Continuing Medical Education Questions: December 2022.

Article Title: Early Liver Transplantation for Severe Alcohol-Associated Hepatitis and a History of Prior Liver Decompensation.

Small Intestinal Bacterial Overgrowth-Pathophysiology and Its Implications for Definition and Management.

The concept of small intestinal bacterial overgrowth (SIBO) arose in the context of maldigestion and malabsorption among patients with obvious risk factors that permitted the small bowel to be colonized by potentially injurious colonic microbiota. Such colonization resulted in clinical signs, symptoms, and laboratory abnormalities that were explicable within a coherent pathophysiological framework. Coincident with advances in medical science, diagnostic testing evolved from small bowel culture to breath tests and on to next-generation, culture-independent microbial analytics. The advent and ready availability of breath tests generated a dramatic expansion in both the rate of diagnosis of SIBO and the range of associated gastrointestinal and nongastrointestinal clinical scenarios. However, issues with the specificity of these same breath tests have clouded their interpretation and aroused some skepticism regarding the role of SIBO in this expanded clinical repertoire. Furthermore, the pathophysiological plausibility that underpins SIBO as a cause of maldigestion/malabsorption is lacking in regard to its purported role in irritable bowel syndrome, for example. One hopes that the application of an ever-expanding armamentarium of modern molecular microbiology to the human small intestinal microbiome in both health and disease will ultimately resolve this impasse and provide an objective basis for the diagnosis of SIBO.

Analysis of Speaker Introduction Formality by Gender at the American College of Gastroenterology 2020 Annual Scientific Meeting.

BACKGROUND: Gender-based differences in the use of professional titles during speaker introductions have been described in other medical specialties. AIMS: Our primary aim was to assess gender-based differences in the formality of speaker introductions at the American College of Gastroenterology 2020 Virtual Annual Scientific Meeting. Our secondary aim was to assess gender-based differences in the formality of speaker self-introductions. METHODS: Reviewed presentations from the American College of Gastroenterology Annual Meeting for gender-based differences in professional title use during speaker introductions and self-introductions. RESULTS: Speakers included 29 women (37.2%) and 49 men (62.8%). We found no significant gender differences in the use of professional titles by introducers (t(67) = - 0.775, p = 0.441) or in self-introductions (36.4% of women vs. 41.9% of men, t(63) = 0.422, p = 0.674). CONCLUSION: The lack of gender differences in professional title use may represent a novel advantage of virtual meeting formats or suggest increased attention to gender bias in introductions.

Small Intestinal Bacterial Overgrowth.

The term "small intestinal bacterial overgrowth" (SIBO) has been used to refer to a disorder resulting from the colonization of the small bowel by an increased number of microorganisms or by the presence of bacteria that are not usual constituents of this part of the gastrointestinal tract. Clinical presentations, often in patients with certain risk factors, can range from a full-blown malabsorption syndrome to such "functional" complaints as bloating and flatulence. SIBO is diagnosed by either culture of a small bowel aspirate or one of several breath tests. Treatment of SIBO entails risk factor modification, correction of nutritional deficiencies, and oral antibiotics.

Continuing Medical Education Questions: March 2021: Irritable Bowel Syndrome in.

Article Title: Irritable Bowel Syndrome in Pregnancy.

Continuing Medical Education Questions: December 2021.

Article Title: Diagnostic Evaluation of Gastric Motor and Sensory Disorders.

Sex Differences in Authorship of Major Gastroenterology Society Guidelines and Technical Reviews.

OBJECTIVES: To analyze the proportion of gastroenterology society guidelines and technical reviews with female authors. METHODS: Retrospective study of the sex of authors of American Association for the Study of Liver Disease (AASLD), American College of Gastroenterology (ACG) and American Gastroenterological Association (AGA) guidelines and technical reviews. RESULTS: Between 2007 and 2019, 21% of authors of AASLD, ACG and AGA guidelines, and technical reviews were female. Eighteen percent of first authors were female. There was a statistically significant increase in female authorship over the past 10 years only for AASLD guidelines. CONCLUSIONS: There were fewer female authors of AASLD, ACG and AGA guidelines, and technical reviews than males. This disparity decreased over time only in AASLD guidelines. Addressing disparities in guideline and technical review authorship may promote academic advancement for female gastroenterologists.

A Review of the Management of Sporadic Colorectal Adenomas in Young People: Is Surveillance Wasted on the Young?

The national incidence of colorectal cancer is increasing in people younger than 50 years old. Although diagnostic colonoscopy is detecting more sporadic adenomas in young adults, there are no guidelines for post-polypectomy surveillance. The aim of this review was to survey the medical literature on the prevalence of sporadic adenomas in young adults, subsequent risk of metachronous neoplasia, and lastly to provide several concluding recommendations for clinical practice. We found that the prevalence of sporadic adenomas in young adults is greater than initially estimated and dependent upon factors such as colonoscopy indication and age. The incidence of metachronous colorectal neoplasia following polypectomy is unclear but does not appear to be greater than that of older adults. Risk factors for metachronous neoplasia include findings on index colonoscopy, male gender, smoking status, and certain medical comorbidities. Upon finding a colorectal adenoma in a young person, we suggest that a detailed family history be obtained to confirm that it is truly sporadic. Testing adenomas for evidence of Lynch syndrome is low yield. Strategies to inform surveillance intervals may include an assessment of risk factors for metachronous neoplasia, although surveillance intervals shorter than those recommended in current guidelines are not warranted. Future research should focus on obtaining long-term, prospective data on the incidence of metachronous neoplasia in diverse patient populations.

Use of Hepatitis C-Positive Donor Livers in Liver Transplantation.

PURPOSE OF REVIEW: The purpose of this article is to review recent literature regarding the use of Hepatitis C virus (HCV) positive donor livers in liver transplantation. Given the prevalence of HCV-positive patients on the waitlist coupled with high waitlist mortality, use of HCV-positive livers may be a means to meet patient needs. This review seeks to primarily answer the following questions: can HCV-positive livers be used safely and effectively? Are new direct acting antiviral medications safe and effective in HCV-positive liver recipients? RECENT FINDINGS: Use of HCV-positive donor livers for liver transplantation in HCV-positive recipients is increasing. These donor livers have equivalent patient and graft survival when compared to HCV-negative donor livers in HCV-positive liver transplant recipients. Recent studies suggest that use of direct acting antiviral medications in HCV-positive liver transplant recipients can be successful, although there is insufficient data for their use in recipients of HCV-positive donor livers. SUMMARY: HCV-positive donor livers may be safely and effectively used in HCV-positive liver transplant recipients. Direct acting antiviral medications appear safe and effective in HCV-positive liver transplant recipients, but data on their efficacy in HCV-positive liver transplant recipients are limited. Future research should focus on the use of HCV-positive donor livers in HCV-negative liver transplant recipients.

Pretransplant echocardiographic parameters as markers of posttransplant outcomes in liver transplant recipients.

Despite advances in liver transplantation and preoperative risk stratification, there remains significant posttransplant morbidity and mortality from cardiovascular and renal disease. There are limited and conflicting data on the role of pretransplant echocardiography to predict these outcomes. The purpose of our study was to determine if pretransplant echocardiographic parameters were associated with posttransplant survival and the development of incident cardiovascular events and chronic kidney disease (CKD). We conducted a retrospective cohort study of 397 adult liver transplant recipients at the University of Pennsylvania from January 1, 2005 to September 30, 2014. Patients with acute liver failure, those without a diagnosis of cirrhosis (eg, polycystic liver disease without portal hypertension), retransplants, and multiorgan transplants were excluded. In multivariable Cox regression models, tricuspid regurgitation graded greater than mild was associated with significantly increased posttransplant mortality (hazard ratio, 1.68; 95% confidence interval [CI], 1.03-2.75; P = 0.04). In multivariable competing risk models, increasing pulmonary artery systolic pressure (PASP) was associated with significantly increased risk of hospitalization for myocardial infarction or heart failure (subhazard ratio per 5 mm Hg increase in PASP, 1.79; 95% CI, 1.48-2.17; P < 0.001). In multivariable competing risk models, increased left ventricular ejection fraction (LVEF) was associated with a numerical but nonsignificant increased risk of stage 4 or 5 CKD (subhazard ratio, 1.11 per 5% increase in LVEF; 95% CI, 0.99-1.24; P = 0.07). In a post hoc analysis, LVEF ≥ 65% was the best cutoff for increased risk of CKD (subhazard ratio, 1.75; 95% CI, 1.06-2.89; P = 0.03). In conclusion, several pretransplant echocardiographic parameters were associated with posttransplant morbidity and mortality, suggesting that pretransplant echocardiography may be used as a tool to risk-stratify patients for posttransplant outcomes.

The impact of laparoscopic anti-reflux surgery in patients with Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE) is a major risk factor for esophageal adenocarcinoma. It is believed that BE is caused by chronic gastro-esophageal reflux disease (GERD). Laparoscopic anti-reflux surgery (LARS) restores the competency of the cardia and may thereby change the natural course of BE. We studied the impact of LARS on the histological profile of BE and on the control of GERD. METHODS: We identified all patients with BE who underwent LARS from 1994 to 2007 and contacted them to assess post-operative GERD symptoms via questionnaire. Endoscopy findings, histology, 24 hour pH monitoring, and manometry were also collected using our prospectively maintained database. Histological regression was defined as either loss of dysplasia or disappearance of BE. RESULTS: Two hundred and fifteen patients met the initial inclusion criteria; in 82 of them histology from post-operative endoscopy was available for review. Endoscopy was performed a median of 8 years (range, 1-16 years) after surgery. Regression of BE occurred in 18 (22%) patients while in 6 (7%) BE progressed to dysplasia or cancer. Thirty-six (43%) patients underwent pre- and post-operative manometry. The median lower esophageal sphincter pressure increased from 9 to 17 mmHg in these patients. Thirty-four (41%) patients underwent pre- and post-operative pH studies. The median DeMeester score decreased from 54 to 9. Sixty-seven (82%) of 82 patients completed the post-operative questionnaire; 86% of these patients reported improvement in heartburn and regurgitation. CONCLUSIONS: LARS was associated with both physiologic and symptomatic control of GERD in patients with BE. LARS resulted in regression of BE in 22% of patients and progression in 7%. Thus, continued surveillance of Barrett's is needed after LARS.

Colchicine-induced degeneration of the micronucleus during conjugation in Tetrahymena.

One of the most dramatic examples of nuclear morphogenesis occurs during conjugation in Tetrahymena when the micronucleus elongates to a size longer than the cell itself. After contraction to a spherical shape, the nucleus moves directly to chromosome separation in the first meiotic division. Here we investigate the consequences of interrupting the elongation process. Colchicine, a microtubule inhibitor, caused retraction of elongated structures. With time, cells began to lose their micronuclei, and by five hours more than half of the paired cells had at least one cell missing a micronucleus. After reversing the colchicine block, existing micronuclei did not undergo elongation again, nor did meiosis occur. These observations indicate that micronuclear elongation is critical to subsequent meiotic division. Further, nuclear elimination occurs, which could be due to meiotic failure or possibly a problem downstream from meiosis. An analysis of the process of colchicine-induced micronuclear degeneration indicated that it was regulated by a caspase-dependent mechanism, characteristic of apoptosis, and then resorbed by a lysosome-dependent autophagic mechanism. Amicronucleate cells failed to grow when returned to nutrient medium, likely because of a lesion in the post-conjugation reconstruction of a functioning oral apparatus. The ease by which a large number of nuclei are induced to "self-destruct" may make this system useful in investigating the link between colchicine treatment and nuclear death in Tetrahymena, and in investigating how nuclear death could be regulated in living cells more generally. Finally, we note that this phenomenon might relate to the evolution of amicronucleate species of Tetrahymena.