Chedid, Victor

This study compares gene expression in mucosa of the terminal ileum, right colon, and left colon in patients with diarrhea- or constipation-predominant irritable bowel syndrome (IBS) and contrasts expression between these two disease entities and also between each entity and mucosa from healthy controls. The study shows there is differential expression of genes related to immune, transmitter, nociceptive, ion channel, and transporter functions, as well as reduced serine protease inhibition, in patients with IBS.

INTRODUCTION: We examined national Google Trends and local healthcare utilization after 3 high-impact gastroenterology publications. METHODS: Changes in US Google Trends and Olmsted County health utilization were studied. RESULTS: Publication views within 30 days were 51,458 ( Imperiale ), 49,759 ( Pimentel ), and 18,750 ( Gomm ). Colonoscopy searches ( P = 0.04) and Cologuard tests performed ( P < 0.01) increased while colonoscopies decreased ( P < 0.01). Searches for rifaximin ( P = 0.05), irritable bowel syndrome ( P < 0.01), diarrhea ( P < 0.01), and rifaximin prescriptions ( P = 0.02) increased. Increase in hydrogen-2 blocker searches ( P = 0.02) and prescriptions ( P < 0.01) and gastroesophageal reflux disease ( P < 0.01) and dementia office visits ( P < 0.01) occurred. DISCUSSION: High-impact gastroenterology publications influence Google searches and local population-based healthcare utilization.

INTRODUCTION: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown. METHODS: We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied. RESULTS: Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery. DISCUSSION: Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases.

INTRODUCTION: Previous studies in patients with irritable bowel syndrome (IBS) showed immune activation, secretion, and barrier dysfunction in duodenal, jejunal, or colorectal mucosa. This study aimed to measure ileal mucosal expression of genes and proteins associated with mucosal functions. METHODS: We measured by reverse transcription polymerase chain reaction messenger RNA (mRNA) expression of 78 genes (reflecting tight junction proteins, chemokines, innate immunity, ion channels, and transmitters) and 5 proteins (barrier, bile acid receptor, and ion exchanger) in terminal ileal mucosa from 11 patients with IBS-diarrhea (IBS-D), 17 patients with IBS-constipation (IBS-C), and 14 healthy controls. Fold changes in mRNA were calculated using 2 (−Δ, ΔCT) formula. Group differences were measured using analysis of variance. Protein ratios relative to healthy controls were based on Western blot analysis. Nominal P values ( P < 0.05) are reported. RESULTS: In ileal mucosal biopsies, significant differences of mRNA expression in IBS-D relative to IBS-C were upregulation of barrier proteins (TJP1, FN1, CLDN1, and CLDN12), repair function (TFF1), and cellular functions. In ileal mucosal biopsies, mRNA expression in IBS-C relative to healthy controls was reduced GPBAR1 receptor, myosin light chain kinase (MYLK in barrier function), and innate immunity (TLR3), but increased mRNA expression of cadherin cell adhesion mechanisms (CTNNB1) and transport genes SLC9A1 (Na-H exchanger [NHE1]) and INADL (indirect effect on ion transport). DISCUSSION: These data support a role of ileal mucosal dysfunction in IBS, including barrier dysfunction in IBS-D and alterations in absorption/secretion mechanisms in IBS-C.

Abstract Background Certolizumab pegol (CZP) has been successfully used for the treatment of Crohn disease (CD); however, real-world data regarding the utility of CZP trough levels (CTLs) are lacking. We aimed to correlate CTL with CD outcomes and to determine frequency of CZP antibodies. Methods Retrospective evaluation of all CD patients on maintenance CZP with CTL obtained between 2016 and 2019. Outcomes included: median CTL, presence of anti-CZP antibodies, biochemical response (BR), clinical response (CR), radiologic response (RR), radiologic healing (RH), and mucosal healing (MH). Results Seventy-seven CD patients were included. Median CTL was 18.9 µg/mL (interquartile range, 7.6–35.4). Twenty-three patients (27.3%) had positive antibody levels, with lower median CTL compared to patients with no antibodies (0.0 vs 29.8; P &lt; 0.0001). Median CTL levels were higher in patients with vs without CR (30.4 vs 10.3 µg/mL; P = 0.0015) and RR (29.6 vs 5.8 µg/mL; P = 0.006). CZP dosing at least every 2 weeks was associated with higher odds of achieving MH (odds ratio, 3.2; 95% confidence interval, 1.03–9.97). CTL resulted in change in clinical management in 62.7% of cases and presence of CMZ antibodies was associated with an odds ratio of 5.83 (95% confidence interval, 1.57–21.73) of change in management. Receiver operating characteristic curve and quartile analysis suggested that CTL &gt;19 µg/mL is associated with increased rates of CR and RR. Conclusions Higher CTL was significantly associated with CR and RR. The rate of CZP antibodies was 27.3%. Our data suggest maintenance CTL of ≥19 µg/mL should be achieved in order to optimize outcomes in clinical practice.

INTRODUCTION: The purpose of this study was to find out whether 3-dimensional (3D)–printed models improved the learners' ability to identify liver segments. METHODS: A total of 116 physicians from 3 disciplines were tested in a cross-over trial at baseline and after teaching with 3D models and 2-dimensional (2D) images. Adjusted multilevel-mixed models were used to compare scores at baseline and after 3D and 2D. RESULTS: Accuracy in identifying hepatic segments was higher with 3D first than 2D (77% vs 69%; P = 0.05) and not significantly improved by a combination of 3D and 2D. Increased confidence in segment identification was highest in trainees after 3D ( P = 0.04). DISCUSSION: 3D-printed models facilitate learning hepatic segmental anatomy.

Goals: To evaluate the diagnostic yield of colonoscopy and esophagogastroduodenoscopy with biopsies and to identify predictors of positive colonic histology in patients with chronic diarrhea. Background: Colonoscopy with biopsies is performed in chronic diarrhea with negative initial work-up. Study: We reviewed electronic medical records of 1022 consecutive patients with chronic diarrhea referred for a first colonoscopy (including 25% open-access referrals). Predictors of positive colonic histology were investigated using logistic regression. Results: Four hundred thirteen patients with macroscopically normal colon were divided into derivation (n=275) and validation (n=138) cohorts. All patients underwent colonoscopy; 369 had ileoscopy (biopsies in 43%), and 289 underwent esophagogastroduodenoscopy (duodenal biopsies in 93%). In patients with endoscopically normal colon, histology was positive in 13.3%: 10.6% microscopic colitis; 1.5% other colitides. Among 358 patients with negative histology, the recorded diagnoses were: 48% unexplained, 25% irritable bowel syndrome, 5.6% small intestinal bacterial overgrowth, and 4.7% bile acid diarrhea. The rates of diagnoses based on positive histologies were 4% for ileal and 5% for duodenal biopsies. Older age [odds ratio (OR)=1.05] was a positive predictor, whereas body mass index (OR=0.93) and duration of diarrhea (OR=0.98) were negative predictors of positive histology. A clinical diagnostic scoring system could correctly predict 41% to 54% of patients with normal colonic histology, with a false-negative rate of 0.8% to 2.6% and a negative predictive value of 95% to 98%. Conclusions: Positive colonic biopsies were detected in <15% of patients with chronic diarrhea with normal colonoscopy; a clinical score correctly predicts likelihood of normal histology in about half the patients.

Buffet meal intake was inversely related to the ability to resist the urge to overeat. Factors associated with ingestive behavior significantly correlated with satiety and gastric accommodation. Gastric capacity during fasting is associated with calorie intake to the point of comfortable fullness; factors associated with ingestive behavior are associated with satiety and gastric accommodation.