Faculty Bibliography

Background Dual-energy CT enterography (DECTE) has been shown to be useful in characterizing Crohn disease activity compared with clinical markers of inflammation but, to the knowledge of the authors, comparison has not been made with histopathologic specimens. Purpose To compare mucosal iodine density obtained at DECTE from Crohn disease-affected bowel with histopathologic specimens from surgically resected ileocolectomy bowel segments or terminal ileum colonoscopic biopsies in the same patients. Materials and Methods This was a retrospective study. Bowel segments in adults with Crohn disease who underwent DECTE from January 2017 to April 2019 within 90 days of ileocolectomy or colonoscopy were retrospectively evaluated with prototype software allowing the semiautomatic determination of inner hyperdense bowel wall (mucosal) mean iodine density, normalized to the aorta. Mean normalized iodine density and clinical activity indexes (Crohn Disease Activity Index [CDAI] and Harvey-Bradshaw Index [HBI]) were compared with histologic active inflammation grades by using two-tailed t tests. Receiver operating characteristic curves were generated for mean normalized iodine density, CDAI, and HBI to determine sensitivity, specificity, and accuracy. A P value less than .05 was considered to indicate statistical significance. Results The following 16 patients were evaluated (mean age, 41 years ± 14 [standard deviation]): 10 patients (five men, five women; mean age, 41 years ± 15) with 19 surgical resection specimens and six patients with terminal ileum colonoscopic mucosal biopsies (four men, two women; mean age, 43 years ± 14). Mean normalized iodine density was 16.5% ± 5.7 for bowel segments with no active inflammation (n = 8) and 34.7% ± 9.7 for segments with any active inflammation (n = 17; P < .001). A 20% mean normalized iodine density threshold had sensitivity, specificity, and accuracy of 17 of 17 (100%; 95% CI: 80.5, 100), six of eight (75%; 95% CI: 35, 97), and 23 of 25 (92%; 95% CI: 74, 99), respectively, for active inflammation. Clinical indexes were similar for patients with and without active inflammation at histopathologic analysis (CDAI score, 261 vs 251, respectively [P = .77]; HBI score, 7.8 vs 6.4, respectively [P = .36]). Conclusion Iodine density from dual-energy CT enterography may be used as a radiologic marker of Crohn disease activity as correlated with histopathologic analysis. © RSNA, 2021 See also the editorial by Ohliger in this issue.

INTRODUCTION/BACKGROUND:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS:We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS:Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION/CONCLUSIONS:Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

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: 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: Digestive symptoms are often seen in COVID-19 patients with poor outcomes. The Viral RNA is mostly positive in the stool of these patients, and has a longer delay before viral clearance. However, its diagnostic value and significance for guiding clinical treatment remain unknown. And the pathologic alterations in the GI tract in COVID-19 patients have not been well defined. We evaluated rectal swab SAS-CoV-2 test and histopathologic changes in the small intestine in autopsy patients.
Design(s): 18 autopsy cases with confirmed SAS-CoV2 infection were included. Nasal, bronchial, and rectal swab SARS-CoV-2 PCR were performed at the time of autopsy. Clinical information included demographics, comorbidities, presenting symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): 83% (15/18) of patients were male. Median age is 50 years. 7/18 (38.9%) patients had diarrhea in addition to cough, fever and other symptoms. Except in one case, all patients had underlying comorbidities of diabetes, hypertension and /or obesity. In the small intestine, acute inflammation was not seen in any cases. 5/18 displayed mild and one showed moderate chronic inflammation. Hypermucinous change was found in six patients but not associated with diarrhea. 3 cases had microthrombi identified in the sections. Notably, obviously increased D dimer in lab tests were noticed in all patients. Postmortem 17/17 (100%) nasal, 18/18 (100%) bronchial and 7/16 (43.8%) rectal swabs showed SARS-CoV-2 PCR positivity. 3 of 7 (42.9%) patients with diarrhea are positive in rectal swab for SARS-CoV-2.
Conclusion(s): There are no specific COVID-19 changes in the small intestine. More investigations are needed, especially on tissues from different locations of the GI tract. Data from rectal swab testing suggests that it is not ideal for diagnosing COVID-19, guiding treatment, or predicting small intestinal pathology

Gastrointestinal (GI) symptoms of SARS-CoV-2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19, and we hypothesize that older patients with significant comorbidities (obesity and cardiovascular) and prolonged hospitalization are susceptible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute-phase reactants, and drug/medication history in 2 elderly male patients admitted for COVID-19 respiratory failure. Both patients had a complicated clinical course and suffered from hematochezia, acute blood loss, and anemia which led to hemodynamic instability requiring blood transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopsies that included changes compatible with ischemia and nonspecific acute inflammation, edema, and increased eosinophils in the lamina propria. Both patients were hemodynamically stable, on prophylactic anticoagulants, multiple antibiotics, and antifungal agents due to respiratory infections at the time of lower GI bleeding. Hematochezia resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. This case report highlights hematochezia as an uncommon GI manifestation of spectrum of COVID-19 complications. The causes of bleeding in these COVID-19 associated cases are likely multifactorial and can be attributed to concomitant etiologies based on their age, multiple comorbid conditions, prolonged hospitalization compounded by lung injury, and hypoxia precipitated by the virus. We hypothesize that rather than a direct viral cytopathic effect, ischemia and hypoperfusion may be unleashed due to the cytokine storm orchestrated by the virus that leads to abnormal coagulation profile. Additional factors that may contribute to ischemic injury are prophylactic use of anticoagulants and polypharmacy. There were no other causes to explain the brisk lower GI bleeding. Presentation of hematochezia was followed by hemodynamic instability that may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.

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