Sex differences impact ergonomic endoscopic training for gastroenterology fellows.

BACKGROUND AND AIMS: Endoscopic-related injuries (ERIs) for gastroenterologists are common and can impact longevity of an endoscopic career. This study examines sex differences in the prevalence of ERIs and ergonomic training during gastroenterology fellowship. METHODS: A 56-item anonymous survey was sent to 709 general and advanced endoscopy gastroenterology fellows at 73 U.S. training programs between May and June 2022. Demographic information was collected along with questions related to endoscopic environment, ergonomic instruction, technique, equipment availability, and ergonomic knowledge. Responses of female and male gastroenterology fellows were compared using χ2 and Fisher exact tests. RESULTS: Of the 236 respondents (response rate, 33.9%), 113 (44.5%) were women and 123 (52.1%) were men. Female fellows reported on average smaller hand sizes and shorter heights. More female fellows reported endoscopic equipment was not ergonomically optimized for their use. Additionally, more female fellows voiced preference for same-gender teachers and access to dial extenders and well-fitting lead aprons. High rates of postendoscopy pain were reported by both sexes, with significantly more women experiencing neck and shoulder pain. Trainees of both sexes demonstrated poor ergonomic awareness with an average score of 68% on a 5-point knowledge-based assessment. CONCLUSIONS: Physical differences exist between male and female trainees, and current endoscopic equipment may not be optimized for smaller hand sizes. This study highlights the urgent need for formal ergonomic training for trainees and trainers with consideration of stature and hand size to enhance safety, comfort, and equity in the training and practice of endoscopy.

Total Proctocolectomy vs Subtotal/total Colectomy for Neoplasia in Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) frequently undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for medically refractory disease or colonic dysplasia/neoplasia. Subtotal colectomy with ileosigmoid or ileorectal anastomosis may have improved outcomes but is not well studied. Due to increased risk for colorectal cancer in PSC-IBD, there is hesitancy to perform subtotal colectomy. We aim to describe the frequency of colorectal dysplasia/neoplasia following IPAA vs subtotal colectomy in PSC-IBD patients. METHODS: We completed a retrospective study from 1972 to 2022 of patients with PSC-IBD who had undergone total proctocolectomy with IPAA or subtotal colectomy. We abstracted demographics, disease characteristics, and endoscopic surveillance data from the EMR. RESULTS: Of 125 patients (99 IPAA; 26 subtotal), the indication for surgery was rectal sparing medically refractory disease (51% vs 42%), dysplasia (37% vs 30%) and neoplasia (11% vs 26%) in IPAA vs subtotal colectomy patients, respectively. On endoscopic surveillance of IPAA patients, 2 (2%) had low-grade dysplasia (LGD) in the ileal pouch and 2 (2%) had LGD in the rectal cuff after an average of 8.4 years and 12.3 years of follow-up, respectively. One (1%) IPAA patient developed neoplasia of the rectal cuff after 17.8 years of surgical continuity. No subtotal colectomy patients had dysplasia/neoplasia in the residual colon or rectum. CONCLUSIONS: In patients with PSC-IBD, there was no dysplasia or neoplasia in those who underwent subtotal colectomy as opposed to the IPAA group. Subtotal colectomy may be considered a viable surgical option in patients with rectal sparing PSC-IBD if adequate endoscopic surveillance is implemented.

We sought to evaluate the risk of developing dysplasia in patients with both inflammatory bowel disease and primary sclerosing cholangitis, following surgery with either total proctocolectomy with ileal pouch-anal anastomosis or subtotal/total colectomy with ileosigmoid or ileorectal anastomosis.

Hydrogen Bonding Compensation on the Convex Solvent-Exposed Helical Face of IA3, an Intrinsically Disordered Protein.

Saccharomyces cerevisiae IA3 is a 68 amino acid peptide inhibitor of yeast proteinase A (YPRA) characterized as a random coil when in solution, folding into an N-terminal amphipathic alpha helix for residues 2-32 when bound to YPRA, with residues 33-68 unresolved in the crystal complex. Circular dichroism (CD) spectroscopy results show that amino acid substitutions that remove hydrogen-bonding interactions observed within the hydrophilic face of the N-terminal domain (NTD) of IA3-YPRA crystal complex reduce the 2,2,2-trifluoroethanol (TFE)-induced helical transition in solution. Although nearly all substitutions decreased TFE-induced helicity compared to wild-type (WT), each construct did retain helical character in the presence of 30% (v/v) TFE and retained disorder in the absence of TFE. The NTDs of 8 different Saccharomyces species have nearly identical amino acid sequences, indicating that the NTD of IA3 may be highly evolved to adopt a helical fold when bound to YPRA and in the presence of TFE but remain unstructured in solution. Only one natural amino acid substitution explored within the solvent-exposed face of the NTD of IA3 induced TFE-helicity greater than the WT sequence. However, chemical modification of a cysteine by a nitroxide spin label that contains an acetamide side chain did enhance TFE-induced helicity. This finding suggests that non-natural amino acids that can increase hydrogen bonding or alter hydration through side-chain interactions may be important to consider when rationally designing intrinsically disordered proteins (IDPs) with varied biotechnological applications.

Intestinal Host Response to SARS-CoV-2 Infection and COVID-19 Outcomes in Patients With Gastrointestinal Symptoms.

BACKGROUND & AIMS: Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and clinical significance. METHODS: Human intestinal biopsy tissues were obtained from patients with COVID-19 (n = 19) and uninfected control individuals (n = 10) for microscopic examination, cytometry by time of flight analyses, and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in 2 large, independent cohorts of hospitalized patients in the United States (N = 634) and Europe (N = 287) using multivariate logistic regressions. RESULTS: COVID-19 case patients and control individuals in the biopsy cohort were comparable for age, sex, rates of hospitalization, and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy in 15 of 17 patients studied. High-dimensional analyses of GI tissues showed low levels of inflammation, including down-regulation of key inflammatory genes including IFNG, CXCL8, CXCL2, and IL1B and reduced frequencies of proinflammatory dendritic cells compared with control individuals. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of sex, age, and comorbid illnesses and despite similar nasopharyngeal SARS-CoV-2 viral loads. Furthermore, there was reduced levels of key inflammatory proteins in circulation in patients with GI symptoms. CONCLUSIONS: These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in patients with COVID-19 presenting with GI symptoms was observed. A potential role of the GI tract in attenuating SARS-CoV-2-associated inflammation needs to be further examined.