Faculty Bibliography

Background: In addition to respiratory distress, GI symptoms have been reported in COVID-19 patients at various stages of the disease. Among the GI symptoms that have been reported, diarrhea, nausea, vomiting, abdominal pain and GI bleeding were often seen. Age and comorbid conditions such as obesity, HTN, DM and/or CAD have been considered as risk factors for COVID-19 patients for severe disease. GI manifestations in COVID-19 patients appeared to act as a sign for a serious condition. The virus has been identified in the stool and in rectal swabs of some infected patients, even after a negative nasopharyngeal test. There is a lack of reports on pathological alterations of the GI tract in COVID-19 infected patients.
Design(s): 16 PCR confirmed COVID-19 patients (11 males and 5 females) were included in the study. Biopsy or resection specimens were taken from the esophagus (4), stomach (6), small intestine (5), appendix (3), colon (5) and gallbladder (3). Clinical information including demographics, comorbidities, GI symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): The age of the patients ranged from 10 to 84 years old, with an average of 47 years. Eight (50%) patients had at least one comorbid condition, two patients (12.5%) had prior history of cancer, and six patients had no significant medical history. Abdominal pain and GI bleeding were the most common presenting symptoms. Histologically, acute and chronic inflammation was seen in 14 of 16, and 15 of 16 cases, respectively. Eight cases showed severe acute inflammation with ulceration. The mucosal changes included nonspecific reactive change, hypermucinous, atrophic/ischemic changes, and necrosis, were indiscriminately noticed in these cases. Four cases showed intraepithelial lymphocytosis. Viral like inclusions were found in four cases. Microthrombi were identified in 5 cases with an average patient age of 60 years. Notably, microthrombi were seen in about 5 out of 8 (62%) patients with comorbidities. The patients with microthrombi had a higher D dimer test value than those without thrombus. Three patients died shortly after operation, and two of them showed microthrombi in the tissue specimens.
Conclusion(s): Acute and chronic inflammation were indiscriminately seen in these cases. Microthrombi were dominantly found in aging patients with comorbidities, suggesting microthrombi in the GI tract may be a histologic indication for severe COVID-19 patients with GI symptoms

BACKGROUND & AIMS/OBJECTIVE:Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized during pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing (scRNA-seq). METHODS:We examined pouch lamina propria CD45+ hematopoietic cells from intestinal tissues of ulcerative colitis patients with (n=15) and without an ileal pouch-anal anastomosis (n=11). Further in silico meta-analysis was performed to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches. RESULTS:In addition to tissue-specific signatures, we identified a population of IL1B/LYZ+ myeloid cells and FOXP3/BATF+ T cells that distinguish inflamed tissues which we further validated in other single cell RNA-seq datasets from IBD patients. Cell type specific transcriptional markers obtained from single-cell RNA-sequencing was used to infer representation from bulk RNA sequencing datasets, which further implicated myeloid cells expressing IL1B and S100A8/A9 calprotectin as interacting with stromal cells, and Bacteroidiales and Clostridiales bacterial taxa. We found that non-responsiveness to anti-integrin biologic therapies in ulcerative colitis patients was associated with the signature of IL1B+/LYZ+ myeloid cells in a subset of patients. CONCLUSIONS:Features of intestinal inflammation during pouchitis and ulcerative colitis are similar, which may have clinical implications for the management of pouchitis. scRNA-seq enables meta-analysis of multiple studies, which may facilitate the identification of biomarkers to personalize therapy for IBD patients.

Background: Although medical schools use behavioral based interviews, most residencies and fellowships use unstructured interviews. The literature suggests that structured interviews help in reducing bias and selecting the best fit applicants, but most faculty lack formal interview training. We created a faculty development workshop to teach GME faculty how to conduct interviews more effectively.
Method(s): 15 GME faculty participated in an interviewing workshop with a group OSCE where they reviewed an applicant's CV and letter of recommendation, and then observed an unstructured interview followed by a structured interview utilizing behavioral based questions. After each simulation, faculty rated the applicant. We discussed the literature on different styles of interviewing including how to evaluate behavioral based questions. We reviewed the prevalence of unconscious bias and illegal questions. Participants worked together to create behavioral based questions tied to the particular needs of their own programs.
Result(s): Faculty rated the candidate in the unstructured interview favorably with 87% responding that the candidate was above average or excellent. Following the structured interview, 78% of faculty rated the candidate average or below average, and were concerned about behavioral issues including applicant's lack of empathy toward a difficult patient and limited insight. In a post-workshop survey, only 50% of faculty reported that their department provides training for interviews, and 50% thought they should have detected a problematic trainee in their interview. 100% of faculty reported motivation to change their interviewing style, and 92% of faculty reported the workshop was moderately, very, or extremely effective in providing tools for interviews.
Conclusion(s): This workshop enabled GME faculty to reflect on their ability to tailor questions to their program's needs. We successfully taught faculty how to utilize structured interviews to choose optimal candidates for their programs. These structured questions, created with the ACGME milestones, were designed to improve the interview reliability and validity by increasing standardization. We believe faculty who improve their interviewing skills will decrease bias, have better match outcomes, and will reduce the likelihood of their trainees requiring remediation for non-cognitive issues

Background: Colorectal carcinoma (CRC) in patients with longstanding inflammatory bowel disease (IBD) is the culmination of an inflammation-dysplasia-cancer sequence. Its molecular pathogenesis is not fully understood, because in addition to adenomatous dysplasia analogous to conventional sporadic adenomatous lesions, dysplasia in IBD can assume other distinctive phenotypically heterogeneous changes, the clinical characteristics and significance of which are largely unknown. We characterized 2 types of unconventional dysplasias; Goblet Cell Deficient (GCD) and Crypt Cell/Terminally Differentiated (CC/TD) by sequencing DNA for cancerrelated hotspots.
Design(s): Nineteen mucosal samples of dysplasia from biopsies or resection specimens of patients with IBD, eleven ulcerative colitis, six Crohn's colitis, two indeterminate colitis) were evaluated at Mount Sinai Hospital. Fourteen as GCD featured tubular crypts lined by monotonous columnar cells with eosinophilic cytoplasm and mildly atypical nuclei and 5 as CC/TD featured tubular crypts lined by differentiated enterocytes, goblet cells, Paneth cells and/or endocrine cells with cytologically atypical nuclei as previously described (1). The slides were de-identified and the presence of dysplasia confirmed by two independent pathologist. DNA extracted from formalin-fixed, paraffin-embedded dysplastic samples containing at least 10% dysplastic cells and from adjacent non-dysplastic mucosa were analyzed for a 50-gene panel of hotspot mutation sequences on an Ion Torrent PGM sequencer with strict quality assurance (50,000 reads, 200X coverage, AQ20). Data was analyzed on Torrent Suite Analysis Software and annotated with Ion Reporter Software.
Result(s): Seven lesions (37%) harbored mutations that have been implicated in the development of carcinoma (GCD, n=4, CC/TD n=3) per Catalogue of Somatic Mutations in Cancer (COSMIC) database, including known mutations of KRAS, p53, IDH1 and FBXW7, however no correlations were observed between the mutations and dysplasia phenotypes or type of IBD. Two lesions contained variants of unknown significance (VUS) in addition to pathogenic mutations (GCD with IDH1, CC/TD with TP53) and two lesions harbored only VUS. (Table presented)
Conclusion(s): Unconventional dysplastic lesions corresponding to GCD and CC/TD harbor pathogenic mutations that are implicated in the development and progression of sporadic CRC

Introduction: Gut fermentation or auto-brewery syndrome is a relatively uncommon medical condition that presents a diagnostic and therapeutic challenge. Case Report: Here we present a unique case of a 45-yearold obese, male, diabetic patient treated with two courses of antibiotics for deviated nasal septum and dental procedure who reported episodes of diarrhea, vomiting, edema, seizures, hallucinations, intermittent fevers, chills, slurred speech, and loss of consciousness precipitated after meals for a duration of 14 months. The patient denied alcohol consumption at any time. His blood ethanol levels, measured on multiple occasions, were elevated and corroborated by a 24-hour meal test administered in the hospital. Small bowel and fecal contents collected during the endoscopic procedures were remarkable for the growth of Saccharomyces cerevisiae from both samples. Gram stain was negative for Salmonella, Shigella, or Campylobacter. A rapid membrane enzyme immunoassay for C difficile antigen and toxins A and B was also negative. The patient responded well to oral fluconazole but relapsed after a month and needed further assessment. Microbiological studies undertaken on gastric and small bowel contents collected during the follow-up upper and lower endoscopic procedures were positive for Candida intermedia, sensitive to fluconazole (0.250 mcg/ mL) and amphotericin B (0.250 mcg/mL). Bacterial cultures showed rare, positive growth for Klebsiella pneumoniae and Enterococcus faecium. The patient responded dramatically to a no-carbohydrate diet and intravenous administration of an antifungal agent through a peripherally inserted central catheter line. The patient has been asymptomatic ever since.
Summary: Auto-brewery syndrome in a setting of diabetes, obesity, and high carbohydrate intake presented with signs and symptoms of elevated serum ethanol levels. The importance of microbiological studies on carefully collected intestinal secretions is emphasized in this report, in the absence of validated diagnostic and treatment protocols in the literature