The bone morphogenetic protein (BMP) family is a class of transforming growth factor (TGF-β) superfamily molecules that have been implicated in neuronal differentiation. We studied the effects of BMP2 and glial cell line-derived neurotrophic factor (GDNF) on inducing differentiation of enteric neurons and the signal transduction pathways involved. Studies were performed using a novel murine fetal enteric neuronal cell line (IM-FEN) and primary enteric neurons. Enteric neurons were cultured in the presence of vehicle, GDNF (100 ng/ml), BMP2 (10 ng/ml), or both (GDNF + BMP2), and differentiation was assessed by neurite length, markers of neuronal differentiation (neurofilament medium polypeptide and β-III-tubulin), and neurotransmitter expression [neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase (TH), choline acetyltransferase (ChAT) and Substance P]. BMP2 increased the differentiation of enteric neurons compared with vehicle and GDNF-treated neurons (P < 0.001). BMP2 increased the expression of the mature neuronal markers (P < 0.05). BMP2 promoted differentiation of NPY-, nNOS-, and TH-expressing neurons (P < 0.001) but had no effect on the expression of cholinergic neurons (ChAT, Substance P). Neurons cultured in the presence of BMP2 have higher numbers of TH-expressing neurons after exposure to 1-methyl 4-phenylpyridinium (MPP+) compared with those cultured with MPP+ alone (P < 0.01). The Smad signal transduction pathway has been implicated in TGF-β signaling. BMP2 induced phosphorylation of Smad1, and the effects of BMP2 on differentiation of enteric neurons were significantly reduced in the presence of Smad1 siRNA, implicating the role of Smad1 in BMP2-induced differentiation. The effects of BMP2 on catecholaminergic neurons may have therapeutic implications in gastrointestinal motility disturbances.

Patients with acute cholangitis require emergent biliary decompression. Those who are hemodynamically unstable on vasopressor support and mechanical ventilation are too critically ill to move outside of the intensive care unit. This prohibits performing Endoscopic Retrograde Cholangiopancreatography (ERCP) in the endoscopy unit. Fluoroscopic guidance is required to confirm deep biliary cannulation during ERCP. There are a few reported cases of bedside ERCP using portable C-arm fluoroscopy unit or ultrasound guided cannulation. We present a unique case of life-saving emergent bedside ERCP in a severely ill patient with cholangitis and septic shock, using simple portable X-ray to confirm biliary cannulation.

Patients hospitalized with Coronavirus Disease 2019 (COVID-19) often have gastrointestinal symptoms, including diarrhea, nausea, vomiting, and abdominal pain.1 However, the rate of gastrointestinal complications in patients with COVID-19 is less well described. Recent reports from a single center have suggested an alarmingly high rate of serious gastrointestinal complications in critically ill patients with COVID-19.2 , 3 In a retrospective review of 92 patients with severe COVID-19 admitted to the intensive care unit (ICU), 44 patients (48%) had ileus, 4 (4%) had intestinal ischemia, and 2 (2%) had Ogilvie syndrome.2 Several other case reports have described intestinal ischemia in the setting of COVID-19.4 However, reports from single centers should be interpreted with caution because of small sample sizes and limited generalizability to patients from wider geographic distributions. The aim of this study was to assess the rate of serious gastrointestinal complications in patients with COVID-19 admitted to the ICU in a large, geographically diverse sample.

AIM: To evaluate rates and predictors of hospital readmission and care fragmentation in patients hospitalized with gastroparesis. METHODS: We identified all adult hospitalizations with a primary diagnosis of gastroparesis in the 2010-2014 National Readmissions Database, which captures statewide readmissions. We excluded patients who died during the hospitalization, and calculated 30 and 90-d unplanned readmission and care fragmentation rates. Readmission to a non-index hospital (i.e., different from the hospital of the index admission) was considered as care fragmentation. A multivariate Cox regression model was used to analyze predictors of 30-d readmissions. Logistic regression was used to determine hospital and patient factors independently associated with 30-d care fragmentation. Patients readmitted within 30 d were followed for 60 d post discharge from the first readmission. Mortality during the first readmission, hospitalization cost, length of stay, and rates of 60-d readmission were compared between those with and without care fragmentation. RESULTS: There were 30064 admissions with a primary diagnosis of gastroparesis. The rates of 30 and 90-d readmissions were 26.8% and 45.6%, respectively. Younger age, male patient, diabetes, parenteral nutrition, ≥ 4 Elixhauser comorbidities, longer hospital stay (> 5 d), large and metropolitan hospital, and Medicaid insurance were associated with increased hazards of 30-d readmissions. Gastric surgery, routine discharge and private insurance were associated with lower 30-d readmissions. The rates of 30 and 90-d care fragmentation were 28.1% and 33.8%, respectively. Younger age, longer hospital stay (> 5 d), self-pay or Medicaid insurance were associated with increased risk of 30-d care fragmentation. Diabetes, enteral tube placement, parenteral nutrition, large metropolitan hospital, and routine discharge were associated with decreased risk of 30-d fragmentation. Patients who were readmitted to a non-index hospital had longer length of stay (6.5 vs 5.8 d, P = 0.03), and higher mean hospitalization cost ($15645 vs $12311, P < 0.0001), compared to those readmitted to the index hospital. There were no differences in mortality (1.0% vs 1.3%, P = 0.84), and 60-d readmission rate (55.3% vs 54.6%, P = 0.99) between the two groups. CONCLUSION: Several factors are associated with the high 30-d readmission and care fragmentation in gastroparesis. Knowledge of these predictors can play a role in implementing effective preventive interventions to high-risk patients.

Background. The value of endoscopy in dyspeptic patients is questionable. Aims. To examine the prevalence of significant endoscopic findings (SEFs) and the utility of alarm features and age in predicting SEFs in outpatients with dyspepsia. Methods. A retrospective analysis of outpatient adults who had endoscopy for dyspepsia. Demographic variables, alarm features, and endoscopic findings were recorded. We defined SEFs as peptic ulcer disease, erosive esophagitis, malignancy, stricture, or findings requiring specific therapy. Results. Of 650 patients included in the analysis, 51% had a normal endoscopy. The most common endoscopic abnormality was nonerosive gastritis (29.7%) followed by nonerosive duodenitis (7.2%) and LA-class A esophagitis (5.4%). Only 10.2% had a SEF. Five patients (0.8%) had malignancy. SEFs were more likely present in patients with alarm features (12.6% versus 5.4%, p = 0.004). Age ≥ 55 and presence of any alarm feature were associated with SEFs (aOR 1.8 and 2.3, resp.). Conclusion. Dyspeptic patients have low prevalence of SEF. The presence of any alarm feature and age ≥ 55 are associated with higher risk of SEF. Endoscopy in young patients with no alarm features has a low yield; these patients can be considered for nonendoscopic approach for diagnosis and management.

Distal esophageal spasm (DES) is a rare major motility disorder in the Chicago classification of esophageal motility disorders (CC). DES is diagnosed by finding of ≥ 20% premature contractions, with normal lower esophageal sphincter (LES) relaxation on high-resolution manometry (HRM) in the latest version of CCv3.0. This feature differentiates it from achalasia type 3, which has an elevated LES relaxation pressure. Like other spastic esophageal disorders, DES has been linked to conditions such as gastroesophageal reflux disease, psychiatric conditions, and narcotic use. In addition to HRM, ancillary tests such as endoscopy and barium esophagram can provide supplemental information to differentiate DES from other conditions. Functional lumen imaging probe (FLIP), a new cutting-edge diagnostic tool, is able to recognize abnormal LES dysfunction that can be missed by HRM and can further guide LES targeted treatment when esophagogastric junction outflow obstruction is diagnosed on FLIP. Medical treatment in DES mostly targets symptomatic relief and often fails. Botulinum toxin injection during endoscopy may provide a temporary therapy that wears off over time. Myotomy through peroral endoscopic myotomy or via surgical Heller myotomy can provide long term relief in cases with persistent symptoms.

AIM: To investigate changes in polyp detection throughout fellowship training, and estimate colonoscopy volume required to achieve the adenoma detection rate (ADRs) and polyp detection rate (PDRs) of attending gastroenterologists. METHODS: We reviewed colonoscopies from July 1, 2009 to June 30, 2014. Fellows' procedural logs were used to retrieve colonoscopy procedural volumes, and these were treated as the time variable. Findings from screening colonoscopies were used to calculate colonoscopy outcomes for each fellow for the prior 50 colonoscopies at each time point. ADR and PDR were plotted against colonoscopy procedural volumes to produce individual longitudinal graphs. Repeated measures linear mixed effects models were used to study the change of ADR and PDR with increasing procedural volume. RESULTS: During the study period, 12 fellows completed full three years of training and were included in the analysis. The average ADR and PDR were, respectively, 31.5% and 41.9% for all fellows, and 28.9% and 38.2% for attendings alone. There was a statistically significant increase in ADR with increasing procedural volume (1.8%/100 colonoscopies, P = 0.002). Similarly, PDR increased 2.8%/100 colonoscopies (P = 0.0001), while there was no significant change in advanced ADR (0.04%/100 colonoscopies, P = 0.92). The ADR increase was limited to the right side of the colon, while the PDR increased in both the right and left colon. The adenoma per colon and polyp per colon also increased throughout training. Fellows reached the attendings' ADR and PDR after 265 and 292 colonoscopies, respectively. CONCLUSION: We found that the ADR and PDR increase with increasing colonoscopy volume throughout fellowship. Our findings support recent recommendations of ≥ 275 colonoscopies for colonoscopy credentialing.

Natural orifice translumenal endoscopic surgery (NOTES) had its origins in numerous small animal studies primarily examining safety and feasibility. In human trials, safety and feasibility remain at the forefront; however, additional logistic, practical, and regulatory requirements must be addressed. The purpose of this paper is to evaluate and summarize published studies to date of NOTES in humans. The literature review was performed using PUBMED and MEDLINE databases. Articles published in human populations between 2007 and 2011 were evaluated. A review of this time period resulted in 48 studies describing procedures in 916 patients. Transcolonic and transvesicular procedures were excluded. The most common procedure was cholecystectomy (682, 75%). The most common approach was transvaginal (721, 79%). 424 procedures (46%) were pure NOTES and 491 (54%) were hybrid NOTES cases. 127 (14%) were performed in the United States of America and 789 (86%) were performed internationally. Since 2007, there has been major development in NOTES in human populations. A preponderance of published NOTES procedures were performed internationally. With further development, NOTES may make less invasive surgery available to a larger human population.

AIM: To investigate whether adenoma and polyp detection rates (ADR and PDR, respectively) in screening colonoscopies performed in the presence of fellows differ from those performed by attending physicians alone. METHODS: We performed a retrospective review of all patients who underwent a screening colonoscopy at Grady Memorial Hospital between July 1, 2009 and June 30, 2015. Patients with a history of colon polyps or cancer and those with poor colon preparation or failed cecal intubation were excluded from the analysis. Associations of fellowship training level with the ADR and PDR relative to attendings alone were assessed using unconditional multivariable logistic regression. Models were adjusted for sex, age, race, and colon preparation quality. RESULTS: A total of 7503 colonoscopies met the inclusion criteria and were included in the analysis. The mean age of the study patients was 58.2 years; 63.1% were women and 88.2% were African American. The ADR was higher in the fellow participation group overall compared to that in the attending group: 34.5% vs 30.7% (P = 0.001), and for third year fellows it was 35.4% vs 30.7% (aOR = 1.23, 95%CI: 1.09-1.39). The higher ADR in the fellow participation group was evident for both the right and left side of the colon. For the PDR the corresponding figures were 44.5% vs 40.1% (P = 0.0003) and 45.7% vs 40.1% (aOR = 1.25, 95%CI: 1.12-1.41). The ADR and PDR increased with increasing fellow training level (P for trend < 0.05). CONCLUSION: There is a stepwise increase in ADR and PDR across the years of gastroenterology training. Fellow participation is associated with higher adenoma and polyp detection.