCT is increased in the early postoperative phase after OLT. Patients with EAD and IRI have a significantly increased PCT maximum on POD 2, and impaired 90-day graft survival. PCT measurement may have potential as an additional outcome predictor in the early phase after OLT, as in our subanalysis of IRI patients, PCT values

Since most pharmacological treatments in case of esophageal food impaction (EFI) are unsuccessful, an endoscopy is usually required to resolve EFI. We present the first results of a budesonide orodispersible tablet (BOT) as a medical treatment option before endoscopy. We evaluated all patients with a suspected EFI to receive BOT before emergent endoscopy at a tertiary hospital between March 2019 and June 2020. A total of eight patients received BOT before endoscopy. Mean age was 50.1 years and 87.5% were male. In 38% (3/8) of patients the EFI resolved without endoscopic intervention. No adverse events occurred. After endoscopy, a diagnosis of EoE was established in 75%. This case series demonstrate the potential of BOT as medical rescue therapy in case of EFI.

Background Cronobacter sakazakii is a foodborne pathogen that causes septicemia, meningitis, and necrotizing enterocolitis in neonates and infants. The current research details the full genome sequences of two extremely persistent C. sakazakii strains (H322 and GK1025B) isolated from powdered infant formula (PIF) manufacturing settings. In addition, the genetic attributes associated with five plasmids, pH322_1, pH322_2, pGK1025B_1, pGK1025B_2, and pGK1025B_3 are described. Materials and Methods Using PacBio single-molecule real-time (SMRT®) sequencing technology, whole genome sequence (WGS) assemblies of C. sakazakii H322 [Sequence type (ST)83, clonal complex [CC] 83) and GK1025B (ST64, CC64) were generated. Plasmids, also sequenced, were aligned with phylogenetically related episomes to determine, and identify conserved and missing genomic regions. Results A truncated ~ 13 Kbp type 6 secretion system (T6SS) gene cluster harbored on virulence plasmids pH322_2 and pGK1025B_2, and a second large deletion (~ 6 Kbp) on pH322_2, which included genes for a tyrosine-type recombinase/integrase, a hypothetical protein, and a phospholipase D was identified. Within the T6SS of pH322_2 and pGK1025B_2, an arsenic resistance operon was identified which is in common with that of plasmids pSP291_1 and pESA3. In addition, PHASTER analysis identified an intact 96.9 Kbp Salmonella SSU5 prophage gene cluster in pH322_1 and pGK1025B_1 and showed that these two plasmids were phylogenetically related to C. sakazakii plasmids: pCS1, pCsa767a, pCsaC757b, pCsaC105731a. Plasmid pGK1025B_3 was identified as a novel conjugative Cronobacter plasmid. Furthermore, WGS analysis identified a ~ 16.4 Kbp type 4 secretion system gene cluster harbored on pGK1025B_3, which contained a phospholipase D gene, a key virulence factor in several host–pathogen diseases. Conclusion These data provide high resolution information on C. sakazakii genomes and emphasizes the need for furthering surveillance studies to link genotype to phenotype of strains from previous investigations. These results provide baseline data necessary for future in-depth investigations of C. sakazakii that colonize PIF manufacturing facility settings and genomic analyses of these two C. sakazakii strains and five associated plasmids will contribute to a better understanding of this pathogen's survival and persistence within various “built environments” like PIF manufacturing facilities.

Introduction We aimed to compare the efficacy of cognitive-behavioral therapy (CBT) among children with functional abdominal pain with an attention control (AC), hypothesizing the superiority of CBT group intervention regarding pain intensity (primary outcome), pain duration and frequency (further primary outcomes), functional disability, and quality of life and coping strategies (key secondary outcomes). Methods We conducted a prospective, multicenter, randomized controlled efficacy trial (RCT) with 4 time points (before intervention, after intervention, 3-month follow-up, and 12-month follow-up). One hundred twenty-seven children aged 7-12 years were randomized to either the CBT (n = 63; 55.6% girls) or the AC (n = 64; 57.8% girls). Results Primary endpoint analysis of the logarithmized area under the pain intensity curve showed no significant difference between groups (mean reduction = 49.04%, 95% confidence interval [CI] -19.98%-78.36%). Treatment success rates were comparable (adjusted odds ratio = 0.53, 95% CI 0.21-1.34, number needed to treat = 16). However, time trend analyses over the course of 1 year revealed a significantly greater reduction in pain intensity (40.9%, 95% CI 2.7%-64.1%) and pain duration (43.6%, 95% CI 6.2%-66.1%) in the CBT compared with the AC, but not in pain frequency per day (1.2, 95% CI -2.7 to 5.2). In the long term, children in the CBT benefitted slightly more than those in the AC with respect to functional disability, quality of life, and coping strategies. Discussion Both interventions were effective, which underlines the role of time and attention for treatment efficacy. However, in the longer term, CBT yielded more favorable results.

Background Vedolizumab (VDZ), a humanised monoclonal antibody against a4ß7‐integrin, has shown efficacy in inflammatory bowel disease (IBD). It is of importance to assess the mid‐to long‐term efficacy of VDZ using real‐life data. Objective Our study aimed to determine the efficacy of VDZ in patients with IBD with and without prior exposure to anti‐tumour necrosis factor (TNF) treatments in a real‐life setting. Furthermore, we investigated confounding factors influencing the remission to VDZ. Methods Patients participating in the Swiss IBD Cohort Study were included in this study. Remission was defined as calprotectin less than 200 mg/kg stool and/or mucosal healing determined by endoscopy. End points were determined between Months 4 and 8 (T1) and between Months 12 and 16 (T2) after VDZ induction. Results Remission was reported in 50.5% (110/218) of patients in T1 (48.7% Crohn's disease [CD] and 52.5% ulcerative colitis [UC]) and 46.8% (102/218) in T2 (47% CD and 46.5% UC). In UC patients, a significantly higher remission rate was achieved in T2 among anti‐TNF‐naive patients (57.7%) compared to anti‐TNF‐experienced patients (34.7%; p = 0.02; odds ratio = 0.39, 95% confidence interval: 0.17–0.87). In patients with CD, no difference could be seen in either evaluation interval. Multivariable analysis showed that disease duration significantly influenced remission rates among UC patients. A late response to VDZ therapy with an achievement of remission in T2 was seen in a fifth of all patients (CD: 21.7%, UC: 20.8%). VDZ treatment was stopped in a third of all patients (31.8%) due to nonresponse, adverse events or aggravation of extra‐intestinal manifestations. Conclusion In a real‐life national cohort setting, VDZ induced remission in more than half of IBD patients. Previous treatment with anti‐TNF agents was associated with a significant lower efficacy of VDZ in UC but not in CD patients.

Purpose Nodal status in colorectal cancer (CRC) is an important prognostic factor, and adequate lymph node (LN) staging is crucial. Whether the number of resected and analysed LN has a direct impact on overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) is much discussed. Guidelines request a minimum number of 12 LN to be analysed. Whether that threshold marks a prognostic relevant cut-off remains unknown. Methods Patients operated for stage I–III CRC were identified from a prospectively maintained database. The impact of the number of analysed LN on OS, CSS and DFS was assessed using Cox regression and propensity score analysis. Results Of the 687 patients, 81.8% had ≥ 12 LN resected and analysed. Median LN yield was 17.0 (IQR 13.0–23.0). Resection and analysis of ≥ 12 LN was associated with improved OS (HR = 0.73, 95% CI: 0.56–0.95, p = 0.033), CSS (HR 0.52, 95% CI: 0.31–0.85, p = 0.030) and DFS (HR = 0.73, 95% CI: 0.57–0.95, p = 0.030) in multivariate Cox analysis. After adjusting for biasing factors with propensity score matching, resection of ≥ 12 LN was significantly associated with improved OS (HR = 0.59; 95% CI: 0.43–0.81; p = 0.002), CSS (HR = 0.34; 95% CI: 0.20–0.60; p p Conclusion Eliminating biasing factors by a propensity score matching analysis underlines the prognostic importance of the number of analysed LN. The set threshold marks the minimum number of required LN but nevertheless represents a cut-off regarding outcome in stage I–III CRC. This analysis therefore highlights the significance and importance of adherence to surgical oncological standards.

Background: Gastroesophageal reflux disease (GERD) is strongly associated with excess body weight. Summary: GERD is characterized by typical symptoms with or without mucosal damage because of retrograde flow of gastric content into the esophagus. An ineffective esophagogastric junction (EGJ) combined with anatomical abnormalities is considered to be causative. The incidence of GERD is strongly associated with excess body weight, reflecting the pathophysiological relevance of the abdominothoracic pressure gradient. Key Message: Weight loss has been demonstrated to be an effective therapy for GERD combined with obesity. In cases in which surgical therapy is indicated, traditional antireflux surgery has led to equivocal results, advocating a proximal Roux-en-Y gastric bypass in these patients to correct both GERD and excess body weight.

BACKGROUND AND AIMS No recommendations exist regarding optimal follow-up schedule in patients with eosinophilic esophagitis (EoE) under maintenance treatment. METHODS We retrospectively evaluated a long-term surveillance concept at the Swiss EoE clinic, where clinical, endoscopic and histological disease activity is assessed annually regardless of EoE symptoms. Data on 159 adult patients under maintenance steroid treatment with available follow-up were analyzed. Patients were classified as having close (duration between visits

The expression of amino acid transporters is known to vary during acute pancreatitis (AP) except for LAT1 (To evaluate the role of LAT1 in the development of and recovery from AP.AP was induced with caerulein (cae) injections in female and male mice expressing LAT1 or after its knockout (LAT1 Cre/LoxP). The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight, assessing microscopical tissue architecture, mRNA and protein expression, protein synthesis, and enzyme activity levels, as well as by testing the recruitment of immune cells by FACS and ELISA.The initial injury, evaluated by measurements of plasma amylase, lipase, and trypsin activity, as well as the gene expression of dedifferentiation markers, did not differ between the groups. However, early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout mice. Especially in females, we observed less mTOR reactivation and dysfunctional autophagy. The later regeneration phase was clearly delayed in female LAT1 knockout mice, which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein (rbpjl) and basic helix-loop-helix family member A15 (mist1). Amylase mRNA and protein levels remained lower, and, strikingly, female LAT1 knockout mice presented signs of fibrosis lasting until day seven. In contrast, pancreas morphology had returned to normal in wild-type littermates.LAT1 supports the regeneration of acinar cells after AP. Female mice lacking LAT1 exhibited more pronounced alterations than male mice, indicating a sexual dimorphism of amino acid metabolism.

To assess response to programmed death-1 (PD-1) monotherapy (nivolumab) in hepatocellular carcinoma (HCC) patients using RECIST1.1, modified RECIST (mRECIST), and immune RECIST (iRECIST). A secondary objective was to identify clinicolaboratory and imaging variables predictive of progressive disease (PD) and overall survival (OS).Patients with HCC treated with nivolumab at a single institution from 5/2016 to 12/2019 with MRI or CT performed ≥ 4 weeks post treatment were retrospectively assessed. Patients who received concurrent locoregional, radiation, or other systemic therapies were excluded. Response was assessed by 2 observers in consensus using RECIST1.1, mRECIST, and iRECIST at 3/6/9/12-month time points. Time to progression (TTP) and OS were recorded. Clinicolaboratory and imaging variables were evaluated as predictors of PD and OS using uni-/multivariable and Cox regression analyses.Fifty-eight patients (42M/16F) were included. 118 target lesions (TL) were identified before treatment. Baseline mean TL size was 49.1 ± 43.5 mm (range 10-189 mm) for RECIST1.1/iRECIST and 46.3 ± 42.3 mm (range 10-189 mm) for mRECIST. Objective response rate (ORR) was 21% for mRECIST/iRECIST/RECIST1.1, with no cases of pseudoprogression. Median OS and median TTP were 717 days and 127 days for RECIST1.1/mRECIST/iRECIST-iUPD (unconfirmed PD). Older age, MELD/Child-Pugh scores, AFP, prior transarterial radioembolization (TARE), and larger TL size were predictive of PD and/or poor OS using mRECIST/iRECIST. The strongest predictor of PD (HR = 2.49, 95% CI 1.29-4.81, p = 0.007) was TARE. The strongest predictor of poor OS was PD by mRECIST/iRECIST at 3 months (HR = 2.26, 95% CI 1.00-5.10, p = 0.05) with borderline significance.Our results show ORR of 21%, equivalent for mRECIST, iRECIST, and RECIST1.1 in patients with advanced HCC clinically treated with nivolumab.

To compare noise texture and accuracy to differentiate uric acid from non-uric acid urinary stones among four different single-source and dual-source DECT approaches in an ex vivo phantom study. Thirty-two urinary stones embedded in gelatin were mounted on a Styrofoam disk and placed into a water-filled phantom. The phantom was imaged using four different DECT approaches: (A) dual-source DECT (DS-DE); (B) 1st generation split-filter single-source DECT (SF1-TB); (C) 2nd generation split-filter single-source DECT (SF2-TB) and (D) 2nd generation split-filter single-source DECT using serial acquisitions (SF2-TS). Two different radiation doses (3 mGy and 6 mGy) were used. Noise texture was compared by assessing the average spatial frequency (fav) of the normalized noise power spectrum (nNPS). ROC curves for stone classification were computed and the accuracy for different dual-energy ratio cutoffs was derived. NNPS demonstrated comparable noise texture among A, C, and D (fav-range 0.18–0.19) but finer noise texture for B (fav = 0.27). Stone classification showed an accuracy of 96.9%, 96.9%, 93.8%, 93.8% for A, B, C, D for low-dose, respectively, and 100%, 96.9%, 96.9%, 100% for routine dose. The vendor-specified cutoff for the dual-energy ratio was optimal except for the low-dose scan in D for which the accuracy was improved from 93.8 to 100% using an optimized cutoff. Accuracy to differentiate uric acid from non-uric acid stones was high among four single-source and dual-source DECT approaches for low- and routine dose DECT scans. Noise texture differed only slightly for the first-generation split-filter approach.

Background: Post hepatectomy liver failure (PHLF) after ALPPS has been related to the discrepancy between liver volume and function. Pre-operative hepatobiliary scintigraphy (HBS) can predict postoperative liver function and guide when it is safe to proceed with major hepatectomy. Aim of this study was to evaluate the role of HBS in predicting PHLF after ALPPS, defining a safe cut-off. Methods: A multicenter retrospective study was approved by the ALPPS Registry. All patients selected for ALPPS between 2012 and 2018, were evaluated. Every patient underwent HBS during ALPPS evaluation. PHLF was reported according to ISGLS definition, considering grade B or C as clinically significant. Results: 98 patients were included. Thirteen patients experienced PHLF grade B or C (14%) following ALPPS-2. The HBS and the daily gain in volume (KGRFLR) of the future liver remnant (FLR) were significantly lower in PHLF B and C (p = .004 and .041 respectively). ROC curves indicated safe cut-offs of 4.1%/day (AUC = 0.68) for KGRFLR, and of 2.7 %/min/m(2) (AUC = 0.75) for HBSFLR. Multivariate analysis confirmed these cut-offs as variables predicting PHLF after ALPPS-2. Conclusion: Patients presenting a KGRFLR

Relapses after therapy with direct-acting antiviral agents (DAA) in chronic hepatitis C virus (HCV) infections are rare due to high efficacy of interferon-free therapy regimens. The presence of resistance-associated substitutions (RAS) in proteins targeted by therapy can lead to lower rates of sustained virological response (SVR) in patients receiving DAA-therapy, and little evidence exists as to how to treat these patients. We present a case of a multi-drug-resistant HCV-genotype-3a-infection in a 50-year-old female without confirmed cirrhosis but with advanced fibrosis (liver stiffness 11.6 kPa) and low viral load. Resistance testing revealed a Y93H mutation in the NS5A gene. Therapies using sofosbuvir and daclatasvir (1 The combination of sofosbuvir, glecaprevir/pibrentasvir and ribavirin could be a rescue therapy after previous relapses on DAA-therapy, especially in patients with relapse after therapy with sofosbuvir, velpatasvir, and voxilaprevir. Rückfälle nach einer Therapie mit direkt antiviral wirkenden Substanzen (DAA) bei Patienten mit chronischer Virushepatitis C (HCV) sind aufgrund der hohen Wirksamkeit dieser Therapeutika selten. Das Auftreten von resistenzassoziierten Substitutionen (RAS) in Proteinen, auf die die Therapie abzielt, kann eine anhaltende Viruselimination (SVR) verhindern, und es existiert wenig Evidenz dazu, wie diese Patienten anschließend behandelt werden sollten. Wir berichten von einer 50-jährigen Patientin mit einer therapieresistenten HCV-Genotyp-3a-Infektion ohne bestätigte Leberzirrhose, aber mit fortgeschrittener Fibrose (Lebersteifigkeit 11,6 kPa) und niedriger Viruslast. Resistenztestungen zeigten eine Y93H-Mutation im NS5A-Gen des Virus. Mehrere Therapieversuche mit Sofosbuvir und Daclatasvir (1.), Sofosbuvir, Velpatasvir und Ribavirin (2.) und mit Sofosbuvir, Velpatasvir und Voxilaprevir (3.) konnten kein SVR erreichen. Es ergaben sich keine Hinweise auf eine eingeschränkte Compliance, da es jeweils nach vier Wochen zu einer schnellen und über den Therapiezeitraum persistierenden Negativierung der Viruslast kam. Als letzte Alternative erhielt die Patientin eine 24-wöchige Therapie mit Sofosbuvir, Glecaprevir/Pibrentasvir und gewichtsadaptiert 1000 mg Ribavirin. Damit erreichte sie ein SVR, entwickelte aber ein hepatozelluläres Karzinom. Die Kombination von Sofosbuvir, Glecaprevir/Pibrentasvir und Ribavirin kann eine effektive Therapie nach Rückfällen auf eine vorherige DAA-Therapie darstellen, insbesondere, wenn ein SVR nach Gabe von Sofosbuvir, Velpatasvir und Voxilaprevir ausbleibt.

Background/Aims: The hepatitis C virus nonstructural 3/4A protease has been shown to cleave protein tyrosine phosphatase nonreceptor type 2 (PTPN2, also known as T cell protein tyrosine phosphatase), thereby inducing a shift from a Th1 toward a nonantiviral Th2 immunity. Ribavirin therapy reverses these effects and supports direct-acting antiviral (DAA) therapy as an immunomodulatory compound and ultimately improves the response to DAA therapy. Here we aimed to assess whether intrahepatic levels of PTPN2 might be used as a clinical prognostic marker for the response to DAA therapy. Methods: Liver biopsies from hepatitis C virus-infected patients with and without cirrhosis were immunohistochemically stained for PTPN2 and scored for staining intensity as well as percentage of hepatocytes positive for nuclear PTPN2 localization. PTPN2 scores were correlated to sustained virologic response after DAA therapy, viral load, serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase (GGT), and the Model for End-Stage Liver Disease (MELD) score at the time of liver biopsy. Results: We did not detect a difference in intrahepatic PTPN2 levels between responders with cirrhosis, responders without cirrhosis, and nonresponders to DAA therapy. There was no correlation between intrahepatic PTPN2 levels and viral load or clinical markers such as liver transaminases, GGT, or the MELD score. Conclusion: Intrahepatic PTPN2 levels assessed via IHC staining do not represent a clinical prognostic marker for the response to DAA therapy.

The purpose of this study was to investigate the impact of obesity on disease activity and disease outcome in patients with inflammatory bowel disease.The impact of obesity on inflammatory bowel disease disease activity and outcome was retrospectively assessed in 3075 patients enrolled in the prospective nation-wide Swiss inflammatory bowel disease cohort between July 2006 and September 2018. Baseline characteristics, disease activity and disease course in 325 obese inflammatory bowel disease patients (body mass index ≥30 kg/mAmong 3075 patients in the prospective Swiss inflammatory bowel disease cohort, 325 patients (10.6%) were obese, namely, 194 Crohn's disease patients, 131 ulcerative colitis, and inflammatory bowel disease-unclassified patients. Disease activity scores were elevated in obese Crohn's disease (Crohn's Disease Activity Index 33 vs 20,Obesity is associated with decreased rates of disease remission and increased risk of complicated disease course in Crohn's disease over a six-year follow-up period. No effects were seen on disease progression and index treatment failure neither in Crohn's disease nor ulcerative colitis.

Background: Westernization, above all associated changes in diet, has been postulated to be one of the most important factors contributing to the increasing incidence in inflammatory bowel disease (IBD), consisting mainly of Crohn’s disease and ulcerative colitis. Summary: Diet represents a crucially important and intuitively relevant topic for IBD patients. Although a substantial number of patients are prone to follow dietary advice from a variety of sources, including the lay press, there is intriguingly little scientific evidence for such an incitement. This may result in physicians being insufficiently informed about various aspects of nutrition, precluding adequate guidance of their patients with IBD. Importantly, IBD patients are at risk to develop deficiencies in iron, vitamin B12, folic acid, and several micronutrients, which may even be more pronounced in patients with active disease and those following a restrictive diet. This review aims to summarize the latest data from clinical and epidemiological studies investigating diet and its effect on the course of the disease and to outline the most important nutrient deficiencies in IBD patients. Key Messages: A western diet with an imbalance between omega-6 (n-6)/omega-3 (n-3) polyunsaturated fatty acids (PUFAs), in favor of n-6 PUFAs, may increase the risk of IBD, whereas a diet high in fruits and vegetables may decrease the risk of IBD. Many approaches to influence the course of IBD with dietary intervention exist. However, to induce or maintain remission in IBD with a change of diet is still in its infancy, and more dietary research is needed before we can apply it in daily practice. Patients with IBD, even in remission, have to be screened regularly for malnutrition.

Single water swallow (SWS) high-resolution manometry (HRM) may miss relevant esophageal motility disorders. Solid test meal (STM) during HRM and lately the functional lumen imaging probe (FLIP) have been shown to be of diagnostic value in the assessment of motility disorders. We aimed to assess the diagnostic yield of STM and FLIP in non-obstructive dysphagia (NOD). Patients assessed for dysphagia with both HRM and FLIP between April 2016 and August 2019 were analyzed for signs of non-obstructive EGJ outflow obstruction (EGJOO) according to Chicago Classification 3.0 (CCv3) and CC adapted for the use with solid swallows (CC-S), followed by an individual group-specific analysis. Five subjects without dysphagia served as control group. Standard HRM- and FLIP-values as well as esophagograms and Eckardt Scores were analyzed. Forty-two patients were identified (male/female, 14/36, median age 62). Twenty-five (59.5%) were diagnosed with EGJOO during STM only (= SWS-negative patients; CC-S). The EGJ distensibility index (EGJ-DI) of symptomatic patients was significantly lower compared to the control group (p = 0.006). EGJ-DI was 2/mmHg in 67% and 88% of patients diagnosed according to CC-S and CCv3, respectively. The IRP during STM showed a significant association to the corresponding EGJ-DI values (p

INTRODUCTION: Magnetic resonance enterography (MRE) is useful for detecting bowel strictures, whereas a number of imaging biomarkers may reflect severity of fibrosis burden in Crohn's disease (CD). This study aimed to verify the association of MRE metrics with histologic fibrosis independent of inflammation. METHODS: This prospective European multicenter study performed MRE imaging on 60 patients with CD with bowel strictures before surgical resection. Locations of 61 histological samples were annotated on MRE examinations, followed by central readings using the Chiorean score and measurement of delayed gain of enhancement (DGE), magnetization transfer ratio, T2-weighted MRI sequences (T2R), apparent diffusion coefficient (ADC), and the magnetic resonance index of activity (MaRIA). Correlations of histology and MRE metrics were assessed. Least Absolute Shrinkage and Selection Operator and receiver operator characteristic (ROC) curve analyses were used to select composite MRE scores predictive of histology and to estimate their predictive value. RESULTS: ADC and MaRIA correlated with fibrosis (R = -0.71, P < 0.0001, and 0.59, P < 0.001) and more moderately with inflammation (R = -0.35, P < 0.01, and R = 0.53, P < 0.001). Lower or no correlations of fibrosis or inflammation were found with DGE, magnetization transfer ratio, or T2R. Least Absolute Shrinkage and Selection Operator and ROC identified a composite score of MaRIA, ADC, and DGE as a very good predictor of histologic fibrosis (ROC area under the curve = 0.910). MaRIA alone was the best predictor of histologic inflammation with excellent performance in identifying active histologic inflammation (ROC area under the curve = 0.966). DISCUSSION: MRE-based scores for histologic fibrosis and inflammation may assist in the characterization of CD stenosis and enable development of fibrosis-targeted therapies and clinical treatment of stenotic patients. ispartof: CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY vol:13 issue:7 ispartof: location:United States status: published

Portal hypertensive polyps (PHPs) are incompletely characterized lesions that can be found in the distal stomach of patients with portal hypertension. We aimed to delineate clinical factors associated with the appearance of these rare polyps. We conducted a cross-sectional study of a cohort with 513 cirrhotic patients comparing patients with and without PHP using descriptive analyses and multivariable logistic regression. To address the problem of missing values, in particular for HVPG and liver stiffness, we used multiple imputation of missing values. The prevalence of macroscopically diagnosed PHP was 3.3% (95% confidence interval 2.0 − 5.4%). In 53% of cases, the correct classification was missed on index gastroscopy. Patients with PHP were older at gastroscopy (65 years vs. 59), had higher hepatic venous pressure gradients (HVPG, 28 mmHg vs. 19 mmHg), higher transient elastography (TE) measurements (50.7 kPa vs. 21.8 kPa) and more often had previous rubber band ligations (RBL, 64.7% vs. 25.8%). The multivariable logistic regression on the outcome macroscopically diagnosed PHP estimated an odds ratio (OR) for HPVG of 1.13 (CI 0.95–1.34), increased liver stiffness of 1.03 (1.00 − 1.07) and previous RBL of 3.84 (1.24 − 11.88), respectively. The prevalence of PHPs in the stomach was higher than assumed in previous studies and misclassification was commonly observed. The appearance of these rare polyps is associated with previous RBL and may correlate with severity of PH. Thus, PHPs may be regarded as marker for relevant PH, but clinical significance of these polyps is still uncertain.

ObjectivesAlterations in the intestinal microbiota are linked with a wide range of autoimmune and inflammatory conditions, including inflammatory bowel diseases (IBD), where pathobionts penetrate the intestinal barrier and promote inflammatory reactions. In patients with IBD, the ability of intestinal macrophages to efficiently clear invading pathogens is compromised resulting in increased bacterial translocation and excessive immune reactions. Here, we investigated how an IBD-associated loss-of-function variant in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene, or loss of PTPN2 expression affected the ability of macrophages to respond to invading bacteria.DesignIBD patient-derived macrophages with wild-type (WT) PTPN2 or carrying the IBD-associated PTPN2 SNP, peritoneal macrophages from WT and constitutive PTPN2-knockout mice, as well as mice specifically lacking PTPN2 in macrophages were infected with non-invasive K12 Escherichia coli, the human adherent-invasive E. coli (AIEC) LF82, or a novel mouse AIEC (mAIEC) strain.ResultsLoss of PTPN2 severely compromises the ability of macrophages to clear invading bacteria. Specifically, loss of functional PTPN2 promoted pathobiont invasion/uptake into macrophages and intracellular survival/proliferation by three distinct mechanisms: Increased bacterial uptake was mediated by enhanced expression of carcinoembryonic antigen cellular adhesion molecule (CEACAM)1 and CEACAM6 in PTPN2-deficient cells, while reduced bacterial clearance resulted from defects in autophagy coupled with compromised lysosomal acidification. In vivo, mice lacking PTPN2 in macrophages were more susceptible to mAIEC infection and mAIEC-induced disease.ConclusionsOur findings reveal a tripartite regulatory mechanism by which PTPN2 preserves macrophage antibacterial function, thus crucially contributing to host defence against invading bacteria.

Secondary Aortoenteric Fistulas (sAEF) are difficult to diagnose and usually result in fatal gastrointestinal (GI) bleeding following aortic repair. Outcomes are largely dependent on a timely diagnosis, but AEFs remain challenging to identify endoscopically and are usually diagnosed on computed tomography (CT) scans. The aim of our study was optimize diagnosis of AEF by identifying patients developing GI bleeding after aortic repair, investigate their clinical course and identify factors specific to different bleeding sources. A retrospective, single-center study capturing all patients developing upper or lower GI bleeding after aortic surgery between January 2009 and March 2020 was performed. Electronic health records were screened for diagnostic codes of the relevant procedures. Bleeding was classified into three groups: AEF with demonstrable fistula, ischemic – macroscopic ulceration plus histological confirmation or imaging and “other” due to other recognized conventional cause, such as peptic ulcer disease. 47 GI bleeding episodes in 39 patients were identified. Of these, 10 episodes (21%) were caused by AEF, 16 (34%) by ischemic ulceration and 21 (45%) due to other causes. Patients with AEF exhibited more frequent hemodynamic instability requiring vasopressors and had higher mortality, while ischemic ulcerations were associated with more recent operation or hypotensive episode. GI bleeding complications are uncommon following aortic surgery. AEF and ischemic ulceration are however frequent bleeding causes in this cohort. In patients presenting with fulminant bleeding, primary CT-scanning should be considered.

Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor that is almost uniformly lethal in humans. Activating mutations of KRAS are found in >90% of human PDACs and are sufficient to promote acinar-to-ductal metaplasia (ADM) during tumor initiation. The roles of miRNAs in oncogenic Kras-induced ADM are incompletely understood. Methods: The Ptf1aCre/+ LSL-KrasG12D/+ and Ptf1aCre/+ LSL-KrasG12D/+ LSL-p53R172H/+ and caerulein-induced acute pancreatitis mice models were used. mir-802 was conditionally ablated in acinar cells to study the function of miR-802 in ADM. Results: We show that miR-802 is a highly abundant and acinar-enriched pancreatic miRNA that is silenced during early stages of injury or oncogenic KrasG12D-induced transformation. Genetic ablation of mir-802 cooperates with KrasG12D by promoting ADM formation. miR-802 deficiency results in de-repression of the miR-802 targets Arhgef12, RhoA, and Sdc4, activation of RhoA, and induction of the downstream RhoA effectors ROCK1, LIMK1, COFILIN1, and EZRIN, thereby increasing F-actin rearrangement. mir-802 ablation also activates SOX9, resulting in augmented levels of ductal and attenuated expression of acinar identity genes. Consistently with these findings, we show that this miR-802–RhoA–F-actin network is activated in biopsies of pancreatic cancer patients and correlates with poor survival. Conclusions: We show miR-802 suppresses pancreatic cancer initiation by repressing oncogenic Kras-induced ADM. The role of miR-802 in ADM fills the gap in our understanding of oncogenic Kras-induced F-actin reorganization, acinar reprogramming, and PDAC initiation. Modulation of the miR-802–RhoA–F-actin network may be a new strategy to interfere with pancreatic carcinogenesis., Gastroenterology, 162 (1), ISSN:0016-5085, ISSN:1097-6779, ISSN:1528-0012