Faculty Bibliography

Introduction: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common cause of hospitalization and is associated with an up to 30% incidence of rebleeding. Data increasingly suggests the over-thescope clip (OTSC) is an effective and safe tool in hemostasis specifically for rebleeding, severe hemorrhage or large ulcers not amenable to standard therapy. Nevertheless, this tool remains underutilized in general gastroenterology (GI) practice and training. We seek to show our outcomes in hemostasis for NVUGIB after competency training of general GI attendings and trainees by our GI hospitalist.
Method(s): We performed a retrospective chart review of patients with NVUGIB who received treatment with OTSC by general GI faculty and trainees at a large quaternary care academic center between July 2019 and May 2022. Procedures were supervised by 6 attendings. Demographics are shown in Table. The primary outcome was 30-day rebleeding at the site of initial hemostasis, defined as clinical signs of bleeding with need for repeat endoscopic intervention or angiography.
Result(s): We identified 52 patients hospitalized for NVUGIB who underwent upper endoscopy with use of the OTSC by general GI attendings and trainees. Of these cases, we observed a 30-day rebleeding rate of 13.5% (n = 7). We observed that patients who rebled had higher readmission rates (71.4% vs 13.3%, p < 0.05). No significant differences were observed in demographics, medical history, presenting labs, ulcer features, or length of stay between the two cohorts (Table). We observed that a majority of lesions were found within the duodenum (69.2%, n = 36), and a majority of these ulcers were large >10mm in size (82.7%, n = 43) in both groups. Of patients undergoing OTSC use for primary hemostasis versus secondary hemostasis, rebleeding rate was 15.6% (n = 5) and 10% (n = 2), respectively. Of patients who rebled, 3 underwent repeat endoscopy alone, and 2 underwent EGD & angiography, and 2 underwent angiography alone. No patients required surgery. There were no complications from OTSC placement.
Conclusion(s): The OTSC is a highly effective tool in the management of NVUGIB specifically in cases of rebleeding, severe hemorrhage, and large ulcers not amenable to standard treatment. The OTSC can be safely and successfully deployed by general gastroenterologists and trainees. Education and competency in OTSC should be encouraged in physicians who treat NVUGIB. (Table Presented)

Introduction: Visual assessment of stigmata of hemorrhage in NVUGIB is the cornerstone of endoscopic therapy. Nevertheless, rebleeding occurs in up to 30% of patients. The endoscopic doppler probe (EDP) is a novel device that can help guide hemostasis by assessing for arterial blood flow (ABF) within an ulcer base despite its visual appearance. It is most helpful when there is ambiguous stigmata or discordance between the stigmata and clinical picture. Ulcers with residual ABF flow following treatment have been associated with higher rates of rebleeding. The use of EDP to confirm eradication of ABF improves rebleeding. Use of the EDP has not been widely adopted. We seek to evaluate the outcomes in hemostasis with use of EDP after competency training of general gastroenterology (GI) attendings and trainees by our GI hospitalist.
Method(s): We performed a retrospective study of patients admitted to a large quaternary care academic medical center with NVUGIB for whom EDP was used during endoscopy (EGD) before and/or after endoscopic treatment. Procedures were performed between January 2021 and May 2022 and were supervised by 4 gastroenterology attendings. Patient demographics and outcomes are listed in Table. The primary outcome was 30-day rebleeding rate, defined as clinical evidence of bleeding plus need for repeat endoscopy or other therapeutic intervention at the location of initial hemostasis as guided by EDP.
Result(s): We identified 37 patients who underwent EGD with EDP. We found a 30-day rebleeding rate of 13.5% (n = 5). Patients who rebled were more likely to be of Hispanic heritage and previously treated with bipolar cautery (p< 0.05). There were no other significant differences (Table). Most ulcers were located within the duodenum (67.6%, n = 25), and most were large (> 10mm in size; 75.7%, n = 28). In 4 patients use of the EDP did not lead to additional endoscopic treatment. None of these patients had rebleeding. For the patients with rebleeding 1 patient required EGD and angiography; 2 patients required repeat EGD only and 2 patients underwent angiography only. No patients required surgery. No intraprocedural complications were identified.
Conclusion(s): The EDP is a highly effective tool in the management of NVUGIB and can be safely and successfully used by general GI attendings and trainees. The EDP provides a treat-to-target approach to hemostasis and improves upon standard visual assessment of stigmata of hemorrhage. Training in EDP should be encouraged in physicians who treat NVUGIB. (Figure Presented)

Introduction: Pseudomelanosis of the upper gastrointestinal tract (GI) is a rare condition characterized by a diffuse black-brown speckled pigmentation within the intestinal mucosa. Usually identified incidentally on endoscopy, upper intestinal pseudomelanosis is more frequently seen in the duodenum, but can rarely also be seen in the gastric body and jejunum. While this condition has been reported in literature, pathogenesis and clinical course are still largely unknown. Here we describe a case of pseudomelanosis in a patient referred for iron deficiency anemia. Case Description/Methods: An 80-year-old woman with a history notable for hypertension, type 2 diabetes, chronic kidney disease, coronary artery disease, gastroesophageal reflux disease, hypothyroidism, and celiac disease was referred for evaluation of iron deficiency anemia. On review, she had undergone screening colonoscopy 2 years ago, notable for scattered diverticulosis, and upper endoscopy 5 years ago notable only for mild gastritis. Medications included: aspirin, hydralazine, metoprolol, losartan, atorvastatin, pantoprazole, ferrous sulfate, and insulin glargine. She initially underwent video capsule endoscopy, revealing mild non-erosive gastropathy and scattered black pigmentation in the duodenum (Figure 1A). She subsequently underwent upper endoscopy demonstrating scattered pigmentation in the gastric antrum, duodenum, and proximal jejunum (Figure 1B). Duodenal biopsies revealed pigment laden macrophages within the mucosa consistent with pseudomelanosis duodeni (Figure 1C).
Discussion(s): Pseudomelanosis of the upper intestinal tract is a rare and poorly understood condition. While considered benign, it has been associated with various conditions including hypertension, diabetes mellites, chronic kidney disease, gastrointestinal bleeding, and with medications including oral iron supplements and diureticsmany of which were seen in this case. Unlike colonic pseudomelanosis, which is histologically characterized by accumulation of lipofuscin within the colonic mucosa and is associated with laxative use, pseudomelanosis of the upper intestinal tract is histologically distinct, characterized by accumulation of ferrous sulfate containing compounds. To date, pathogenesis of the condition remains unclear. Given the rarity of upper intestinal pseudomelanosis, prognosis and treatment have also yet to be determined. This reports aims to increase awareness of this rare and incompletely understood condition

During meiosis, programmed double strand breaks (DSBs) are repaired preferentially between homologs to generate crossovers that promote proper chromosome segregation at Meiosis I. In many organisms, there are two strand exchange proteins, Rad51 and the meiosis-specific Dmc1, required for interhomolog (IH) bias. This bias requires the presence, but not the strand exchange activity of Rad51, while Dmc1 is responsible for the bulk of meiotic recombination. How these activities are regulated is less well established. In dmc1Δ mutants, Rad51 is actively inhibited, thereby resulting in prophase arrest due to unrepaired DSBs triggering the meiotic recombination checkpoint. This inhibition is dependent upon the meiosis-specific kinase Mek1 and occurs through two different mechanisms that prevent complex formation with the Rad51 accessory factor Rad54: (i) phosphorylation of Rad54 by Mek1 and (ii) binding of Rad51 by the meiosis-specific protein Hed1. An open question has been why inhibition of Mek1 affects Hed1 repression of Rad51. This work shows that Hed1 is a direct substrate of Mek1. Phosphorylation of Hed1 at threonine 40 helps suppress Rad51 activity in dmc1Δ mutants by promoting Hed1 protein stability. Rad51-mediated recombination occurring in the absence of Hed1 phosphorylation results in a significant increase in non-exchange chromosomes despite wild-type levels of crossovers, confirming previous results indicating a defect in crossover assurance. We propose that Rad51 function in meiosis is regulated in part by the coordinated phosphorylation of Rad54 and Hed1 by Mek1.

[This corrects the article DOI: 10.1371/journal.pgen.1006226.].