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While the World Health Organization's recommendation of syndromic sentinel surveillance for influenza is an efficient method to collect high-quality data, limitations exist. Aligned with the Research Recommendation 1.1.2 of the WHO Public Health Research Agenda for Influenza-to identify reliable complementary influenza surveillance systems which provide real-time estimates of influenza activity-we performed a scoping review to map the extent and nature of published literature on the use of non-traditional sources of syndromic surveillance data for influenza.We searched three electronic databases (PubMed, Web of Science, and Scopus) for articles in English, French, and Spanish, published between January 1 2007 and January 28 2022. Studies were included if they directly compared at least one non-traditional with a traditional influenza surveillance system in terms of correlation in activity or timeliness.We retrieved 823 articles of which 57 were included for analysis. Fifteen articles considered electronic health records (EHR), 11 participatory surveillance, 10 online searches and webpage traffic, seven Twitter, five absenteeism, four telephone health lines, three medication sales, two media reporting, and five looked at other miscellaneous sources of data. Several articles considered more than one non-traditional surveillance method.We identified eight categories and a miscellaneous group of non-traditional influenza surveillance systems with varying levels of evidence on timeliness and correlation to traditional surveillance systems. Analyses of EHR and participatory surveillance systems appeared to have the most agreement on timeliness and correlation to traditional systems. Studies suggested non-traditional surveillance systems as complements rather than replacements to traditional systems.

N-methyl-d-aspartate receptors (NMDARs) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are excitatory neurotransmission receptors of the central nervous system and play vital roles in synaptic plasticity. Although not fully elucidated, visceral hypersensitivity is one of the most well-characterized pathophysiologic abnormalities of functional gastrointestinal diseases and appears to be associated with increased synaptic plasticity. In this study, we review the updated findings on the physiology of NMDARs and AMPARs and their relation to visceral hypersensitivity, which propose directions for future research in this field with evolving importance.

Background: Although indications for evaluation and treatment of Helicobacter pylori (H. pylori) infection are broadening to include primary prevention for gastric adenocarcinoma, potential adverse effects on gut microbiota have been raised. We performed a systematic review and meta-analysis to evaluate the effects of H. pylori therapy on gut microbiota. Methods: PubMed, EMBASE, Cochrane Library and Web of Science (to 4/2021) were searched for studies quantitatively evaluating microbiota before and after H. pylori therapy. Meta-analysis was performed to assess early (

BACKGROUND The efficacy and factors associated with patient outcomes for a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) compared with traditional dietary advice (TDA) based on modified National Institute for Clinical Excellence guidelines for irritable bowel syndrome with diarrhea (IBS-D) in regions consuming a non-Western diet are unclear. OBJECTIVES We aimed to determine the efficacy of an LFD compared with TDA for the treatment of IBS-D in Chinese patients and to investigate the factors associated with favorable outcomes. METHODS One hundred and eight Chinese IBS-D patients (Rome III criteria) were randomly assigned to an LFD or TDA. The primary endpoint was a ≥50-point reduction in the IBS Severity Scoring System at 3 wk. Fecal samples collected before and after the dietary intervention were assessed for changes in SCFAs and microbiota profiles. A logistic regression model was used to identify predictors of outcomes. RESULTS Among the 100 patients who completed the study, the primary endpoint was met in a similar number of LFD (30 of 51, 59%) and TDA (26 of 49, 53%) patients (∆6%; 95% CI: -13%, 24%). Patients in the LFD group achieved earlier symptomatic improvement in stool frequency and excessive wind than those following TDA. LFD reduced carbohydrate-fermenting bacteria such as Bifidobacterium and Bacteroides, and decreased saccharolytic fermentation activity. This was associated with symptomatic improvement in the responders. High saccharolytic fermentation activity at baseline was associated with a higher symptom burden (P = 0.01) and a favorable therapeutic response to the LFD (log OR: 4.9; 95% CI: -0.1, 9.9; P = 0.05). CONCLUSIONS An LFD and TDA each reduced symptoms in Chinese IBS-D patients; however, the LFD achieved earlier symptomatic improvements in stool frequency and excessive wind. The therapeutic effect of the LFD was associated with changes in the fecal microbiota and the fecal fermentation index. At baseline, the presence of severe symptoms and microbial metabolic dysbiosis characterized by high saccharolytic capability predicted favorable outcomes to LFD intervention.This trial was registered at clinicaltrials.gov as NCT03304041.

Background and Aims Prophylactic clips to prevent delayed polypectomy bleeding (DPB) after endoscopic resection of large colorectal polyps remains controversial. We performed a systematic review and meta-analysis to evaluate the efficacy of prophylactic clips for preventing DPB by synthesizing the results of randomized trials. Methods PubMed, Cochrane Library, and EMBASE were searched to October 2019 to identify randomized controlled trials evaluating the efficacy of placing prophylactic clips to reduce DPB after resection of large (≥10 mm) colorectal polyps. The primary outcome was DPB defined by GI bleeding after the conclusion of the colonoscopy. Results Eight studies (n = 3415) met the study criteria, all with a low risk of bias. The overall pooled incidence of DPB was 3.9% (95% confidence interval [CI], 2.4%-5.4%) in patients receiving endoscopic resection of colorectal polyps ≥10 mm. Placing prophylactic clips reduced DPB in patients receiving prophylactic clips (relative risk [RR], 0.61; 95% CI, 0.43-0.85; I2 = 37.8%) compared with no clips with a number needed to treat (NNT) of 52 (95% CI, 31-163). In stratified analyses, placing clips was associated with reduced risks of DPB in patients with polyps ≥20 mm (RR, 0.54; 95% CI, 0.35-0.84; I2 = 0.0%; NNT, 30), nonpedunculated morphology (RR, 0.54; 95% CI, 0.36-0.81; I2 = 0.0%; NNT, 39), and located proximal to the hepatic flexure (RR, 0.49; 95% CI, 0.31-0.78; I2 = 54.8%; NNT, 25) compared with no clips. Conclusions Prophylactic clips after endoscopic resection of colorectal polyps ≥10 mm demonstrated a modest reduction in the risk of DPB. Larger reductions were observed in patients with polyps ≥20 mm, nonpedunculated morphology, or located proximal to the hepatic flexure.

Type 2 resistant starch (RS2) is a fermentable dietary fiber conferring health benefits. We investigated the effects of RS2 on host, gut microbiota, and metabolites in aged mice on high-fat diet. In eighteen-month old mice randomly assigned to control, high-fat (HF), or high-fat+20% RS2 (HFRS) diet for 16 weeks, RS2 reversed the weight gain and hepatic steatosis induced by high-fat diet. Serum and fecal LPS, colonic IL-2 and hepatic IL-4 mRNA expressions decreased while colonic mucin 2 mRNA and protein expressions increased in the HFRS compared to the HF and the control group. 16s rRNA sequencing of fecal microbial DNA demonstrated that RS2 decreased the abundance of pathogen taxa associated with obesity, inflammation, and aging including Desulfovibrio (Proteobacteria phylum), Ruminiclostridium 9, Lachnoclostridium, Helicobacteria, Oscillibacter, Alistipes, Peptococcus, and Rikenella. Additionally, RS2 increased the colonic butyric acid by 2.6-fold while decreasing the isobutyric and isovaleric acid levels by half compared to the HF group. Functional analyses based on Clusters of Orthologous Groups showed that RS2 increased carbohydrate while decreasing amino acid metabolism. These findings demonstrate that RS2 can reverse weight gain, hepatic steatosis, inflammation, and increased intestinal permeability in aged mice on high-fat diet mediated by changes in gut microbiome and metabolites.

This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy.Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 15). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea).In total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder DStatistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.

An array of isoforms of the nuclear estrogen receptor alpha (ER-α) protein contribute to heterogeneous response in breast cancer (BCa); yet, a single-cell analysis tool that distinguishes the full-length ER-α66 protein from the activation function-1 deficient ER-α46 isoform has not been reported. Specific detection of protein isoforms is a gap in single-cell analysis tools, as the de facto standard immunoassay requires isoform-specific antibody probes. Consequently, to scrutinize hormone response heterogeneity among BCa tumor cells, we develop a precision tool to specifically measure ER-α66, ER- α46, and eight ER-signaling proteins with single-cell resolution in the highly hetero-clonal MCF-7 BCa cell line. With a literature-validated pan-ER immunoprobe, we distinguish ER-α66 from ER-α46 in each individual cell. We identify ER-α46 in 5.5% of hormone-sensitive (MCF-7) and 4.2% of hormone-insensitive (MDA-MB-231) BCa cell lines. To examine whether the single-cell immunoblotting can capture cellular responses to hormones, we treat cells with tamoxifen and identify different sub-populations of ER-α46: (i) ER-α46 induces phospho-AKT at Ser473, (ii) S6-ribosomal protein, an upstream ER target, activates both ER-α66 and ER-α46 in MCF-7 cells, and (iii) ER-α46 partitions MDA-MB-231 subpopulations, which are responsive to tamoxifen. Unlike other single-cell immunoassays, multiplexed single-cell immunoblotting reports–in the same cell–tamoxifen effects on ER signaling proteins and on distinct isoforms of the ER-α protein.

Background In a global, phase III, open-label, noninferiority trial (REFLECT), lenvatinib demonstrated noninferiority to sorafenib in overall survival and a statistically significant increase in progression-free survival in patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib became the first agent in more than 10 years to receive approval as first-line therapy for unresectable HCC, along with the previously approved sorafenib. The objective of this study was to determine the comparative cost-effectiveness of lenvatinib and sorafenib as a first-line therapy of unresectable HCC. Materials and methods A state-transition model of unresectable HCC was developed in the form of a cost-utility analysis. The model time horizon was 5 years; the efficacy of the model was informed by the REFLECT trial, and costs and utilities were obtained from published literature. Probabilistic sensitivity analyses and subgroup analyses were performed to test the robustness of the model. Results Lenvatinib dominated sorafenib in the base case analysis. A probabilistic sensitivity analysis indicated that lenvatinib remains a cost-saving measure in 64.87% of the simulations. However, if the cost of sorafenib was reduced by 57%, lenvatinib would no longer be the dominant strategy. Conclusion Lenvatinib offered a similar clinical effectiveness at a lower cost than sorafenib, suggesting that lenvatinib would be a cost-saving alternative in treating unresectable HCC. However, lenvatinib may fail to remain cost-saving if a significantly cheaper generic sorafenib becomes available. Implications for practice This analysis suggests an actionable clinical policy that will achieve cost saving. This cost-utility analysis showed that lenvatinib had a similar clinical effectiveness at a lower cost than sorafenib, indicating that lenvatinib may be a cost-saving measure in patients with unresectable HCC, in which $23,719 could be saved per patient. The introduction of a new therapeutic option for the first time in 10 years in Canada provides an important opportunity for clinicians, researchers, and health care decision-makers to explore potential modifications in recommendations and practice guidelines.

BACKGROUND: Currently, there are no pharmacological options available for the treatment of non-alcoholic steatohepatitis (NASH). In the 18-month interim analysis of an ongoing randomized, placebo-controlled phase 3 trial (REGENERATE), early results demonstrated that obeticholic acid (OCA) 25 mg significantly improved fibrosis with no worsening of NASH among patients with NASH and fibrosis compared with placebo (PBO). This study aimed to assess the potential cost-effectiveness of OCA compared with PBO in NASH patients. METHODS: A state-transition model was developed to perform a cost-utility analysis comparing two treatment strategies, PBO and OCA 25 mg, from a Canadian public payer perspective. The model time horizon was lifetime with annual cycle lengths. Cost and utility parameters were discounted at 1.5% annually. The efficacy data were obtained from the REGENERATE trial, and costs and utilities were derived from other published literature. Probabilistic and deterministic sensitivity analyses were performed to test the robustness of the model. RESULTS: Treatment with OCA led to reductions of 3.58% in decompensated cirrhosis cases, 3.95% in hepatocellular carcinoma, 7.88% in liver transplant, and 6.01% in liver-related death. However, at an annual price of CAD $36,000, OCA failed to be cost-effective compared with PBO at an incremental cost-effectiveness ratio of $815,514 per quality-adjusted life year (QALY). An 88% reduction in drug price to an annual cost of $4,300 would make OCA cost-effective at a willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: OCA failed to be cost-effective compared with PBO, despite demonstrating clinical benefits due to a high drug cost. A significant price reduction would be needed to make the drug cost-effective.

Study Objectives To examine in a subsample at the screening phase of a clinical trial of a β-amyloid (Aβ) antibody whether disturbed sleep and altered 24-hour rest/activity rhythms (RARs) may serve as markers of preclinical Alzheimer’s disease (AD). Methods Overall, 26 Aβ-positive (Aβ+) and 33 Aβ-negative (Aβ−) cognitively unimpaired participants (mean age = 71.3 ± 4.6 years, 59% women) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies, respectively, wore actigraphs for 5.66 ± 0.88 24-hour periods. We computed standard sleep parameters, standard RAR metrics (mean estimating statistic of rhythm, amplitude, acrophase, interdaily stability, intradaily variability, relative amplitude), and performed a novel RAR analysis (function-on-scalar regression [FOSR]). Results We were unable to detect any differences between Aβ+ and Aβ− participants in standard sleep parameters or RAR metrics with our sample size. When we used novel FOSR methods, however, Aβ+ participants had lower activity levels than Aβ− participants in the late night through early morning (11:30 pm to 3:00 am), and higher levels in the early morning (4:30 am to 8:30 am) and from midday through late afternoon (12:30 pm to 5:30 pm; all p < .05). Aβ+ participants also had higher variability in activity across days from 9:30 pm to 1:00 am and 4:30 am to 8:30 am, and lower variability from 2:30 am to 3:30 am (all p < .05). Conclusions Although we found no association of preclinical AD with standard actigraphic sleep or RAR metrics, a novel data-driven analytic method identified temporally “local” RAR alterations in preclinical AD.

Background and Aims Inflammatory bowel disease (IBD) is associated with gut dysbiosis and dysregulation of bile acid metabolism. A high luminal content of deoxycholic acid (DCA) with consumption of a Westernised diet is implicated in the pathogenesis of IBD. The aim of the study is to explore the role of intestinal microbiota and bile acid metabolism in mice with DCA-induced intestinal inflammation. Methods Wild-type C57BL mice, 4 weeks old, were fed with AIN-93G (control diet), AIN-93G+0.2% DCA, AIN-93G+0.2% DCA+6 weeks of fexaramine (FXR agonist), or AIN-93G+0.2% DCA+antibiotic cocktail, for 24 weeks. Histopathology, western blotting, and qPCR were performed on the intestinal tissue. Faecal microbiota was analysed by 16S rDNA sequencing. Faecal bile acid and short chain fatty acid (SCFA) levels were analysed by chromatography. Results Gut dysbiosis and enlarged bile acid pool were observed in DCA-treated mice, accompanied by a lower farnesoid X receptor (FXR) activity in the intestine. Administration of fexaramine mitigated DCA-induced intestinal injury, restored intestinal FXR activity, activated fibroblast growth factor 15, and normalised bile acid metabolism. Furthermore, fexaramine administration increased the abundance of SCFA-producing bacteria. Depletion of the commensal microbiota with antibiotics decreased the diversity of the intestinal microbiota, attenuated bile acid synthesis, and reduced intestinal inflammation induced by DCA. Conclusions DCA induced-intestinal inflammation is associated with alterations of gut microbiota and bile acid profiles. Interventions targeting the gut microbiota-FXR signalling pathway may reduce DCA-induced intestinal disease.

Introduction Patients with atrophic gastritis (AG) or gastric intestinal metaplasia (GIM) have elevated risk of gastric adenocarcinoma. Endoscopic screening and surveillance have been implemented in high incidence countries. The study aimed to evaluate the accuracy of a deep convolutional neural network (CNN) for simultaneous recognition of AG and GIM. Methods Archived endoscopic white light images with corresponding gastric biopsies were collected from 14 hospitals located in different regions of China. Corresponding images by anatomic sites containing AG, GIM, and chronic non-AG were categorized using pathology reports. The participants were randomly assigned (8:1:1) to the training cohort for developing the CNN model (TResNet), the validation cohort for fine-tuning, and the test cohort for evaluating the diagnostic accuracy. The area under the curve (AUC), sensitivity, specificity, and accuracy with 95% confidence interval (CI) were calculated. Results A total of 7,037 endoscopic images from 2,741 participants were used to develop the CNN for recognition of AG and/or GIM. The AUC for recognizing AG was 0.98 (95% CI 0.97-0.99) with sensitivity, specificity, and accuracy of 96.2% (95% CI 94.2%-97.6%), 96.4% (95% CI 94.8%-97.9%), and 96.4% (95% CI 94.4%-97.8%), respectively. The AUC for recognizing GIM was 0.99 (95% CI 0.98-1.00) with sensitivity, specificity, and accuracy of 97.9% (95% CI 96.2%-98.9%), 97.5% (95% CI 95.8%-98.6%), and 97.6% (95% CI 95.8%-98.6%), respectively. Discussion CNN using endoscopic white light images achieved high diagnostic accuracy in recognizing AG and GIM.

Objectives The objective of this study was to use a decision-analytic model to examine the potential economic impact of establishing a remunerated programme for pharmacists prescribing for minor ailments (PPMA) in Ontario, Canada. Methods A novel decision tool was developed to assess the economic impact of pharmacists prescribing for upper respiratory tract infections (URTIs), contact dermatitis (CD) and conjunctivitis by performing a cost-minimization analysis from a public payer perspective. Two prescribing strategies were compared: (1) PPMA, where patients may seek care from pharmacists or physicians, and (2) the usual care model (UCM), where all patients receive care from physicians. Two remuneration models for the PPMA strategy were also compared: (1) a prescription-detached scenario (PDS), where pharmacists were remunerated CAD$18.00 for each consultation, and (2) a Prescription-Attached Scenario (PAS), where pharmacists were only remunerated if a decision to prescribe was made. Key findings At a service uptake rate of 38% for the PDS, the PPMA model led to savings of $7.51, $4.08 and $5.15 per patient for URTIs, CD and conjunctivitis, respectively. Per 30 000 patients, the PPMA model for these minor ailments was projected to lead to cumulative reductions in visits to the emergency department, family physician and walk-in clinics by 799, 3677 and 5090, respectively. Conclusions The results of the study strongly suggest that enabling community pharmacists to assess and prescribe for minor ailments could potentially lead to large savings for the government in Ontario, Canada. In 100% of the PAS scenarios simulated, pharmacists as prescribers led to cost savings.

Background Current literature indicates that direct-acting antivirals (DAAs) are cost-effective to treat compensated cirrhotic patients with hepatitis C. Although already funded by public payers, it is unknown whether it is economical to reimburse DAAs within the more advanced decompensated cirrhosis population. Methods A state-transition model was developed to conduct a cost-utility analysis of sofosbuvir-velpatasvir (SOF/VEL) plus ribavirin regimen for 12 weeks. The evaluated cohort had a mean age of 58 years and Child-Turcotte-Pugh (CTP) class B cirrhosis with decompensated symptoms. A scenario analysis was performed on CTP C patients. We used a payer perspective, a lifetime time horizon and a 1.5% annual discount rate. Results While SOF/VEL plus ribavirin treatment for 12 weeks increased costs by $156 676, it provided an extra 4.00 quality-adjusted life years (QALYs) compared to best supportive care (no DAA therapy). With an incremental cost-effectiveness ratio of $39 169 per QALY, SOF/VEL plus ribavirin was determined to be cost-effective at a willingness to pay of $50 000 per QALY. SOF/VEL reduced liver-related deaths and reduced progression to CTP C cirrhosis by 20.4% and 21.9%, respectively. On the contrary, SOF/VEL regimen resulted in increases in liver transplants and hepatocellular carcinoma (HCC) by 54.0% and 42.5%, respectively. Similar results were found for CTP C patients. Conclusion This analysis informs payers that SOF/VEL should continue to be reimbursed in decompensated hepatitis C patients. It also supports the recommendations by the American Association for the Study of Liver Diseases to continue screening for HCC in decompensated cirrhotic patients who have achieved sustained virologic response.

OBJECTIVES: Although early biliary drainage improves outcomes in patients with acute cholangitis, the optimal time to perform endoscopic retrograde cholangiopancreatography (ERCP) is controversial. Our aim was to evaluate the impact of timing of ERCP on mortality in hospitalized patients with acute cholangitis. METHODS: We searched PubMed, EMBASE, and The Cochrane Library (until February 2019) for studies evaluating the impact of timing of ERCP (

The role of protease activated receptor-2 (PAR-2) in the pathogenesis of abdominal pain in irritable bowel syndrome (IBS) is not well defined. To investigate the role of PAR-2-mediated visceral hypersensitivity in a post-infectious IBS (PI-IBS) mouse model. T. spiralis-infected PI-IBS mouse model was used. Fecal serine protease activity and intestinal mast cells were evaluated. Intestinal permeability was assessed by urine lactulose/mannitol ratio, and colonic expressions of PAR-2 and tight junction (TJ) proteins were examined by Western blot. Intestinal immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was evaluated by abdominal withdrawal reflex in response to colorectal distention. Colonic PAR-2 expression as well as fecal serine protease activity and intestinal mast cell counts were elevated in PI-IBS compared to the control mice. Decreased colonic TJ proteins expression, increased lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and visceral hypersensitivity were observed in PI-IBS compared to the control mice. Administration of PAR-2 agonist in control mice demonstrated similar changes observed in PI-IBS mice, while PAR-2 antagonist normalized the increased intestinal permeability and reduced visceral hypersensitivity observed in PI-IBS mice. PAR-2 activation increases intestinal permeability leading to immune activation and visceral hypersensitivity in PI-IBS mouse model.

Outcomes of furazolidone- and amoxicillin-based quadruple therapy for Helicobacter pylori infection and predictors of failed eradication

Background and Aim Dietary factors and immune dysfunction may induce symptoms in patients with functional dyspepsia (FD). The aim of the study was to evaluate whether gluten consumption impacts symptom onset in patients with FD and to evaluate for possible histologic alterations in the duodenum of patients with FD. Methods We prospectively enrolled 101 patients newly diagnosed with FD and 31 asymptomatic controls. Specific FD symptoms and gluten consumption patterns were evaluated by self-reported questionnaires. Tight junction protein (claudin-1) expression and presence of intraepithelial lymphocyte (IEL) infiltration in the bulb (D1) and second portion (D2) of the duodenum were assessed by immunohistochemistry. Results Wheat bun consumption had higher frequency (P = 0.047) and increased average consumption (P = 0.01) scores in patients with FD compared with the control group. Of the 101 patients with FD, early satiety (P = 0.03) was associated with increased wheat bun consumption frequency score. On histologic evaluation, claudin-1 expression was decreased in D1 (0.003 ± 0.001 vs 0.012 ± 0.002, P = 0.003) and D2 (0.002 ± 0.0004 vs 0.012 ± 0.001, P

AIM To determine whether fructo-oligosaccharide (FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids (SCFA) in an irritable bowel syndrome (IBS) mouse model. METHODS Mice were randomly assigned to daily oral gavage of saline solution with or without FOS (8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress (WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field (HPF), respectively. RESULTS Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid (2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid (0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid (0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA (3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin (IL)-23 mRNA (4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1β mRNA (2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum (12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon (6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS. CONCLUSION FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production.

// Lijun Du 1 , John J. Kim 1, 2 , Binrui Chen 1 , Shuwen Zhu 1 and Ning Dai 1 1 Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China 2 Division of Gastroenterology, Loma Linda University Medical Center, Loma Linda, CA, USA Correspondence to: Ning Dai, email: ndaicn@zju.edu.cn Keywords: marital status; esophageal cancer; survival; surveillance; epidemiology Received: January 04, 2017 Accepted: August 23, 2017 Published: October 07, 2017 ABSTRACT The impact of marital status on survival among patients with esophageal cancer has not been evaluated in the U.S. population in depth. The aim of the study was to investigate the impact of marital status on survival among patients diagnosed with esophageal cancer. The Surveillance, Epidemiology, and End Results (SEER) database was utilized to identify patients diagnosed with esophageal cancer between 1973 and 2013. Cox regression analysis was performed to evaluate for association between marital status on both cancer-specific and overall survival. Of the 69,139 patients with esophageal cancer, 35,863 (52%) had adenocarcinoma and 21,573 (31%) had distant SEER stage. At the time of diagnosis, 39,805 (57%) patients were married, 10,116 (15%) were single, 8,417 (12%) were divorced or separated, and 10,801 (16%) were widowed. Married patients had superior cancer-specific and overall survival compared to unmarried patients. Multivariate analysis demonstrated that single (adjusted hazard ratio (HR)=1.14, 95%CI 1.11-1.17; P

ERCP is recommended for patients considered high risk for choledocholithiasis after biochemical testing and abdominal US. Our aim was to determine whether the American Society for Gastrointestinal Endoscopy (ASGE) guidelines accurately select patients for whom the risk of ERCP is justified.Consecutive patients hospitalized with suspected choledocholithiasis at Sir Run Run Shaw Hospital who received biochemical testing, abdominal US, and definitive testing for choledocholithiasis (MRCP, EUS, ERCP, intraoperative cholangiogram, and/or common bile duct [CBD] exploration) were identified. Patients with choledocholithiasis on abdominal US, with bilirubin levels4 mg/dL (normal values1.2 mg/dL), bilirubin levels ≥1.8 mg/dL plus a dilated CBD and/or clinical cholangitis were considered high risk per ASGE guidelines.Of 2724 patients with suspected choledocholithiasis, 1171 (43%) met high-risk criteria. Definitive testing (MRCP in 2442 [90%], EUS in 67 [2%], ERCP in 659 [24%], intraoperative cholangiogram in 229 [8%], and CBD exploration in 447 [16%]) revealed choledocholithiasis in 1076 [40%] patients. The specificity of the ASGE high-risk criteria was 74% (95% confidence interval [CI], 72%-77%) and positive predictive value was 64% (95% CI, 61%-67%). Using a more restrictive criteria (choledocholithiasis on abdominal US, bilirubin4 mg/dL plus dilated CBD) improved the specificity to 94% (95% CI, 93%-95%) and positive predictive value to 85% (95% CI, 82%-88%). Doubling or more of bilirubin to4 mg/dL and ≥1.8 mg/dL at second testing had specificities of 98% (95% CI, 96%-99%) and 95% (95% CI, 93%-96%), with positive predictive values of 62% (95% CI, 48%-76%) and 54% (95% CI, 44%-65%), respectively.Although ASGE high-risk criteria demonstrated50% probability of the patient having choledocholithiasis, more than a third of the patients would receive diagnostic ERCPs. Criteria with choledocholithiasis on abdominal US and/or bilirubin levels4 mg/dL plus a dilated CBD showed higher specificity and positive predictive value.

Intestinal dysmotility and immune activation are likely involved in the pathogenesis of small intestinal bacteria overgrowth (SIBO) in irritable bowel syndrome (IBS). We aimed at investigating the role of interstitial cells of Cajal (ICC) and intestinal inflammation in the development of SIBO using a post-infectious IBS (PI-IBS) mouse model.NIH mice were randomly infected with Trichinella spiralis. Visceral sensitivity and stool pattern were assessed at 8-weeks post-infection (PI). Intestinal bacteria counts from jejunum and ileum were measured by quantitative real-time PCR to evaluate the presence of SIBO. ICC density, intraepithelial lymphocytes (IELs) counts, and intestinal cytokine levels (IL1-β, IL-6, toll-like receptor-4 (TLR-4), IL-10) in the ileum were examined.PI-IBS mice demonstrated increased visceral sensitivity compared with the control group. One-third of the PI-IBS mice developed SIBO (SIBO+/PI-IBS) and was more likely to have abnormal stool form compared with SIBO negative PI-IBS (SIBO-/PI-IBS) mice but without difference in visceral sensitivity. SIBO+/PI-IBS mice had decreased ICC density and increased IELs counts in the ileum compared with SIBO-/PI-IBS mice. No difference in inflammatory cytokine expression levels were detected among the groups except for increased TLR-4 in PI-IBS mice compared with the control group.Development of SIBO in PI-IBS mice was associated with reduced ICC density and increased IELs counts in the ileum. Our findings support the role of intestinal dysmotility and inflammation in the pathogenesis of SIBO in IBS and may provide potential therapeutic targets.

Plastic biliary stents are commonly placed during endoscopic retrograde cholangiopancreatography (ERCP) and should be removed or replaced within 3 months to reduce the risk of stent obstruction. The aim of the study was to identify predictors and outcomes of patients who had delayed plastic biliary stent removal following ERCP.Consecutive patients who received ERCP with plastic biliary stent placement at Loma Linda University Medical Center (10/2004-6/2013) were identified. Delayed removal was defined as presence of stent3 months after index ERCP. Multivariable regression analysis to identify baseline characteristics associated with delayed removal was performed. Clinical outcomes of stent obstruction (e.g., cholangitis, hospitalization, intensive care) were also collected for those with delayed removal.Among 374 patients undergoing ERCP with plastic biliary stent, 71 (19%) had delayed stent removal. Patients who had anesthesia assistance (AOR = 3.8, 95%CI 1.2-11.4), non-English primary language (AOR = 3.0, 95%CI 1.5-6.2), and outpatient ERCP (AOR = 2.0, 95%CI 1.1-3.4) had increased while choledocholithiasis (AOR = 0.5, 95%CI 0.3-0.99) had lower odds of delayed stent removal. Among those with delayed removal, 13 (18%) were hospitalized for stent obstruction (5 (7%) had cholangitis, 8 (11%) were hospitalized for more than a week, and 3 (4%) required intensive care).Almost one-fifth of patients who underwent ERCP with plastic biliary stent placement had delayed removal with nearly one-fifth of these patients requiring hospitalization for stent obstruction. Targeting patients at risk by improving communication and ease of scheduling an ERCP may reduce preventable adverse events associated with delayed biliary stent removal.

// Lijun Du 1 , John J. Kim 1,2 , Jinhua Shen 1,3 , Binrui Chen 1 and Ning Dai 1 1 Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China 2 Division of Gastroenterology, Loma Linda University Medical Center, Loma Linda, USA 3 Department of Gastroenterology, Affiliated Hospital of Shaoxing University, Shaoxing, China Correspondence to: Ning Dai, email: // Keywords : KRAS, TP53, mutation, inflammatory bowel disease, colorectal cancer Received : September 18, 2016 Accepted : December 27, 2016 Published : January 07, 2017 Abstract Although KRAS and TP53 mutations are common in both inflammatory bowel disease-associated colorectal cancer (IBD-CRC) and sporadic colorectal cancer (S-CRC), molecular events leading to carcinogenesis may be different. Previous studies comparing the frequency of KRAS and TP53 mutations in IBD-CRC and S-CRC were inconsistent. We performed a meta-analysis to compare the presence of KRAS and TP53 mutations among patients with IBD-CRC, S-CRC, and IBD without dysplasia. A total of 19 publications (482 patients with IBD-CRC, 4,222 with S-CRC, 281 with IBD without dysplasia) met the study inclusion criteria. KRAS mutation was less frequent (RR=0.71, 95%CI 0.56-0.90; P =0.004) while TP53 mutation was more common (RR=1.24, 95%CI 1.10-1.39; P