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Background & AimsPancreatic ductal adenocarcinoma (PDAC) is highly lethal, and any clues to understanding its elusive etiology could lead to breakthroughs in prevention, early detection, or treatment. Observational studies have shown a relationship between pancreas fat accumulation and PDAC, but the causality of this link is unclear. We therefore investigated whether pancreas fat is causally associated with PDAC using two-sample Mendelian randomization.MethodsWe leveraged eight genetic variants associated with pancreas fat (P-8) from a genome-wide association study (GWAS) in the UK Biobank (25,617 individuals), and assessed their association with PDAC in the Pancreatic Cancer Cohort Consortium I-III and the Pancreatic Cancer Case-Control Consortium dataset (8,275 PDAC cases and 6,723 non-cases). Causality was assessed using the inverse-variance weighted method. Although none of these genetic variants were associated with body mass index (BMI) at genome-wide significance, we further conducted a sensitivity analysis excluding genetic variants with a nominal BMI association in GWAS summary statistics from the UK Biobank and the Genetic Investigation of Anthropometric Traits consortium dataset (806,834 individuals).ResultsGenetically determined higher levels of pancreas fat using the eight genetic variants was associated with increased risk of PDAC. For one standard deviation increase in pancreas fat levels (i.e., 7.9% increase in pancreas fat fraction), the odds ratio of PDAC was 2.46 (95%CI:1.38-4.40, P=0.002). Similar results were obtained after excluding genetic variants nominally linked to BMI (odds ratio:3.79, 95%CI:1.66-8.65, P=0.002).ConclusionsThis study provides genetic evidence for a causal role of pancreas fat in the pathogenesis of PDAC. Thus, reducing pancreas fat could lower the risk of PDAC.

Although respiratory rate has been a sensitive predictor for prognosis in acute settings, resting respiratory rate (RRR) is undervalued in chronic care. The clinical significance of RRR among older people is not well documented.We investigated the association between RRR and all-cause mortality among older outpatients.A retrospective cohort study exhaustively included patients who had undergone medical checkups in a facility between April 2017 and March 2018 and followed up for at least 2 years. We excluded patients who were less than 60 years of age or had not undergone regular outpatient appointments. Sex, age, smoking habits, history of hospitalization, polypharmacy, long-term care insurance certification status, Mazzaglia index, pulse rate, systolic blood pressure, and Charlson Comorbidity Index were measured at the baseline medical checkup. Survival was confirmed by chart review and by contacting physicians in charge. The risk ratios were estimated by converting the odds ratios derived from the multivariable logistic regression models.Of the 853 patients who underwent baseline checkups, 749 were enrolled in the analyses; death occurred in 53 patients (7.1%), with no loss to follow-up. The RRR was independently associated with all-cause mortality after adjusting for covariates [adjusted risk ratio of RRR per 1 bpm = 1.14, 95% confidence interval (CI): 1.06 - 1.22].Given the independent association of RRR for existing predictors, this simple index seems worthy of consideration in further studies aimed at defining its predictive role in older people and in different settings.RRR was independently associated with all-cause mortality.

Fat accumulation outside subcutaneous adipose tissue often has unfavourable effects on systemic metabolism. In addition to non-alcoholic fatty liver disease, which has received considerable attention, pancreatic fat has become an important area of research throughout the past 10 years. While a number of diagnostic approaches are available to quantify pancreatic fat, multi-echo Dixon MRI is currently the most developed method. Initial studies have shown associations between pancreatic fat and the metabolic syndrome, impaired glucose metabolism and type 2 diabetes mellitus. Pancreatic fat is linked to reduced insulin secretion, at least under specific circumstances such as prediabetes, low BMI and increased genetic risk of type 2 diabetes mellitus. This Review summarizes the possible causes and metabolic consequences of pancreatic fat accumulation. In addition, potential therapeutic approaches for addressing pancreatic fat accumulation are discussed. There is growing evidence that fat accumulation in the pancreas can have consequences for metabolic health. This Review discusses the methods for detecting pancreatic fat and the potential causes and pathogenic consequences of pancreatic fat accumulation.

Objective: The intrauterine environment is known to affect the offspring’s long-term risk for obesity and diabetes. Previous data show that maternal metabolism and gestational weight gain (GWG) are associated with fetal autonomic nervous system (ANS) function, which can be assessed with heart rate variability (HRV). We investigated whether this association is also present in 2-year-old children and addressed the impact of gestational diabetes (GDM). Research design and methods: We examined the 2-year-old offspring of mothers who had undergone a 5-point, 75 g oral glucose tolerance test during pregnancy. To assess HRV, a 10-minute ECG was recorded, and time domain and frequency domain parameters were analyzed. Body composition was assessed using bioelectrical impedance testing. Results: We examined 67 children (33 girls, 34 boys), 30 of whom were born to mothers with treated GDM and normoglycemic pregnancies (NGT), respectively. No differences were found between the groups with regard to birth weight, weight at the age of 2 years, and body fat content. We observed that GWG was associated with heart rate and HRV, indicating that children of mothers with low GWG had a lower parasympathetic tone. This association was detected in NGT-exposed—but not in GDM-exposed—children. HR and HRV correlated with body fat and fat-free mass in children from normoglycemic pregnancies only. Conclusion: We found that the impact of maternal GWG on offspring ANS function was missing in the presence of treated GDM. The balance of the ANS was related to offspring body composition in children from NGT pregnancies only. Our results suggest that maternal weight gain during pregnancy has a critical impact on the developing ANS, which might be disturbed in the presence of GDM.

Primary tumor resection (PTR) before commencing systemic chemotherapy in patients with stage IV colorectal cancer and unresectable metastases (mCRC) remains controversial. This study aimed to assess whether PTR before systemic chemotherapy is associated with mortality in mCRC patients, after adjusting for confounding factors, such as the severity of the primary tumor and metastatic lesions. We analyzed hospital-based cancer registries from nine designated cancer hospitals in Fukushima Prefecture, Japan. Patients were divided into two groups (PTR and non-PTR), based on whether PTR was performed as initial therapy for mCRC or not. The primary outcome was all-cause mortality. Kaplan–Meier survival analysis was performed, and survival estimates were compared using the log-rank test. Adjusted hazard ratios were calculated using Cox regression to adjust for confounding factors. All tests were two-sided; P-values

Introduction Helicobacter pylori eradication therapy requires a complex prescribing schedule combining clarithromycin, amoxicillin, and a proton-pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB, vonoprazan). To reduce the burden of complex prescribing and increase adherence, a vonoprazan triple-drug blister pack comprising all three medications was launched in June 2016. This study aimed to assess the impact of the combination blister pack on eradication success rate in Japan immediately after launch. Methods We performed an interrupted time series analysis using a large administrative claims database of 7,300,000 insured individuals. We identified 36,570 patients who received first-line clarithromycin triple therapy from June 2015 to May 2016 (prelaunch) and 35,721 who received the same therapy from July 2016 to June 2017 (post-launch). The primary outcome was the success rate of clarithromycin triple therapy and the secondary outcomes were proportion of vonoprazan use and proportion of combination blister pack use. Results The success rate of clarithromycin triple therapy increased by 2.44% (95% confidence interval [CI] 1.36–3.52; P

Objective The establishment of a department of general internal medicine (GIM) has been shown to improve the clinical outcomes among patients treated in GIM departments but the effect on practice patterns in other departments remains unclear. We evaluated the association between the establishment of a GIM department and the use of blood cultures, an indicator of quality of care of infectious diseases, in other departments. Methods This study was conducted between 2013 and 2017 in a community hospital which established a new GIM department in 2015, with a mandate to improve the quality of care of the hospital including infectious disease management. The primary outcome was the change in the number of blood culture episodes per calendar month in other departments before and after establishment of the GIM department. The secondary outcome was the change in the blood culture episodes per month, indexed to 1,000 patient-days, during the same time. Using 2015 as the phase-in period, interrupted time series analyses were used to evaluate the change in the outcome variables. Results In departments other than GIM, there were 284 blood cultures prior to the establishment of the GIM department (2013-2014) and 853 afterwards (2016-2017). The number of blood culture episodes in other departments increased by 10.7 (95%CI: 0.39-21.0, p=0.042) per calendar month after the establishment of the GIM department; blood culture episodes / calendar month / 1,000 patient-days increased by 0.55 (95%CI: 0.03-1.07 p=0.037). Conclusion These results indicate that a GIM department in a community hospital can improve the quality of care in other departments.

Thin, metallic wires can easily penetrate the gastrointestinal system if ingested and cause serious cardiac issues in children. We report a pediatric case of such an object that caused cardiac tamponade after lodging in the left ventricle. The wire was extracted without cardiopulmonary bypass and a full recovery was made. Cardiac issues after ingestion of foreign objects are rare but immediate surgery is required for resolution.

Two spirometry criteria have been proposed for early chronic obstructive pulmonary disease (COPD) in young smokers: 1) forced expiratory volume in 1 s (FEVThis retrospective study analysed medical check-up data from 13,010 consecutive subjects aged50 years who underwent current and 3 previous spirometry tests in Japan. Current ≥10 pack-year smokers were the main focus of analysis; those meeting one or more spirometry criteria were diagnosed with early COPD. Early COPD was categorized into three subtypes: FEVOf the 1579 current ≥ 10 pack-year smokers, 488 (30.9%) met the early COPD criteria. Multivariate multinomial logistic models adjusted for age, sex, height, body mass index (BMI) and smoking history indicated that past BMI increase and low exercise were associated with higher type 2 early COPD incidence (odds ratio (OR) [95% confidence interval (CI)] = 4.30 [3.10, 6.04], and 0.80 [0.69, 0.93], respectively) but not with higher type 1 incidence. A history of asthma was associated with higher type 3 incidence (OR [95% CI] = 1.98 [1.18, 3.07]).The 3 types of spirometry-based early COPD have different clinical factors. Their trajectories should be explored in longitudinal studies.

Treatment for unresectable distal malignant biliary obstruction (DMBO) involves placing a 10-mm covered self-expandable metallic stent (CSEMS). In recurrent biliary obstruction (RBO), replacement of the CSEMS is recommended; however, the appropriate stent type remains unknown. We speculated that large-bore CSEMSs would provide longer patency. We compared the efficacy of 10-mm and 12-mm CSEMS in patients with RBO.We retrospectively retrieved data on patients who underwent CSEMS replacement from the endoscopic database. We investigated the time to RBO (TRBO) after CSEMS replacement. The hazard ratio (HR) for the the second TRBO was estimated using the Cox proportional hazard model. The estimated median second TRBO was determined using the Kaplan-Meier method.Among the 493 patients with DMBOs treated with 10-mm CSEMS, 48 and 29 patients underwent re-intervention with 10-mm and 12-mm CSEMS, respectively. The use of 12-mm CSEMS was inversely associated with second TRBO (multivariable-adjusted HR, 0.62; 95% CI, 0.39-0.98; P = .042). The estimated median second TRBO was greater with the 12 mm CSEMS than with the 10 mm variety (562 days vs 207 days; P = .019).The second intervention with 12-mm CSEMS was associated with a longer TRBO.

Endoscopic ultrasonography is an important examination for periampullary diseases. The duodenum is filled with water to ensure a clear image and distend the duodenal wall without burying the papilla within duodenal folds; however, peristalsis frequently makes it difficult to maintain water within the duodenum. The gel immersion method (intestine is filled with viscosity gel) has recently been attracting attention. We evaluated the usefulness of using this method for endoscopic ultrasonography to detect and delineate the major duodenal papilla.Fifty-nine consecutive patients who underwent gel immersion-endoscopic ultrasonography between February and March 2021 were included retrospectively. The papilla was observed by filling the duodenum with clear viscosity gel. Outcomes were the rate of duodenal distention, delineation rates of the papilla, the time required for delineation, volume of the gel used, and adverse events.Duodenal distention was excellent, good, and poor in 58%, 34%, and 7% of cases, respectively. The delineation rates of the papilla in the axial and longitudinal views were 98% and 66%, respectively. The median time required to delineate the papilla in each view was 3.1 (range, 1.0-1.4) and 7.9 (1.9-28.6) min; the median volume of the gel used was 80 (30-150) ml and 100 (50-200) ml, respectively. No adverse events were noted.Gel immersion-endoscopic ultrasonography provided sufficient duodenal distention, leading to high rates of detection and delineation of the papilla using a small volume of gel within a short time. This method may be useful for the evaluation of the ampullary region.

BACKGROUND: Crohn's disease (CD) is a disease with an impaired immune response characterized by chronic, relapsing‐remitting, and progressive inflammation mainly affecting the gastrointestinal tract. Certolizumab pegol (CZP) is a biological agent that regulates the impaired immune response by controlling tumour necrosis factor‐α (TNFα). However, the efficacy and safety of long‐term administration of CZP for people with CD with inflammation under control are not well understood. OBJECTIVES: To assess the efficacy and safety of CZP for maintenance of remission in people with CD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, and conference abstracts from inception to 23 March 2022. We contacted pharmaceutical companies involved with the production of CZP for further relevant information. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing CZP with placebo in adults with CD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. The main outcomes were failure to maintain clinical remission at week 26, failure to maintain clinical response at week 26, and serious adverse events. We planned to perform meta‐analyses including all available studies if similar enough for pooling to be appropriate and calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes. We analyzed the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH) to indicate the magnitude of treatment effects. The same two review authors independently evaluated the risk of bias by using the Cochrane RoB 2 tool and evaluated the certainty of evidence using the GRADE framework. MAIN RESULTS: We identified one study meeting our prespecified eligibility criteria. The included study enrolled 428 adults with CD who responded to induction therapy with CZP 400 mg at weeks 0, 2, and 4. The study evaluated long‐term efficacy and safety of CZP administered subcutaneously every four weeks compared with placebo. The proportion of participants who failed to maintain clinical remission at week 26 was 52.3% (113/216) in the CZP group compared to 71.7% (152/212) in the placebo group. Treatment of CZP probably results in a large reduction in failure to maintain clinical remission at week 26 (RR 0.73, 95% CI 0.63 to 0.85). The NNTB was 5 (95% CI 4 to 9). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged the certainty of evidence as moderate due to the low number of events occurred. The proportion of participants who failed to maintain clinical response at week 26 was 37.5% (81/216) in the CZP group compared to 64.2% (136/212) in the placebo group. Treatment of CZP probably results in a large reduction in failure to maintain clinical response at week 26 (RR 0.58, 95% CI 0.48 to 0.71). The NNTB was 4 (95% CI 3 to 5). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged the certainty of evidence as moderate due to the low number of events occurred. The proportion of participants who developed serious adverse events was 5.6% (12/216) in the CZP group compared to 6.6% (14/212) in the placebo group. Treatment of CZP may lead to no difference in serious adverse events compared to placebo when used as a remission maintenance treatment (RR 0.84, 95% CI 0.40 to 1.78). The NNTB was 95 (95% CI NNTH 19 to NNTB 25). We evaluated the risk of bias for this outcome as low. We evaluated the certainty of evidence as low due to the low number of events occurred and the CIs were not sufficiently narrow. AUTHORS' CONCLUSIONS: CZP probably results in a large reduction in failure to maintain clinical remission and response at week 26 in people with CD. The evidence suggests that CZP may lead to no difference in serious adverse events compared to placebo when used as a remission maintenance treatment. However, the current studies are limited to 26 weeks of follow‐up and only included adults. Therefore, these conclusions cannot be used to guide longer term treatment or for treatment in children at present.

Fat accumulation in the liver, pancreas, skeletal muscle, and visceral bed relates to type-2 diabetes (T2D). However, the distribution of fat among these compartments is heterogenous and it is unclear whether specific distribution patterns indicate high T2D risk. We therefore investigated fat-distribution patterns and their link to future T2D. From 2168 individuals without diabetes who underwent computed tomography in Japan, this case-cohort study included 658 randomly selected individuals and 146 incident cases of T2D over 6 years of follow-up. Using data-driven analysis (k-means) based on fat content in the liver, pancreas, muscle, and visceral bed, we identified four fat-distribution clusters: Hepatic steatosis, Pancreatic steatosis, Trunk myosteatosis, and Steatopenia. Compared with the Steatopenia cluster, the adjusted hazard ratios (95% CIs) for incident T2D were 4.02 (2.27-7.12) for the Hepatic steatosis cluster, 3.38 (1.65-6.91) for the Pancreatic steatosis cluster, and 1.95 (1.07-3.54) for the Trunk myosteatosis cluster. The clusters were replicated in 319 German individuals without diabetes who underwent magnetic resonance imaging and metabolic phenotyping. The distribution of AUC-glucose across the four clusters found in Germany was similar to the distribution of T2D risk across the four clusters in Japan. Insulin sensitivity and insulin secretion differed across the four clusters. Thus, we identified patterns of fat distribution with different T2D risks presumably due to differences in insulin sensitivity and insulin secretion.

Objective: Fat accumulation in liver, pancreas, skeletal muscle, and visceral bed relates to type 2 diabetes (T2D) . However, distribution of fat in these compartments is heterogenous and it is unclear if specific distribution patterns indicate high T2D risk. We therefore investigated fat distribution patterns and their link to future T2D. Methods: From 2168 individuals without diabetes undergoing computed tomography in Japan, this case-cohort study included 658 randomly selected individuals and 146 incident cases of T2D with a 6-year follow-up. Data-driven analysis (k-means) was applied to develop clusters based on fat content in liver, pancreas, muscle, and visceral bed. Hazard ratios (HRs) for association of clusters and incident T2D were estimated using weighted Cox regression. In 3 individuals without diabetes with magnetic resonance imaging and metabolic phenotyping in Germany, cluster validation with additional assessment of glycemic traits from OGTTs was conducted. Results: We identified four clusters of fat distribution: cluster 1 (Hepatic steatosis cluster) , cluster 2 (Pancreatic steatosis cluster) , cluster 3 (Myosteatosis dominant cluster) , cluster 4 (Steatopenic cluster) . Compared with Steatopenic cluster, the adjusted-HRs (95%CIs) for incident T2D were 4.02 (2.27-7.12) in Hepatic steatosis cluster, 3.38 (1.65-6.91) in Pancreatic steatosis cluster, and 1.95 (1.07-3.54) in Myosteatosis dominant cluster. The clusters were replicated in the German cohort with similar distribution of AUC-glucose to the diabetes hazard in the Japanese cohort. Insulin sensitivity and insulin secretion were different across clusters with the lowest insulin sensitivity and highest insulin secretion in Hepatic steatosis cluster. Conclusions: Extending evidence about fat accumulation in single compartments, we identified specific patterns of fat distribution with different T2D risk presumably due to differences in insulin sensitivity and insulin secretion. Disclosure H.Yamazaki: None. N.Stefan: Advisory Panel; Gilead Sciences, Inc., GlaxoSmithKline plc., Sanofi, Consultant; AstraZeneca, Intercept Pharmaceuticals, Inc., Novo Nordisk, Pfizer Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp. A.Fritsche: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. A.L.Birkenfeld: None. R.Wagner: Advisory Panel; Akcea Therapeutics, Daiichi Sankyo, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. M.Heni: Advisory Panel; Boehringer Ingelheim International GmbH, Research Support; Boehringer Ingelheim International GmbH, Sanofi, Speaker's Bureau; Amryt Pharma Plc, Boehringer Ingelheim International GmbH, Novo Nordisk. S.Tauchi: None. J.Machann: None. T.Haueise: None. Y.Yamamoto: None. M.Dohke: None. N.Hanawa: None. Y.Kodama: Other Relationship; Eisai Co., Ltd. A.Katanuma: None. Funding the German Center for Diabetes Research (DZD, 01GI0925) , the state of Baden-Württemberg (32-5400/58/2, Forum Gesundheitsstandort Baden-Württemberg) , and JSPS KAKENHI Grant Number 19K16978

Cold snare defect protrusions (CSDPs) include muscularis mucosa (MM) and submucosa tissue. CSDPs are thought to result from fragmentation of the specimen during shallow excision. Our aim in this study was to clarify whether CSDPs are associated with polyp fragmentation.We retrospectively analyzed 1026 neoplastic colorectal polyps resected by cold snare polypectomy for which the presence or absence of CSDPs was assessed from the endoscopic image. All prepared specimens were reviewed and assessed for the presence or absence of polyp fragmentation, and the proportion of MM on the stump was measured. In addition, the risk factors for CSDP occurrence were evaluated.CSDPs occurred in 116 of the 1026 polyps (11.3%). Polyp fragmentation was significantly associated with the occurrence of CSDP on univariate analysis (odds ratio [OR], 3.74; P .001) and multivariate analysis (OR, 3.13; P .001). The proportion of MM50% was significantly lower in the CSDP group than in the non-CSDP group (51.5% vs 70.9%, P .001). CSDPs were significantly associated with a large polyp size (OR, 1.32; P = .007) and a large specimen size (OR, 1.24; P .001) on multivariate analysis.The occurrence of CSDP was associated with less MM on the stump and fragmentation of the specimen. Clinically, the presence of CSDP is a good indicator of polyp fragmentation.

An endovascular arteriovenous fistula is a recent technological advancement in hemodialysis vascular access. This systematic review and meta-analysis aimed to investigate the efficacy and safety of endovascular arteriovenous fistula (eAVF) creation compared with surgical arteriovenous fistula (sAVF) creation among patients with chronic kidney disease. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Clinical Trials.gov, and the WHO International Clinical Trials Registry Platform until May 2021 to perform meta-analyses using random-effects models. Pre-specified primary outcomes were fistula maturation, procedure-related complications, and patient satisfaction. Secondary outcomes were procedural technical success, procedure time, all adverse events, and medical expenditure. The risk of bias in non-randomized studies of the interventions assessment tool, and the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach were used to assess the quality of individual studies and the body of evidence, respectively. In seven studies including 860 patients, endovascular arteriovenous fistula creation had little to no effect on fistula maturation (odds ratio, 0.58; 95% confidence intervals, 0.05 to 6.91). Meta-analysis could not be performed for procedure-related complications and patient satisfaction due to insufficient data. For secondary outcomes, endovascular arteriovenous fistula resulted in a slight to no difference in procedural technical success (odds ratio, 0.69: 95% confidence intervals, 0.04 to 11.98) and all adverse events (odds ratio, 6.31; 95% confidence intervals, 0.64 to 62.22). Endovascular fistula creation incurred less medical expenditure than sAVF (mean difference, USD 12760; 95% confidence intervals, -19710 to -5820). Meta-analysis for procedure time was not performed because one of the studies had a critical risk of bias. All of these outcomes were of low certainty of evidence or very low certainty of evidence. There was limited evidence for supporting endovascular arteriovenous fistula creation over conventional surgical arteriovenous fistula creation for patients with chronic kidney disease. Multicenter randomized controlled trials are needed to confirm the efficacy and safety of eAVFs in selected populations.

Although covered self-expandable metal stents (CSEMSs) are associated with the risk of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis due to pancreatic duct (PD) orifice obstruction, they are often used for biliary drainage treatment in malignant biliary obstruction (MBO). This study aimed to investigate the efficacy of PD stenting in preventing post-ERCP pancreatitis after CSEMS implantation.This retrospective cohort study analyzed 554 patients with transpapillary CSEMS for MBO. Patients with noninitial deployment, benign disease, CSEMS deployment above the papilla, surgically altered anatomy, uncovered self-expandable metal stents, multiple thin self-expandable metal stents, and unavailable procedure videos were excluded. Logistic regression analysis estimated the association between PD stenting and post-ERCP pancreatitis incidence. We adjusted for age, sex, pancreatitis history, prophylactic rectal nonsteroidal anti-inflammatory drug use, naïve papilla, MBO etiology, and prolonged biliary cannulation time.Among 554 patients, 67 (12.1%) experienced post-ERCP pancreatitis. Post-ERCP pancreatitis was recorded in 13.7% of patients in the non-PD stenting and 4.3% in the PD stenting groups. Pancreatic duct stenting was associated with lower risks of post-ERCP pancreatitis (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.099-0.79; P = 0.028). In multivariable analysis, the association between PD stenting and lower post-ERCP pancreatitis incidence was consistent (OR 0.19; 95% CI 0.062-0.58; P = 0.0034).Pancreatic duct stenting could reduce the risk of post-ERCP pancreatitis after CSEMSs.

Objective Diet is implicated in the aetiopathogenesis of inflammatory bowel disease (IBD) and in generating symptoms. Few studies have explored dietary practices in people with IBD, in which participants perceived strong links between diet in triggering flares and maintaining remission. Fewer studies have explored dietary habits in self-reported remission. Our aim was to describe dietary practices and beliefs in those with inactive ulcerative colitis. Methods A questionnaire was developed and prospectively administered to 208 participants with inactive ulcerative colitis attending IBD clinics. Results Thirty-one percent believed diet was the initiating factor for ulcerative colitis with 37% believing diet could trigger relapse. Fifty-nine percent avoided dietary items to prevent relapse. Most frequently avoided were spicy (43%) and fatty (38%) foods, alcohol (27%), carbonated drinks (26%), coffee (24%) and milk products (21%). Females were more likely to practice dietary avoidance (P = 0.007). Twenty-three percent had used exclusion diets, most commonly gluten- or lactose-free. Those reporting relapse in the previous year were more likely to avoid the same menu as their family (P = 0.01) and females were less likely to eat out in order to prevent relapse (P = 0.004). Information resources guiding food avoidance included participants' own experiences (90%), healthcare professionals' advice (19%) and the internet (11%). Conclusion People with inactive ulcerative colitis hold dietary beliefs and display practices with a high level of consistency around perceived triggers. Food avoidance whilst in remission raises the possibility of visceral hypersensitivity or altered physiology alongside psychosocial, neurocognitive or co-existing functional factors.

Reactive Oxygen Species (ROS) are a natural byproduct of oxygen metabolism. At physiological levels, ROS regulate multiple cellular processes like proliferation, migration, and differentiation. Increased levels of ROS are associated with pathological conditions, such as inflammation and vascular calcification, where they elicit cytotoxic effects. These contrasting outcomes of ROS have also been reported in osteogenic precursor cells. However, the role of ROS in committed osteogenic cells has not been investigated. Cytotoxic and physiologic effects have also been demonstrated for extracellular phosphate (P(i)). Specifically, in committed osteogenic cells P(i) stimulates their major function (mineralization), however in osteogenic precursors and endothelial cells P(i) cytotoxicity has been reported. Interestingly, P(i) cytotoxic effects have been associated with ROS production in the pathological vascular mineralization. In this study, we investigated a molecular mechanistic link between elevated P(i) and ROS production in the context of the mineralization function of committed osteogenic cells. Using committed osteogenic cells, 17IIA11 odontoblast-like cell and MLO-A5 osteoblast cell lines, we have unveil that P(i) enhances intracellular ROS production. Furthermore, using a combination of mineralization assays and gene expression analyses, we determined that P(i)-induced intracellular ROS supports the physiological mineralization process. In contrast, the exogenous ROS, provided in a form of H(2)O(2), was detrimental for osteogenic cells. By comparing molecular signaling cascades induced by extracellular ROS and P(i), we identified differences in signaling routes that determine physiologic versus toxic effect of ROS on osteogenic cells. Specifically, while both extracellular and P(i)-induced intracellular ROS utilize Erk1/2 signaling mediator, only extracellular ROS induces stress-activated mitogen-activated protein kinases P38 and JNK that are associated with cell death. In summary, our results uncovered a physiological role of ROS in the P(i)-induced mineralization through the molecular pathway that is distinct from ROS-induced cytotoxic effects.

Only a few studies have longitudinally evaluated whether fatty pancreas increases the risk of type-2 diabetes (T2D), and their results were inconsistent. Fatty pancreas is closely linked to overweight and obesity, but previous studies did not exclude overweight or obese individuals. Therefore, in this cohort study, we investigated the association between fatty pancreas and T2D incidence in lean individuals. Between 2008 and 2013, 1478 nondiabetic lean individuals (i.e. body-mass index