Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome.

BACKGROUND & AIMS: Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact of these compounds on the intestinal microbiota and intestinal health have been demonstrated in animal and in vitro models, impact of these food additives in healthy humans remains poorly characterized. METHODS: To examine this notion in humans, we performed a double-blind controlled-feeding study of the ubiquitous synthetic emulsifier carboxymethylcellulose (CMC) in which healthy adults consumed only emulsifier-free diets (n = 9) or an identical diet enriched with 15 g per day of CMC (n = 7) for 11 days. RESULTS: Relative to control subjects, CMC consumption modestly increased postprandial abdominal discomfort and perturbed gut microbiota composition in a way that reduced its diversity. Moreover, CMC-fed subjects exhibited changes in the fecal metabolome, particularly reductions in short-chain fatty acids and free amino acids. Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition. CONCLUSIONS: These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome (ClinicalTrials.gov, number NCT03440229).

A study analyzing outcomes after bariatric surgery by primary language.

BACKGROUND: Communication is key to success in bariatric surgery. This study aims to understand how outcomes after bariatric surgery differ between patients with a non-English primary language and those with English as their primary language. METHODS: This retrospective, observational cohort study of bariatric surgery patients age ≥ 18 years utilized the Michigan, Maryland, and New Jersey State Inpatient Databases and State Ambulatory Surgery and Services Databases, 2016 to 2018. Patients were classified by primary spoken language: English and non-English. Primary outcome was complications. Secondary outcomes included length of stay (LOS) and cost, with cost calculated using cost-to-charge ratios provided by Healthcare Cost and Utilization Project and reported in 2019 United States dollars. Multivariable regression models (logistic, Poisson, and quantile) were used to examine associations between primary language and outcomes. Given the uneven distribution of race by primary language, interaction terms were used to examine conditional effects of race. RESULTS: Among 69,749 bariatric surgery patients, 2811 (4.2%) spoke a non-English primary language. Covariates, notably race distribution, and unadjusted outcomes differed significantly by primary language. However, after adjustment, non-English primary language was not associated with significantly increased odds of complications (odds ratio 1.24, p = 0.389), significantly different LOS (- 0.02 days, p = 0.677), nor significantly different mean healthcare costs (- $265, p = 0.309). There were no significant conditional effects of race seen among outcomes. CONCLUSIONS: Though non-English primary language was associated with a significantly different distribution of observable characteristics (including race, income quartile, and insurance type), after adjustment, non-English primary language was not associated with significant differential risk of adverse outcomes after bariatric surgery, and there were no significant conditional effects of race. As such, this study suggests that disparities in bariatric surgery by primary spoken language more likely related to access to care, or the pre- and post-hospital care continuum, rather than index hospitalization after surgery.

Global Microbiota-Dependent Histone Acetylation Patterns Are Irreversible and Independent of Short Chain Fatty Acids.

BACKGROUND AND AIMS: Although germ-free mice are an indispensable tool in studying the gut microbiome and its effects on host physiology, they are phenotypically different than their conventional counterparts. While antibiotic-mediated microbiota depletion in conventional mice leads to physiologic alterations that often mimic the germ-free state, the degree to which the effects of microbial colonization on the host are reversible is unclear. The gut microbiota produce abundant short chain fatty acids (SCFAs), and previous studies have demonstrated a link between microbial-derived SCFAs and global hepatic histone acetylation in germ-free mice. APPROACH AND RESULTS: We demonstrate that global hepatic histone acetylation states measured by mass spectrometry remained largely unchanged despite loss of luminal and portal vein SCFAs after antibiotic-mediated microbiota depletion. In contrast to stable hepatic histone acetylation states, we see robust hepatic transcriptomic alterations after microbiota depletion. Additionally, neither dietary supplementation with supraphysiologic levels of SCFA nor the induction of hepatocyte proliferation in the absence of microbiota-derived SCFAs led to alterations in global hepatic histone acetylation. CONCLUSIONS: These results suggest that microbiota-dependent landscaping of the hepatic epigenome through global histone acetylation is static in nature, while the hepatic transcriptome is responsive to alterations in the gut microbiota.

Clinical presentation and surgical outcomes in primary aldosteronism differ by race.

BACKGROUND: Primary aldosteronism (PA) is the most common cause of secondary hypertension; early diagnosis and intervention correlate with outcomes. We hypothesized that race may influence clinical presentation and outcomes. METHODS: We conducted a retrospective analysis of patients with PA (1997-2017) who underwent adrenal vein sampling (AVS). Patients were classified by self-reported race as black or non-black. Improvement was defined as postoperative decrease in mean arterial pressure (MAP), antihypertensive medications (AHM), or both. RESULTS: Among patients undergoing AVS (n = 443), 287 underwent adrenalectomy. Black patients (28.2%) had higher body mass index (33.9 vs 31.8 kg/m2 ; P = .01), longer median duration of hypertension (12 vs 10 years; P = .003), higher modified Elixhauser comorbidity index (2 vs 1; P = .004), and lower median income ($47 134 vs $78 280; P < .001). Black patients had similar aldosterone:renin ratios (150 vs 135.6 [ng/dL]/[ng·mL·-1 hr-1 ]; P = .23) compared to non-blacks. At long-term follow-up, black patients had a similar requirement for AHM (1 vs 0; P = .13) but higher MAP (100.6 vs 95.3 mm Hg; P = .004). CONCLUSION: Black patients present with longer duration of hypertension and more comorbidities. They are equally likely to lateralize on AVS, suggesting similar disease phenotype. However, black patients demonstrate less improvement with adrenalectomy; this may reflect a delay in diagnosis or concomitant essential hypertension.

The Microbiome-Host Interaction as a Potential Driver of Anastomotic Leak.

PURPOSE OF REVIEW: The goal of this paper is to review current literature on the gut microbiome within the context of host response to surgery and subsequent risk of developing complications, particularly anastomotic leak. We provide background on the relationship between host and gut microbiota with description of the role of the intestinal mucus layer as an important regulator of host health. RECENT FINDINGS: Despite improvements in surgical technique and adherence to the tenets of creating a tension-free anastomosis with adequate blood flow, the surgical community has been unable to decrease rates of anastomotic leak using the current paradigm. Rather than adhere to empirical strategies of decontamination, it is imperative to focus on the interaction between the human host and the gut microbiota that live within us. The gut microbiome has been found to play a potential role in development of post-operative complications, including but not limited to anastomotic leak. Evidence suggests that peri-operative interventions may have a role in instigating or mitigating the impact of the gut microbiota via disruption of the protective mucus layer, use of multiple medications, and activation of virulence factors. The microbiome plays a potential role in the development of surgical complications and can be modulated by peri-operative interventions. As such, further research into this relationship is urgently needed.

Breast cancer subtype distribution is different in normal weight, overweight, and obese women.

PURPOSE: Obesity is associated with tumor promoting pathways related to insulin resistance and chronic low-grade inflammation which have been linked to various disease states, including cancer. Many studies have focused on the relationship between obesity and increased estrogen production, which contributes to the pathogenesis of estrogen receptor-positive breast cancers. The link between obesity and other breast cancer subtypes, such as triple-negative breast cancer (TNBC) and Her2/neu+ (Her2+) breast cancer, is less clear. We hypothesize that obesity may be associated with the pathogenesis of specific breast cancer subtypes resulting in a different subtype distribution than normal weight women. METHODS: A single-institution, retrospective analysis of tumor characteristics of 848 patients diagnosed with primary operable breast cancer between 2000 and 2013 was performed to evaluate the association between BMI and clinical outcome. Patients were grouped based on their BMI at time of diagnosis stratified into three subgroups: normal weight (BMI = 18-24.9), overweight (BMI = 25-29.9), and obese (BMI > 30). The distribution of breast cancer subtypes across the three BMI subgroups was compared. RESULTS: Obese and overweight women were more likely to present with TNBC and normal weight women with Her2+ breast cancer (p = 0.008). CONCLUSIONS: We demonstrated, for the first time, that breast cancer subtype distribution varied significantly according to BMI status. Our results suggested that obesity might activate molecular pathways other than the well-known obesity/estrogen circuit in the pathogenesis of breast cancer. Future studies are needed to understand the molecular mechanisms that drive the variation in subtype distribution across BMI subgroups.

Observational cohort investigating health outcomes and healthcare costs after metabolic and bariatric surgery: a study protocol.

INTRODUCTION: As the rate of obesity increases, so does the incidence of obesity-related comorbidities. Metabolic and bariatric surgery (MBS) is the most effective treatment for obesity, yet this treatment is severely underused. MBS can improve, resolve, and prevent the development of obesity-related comorbidities; this improvement in health also results in lower healthcare costs. The studies that have examined these outcomes are often limited by small sample sizes, reliance on outdated data, inconsistent definitions of outcomes, and the use of simulated data. Using recent real-world data, we will identify characteristics of individuals who qualify for MBS but have not had MBS and address the gaps in knowledge around the impact of MBS on health outcomes and healthcare costs. METHODS AND ANALYSIS: Using a large US employer-based retrospective claims database (Merative), we will identify all obese adults (21+) who have had a primary MBS from 2016 to 2021 and compare their characteristics and outcomes with obese adults who did not have an MBS from 2016 to 2021. Baseline demographics, health outcomes, and costs will be examined in the year before the index date, remission and new-onset comorbidities, and healthcare costs will be examined at 1 and 3 years after the index date. ETHICS AND DISSEMINATION: As this was an observational study of deidentified patients in the Merative database, Institutional Review Board approval and consent were exempt (in accordance with the Health Insurance Portability and Accountability Act Privacy Rule). An IRB exemption was approved by the wcg IRB (#13931684). Knowledge dissemination will include presenting results at national and international conferences, sharing findings with specialty societies, and publishing results in peer-reviewed journals. All data management and analytic code will be made available publicly to enable others to leverage our methods to verify and extend our findings.

Equity in bariatric surgery use: a cohort study.

BACKGROUND: Metabolic and bariatric surgery (MBS) is the most effective and durable treatment for obesity; however, access to MBS is not equitable. OBJECTIVE: To determine the rate of MBS among eligible adults with obesity by demographics, health characteristics, and geography to better define populations that would benefit from resources to reduce barriers to access for this treatment. SETTING: Adults with obesity were identified in the US employer-based retrospective claims database (Merative™). METHODS: Rates of MBS were examined across demographics (age, sex, region, year, health plan type) health characteristics (obesity-related comorbidities, healthcare costs, inpatient admissions), and by state. Given differences in coverage requirements, rates are examined for 2 populations: Class 2 (BMI 35-39.9 kg/m2) and Class 3 (BMI 40+ kg/m2) obesity. RESULTS: Of the 777,565 eligible adults, 49,371 (6.4%) had MBS; 3.2% of those with Class 2 and 8.3% of those with Class 3 obesity had MBS. MBS rates varied substantially by demographic and health characteristics, ranging from 1% to 14%, and from 2% to 41% among those with Class 2 and Class 3 obesity, respectively. Geographically, rates ranged from 0% (Hawaii) to 7.4% (New Mexico) for those with Class 2 Obesity and from 4.2% (Hawaii) to 15.3% (Mississippi) among those with Class 3 Obesity. CONCLUSIONS: Use of MBS among eligible adults with obesity varies substantially across characteristics, indicating inequity in access to this treatment. To ensure greater access to the most effective treatment for obesity, policies should be implemented to reduce or eliminate barriers to care.

Preoperative Exclusive Enteral Nutrition Is Associated With Reduced Skin and Soft Tissue and Intra-abdominal Infections in Patients With Crohn's Disease Undergoing Intestinal Surgery: Results from a Meta-Analysis.

BACKGROUND: Malnutrition is an independent risk factor for adverse postoperative outcomes and is common among patients with Crohn's disease (CD). The objective of this meta-analysis was to precisely quantify the association of preoperative exclusive enteral nutrition (EEN) and total parenteral nutrition (TPN) with surgical outcomes in patients undergoing intestinal surgery for CD. METHODS: PubMed, Embase, and Scopus were queried for comparative studies evaluating the impact of preoperative nutritional support on postoperative outcomes in patients undergoing surgery for CD. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2. RESULTS: Fourteen studies, all nonrandomized cohort studies, met inclusion criteria for studying EEN. After pooling data from 14 studies (874 EEN treated and 1044 control patients), the relative risk of intra-abdominal septic complications was decreased 2.1-fold in patients receiving preoperative EEN (relative risk 0.47, 95% confidence interval [CI], 0.35-0.63, I2 = 0.0%). After pooling data from 9 studies (638 EEN treated and 819 control patients), the risk of skin and soft tissue infection was decreased 1.6-fold (relative risk 0.63; 95% CI, 0.42-0.94, I2 = 42.7%). No significant differences were identified in duration of surgery, length of bowel resected, or operative blood loss. Among the 9 studies investigating TPN, no significant differences were identified in infectious outcomes. CONCLUSIONS: Preoperative nutritional optimization with EEN was associated with reduced risk of infectious complications in CD patients undergoing intestinal surgery. Preoperative nutritional support with EEN should be considered for optimizing outcomes in CD patients requiring bowel resection surgery.

Pooled data from this meta-analysis demonstrated significantly decreased rates of skin/soft tissue and intra-abdominal infections following intestinal surgery for Crohn's disease after preoperative treatment with exclusive enteral nutrition.

Trends in bariatric surgery training: bariatric operations performed by Fellowship Council trainees from 2012 to 2019.

BACKGROUND: The American Society for Metabolic and Bariatric Surgery (ASMBS) Fellowship Certificate was created to ensure satisfactory training and requires a minimum number of anastomotic cases. With laparoscopic sleeve gastrectomy becoming the most common bariatric procedure in the United States, this may present a challenge for fellows to obtain adequate numbers for ASMBS certification. OBJECTIVES: To investigate bariatric fellowship trends from 2012 to 2019, the types, numbers, and approaches of surgical procedures performed by fellows were examined. SETTING: Academic training centers in the United States. METHODS: Data were obtained from Fellowship Council records of all cases performed by fellows in ASMBS-accredited bariatric surgery training programs between 2012 and 2019. A retrospective analysis using standard descriptive statistical methods was performed to investigate trends in total case volume and cases per fellow for common bariatric procedures. RESULTS: From 2012 to 2019, sleeve gastrectomy cases performed by all Fellowship Council fellows nearly doubled from 6,514 to 12,398, compared with a slight increase for gastric bypass, from 8,486 to 9,204. Looking specifically at bariatric fellowships, the mean number of gastric bypass cases per fellow dropped over time, from 91.1 cases (SD = 46.8) in 2012-2013 to 52.6 (SD = 62.1) in 2018-2019. Mean sleeve gastrectomy cases per fellow increased from 54.7 (SD = 31.5) in 2012-2013 to a peak of 98.6 (SD = 64.3) in 2015-2016. Robotic gastric bypasses also increased from 4% of all cases performed in 2012-2013 to 13.3% in 2018-2019. CONCLUSIONS: Bariatric fellowship training has seen a decrease in gastric bypasses, an increase in sleeve gastrectomies, and an increase in robotic surgery completed by each fellow from 2012 to 2019.

CT imaging-derived phenotypes for abdominal muscle and their association with age and sex in a medical biobank.

The study of muscle mass as an imaging-derived phenotype (IDP) may yield new insights into determining the normal and pathologic variations in muscle mass in the population. This can be done by determining 3D abdominal muscle mass from 12 distinct abdominal muscle regions and groups using computed tomography (CT) in a racially diverse medical biobank. To develop a fully automatic technique for assessment of CT abdominal muscle IDPs and preliminarily determine abdominal muscle IDP variations with age and sex in a clinically and racially diverse medical biobank. This retrospective study was conducted using the Penn Medicine BioBank (PMBB), a research protocol that recruits adult participants during outpatient visits at hospitals in the Penn Medicine network. We developed a deep residual U-Net (ResUNet) to segment 12 abdominal muscle groups including the left and right psoas, quadratus lumborum, erector spinae, gluteus medius, rectus abdominis, and lateral abdominals. 110 CT studies were randomly selected for training, validation, and testing. 44 of the 110 CT studies were selected to enrich the dataset with representative cases of intra-abdominal and abdominal wall pathology. The studies were divided into non-overlapping training, validation and testing sets. Model performance was evaluated using the Sørensen-Dice coefficient. Volumes of individual muscle groups were plotted to distribution curves. To investigate associations between muscle IDPs, age, and sex, deep learning model segmentations were performed on a larger abdominal CT dataset from PMBB consisting of 295 studies. Multivariable models were used to determine relationships between muscle mass, age and sex. The model's performance (Dice scores) on the test data was the following: psoas: 0.85 ± 0.12, quadratus lumborum: 0.72 ± 0.14, erector spinae: 0.92 ± 0.07, gluteus medius: 0.90 ± 0.08, rectus abdominis: 0.85 ± 0.08, lateral abdominals: 0.85 ± 0.09. The average Dice score across all muscle groups was 0.86 ± 0.11. Average total muscle mass for females was 2041 ± 560.7 g with a high of 2256 ± 560.1 g (41-50 year old cohort) and a change of - 0.96 g/year, declining to an average mass of 1579 ± 408.8 g (81-100 year old cohort). Average total muscle mass for males was 3086 ± 769.1 g with a high of 3385 ± 819.3 g (51-60 year old cohort) and a change of - 1.73 g/year, declining to an average mass of 2629 ± 536.7 g (81-100 year old cohort). Quadratus lumborum was most highly correlated with age for both sexes (correlation coefficient of - 0.5). Gluteus medius mass in females was positively correlated with age with a coefficient of 0.22. These preliminary findings show that our CNN can automate detailed abdominal muscle volume measurement. Unlike prior efforts, this technique provides 3D muscle segmentations of individual muscles. This technique will dramatically impact sarcopenia diagnosis and research, elucidating its clinical and public health implications. Our results suggest a peak age range for muscle mass and an expected rate of decline, both of which vary between genders. Future goals are to investigate genetic variants for sarcopenia and malnutrition, while describing genotype-phenotype associations of muscle mass in healthy humans using imaging-derived phenotypes. It is feasible to obtain 3D abdominal muscle IDPs with high accuracy from patients in a medical biobank using fully automated machine learning methods. Abdominal muscle IDPs showed significant variations in lean mass by age and sex. In the future, this tool can be leveraged to perform a genome-wide association study across the medical biobank and determine genetic variants associated with early or accelerated muscle wasting.

Risk factors affecting operative approach, conversion, and morbidity for adrenalectomy: a single-institution series of 402 patients.

BACKGROUND: Risk factors for selecting patients for open adrenalectomy (OA) and for conversion are limited in most series. This study aimed to investigate variables that are important in selecting patients for OA, predict risk of conversion from laparoscopic adrenalectomy (LA), and impact 30-day outcomes of OA and LA. METHODS: A retrospective cohort study of prospectively collected data was conducted. Patients (≥ 16 years old) who underwent adrenalectomy in the Division of General Surgery at Barnes-Jewish Hospital (1993-2010) were grouped by operative approach (LA vs. OA) and compared using nonparametric tests and regression analyses (α < 0.05). RESULTS: In total, 402 patients underwent 422 adrenalectomies. Compared to LA patients, those in the OA group were older (p = 0.02), had higher ASA scores (p = 0.04), larger tumor size (p < 0.01), and fewer functioning lesions (p < 0.01). OA patients more often required concurrent procedures (p < 0.01), had a longer operative time (p = 0.04), more intraoperative complications (p = 0.02), higher estimated blood loss (EBL), and larger transfusion requirement. Preoperative factors that predicted selection for OA were higher patient age (p = 0.01), higher ASA score (p = 0.03), larger tumor size (p < 0.01), nonfunctioning lesion (p < 0.01), diagnosis of adrenocortical carcinoma (p < 0.01), and the need for concomitant procedures (p < 0.01). Conversion to open or hand-assisted approach occurred in 6.2 % of LA patients. Preoperative risks for conversion included large tumor size (>8 cm) and need for concomitant procedures (p < 0.01). Multivariate analysis revealed that large indeterminate adrenal mass, adrenocortical carcinoma, tumor size (>6 cm), an open operation, conversion, concomitant procedures, operative time >180 min, and EBL >200 mL were predictors of 30-day morbidity. CONCLUSIONS: Adrenal tumor size and need for concurrent procedures significantly impact the selection of patients for OA, the likelihood of conversion, and perioperative morbidity. These metrics should be considered when assessing operative approach and risks for adrenalectomy.

Relationships between body fat distribution and metabolic syndrome traits and outcomes: A mendelian randomization study.

BACKGROUND: Obesity is a complex, multifactorial disease associated with substantial morbidity and mortality worldwide. Although it is frequently assessed using BMI, many epidemiological studies have shown links between body fat distribution and obesity-related outcomes. This study examined the relationships between body fat distribution and metabolic syndrome traits using Mendelian Randomization (MR). METHODS/FINDINGS: Genetic variants associated with visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and gluteofemoral adipose tissue (GFAT), as well as their relative ratios, were identified from a genome wide association study (GWAS) performed with the United Kingdom BioBank. GWAS summary statistics for traits and outcomes related to metabolic syndrome were obtained from the IEU Open GWAS Project. Two-sample MR and BMI-controlled multivariable MR (MVMR) were performed to examine relationships between each body fat measure and ratio with the outcomes. Increases in absolute GFAT were associated with a protective cardiometabolic profile, including lower low density lipoprotein cholesterol (ß: -0.19, [95% CI: -0.28, -0.10], p < 0.001), higher high density lipoprotein cholesterol (ß: 0.23, [95% CI: 0.03, 0.43], p = 0.025), lower triglycerides (ß: -0.28, [95% CI: -0.45, -0.10], p = 0.0021), and decreased systolic (ß: -1.65, [95% CI: -2.69, -0.61], p = 0.0019) and diastolic blood pressures (ß: -0.95, [95% CI: -1.65, -0.25], p = 0.0075). These relationships were largely maintained in BMI-controlled MVMR analyses. Decreases in relative GFAT were linked with a worse cardiometabolic profile, with higher levels of detrimental lipids and increases in systolic and diastolic blood pressures. CONCLUSION: A MR analysis of ASAT, GFAT, and VAT depots and their relative ratios with metabolic syndrome related traits and outcomes revealed that increased absolute and relative GFAT were associated with a favorable cardiometabolic profile independently of BMI. These associations highlight the importance of body fat distribution in obesity and more precise means to categorize obesity beyond BMI.

Gastroparesis: an evidence-based review for the bariatric and foregut surgeon.

Gastroparesis is a gastric motility disorder characterized by delayed gastric emptying. It is a rare disease and difficult to treat effectively; management is a dilemma for gastroenterologists and surgeons alike. We conducted a systematic review of the literature to evaluate current diagnostic tools as well as treatment options. We describe key elements in the pathophysiology of the disease, in addition to current evidence on treatment alternatives, including nutritional considerations, medical and surgical options, and related outcomes.

Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease.

Complications of short bowel syndrome (SBS) include malabsorption and bacterial overgrowth, requiring prolonged dependence on parenteral nutrition (PN). We hypothesized that the intolerance of whole food in some SBS patients might be due to the effect of dietary fiber on the gut microbiome. Shotgun metagenomic sequencing and targeted metabolomics were performed using biospecimens collected from 55 children with SBS and a murine dietary fiber model. Bioinformatic analyses were performed on these datasets as well as from a healthy human dietary intervention study. Compared to healthy controls, the gut microbiota in SBS had lower diversity and increased Proteobacteria, a pattern most pronounced in children on PN and inversely correlated with whole food consumption. Whole food intake correlated with increased glycoside hydrolases (GH) and bile salt hydrolases (BSH) with reduced fecal conjugated bile acids suggesting that dietary fiber regulates BSH activity via GHs. Mechanistic evidence supporting this notion was generated via fecal and plasma bile acid profiling in a healthy human fiber-free dietary intervention study as well as in a dietary fiber mouse experiment. Gaussian mixture modeling of fecal bile acids was used to identify three clinically relevant SBS phenotypes. Dietary fiber is associated with bile acid deconjugation likely via an interaction between gut microbiota BSHs and GHs in the small intestine, which may lead to whole food intolerance in patients with SBS. This mechanism not only has potential utility in clinical phenotyping and targeted therapeutics in SBS based on bile acid metabolism but may have relevance to other intestinal disease states.

Re-examining chemically defined liquid diets through the lens of the microbiome.

Trends in nutritional science are rapidly shifting as information regarding the value of eating unprocessed foods and its salutary effect on the human microbiome emerge. Unravelling the evolution and ecology by which humans have harboured a microbiome that participates in every facet of health and disease is daunting. Most strikingly, the host habitat has sought out naturally occurring foodstuff that can fulfil its own metabolic needs and also the needs of its microbiota, each of which remain inexorably connected to one another. With the introduction of modern medicine and complexities of critical care, came the assumption that the best way to feed a critically ill patient is by delivering fibre-free chemically defined sterile liquid foods (that is, total enteral nutrition). In this Perspective, we uncover the potential flaws in this assumption and discuss how emerging technology in microbiome sciences might inform the best method of feeding malnourished and critically ill patients.

Maternal gut microbiota reflecting poor diet quality is associated with spontaneous preterm birth in a prospective cohort study.

BACKGROUND: A processed diet, high in fat and low in fiber, is associated with differences in the gut microbiota and adverse health outcomes in humans; however, little is known about the diet-microbiota relation and its impact on pregnancy. Spontaneous preterm birth (SPTB), a pregnancy outcome with serious short- and long-term consequences, occurs more frequently in black and in obese women in the United States. OBJECTIVES: In a prospective, case-control sample matched for race and obesity (cases = 16, controls = 32), we compared the fecal gut microbiota, fecal and plasma metabolites, and diet in the late second trimester. We hypothesized that a Western diet would be associated with reduced microbiota richness and a metabolic signature predicting incidence of SPTB. METHODS: The fecal microbiota was characterized by 16S-tagged sequencing and untargeted metabolomics was used to analyze both plasma and fecal metabolites. Wilcoxon's rank-sum test was used for the comparison of microbiota genera, α-diversity, fecal and plasma metabolites, and dietary variables between term and SPTB. ß-Diversity was analyzed using permutational multivariate ANOVA, and metabolite associations were assessed by module analysis. RESULTS: A decrease in α-diversity was strongly associated with the development of SPTB, especially in the taxonomic class of Betaproteobacteria. Of 824 fecal metabolites, 22 metabolites (mostly lipids) differed between cases and controls (P < 0.01), with greater DHA (22:6n-3) and EPA (20:5n-3) in cases [false discovery rate (FDR) < 0.2]. The most significant fecal metabolite module (FDR-adjusted P = 0.008) was dominated by DHA and EPA. Dietary saturated fat (primarily palmitate) intake was greater in cases (31.38 ± 7.37 compared with 26.08 ± 8.62 g, P = 0.045) and was positively correlated with fecal DHA and EPA (P < 0.05). CONCLUSIONS: Reduced α-diversity of the gut microbiota and higher excretion of omega-3 (n-3) fatty acids in stool may provide a novel biomarker signature predicting SPTB in women with a low-fiber, high-fat diet. Further investigation of these markers in a larger sample is needed for validation.

The Effects of the Affordable Care Act on Utilization of Bariatric Surgery.

INTRODUCTION: The Affordable Care Act (ACA) expanded Medicaid (ME) and instituted Essential Health Benefits (EHB) that included bariatric surgery coverage on a state-by-state opt-in basis, increasing insurance coverage of bariatric surgery. MATERIALS AND METHODS: Using a difference-in-differences framework, changes in bariatric surgery rates, defined as utilization in the population of people with obesity, before and after the ACA were evaluated in four states. Bariatric surgery procedure data were taken from the Healthcare Cost and Utilization Project's State In-patient Database 2012-2015. Adjusted multivariable regressions were run in the Medicaid and commercially insured populations. RESULTS: We identified 36,456 bariatric surgeries across the 286 Health Service Areas and time periods, with 31,732 covered by commercial insurers and 4724 covered by Medicaid. An unadjusted increase in utilization rates was seen in the Medicaid and Commercial populations in both ME- and EHB-covered states as well as non-expansion and EHB opt-out states over time. In the Medicaid population, after adjusting for confounders, there was a significant increase of 24.77 cases per 100,000 people with obesity (95% confidence interval: 12.41, 37.13) in the expansion states relative to the control and pre-period. The commercial population experienced a nonsignificant change in the rates of bariatric surgery, decreasing by 2.89 cases per 100,000 people with obesity (95% confidence interval: - 21.59, 15.81). CONCLUSIONS: There was a significant increase in bariatric surgery rates among Medicaid beneficiaries associated with Medicaid expansion, but there was no change among the commercially insured.

Validation and improvement of a highly predictive bariatric surgery mortality risk calculator to include sleeve gastrectomy using MBSAQIP 2015-2017 data.

BACKGROUND: Initial development of a prominent bariatric surgery mortality risk calculator comprising cases that now account for <10% of commonly performed operations. Whether the previously highly predictive model is valid with more recent data is unknown. OBJECTIVES: To validate and improve a bariatric-surgery-specific mortality calculator with updated case mix and outcomes data. SETTING: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program-accredited bariatric surgery programs. METHODS: The Metabolic and Bariatric Accreditation and Quality Improvement Program Participant Use File from years 2015 to 2017 was used for the analysis. C-statistics were calculated with observed death as the outcome and estimated 30-day mortality risk as the only predictor and receiver operating characteristic curve was plotted. Similar analyses were repeated for each body mass index (BMI) subgroup. Backward selection logistic regression was used to investigate the potential of improving the robustness of the model. RESULTS: Patients were predominantly female (n = 446,149, 80.4%) and white (n = 409,350, 73.7%) with a mean (standard deviation) age of 45.4 (12.0) years and BMI of 44.5 (8.4) kg/m2, and the most commonly performed operation was sleeve gastrectomy (n = 338,061, 60.9%). Assessing previous model using present data, area under the curve was .7412. By BMI subgroup, area under the curve for BMI <45 kg/m2 was .7645, for BMI 45 to 60 kg/m2 was .7586, and for BMI >60 kg/m2 was .6576. DISCUSSION: The present study found that the model previously developed maintains discrimination with changing surgical procedures. Though variables in the initial calculator are helpful, additional factors should be considered when weighing risk, such as sex, previous surgery, and renal function. Future studies are needed to determine whether changes in modifiable risk factors will impact mortality rates.

Laparoscopic Sleeve Gastrectomy Carries a Lower Perioperative Mortality Including Sudden Cardiac Death over Roux-en-Y Gastric Bypass in Patients with a Prior Cardiac History: An MBSAQIP Analysis.

BACKGROUND: Although bariatric surgery has proven beneficial for those with cardiovascular disease (CVD), the overall and procedure-specific risk associated with bariatric surgery in this patient population remains unknown. DESIGN: Patients who underwent primary laparoscopic, laparoscopic-assisted, or robotic-assisted Roux-En-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at a MBSAQIP-accredited center were included (n = 494,611). Exposures include history of MI, PCI, or cardiac surgery who underwent RYGB or SG. Outcome measures were 30-day mortality, perioperative cardiac arrest, and rehospitalization. RESULTS: Of 494,611 patients enrolled in MBSAQIP, 15,923 had a history of MI, PCI, or cardiac surgery (prior cardiac history). Patient history of MI, PCI, and cardiac surgery was associated with significantly increased adjusted risk of perioperative cardiac arrest requiring CPR (OR: 2.31, 2.12, 2.42, respectively) and adjusted 30-day mortality (OR: 1.72, 1.50, 1.68, respectively). Prior cardiac history was associated with increased adjusted 30-day readmission rate (MI - OR, 1.42; PCI - OR, 1.45; and cardiac surgery - OR, 1.68). Further, 30-day postoperative readmission, postoperative cardiac arrest, and death were lower for patients undergoing SG compared to RYGB (OR: 0.48, 0.49, and 0.54 respectively). CONCLUSION AND RELEVANCE: Prior cardiac history was associated with significant greater risk of perioperative cardiac arrest and 30-day mortality among patients undergoing bariatric surgery. SG was associated with less adverse events than RYGB among this population. While there is a clear benefit to weight loss in patients with CVD, it is important to consider whether cardiac patients considering bariatric surgery may require additional preoperative optimization, perioperative interventions, and postoperative monitoring.