Obesity, organ failure, and transplantation: a review of the role of metabolic and bariatric surgery in transplant candidates and recipients.

Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.

Obesity, organ failure, and transplantation: A review of the role of metabolic and bariatric surgery in transplant candidates and recipients.

Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.

The SAGES MASTERS program bariatric surgery pathway selects 10 seminal publications on adjustable gastric banding.

BACKGROUND: Bariatric surgery is one of the clinical pathways of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program, and laparoscopic adjustable gastric banding (LAGB) is one of the three anchoring bariatric procedures. To improve surgeon lifelong learning, the Masters Program seeks to identify sentinel articles of each of the 3 bariatric anchoring procedures. In this article, we present the top 10 articles on LAGB. METHODS: A systematic literature search of papers on LAGB was completed, and publications with the most citations and citation index were selected and shared with SAGES Metabolic and Bariatric Surgery Committee members for review. The individual committee members then ranked these papers, and the top 10 papers were chosen based on the composite ranking. RESULTS: The top 10 sentinel publications on LAGB contributed substantially to the body of literature related to the procedure, whether for surgical technique, novel information, or outcome analysis. A summary of each paper including expert appraisal and commentary is presented here. CONCLUSION: These seminal articles have had significant contribution to our understanding and appreciation of the LAGB procedure. Bariatric surgeons should use this resource to enhance their continual education and acquisition of specialized skills.

Genetics of vegetarianism: A genome-wide association study.

A substantial body of evidence points to the heritability of dietary preferences. While vegetarianism has been practiced for millennia in various societies, its practitioners remain a small minority of people worldwide, and the role of genetics in choosing a vegetarian diet is not well understood. Dietary choices involve an interplay between the physiologic effects of dietary items, their metabolism, and taste perception, all of which are strongly influenced by genetics. In this study, we used a genome-wide association study (GWAS) to identify loci associated with strict vegetarianism in UK Biobank participants. Comparing 5,324 strict vegetarians to 329,455 controls, we identified one SNP on chromosome 18 that is associated with vegetarianism at the genome-wide significant level (rs72884519, ß = -0.11, P = 4.997 x 10-8), and an additional 201 suggestively significant variants. Four genes are associated with rs72884519: TMEM241, RIOK3, NPC1, and RMC1. Using the Functional Mapping and Annotation (FUMA) platform and the Multi-marker Analysis of GenoMic Annotation (MAGMA) tool, we identified 34 genes with a possible role in vegetarianism, 3 of which are GWAS-significant based on gene-level analysis: RIOK3, RMC1, and NPC1. Several of the genes associated with vegetarianism, including TMEM241, NPC1, and RMC1, have important functions in lipid metabolism and brain function, raising the possibility that differences in lipid metabolism and their effects on the brain may underlie the ability to subsist on a vegetarian diet. These results support a role for genetics in choosing a vegetarian diet and open the door to future studies aimed at further elucidating the physiologic pathways involved in vegetarianism.

Comparing the Efficacy and Safety of Obeticholic Acid and Semaglutide in Patients With Non-Alcoholic Fatty Liver Disease: A Systematic Review.

Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of developing progressive fibrosis, cirrhosis, and hepatocellular carcinoma. As of now, there are no FDA-approved treatments for NAFLD/non-alcoholic steatohepatitis (NASH) or its associated fibrosis. Although many drugs are under clinical trial, both obeticholic acid (OCA) and semaglutide are among the few that have reached phase III clinical trials, but they were never compared. We decided to conduct a systematic review of randomized controlled trials and meta-analyses. A total of 6,589 articles were found after searching PubMed, OVID Embase, OVID Medline, PubMed Central, and clinicaltrials.gov. Only full-text peer-reviewed articles published in the past six years were put through the Cochrane bias assessment tool or the Assessment of Multiple Systematic Reviews (AMSTAR) tool to screen for bias. After strict quality assessment, data from five randomized controlled trials (n=2,694) and three systematic reviews/meta-analysis (n=8,898) was extracted and included. The data extraction from these studies showed that semaglutide and OCA cause histological improvement, but NASH resolution is exclusive to semaglutide. Although high doses of OCA can cause dyslipidemia and severe pruritus, it is the only therapeutic that causes improvement in NASH-associated hepatic fibrosis. Semaglutide is the safest option among the two and leads to significant weight loss compared to OCA; thus, a better outcome on hepatic steatosis follows. The indications of each of these drugs should be based on the NAFLD activity score and NASH fibrosis stage. OCA should be used with caution among patients with hyperlipidemia and ischemic heart disease as it may make these conditions worst.

A Better Understanding of Moyamoya in Trisomy 21: A Systematic Review.

Moyamoya disease is defined as stenosis of the internal carotid artery or the middle, anterior or posterior cerebral arteries with considerable collateral development. This collateral vessel has a particular appearance in angiographic examinations. Moyamoya syndrome is a term used to describe when moyamoya disease occurs in conjunction with other systemic disorders. One of the associations is Down syndrome. Moyamoya syndrome is very common in patients with Down syndrome, and the cause for this is unknown. The majority of patients present in their first decade, with the clinical presentation varying with age. The cause of moyamoya syndrome in people with trisomy 21 is unknown. This research aimed to learn more about the genesis and pathology of moyamoya syndrome in people with Down syndrome. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct this systematic review. Several publications connected to this topic were searched through a comprehensive database search. They were narrowed down to a final number of ten articles after applying inclusion and exclusion criteria and analyzing the quality of each work. Several possibilities were presented in these final papers to explain the link between moyamoya syndrome and trisomy 21. Trisomy 21 patients have a genetic predisposition to vascular problems. The RNF213 gene may interact with the genes on chromosome 21 that influence vascular physiology and elasticity in patients with Down syndrome, resulting in the whole picture of moyamoya syndrome.

Accuracy of Point-of-Care-Ultrasonography in Confirming Shoulder Reduction in Emergency Departments.

Aims Accurate identification of the successful reduction of a dislocated shoulder could avoid additional episodes of procedural sedation and repeated performance of X-rays. The objective of this study was to assess the diagnostic accuracy of point-of-care-ultrasound (POCUS) in the confirmation of a successful joint reduction in patients with shoulder dislocation. Methods This was a single-centre, prospective observational study set in an urban academic ED in Ireland, with a convenience sample of adult patients with shoulder dislocation on X-ray. Ultrasound was performed on participants before and after joint reduction using a posterior approach technique. The operator's confidence levels were recorded after image acquisition. Results Thirty-three subjects were recruited. All dislocations were correctly identified on pre-reduction US, indicating a sensitivity of 100% (CI 89.42 - 100). Post-reduction US confirmed successful reduction in 30 subjects that were subsequently reported as such on X-Ray, giving it a specificity of 100% (CI 88.43 - 100). Failure to achieve reduction was correctly identified on US in three cases, resulting in post-reduction US Sensitivity of 100% (CI 29.24 - 100) and 100% accuracy (CI 89.42 - 100). Conclusion This study has shown that POCUS, with a posterior approach technique, has 100% sensitivity and specificity in confirming successful shoulder reduction in the ED.

Distinctive Flow Cytometric and Mutational Profile of Acute Myeloid Leukemia With t(8;16)(p11;p13) Translocation.

OBJECTIVES: Acute myeloid leukemia (AML) with t(8;16)(p11;p13) abnormalities is a rare, aggressive, and diagnostically challenging subtype that results in KAT6A-CREBBP gene fusion. METHODS: To investigate their immunophenotype and genomic features, we identified 5 cases of AML with t(8;16) through a retrospective review of the databases at Northwestern Memorial Hospital in Chicago, IL, and Washington University Medical Center, in St Louis, MO. RESULTS: In all, 4 of 5 cases were therapy related and 1 was possibly therapy related. The leukemic blasts showed distinctive features, including bright CD45 expression and remarkably high side scatter that overlapped with maturing myeloid elements, making the blasts difficult to identify on initial examination. They were positive for CD13, CD33, and CD64 and negative for CD34 and CD117. Next-generation sequencing profiling of 4 cases revealed pathogenic ASXL1 (2 cases), FLT3-tyrosine kinase domain (TKD) mutations (2 cases), and other pathogenic mutations. In 3 patients, t(8;16) was the sole cytogenetic abnormality; additional aberrations were found in 2 patients. Single nucleotide polymorphism microarray revealed 1 case with 7q deletion as a secondary clone. CONCLUSIONS: Our data highlight the distinctive immunophenotypic profile of AML with t(8;16), which, along with its unique morphology, often presents a diagnostic challenge. We showed that mutations of either ASXL1 or FLT3-TKD are seen in most cases of this leukemia.

Newly diagnosed enhancing lesions: Steroid initiation may impede diagnosis of lymphoma involving the central nervous system.

Establishing the pathologic diagnosis of central nervous system (CNS) lymphoma can be challenging, yet management of this potentially curable disease depends heavily on it. One avoidable impediment to obtaining an accurate and timely diagnosis is the pre-operative administration of steroids, which causes tumor involution and prevents appropriate sampling of viable tissue. We discuss a case of primary CNS lymphoma that highlights the evolution of the disease and the attempts to establish a diagnosis in the setting of prior administration of corticosteroids. Familiarity with these clinical scenarios will help others avoid delays in patient care that results from delayed diagnosis.

Comprehensive molecular genetic studies of Epstein-Barr virus-negative aggressive Natural killer-cell leukemia/lymphoma.

EBV-negative aggressive NK-cell leukemia/lymphoma (ANKL) is a recently recognized, rare NK-cell neoplasm that preferentially affects non-Asians and has a fulminant clinical course. Little is known about the genetic alterations of this disease. In this study, we performed comprehensive molecular genetic studies, including chromosomal analysis, fluorescence in situ hybridization, single nucleotide polymorphism (SNP) microarray, and next-generation sequencing (NGS), on 4 patients diagnosed in our institution. The results demonstrated that our EBV-negative ANKLs have highly complex genomic profiles characterized by near-triploid/near-tetraploid karyotype (3 of 3) with numerous structural abnormalities, inactivation of TP53 (3 of 3), overexpression of c-Myc (4 of 4), strong expression of PD-L1 in neoplastic cells (2 of 4), and gain of the 11q23-ter region (2 of 2). Our study provides important insights of EBV-negative ANKL, which share many of the genetic features with their EBV-positive counterpart. The strong expression of Programmed death-ligand 1 (PD-L1) suggests that immune checkpoint inhibitors may be further explored as a potential therapeutic option for this highly aggressive, chemotherapy-resistant NK-cell neoplasm.

Incidence of GERD, esophagitis, Barrett's esophagus, and esophageal adenocarcinoma after bariatric surgery.

BACKGROUND: Some bariatric procedures have been associated with increased gastroesophageal reflux disease (GERD) symptoms; however, there are limited data on the long-term changes to the esophagus across bariatric procedures, and how preoperative esophageal disease is impacted by bariatric surgery. OBJECTIVES: To estimate incidence of GERD, esophagitis, Barrett's esophagus, and esophageal adenocarcinoma before and after bariatric surgery and to identify potential risk factors for these conditions. SETTING: Retrospective analysis of New York State Database (SPARCS). METHODS: Adult patients undergoing bariatric surgery (Roux-en-Y gastric bypass, adjustable gastric banding, laparoscopic sleeve gastrectomy, and biliopancreatic diversion) from 1995 to 2010. Multivariable Cox proportional hazard models were used to examine the association between preoperative diagnosis, surgery type, and postoperative diagnosis. RESULTS: A total of 48,967 records were analyzed; 30.3% had a diagnosis of GERD at the time of surgery and .4% had a diagnosis of esophagitis and Barrett's. Preoperative GERD/esophagitis/Barrett's was associated with higher risk of GERD, esophagitis, and Barrett's, but not esophageal adenocarcinoma, postoperatively. Roux-en-Y gastric bypass patients had lowest risk of being diagnosed with GERD postoperatively. Overall, esophageal adenocarcinoma incidence in the sample was .04%; the rate among patients with preoperative GERD and Barrett's was .1% and .9%, respectively. Incidence of esophageal adenocarcinoma did not differ by bariatric surgery type. CONCLUSIONS: Preoperative diagnosis is a risk factor for postoperative esophageal disease after bariatric surgery. Adjustable gastric banding and laparoscopic sleeve gastrectomy are associated with higher risk of postoperative GERD and esophagitis compared with Roux-en-Y gastric bypass. Incidence of esophageal adenocarcinoma did not differ by surgery type.

Surgeon variation in severity of reflux symptoms after sleeve gastrectomy.

BACKGROUND: Prior studies have demonstrated an increase in gastroesophageal reflux after laparoscopic sleeve gastrectomy (LSG). However, it is unknown whether symptom severity varies or if outcomes are surgeon-specific. METHODS: A validated reflux symptom survey was obtained at baseline and at 1 year after primary LSG on 7358 patients participating in a state-wide quality improvement collaborative between 2013 and 2018. Patients with worsening symptoms after surgery were divided into terciles based on the degree of increase in survey score (0 = no symptoms, 50 = max symptoms). Surgeon-level data was obtained on 52 bariatric surgeons performing at least 25 LSG cases/year during the study period. Surgeon characteristics, operative experience, and risk-adjusted 30-day complication rates were compared between surgeons in the highest tercile for moderate worsening of symptoms vs those in the lowest. RESULTS: A total of 2294 (31.2%) patients had worsening symptoms of reflux after sleeve gastrectomy. Overall mean increase in severity score was 6.11 (range 1 to 48) and patients with minimal, mild, and moderate symptoms had a mean increase of 1.4, 4.2, and 13.8, respectively. There were no significant differences in surgeon-specific characteristics when comparing surgeons in the highest tercile for moderate worsening of symptoms (44.7% of patients) vs those in the lowest tercile (18.7% of patients). In addition, there were no significant differences in risk-adjusted rates of overall complications (3.70% vs. 4.33%, p = 0.686), endoscopic dilations (2.83% vs. 1.91%, p = 0.417), or concurrent hiatal hernia repair (34.3% vs. 27.0%, p = 0.415) between surgeons in the highest and lowest terciles. CONCLUSIONS: We found that 1/3 of patients had worsening symptoms of reflux after LSG and that severity of symptoms varied. Surgeons with the highest rates of worsening reflux had similar operative experience and complication rates than those with the lowest. Further assessment of operative technique and skill may be informative.

Is it worth it? Determining the health benefits of sleeve gastrectomy in patients with a body mass index <35 kg/m2.

BACKGROUND: Criteria for undergoing sleeve gastrectomy (SG) is restricted among patients with a body mass index (BMI) <35 kg/m2. OBJECTIVES: To determine if low-BMI patients experience similar health benefits after SG compared with patients with a BMI ≥35 kg/m2. SETTING: Teaching and nonteaching hospitals in Michigan. METHODS: Patients with a BMI <35 kg/m2 at the time of primary SG were identified between 2006 and 2018 (n = 1073, 2.4%). Patient characteristics, 30-day risk-adjusted complication rates, and patient reported outcomes were compared with all patients who underwent SG with a BMI ≥35 kg/m2 (n = 44,511, mean BMI 46.7 kg/m2). RESULTS: Low-BMI patients were more likely to be older (50.7 versus 45.4 yr, P < .0001), have diabetes (36.7 versus 30.9%, P < .0001), hypertension (54.2% versus 51.0%, P = .0372), and hyperlipidemia (57.1% versus 44.8%, P < .0001). Both groups had comparable rates of discontinuation of medications for hypertension (59.7% versus 54.1%, P = .0570), hyperlipidemia (54.3% versus 52.2%, P = .5537), and diabetes (oral, 79.2% versus 78.1%, P = .7294; insulin, 64.2% versus 62.2%, P = .7438). However, low-BMI patients were more likely to achieve a healthy BMI (i.e., BMI ≤25 kg/m2; 36.3% versus 6.01%, P < .0001), and had higher body image scores (50.6 versus 42.4, P < .0001). CONCLUSIONS: Despite being older and with higher rates of metabolic disease, low-BMI patients reported high-resolution rates for diabetes, hypertension, and hyperlipidemia (>50%) and were more likely to achieve a healthy weight after SG. Abolishing the BMI threshold for SG among patients with metabolic disease should be considered.

The influence of gastroesophageal reflux symptoms on patient satisfaction after sleeve gastrectomy.

BACKGROUND: Sleeve gastrectomy has become the most common procedure performed for weight loss. But emerging data indicate that this procedure can result in lifestyle-limiting gastroesophageal reflux disease. The influence of these gastroesophageal reflux disease symptoms on patient satisfaction with the procedure has not been explored. METHODS: Using a statewide, bariatric-specific data registry, we studied 6,608 patients who underwent laparoscopic sleeve gastrectomy from 2013 to 2017. We used the Gastroesophageal Reflux Disease Health-Related Quality of Life questionnaire, which is 10 questions, each ranging from 0 (no symptoms) to 5 (severe symptoms). To assess the impact of sleeve gastrectomy on patient satisfaction, we calculated the change in this score at baseline versus 1 year after the procedure. We stratified the change in the gastroesophageal reflux disease score into 5 even-sized groups (quintiles). We then examined the relationship between change in the gastroesophageal reflux disease score and patient satisfaction at 1 year. We used generalized linear mixed models to assess the variation in patient satisfaction explained by the change in the gastroesophageal reflux disease score, excess body weight loss at 1 year, and other patient outcomes (serious complications, readmission, and reoperations). We controlled for patient factors (age, sex, race, and comorbidities) and year of sleeve gastrectomy. RESULTS: The average change in the gastroesophageal reflux disease score was 1.62 (range: -48 to 48); however, the change in the gastroesophageal reflux disease score varied across quintiles with a -7.3-point (range: -48 to -3) worsening in the bottom quintile versus a 2.6-point (range: 7 to 48) improvement in the top quintile. Overall, 77.7% of patients were satisfied, but the proportion of patients satisfied was highly dependent on whether their reflux symptoms improved or worsened. Only 48.9% in the bottom quintile were satisfied, compared with 78.1% in the top quintile (<.0001). In the multivariate model, changes in patient-reported gastroesophageal reflux disease score were the most predictive of patient satisfaction, explaining 10.1% of the variation in 1 year satisfaction. Among patients in the bottom quintile, reflux symptoms explained 30.2% of variation compared with 2.3% in quintiles with little change or improvement in reflux. Moreover, excess body weight loss explained only 2% of variation in satisfaction and <1% was explained by patient outcomes (serious complications, readmissions, reoperations, or surgical complications). CONCLUSION: In this statewide study of sleeve gastrectomy, we demonstrated that gastroesophageal reflux symptoms are an important determinant of 1 year satisfaction, particularly among patients whose symptoms worsened the most.

Accreditation Council for Graduate Medical Education Self-Study for Pathology: One Institution's Experience and Lessons Learned.

CONTEXT.­: The Accreditation Council for Graduate Medical Education (ACGME) established a new system for accreditation of residency and fellowship programs in 2013. One key aspect of the Next Accreditation System is the 10-year self-study, which requires programs to conduct a comprehensive self-evaluation, including development of program aims and analysis of strengths, weaknesses, and environmental context, in order to plan improvements and take the program to the next level. OBJECTIVE.­: To provide a review of the recent changes and current state of ACGME accreditation, with a focus on the new 10-year self-study, and to share our institution's experience with conducting the first self-study of our pathology residency and accredited fellowship programs in 2018. DATA SOURCES.­: Review of English-language literature, published resources from the ACGME, and materials/data from our department's 2018 self-study. CONCLUSIONS.­: The self-study process now required for ACGME accreditation is a useful way to assess program strengths and weaknesses in the context of current environmental and institutional factors, and helps develop an effective framework for improvements geared at achieving program aims and taking the program to the next level. Additionally, conducting residency and fellowship self-studies together allows for collaboration, effective use of shared resources, and the development of a cohesive educational mission.

Early postoperative diet after bariatric surgery: impact on length of stay and 30-day events.

BACKGROUND: Pathways for enhanced recovery after surgery (ERAS) have been shown to improve length-of-stay (LOS) and post-operative complications across various surgical fields, however there is a lack of evidence-based studies in bariatric surgery. Specifically, the value of early feeding within an ERAS program in bariatric surgery is unclear. The objective of the current study was to determine the effect of early feeding on LOS for patients who underwent primary or revisional laparoscopic sleeve gastrectomy (LSG) and Roux-en-y gastric bypass (RYGB). METHODS: Retrospective single institution study of implementation of a new diet protocol in which initiation of oral intake changed from post-operative day 1 to day 0. LOS and 30-day events were compared. Patients were excluded if they were planned for 23-h stay, had significant intra-operative complications, or required reoperation within the same admission. Mann-Whitney U tests were done to compare LOS and chi-squared tests to compare 30-day events pre- and post-intervention. RESULTS: A total of 244 patients were included; 84.4% were primary cases. 50.8% of cases occurred prior to early feeding implementation. Median age was 43.5 years (IQR 33-53) and majority of patients were female (78.7%). Median LOS was 32.6 (IQR 30.0-50.6). Median LOS across the whole sample was shorter in the early feeding group (36.2 vs. 31.0 h; p < 0.001). This difference remained statistically significant for primary, but not revisional cases. Post-operative events at 30 days were similar between pre- and post-intervention groups. CONCLUSIONS: Early feeding the day of surgery is associated with significantly shorter LOS for patients who undergo bariatric surgery with no difference in 30-day readmissions.