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Background and Aims Lumen-apposing metal stents (LAMSs) provide an endoscopic method for management of walled-off necrosis (WON) and a gateway for the performance of endoscopic necrosectomy (EN). However, bleeding may occur in up to 20% of EN procedures. Predictive factors for bleeding in this patient population are unknown, and there is no agreed-upon algorithm for management of bleeding. The aim of this study was to evaluate preprocedural risk factors for bleeding in patients undergoing endoscopic drainage or EN for WON. Methods A retrospective cohort of patients undergoing EN for WON was reviewed. Demographics, comorbidities, concurrent medications, and etiology of pancreatitis were recorded. Pre-, peri-, and postprocedural clinical variables were compared using Chi-squared test and independent t-test. Results Between June 2014 and October 2020, 536 EN were performed in 151 patients. Intraprocedural bleeding occurred during 28 procedures (5.2%) in 18 patients (11.9%.) Endoscopic hemostasis was attempted in 8 patients (10 procedures). Eight patients (10 procedures) in total were treated by IR. Thrombocytopenia (p = 0.006) and cirrhosis (p = 0.049) were associated with intraprocedural bleeding, although thrombocytopenia was present in only one patient. Identification of a vessel within the cavity endoscopically was also associated with bleeding (p Conclusions EN for WON was associated with a 5.2% per procedure risk of bleeding and an 11.9% per-patient bleeding risk. Identification of a vessel within the cavity during endoscopy is predictive of bleeding during EN. Patients who require more transfusions before endoscopy may require earlier intervention by IR.

Background and Aims Stent misdeployment (SM) has hindered the dissemination of EUS-guided gastroenterostomy (EUS-GE) for gastric outlet obstruction (GOO) management. We aimed to provide a classification system for SM during EUS-GE and study clinical outcomes and management accordingly. Methods This is a retrospective study involving 16 tertiary care centers (8 in the United States, 8 in Europe) from March 2015 to December 2020. Patients who developed SM during EUS-GE for GOO were included. We propose classifying SM into 4 types. The primary outcome was rate and severity of SM (per American Society for Gastrointestinal Endoscopy lexicon), whereas secondary outcomes were clinical outcomes and management of dislodgement according to the SM classification type, in addition to salvage management of GOO after SM. Results From 467 EUS-GEs performed for GOO during the study period, SM occurred in 46 patients (9.85%). Most SMs (73.2%) occurred during the first 13 EUS-GE cases by the performing operators. SM was graded as mild (n = 28, 60.9%), moderate (n = 11, 23.9%), severe (n = 6, 13.0%), or fatal (n = 1, 2.2%), with 5 patients (10.9%) requiring surgical intervention. Type I SM was the most common (n = 29, 63.1%), followed by type II (n = 14, 30.4%), type IV (n = 2, 4.3%), and type III (n = 1, 2.2%). Type I SM was more frequently rated as mild compared with type II SM (75.9% vs 42.9%, P = .04) despite an equivalent rate of surgical repair (10.3% vs 7.1%, P = .7). Overall, 4 patients (8.7%) required an intensive care unit stay (median, 2.5 days). The median length of stay was 4 days after SM. Conclusions Although SM is not infrequent during EUS-GE, most are type I, mild/moderate in severity, and can be managed endoscopically with a surgical intervention rate of approximately 11%.

Background and study aims The use of lumen apposing metal stents (LAMS) during EUS-guided transmural drainage (EUS-TD) of pancreatic walled-off necrosis (WON) has gained popularity. Data supporting their use in WON over plastic stents (PS), however, remain scarce. The aim of this study was to compare the clinical efficacy of LAMS (Axios, Boston Scientific) with PS in WON. Patients and methods This was a multicenter, retrospective study involving 14 centers. Consecutive patients who underwent EUS-TD of WON (2012 – 2016) were included. The primary end point was clinical success defined as WON size ≤ 3 cm within a 6-month period without need for percutaneous drainage (PCD) or surgery. Results A total of 189 patients (mean age 55.2 ± 15.6 years, 34.9 % female) were included (102 LAMS and 87 PS). Technical success rates were similar: 100 % in LAMS and 98.9 % in PS (P = 0.28). Clinical success was attained in 80.4 % of LAMS and 57.5 % of PS (P = 0.001). Rate of PCD was similar (13.7 % LAMS vs. 16.3 % PS, P = 0.62), while PS was associated with a greater need for surgery (16.1 % PS vs. 5.6 % LAMS, P = 0.02). Adverse events (AEs) were observed in 9.8 % of LAMS and 10.3 % of PS (P = 0.90) and were rated as severe in 2.0 % and 6.9 %, respectively (P = 0.93). After excluding patients with Conclusions When compared to PS, LAMS in WON is associated with higher clinical success, shorter procedure time, lower need for surgery, and lower rate of recurrence.

BACKGROUND: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, SARS-CoV-2 initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. METHODS: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 106 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). FINDINGS: We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=

Video Video 1 EGD, which showed obstructed distal flange of the gastrojejunal lumen-apposing metal stent (LAMS) by the contralateral jejunal wall. Two double-pigtail stents were placed across the LAMS to relieve the obstruction.

Background Larger caliber lumen-apposing stents (LAMSs) have been increasingly used in the management of pancreatic fluid collections, specifically when solid debris is present; however, their advantages over smaller caliber plastic stents in the management of pancreatic pseudocysts are unclear. The aim of this study was to investigate the safety and efficacy of LAMS specifically in the management of pancreatic pseudocysts compared with double-pigtail plastic stents (DPPSs). Methods We performed a multicenter, international, retrospective study between January 2012 and August 2016. A total of 205 patients with a diagnosis of pancreatic pseudocysts were included, 80 patients received LAMSs and 125 received DPPSs. Measured outcomes included clinical success, technical success, adverse events, stent dysfunction, pancreatic pseudocyst recurrence, and need for surgery. Results Technical success was similar between the LAMS and the DPPS groups (97.5 % vs. 99.2 %; P = 0.32). Clinical success was higher for LAMSs than for DPPSs (96.3 % vs. 87.2 %; P = 0.03). While the need for surgery was similar between the two groups (1.3 % vs. 4.9 %, respectively; P = 0.17), the use of percutaneous drainage was significantly lower in the LAMS group (1.3 % vs. 8.8 %; P = 0.03). At 6-month follow-up, the recurrence rate was similar between the groups (6.7 % vs 18.8 %, respectively; P = 0.12). The rate of adverse events was significantly higher in the DPPS group (7.5 % vs. 17.6 %; P = 0.04). There was no difference in post-procedure mean length of hospital stay (6.3 days [standard deviation 27.9] vs. 3.7 days [5.7]; P = 0.31). Conclusion When compared to DPPSs, LAMSs are a safe, feasible, and effective modality for the treatment of pancreatic pseudocysts and are associated with a higher rate of clinical success, shorter procedure time, less need for percutaneous interventions, and a lower overall rate of adverse events.

Epiphrenic (pulsion) esophageal diverticula can occur in the setting of underlying esophageal motility disorders such as achalasia and present a unique management challenge to the gastroenterologist. Asymptomatic diverticula do not require treatment, but symptomatic diverticula require therapy targeted to the underlying esophageal motility disorder, or else the diverticula will recur. Generally, laparoscopic or combined laparoscopic/thoracoscopic myotomy, diverticulectomy, and anterior fundoplication are required. However, therapeutic options for epiphrenic diverticula are evolving as peroral endoscopic myotomy (POEM) becomes more commonplace. We review two cases of achalasia complicated by epiphrenic diverticula at our institution. In the first case, type II achalasia was identified and the patient underwent laparoscopic myotomy. In the second case, type III achalasia was present and the patient underwent successful POEM. We discuss the presentation, pathophysiology, and management of epiphrenic diverticula as well as the expanding role for POEM in diverticula.

Background and Aims The American Society for Gastrointestinal Endoscopy recommends prophylactic pancreatic duct stent placement (PPS) and rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the incidence and severity of post-ERCP pancreatitis (PEP) in high-risk individuals and suggests that rectal indomethacin may decrease the risk and severity of PEP in average-risk individuals. The European Society for Gastrointestinal Endoscopy recommends rectal indomethacin for all patients undergoing ERCP. Previous surveys of European endoscopists revealed low adoption of PPS or rectal NSAIDs to prevent PEP. We sought to capture current practice in the prevention of PEP among endoscopists in the United States involved in advanced endoscopy fellowship programs. Methods An anonymous online 16-item survey was e-mailed to 233 advanced endoscopists involved in advanced endoscopy fellowship programs. Results Of the 233 endoscopists who were invited to participate, 62 responded (26.7%). Most respondents reported working in tertiary referral centers (57; 95.0%) and performing ERCP for greater than 5 years (44; 74.6%). All respondents (60; 100.0%) reported working with fellows. Most PPS users (41; 72.0%) reported use of PPS in high-risk patients only and using PPS for PEP in ≤25% of ERCPs (38; 64.4%). Most respondents reported using rectal NSAIDs for high-risk patients only (34; 59.7%) compared with respondents (23; 40.1%) who reported using rectal NSAIDs for prevention of PEP in average-risk patients undergoing ERCP. Most respondents (49; 83.0%) also reported using rapid intravenous fluids to prevent PEP. Conclusions Among endoscopists involved in advanced endoscopy fellowships in the United States, rectal NSAIDs are used more frequently than PPS in the prevention of PEP. Despite mounting evidence supporting the use of rectal NSAIDs to prevent PEP in average-risk patients, less than half of the respondents in this survey reported such practice.

Background and Aims EMR is used widely for treatment of nonpedunculated colorectal adenomas ≥ 2 cm. Recurrence at the resection site occurs in 10% to 30% of cases. Methods Records of consecutive patients referred for endoscopic resection over a 4-year period were reviewed retrospectively. In the first part of the study period, our routine practice was to use argon plasma coagulation (APC) to treat all visible residual neoplasia after exhaustive attempts at snare resection during EMR. In the second part of the study period, we changed our practice to use avulsion to treat all visible residual neoplasia after exhaustive attempts at snare resection during EMR. We analyzed the effect of this change in practice on recurrence rates after EMR. Results Two hundred twenty-three resected lesions were analyzed. Fifty-nine (26%) were treated with en-bloc EMR, 55 (25%) by piecemeal EMR with complete snare removal of all visible neoplasia, 63 (28%) by piecemeal EMR with APC of visible residual neoplasia, and 46 (21%) by piecemeal EMR with avulsion of visible residual neoplasia. There was no significant difference in adverse event rates among the 4 groups. The recurrence rates on follow-up colonoscopy were 4.2%, 3.0%, 59.3%, and 10.3%, respectively. The recurrence rate for patients treated with avulsion was significantly lower than for those treated with APC (odds ratio, .079; P Conclusions After exhaustive attempts at snare resection during EMR, avulsion is superior to APC for treatment of residual visible neoplasia. Compared with APC, avulsion significantly decreases the recurrence rate without significantly increasing the risk of the procedure.

Piecemeal endoscopic mucosal resection (EMR) is the standard treatment of nodular Barrett’s esophagus dysplasia and T1a cancer. Piecemeal resection may be incomplete and makes precise histologic assessment difficult. Endoscopic submucosal dissection (ESD) is a technique that enables en-bloc resection but has not gained widespread acceptance due to its technical difficulty, risk and long procedure time. We developed a protocol consisting of a combination of a limited ESD with supplementary EMR in the same session if necessary, designed to increase en-bloc resection of the most worrisome neoplastic area while maximizing the rate of complete resection of dysplasia. Records of consecutive patients referred for treatment during a 2-year period were reviewed. Eleven patients were treated: two with ESD and nine with combined ESD/EMR. Eight patients had mucosal lesions; three patients had submucosally invasive cancer and were referred to surgery. Five of the 8 mucosal lesions were removed en-bloc by ESD with dysplasia-free margins. Two patients with T1a cancer had low-grade dysplasia in the ESD margins and removal of all dysplasia on EMR. One patient with T1a cancer had high-grade dysplasia in the ESD margins and on EMR. He required a second endoscopy to remove residual neoplasia. There were no adverse events. The mean procedure time was 66.4 ± 15.1 min. Combining a limited ESD with EMR in the same session enables efficient treatment of visible dysplastic lesions in Barrett’s esophagus.

To discuss the rationale for the widespread application of endoscopic mucosal resection (EMR) rather than endoscopic submucosal dissection (ESD) in Western centers. In Western centers, EMR is the treatment of choice for most non-pedunculated colorectal adenomas >2 cm in size. EMR is sufficiently effective and safe to be performed without post-procedure hospitalization. Advances in EMR have led to reduced recurrence rates, and recent studies have demonstrated excellent outcomes with endoscopic treatment of recurrent adenomas. While studies from Asia have demonstrated lower recurrence rates with ESD, concern about the higher perforation risk and lengthy procedure time of ESD are two of the barriers preventing widespread adoption of ESD in the West. EMR is likely to continue as the dominant method for the treatment of large colorectal adenomas in Western centers until the limitations of ESD are overcome.

Foreign body aspirations that are not recognized at the time of aspiration can lead to insidious symptoms that can present a diagnostic challenge. We report the case of a 70-year-old man presenting with postobstructive pneumonia 2 months after aspirating his own tooth during a meal. He had been mistakenly diagnosed with asthma and treated with bronchodilators before a computed tomography scan of the thorax revealed the impacted tooth in his left bronchus. We review the clinical features and microbiology of postobstructive pneumonia and discuss the rationale of its treatment.

Phenazopyridine is a commonly used urinary analgesic available throughout the United States. Ingestion of large quantities can lead to methemoglobinemia, hemolytic anemia, jaundice, and acute renal failure. We report a case of a 78-year-old male with previously normal renal function who developed acute renal failure and jaundice without methemoglobinemia or hyperbilirubinemia after taking nearly 8 g of phenazopyridine over the course of 4 days. Initially presenting with oliguria, the urine output began to increase by day 2 of his admission, and the creatinine peaked 11 days after he began taking phenazopyridine, and he was discharged safely soon after. To our knowledge, this is the first such case of renal failure and jaundice without methemoglobinemia or hemolytic anemia in an adult patient with normal renal function.

Modeling sequence evolution on phylogenetic trees is a useful technique in computational biology. Especially powerful are models which take account of the heterogeneous nature of sequence evolution according to the "grammar" of the encoded gene features. However, beyond a modest level of model complexity, manual coding of models becomes prohibitively labor-intensive. We demonstrate, via a set of case studies, the new built-in model-prototyping capabilities of XRate (macros and Scheme extensions). These features allow rapid implementation of phylogenetic models which would have previously been far more labor-intensive. XRate's new capabilities for lineage-specific models, ancestral sequence reconstruction, and improved annotation output are also discussed. XRate's flexible model-specification capabilities and computational efficiency make it well-suited to developing and prototyping phylogenetic grammar models. XRate is available as part of the DART software package: http://biowiki.org/DART ., 34 pages, 3 figures, glossary of XRate model terminology

The dsRNA gene segment coding for the major outer shell glycoprotein of a human rotavirus (Hu/Australia/5/77, serotype 2) was converted into DNA and cloned into the PstI site of the plasmid pBR322. The cloned gene was sequenced and found to be 1062 bp long with one long open reading frame capable of coding for a protein 326 amino-acids. When this gene sequence was compared to the published sequences of the corresponding genes of two animal rotaviruses, SA11 (simian) and UK (bovine), all three were found to be closely related (74-78%). The predicted amino-acid sequences of the three genes were also highly conserved (75-86%), despite the fact that the three viruses belong to different serotypes.