Search

Roxana Chis,1 Simon Hew,2 Wilma Hopman,3 Lawrence Hookey,2 Robert Bechara2 1Division of Internal Medicine, Kingston Health Sciences Centre, Queen’s University, Kingston, Ontario, Canada; 2Division of Gastroenterology, Kingston Health Sciences Centre, Queen’s University, Kingston General Hospital, Kingston, Ontario, Canada; 3Research Institute, Kingston Health Sciences Centre, Queen’s University, Kingston, Ontario, CanadaCorrespondence: Robert BecharaDivision of Gastroenterology, Queens University, Kingston Health Sciences Center, 166 Brock Street, Kingston, Ontario K7L1A8, CanadaTel + 613 544 3400Email bechara.robert@gmail.comPurpose: Patients with Barrett’s esophagus (BE) undergo surveillance endoscopies to assess for pre-cancerous changes. We developed a simple endoscopic classification method for predicting non-dysplastic BE (NDBE), low-grade dysplasia (LGD)/indefinite for dysplasia (ID) and high-grade dysplasia (HGD)/early esophageal adenocarcinoma (EAC).Patients and Methods: Twenty-two patients with BE underwent endoscopy using the PENTAX Medical MagniView gastroscope and OPTIVISTA processor. Sixty-six video-still images were analyzed to characterize the microsurface, microvasculature and the presence of a demarcation line. Class A was characterized by regular microvascular and microsurface patterns and absence of a demarcation line, class B by changes in the microvascular and/or microsurface patterns compared to the background mucosa with presence of a demarcation line, and class C by irregular microvascular and/or irregular microsurface patterns with presence of a demarcation line.Results: Of the class A images, 97.9% were NDBE. For class B, 69.2% were LGD/ID and 30.8% NDBE. One hundred percent of the class C samples were HGD/EAC. The sensitivity of our classification system was 93.8%, specificity 92%, positive predictive value 78.9%, negative predictive value 97.9% and an accuracy 92.4%.Conclusion: In this study, we developed a simple classification system for the prediction of NDBE, LGD/ID and HGD/EAC. Its real-time clinical applicability will be validated prospectively.Keywords: Barrett’s esophagus, BE, dysplasia, enhanced endoscopy, esophageal adenocarcinoma

Background During the course of inflammatory bowel disease (IBD), approximately 20% of patients with ulcerative colitis (UC) and 80% of Crohn’s disease (CD) patients will require surgery. The most common operation is total proctocolectomy and ileoanal pouch anastomosis (IPAA) for UC patients and ileocecal (IC) resection for CD. In pregnant IBD patients, guidelines name the presence of IPAA as a relative indication for Cesarean section (C-section). The effect of prior IBD-related surgery on mode of delivery and pregnancy-related outcomes remains unknown. Aims To describe pregnancy-related outcomes in pregnant women with IBD who have undergone prior IBD-related surgery. Methods We performed a retrospective cohort study of pregnant women with IBD including those with prior IBD-related surgeries including IPAA, IC resection, total or partial colectomy and ileostomy formation who delivered an infant at our medical center from 2016 to 2020. We assessed the mode of delivery, delivery characteristics (emergency vs. planned C-section) and maternal and neonatal outcomes Results Fifty-six UC patients and 64 CD patients were included in the analysis, of which 10 and 24 had undergone prior IBD-related surgery, respectively. The mean age at conception was 34.10 years in the surgical UC group and 30.30 years in the surgical CD group. Mode of delivery: C-section rates were higher in post-surgical compared to non-surgical UC patients (70% vs. 30.4%, p = 0.02). Similar numbers of C-sections were performed emergently in the surgical compared to non-surgical UC group (10% vs. 18%, p = 0.53). Comparatively, there was no significant difference in C-section rates in post -surgical compared to non-surgical CD mothers (50% vs. 40%, p = 0.44), with 13% performed emergently in both groups. Maternal outcomes: Gestational diabetes developed in 10% of surgical UC and 4.5% of surgical CD patients. Premature rupture of membranes developed in 10% of surgical UC and 9.1% of surgical CD patients. There was no difference in pre-eclampsia rates in the surgical and non-surgical CD groups (9.1% vs 13.2%, p = 0.64). Neonatal outcomes: There was no significant difference in pre-term birth rates in post-surgical compared to non-surgical UC mothers (10% vs. 15.2%, p = 0.67) or in surgical compared to non-surgical CD mothers (13.6% vs. 5.1%, p = 0.29). Neonatal Intensive Care Unit (NICU) requirements were higher in infants born to post-surgical CD compared to non-surgical CD mothers (18.2% vs. 2.7%, p = 0.04). More low birth weight (LBW) infants were born to post-surgical CD vs non-surgical CD mothers (13.6% vs. 0%, p = 0.02). Conclusions Women with IBD who have had prior IBD-related surgery may be at increased risk of developing adverse gestational and neonatal outcomes. Women with surgical UC have an increased incidence of Cesarean delivery. Funding Agencies None

There is an old saying that a person with their health has 1000 dreams, but a person without it only has one. My husband and I met eight years ago in Key West, Florida. He lived in the United States and I, in Canada. Many flights, FaceTime calls, text messages, emails, phone calls and a wedding

The human gastrointestinal tract (GI) is home to an exceptionally diverse bacterial community, collectively referred to as the gut microbiota. These microbes play a pivotal role in modulating host physiology and immune response, in both gastrointestinal health and disease. There is evidence that alterations leading to an imbalance of the constituents of the gut microbiota, or dysbiosis, may contribute to several intestinal and extra-intestinal pathological states. These discoveries have led to exciting new microbe-based therapeutic developments, including reconstitution of bacterial communities, to reverse and correct dysbiosis. For instance, fecal microbiota transplantation (FMT), the process of infusing fecal matter from a healthy donor into a sick patient to restore a healthy microbiome in the recipient, has been used to treat recurrent Clostridium difficile infection (rCDI) and may hold promise for other gastrointestinal conditions. This chapter focuses on the key aspects of FMT, including methodology, physician and patient attitudes, safety and regulation, and its therapeutic potential for the treatment of rCDI and other gastrointestinal conditions, including inflammatory bowel disease, obesity, irritable bowel syndrome, and colorectal cancer.

Calnexin (CNX) is an endoplasmic reticulum (ER) quality control chaperone that has been implicated in ER stress. ER stress is a prominent pathological feature of various pathologic conditions, including cardiovascular diseases. However, the role of CNX and ER stress has not been studied in the heart. In the present study, we aimed to characterize the role of CNX in cardiomyocyte physiology with respect to ER stress, apoptosis, and cardiomyocyte Ca(2+) cycling. We demonstrated significantly decreased CNX mRNA and protein levels by LentiVector mediated transduction of targeting shRNAs. CNX silenced cardiomyocytes exhibited ER stress as evidenced by increased GRP78 and ATF6 protein levels, increased levels of spliced XBP1 mRNA, ASK-1, ERO1a, and CHOP mRNA levels. CNX silencing also led to significant activation of caspases-3 and -9. This activation of caspases was associated with hallmark morphological features of apoptosis including loss of sarcomeric organization and nuclear integrity. Ca(2+) imaging in live cells showed that CNX silencing resulted in Ca(2+) transients with significantly larger amplitudes but decreased frequency and Ca(2+) uptake rates in the basal state. Interestingly, 5 mM caffeine stimulated Ca(2+) transients were similar between control and CNX silenced cardiomyocytes. Finally, we demonstrated that CNX silencing induced the expression of the L-type voltage dependent calcium channel (CAV1.2) but reduced the expression of the sarcoplasmic reticulum ATPase (SERCA2a). In conclusion, this is the first study to demonstrate CNX has a specific role in cardiomyocyte viability and Ca(2+) cycling through its effects on ER stress, apoptosis and Ca(2+) channel expression.

α-Crystallin B (cryAB) is the most abundant small heat shock protein in cardiomyocytes (CMs) and has been shown to have potent antiapoptotic properties. Because the mechanism by which cryAB prevents apoptosis has not been fully characterized, we examined its protective effects at the cellular level by silencing cryAB in mouse neonatal CMs using lentivector-mediated transduction of short hairpin RNAs. Subcellular fractionation of whole hearts showed that cryAB is cytosolic under control conditions, and after H2O2 exposure, it translocates to the mitochondria. Phosphorylated cryAB (PcryAB) is mainly associated with the mitochondria, and any residual cytosolic PcryAB translocates to the mitochondria after H2O2 exposure. H2O2 exposure caused increases in cryAB and PcryAB levels, and cryAB silencing resulted in increased levels of apoptosis after exposure to H2O2. Coimmunoprecipitation assays revealed an apparent interaction of both cryAB and PcryAB with mitochondrial voltage-dependent anion channels (VDAC), translocase of outer mitochondrial membranes 20 kDa (TOM 20), caspase 3, and caspase 12 in mouse cardiac tissue. Our results are consistent with the conclusion that the cardioprotective effects of cryAB are mediated by its translocation from the cytosol to the mitochondria under conditions of oxidative stress and that cryAB interactions with VDAC, TOM 20, caspase 3, and caspase 12 may be part of its protective mechanism.