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Obesity is increasing at an alarming rate. The effectiveness of currently available strategies for the treatment of obesity (including pharmacologic, surgical, and behavioral interventions) is limited. Understanding the neurobiology of appetite and the important drivers of energy intake (EI) can lead to the development of more effective strategies for the prevention and treatment of obesity. Appetite regulation is complex and is influenced by genetic, social, and environmental factors. It is intricately regulated by a complex interplay of endocrine, gastrointestinal, and neural systems. Hormonal and neural signals generated in response to the energy state of the organism and the quality of food eaten are communicated by paracrine, endocrine, and gastrointestinal signals to the nervous system. The central nervous system integrates homeostatic and hedonic signals to regulate appetite. Although there has been an enormous amount of research over many decades regarding the regulation of EI and body weight, research is only now yielding potentially effective treatment strategies for obesity. The purpose of this article is to summarize the key findings presented in June 2022 at the 23rd annual Harvard Nutrition Obesity Symposium entitled "The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets." Findings presented at the symposium, sponsored by NIH P30 Nutrition Obesity Research Center at Harvard, enhance our current understanding of appetite biology, including innovative techniques used to assess and systematically manipulate critical hedonic processes, which will shape future research and the development of therapeutics for obesity prevention and treatment.

Objective To characterize longitudinal changes in blood biomarkers, leukocyte composition, and gene expression following laparoscopic sleeve gastrectomy (LSG). Background LSG is an effective treatment for obesity, leading to sustainable weight loss and improvements in obesity-related comorbidities and inflammatory profiles. However, the effects of LSG on immune function and metabolism remain uncertain. Methods Prospective data were collected from 23 enrolled human subjects from a single institution. Parameters of weight, comorbidities, and trends in blood biomarkers and leukocyte subsets were observed from preoperative baseline to 1 year postsurgery in 3-month follow-up intervals. RNA sequencing was performed on pairs of whole blood samples from the first 6 subjects of the study (baseline and 3 months postsurgery) to identify genome-wide gene expression changes associated with undergoing LSG. Results LSG led to a significant decrease in mean total body weight loss (18.1%) at 3 months and among diabetic subjects a reduction in hemoglobin A1c. Improvements in clinical inflammatory and hormonal biomarkers were demonstrated as early as 3 months after LSG. A reduction in neutrophil-lymphocyte ratio was observed, driven by a reduction in absolute neutrophil counts. Gene set enrichment analyses of differential whole blood gene expression demonstrated that after 3 months LSG induced transcriptomic changes not only in inflammatory cytokine pathways but also in several key metabolic pathways related to energy metabolism. Conclusions LSG induces significant changes in the composition and metabolism of immune cells as early as 3 months postoperatively. Further evaluation is required of bariatric surgery’s effects on immunometabolism and the consequences for host defense and metabolic disease.

This experiment was designed to study the effects of a hydroalcoholic fruit extract from Withania coagulans (WC) and α-tocopherol acetate (α-Toc) in diets containing oxidised oil on growth performa...

Obesity is a well-established risk factor for endometrial cancer and is thought to adversely affect outcomes. The impact of significant and sustained weight loss as achieved by bariatric surgery for women with endometrial cancer is not well understood. We performed an institutional retrospective review of patients who underwent bariatric surgery and were diagnosed with premalignant or malignant uterine disease from 1989 to 2019 (n=171). We compared tumor characteristics and cancer-specific outcomes in patients diagnosed with uterine disease before (“PRE” group) or after (“POST” group) undergoing bariatric surgery and in a BMI- and age-matched cohort who did not undergo bariatric surgery. Of the 171 patients, 120 were in the PRE group and 51 in the POST group. The POST group was more likely to have adenocarcinoma (68.6 vs 45.0%, p=0.012) and more likely to have a minimally invasive hysterectomy (80.9 vs 46.2%, p

Bariatric surgery is the most effective treatment for obesity; however, some patients experience significant weight regain. Weight loss medications (WLM) are being increasingly used in surgery patients with limited evidence. We examine weight loss outcomes in patients using WLM after bariatric surgery. In a retrospective study, 197 bariatric surgery patients who started WLM between 2016 and 2019 at a single center were analyzed. Patients were categorized into 3 groups based on outcomes of the initial surgery: (1) Weight regainers (WR) = achieved goal weight loss after surgery (15% total body weight loss (TBWL) for sleeve gastrectomy (SG) and 25% TBWL for Roux-en-Y gastric bypass (RYGB)) with subsequent regain of > 20% of weight lost; (2) Adequate weight loss (AWL) = achieved goal weight loss without > 20% weight regain; (3) Non-responders (NR) = never achieved goal weight loss. Weight loss and medication use patterns were analyzed. Among the three categories, there was no significant difference in duration of medical therapy or %TBWL with medications. RYGB patients lost more weight than SG patients using WLM (p = 0.03). Of the medications used, patients treated with phentermine + topiramate had the highest likelihood of achieving 5%, 10%, and 15% weight loss. Compared to other 2 groups, AWL group initiated WLM earlier and experienced more weight loss when compared to their pre-operative weight or post-operative nadir. RYGB patients respond better to WLM than SG patients. Those who had started WLM before regaining weight (AWL) experienced greater overall weight loss, suggesting that proactive medical therapy at the time of weight plateau can help with greater total weight loss. Phentermine + topiramate is the most effective WLM in post-bariatric surgery patients.

Colorectal cancer (CRC) remains the third leading cause of cancer death in the United States with an alarming rise among young (1 Epidemiologically, obesity appears to be a risk factor for CRC.1 Although bariatric surgery has been shown to be associated with decreased risk for most cancers, studies to date on bariatric surgery and CRC continue to yield conflicting results.2 One possible explanation for this seeming irreconcilability is the inherent heterogeneity of CRC with its varied mechanisms. This is likely compounded by the differing bariatric operations currently employed. Here, we sharpen our focus and investigate how the most performed bariatric operation, sleeve gastrectomy (SG), affects colitis-associated CRC. Using a murine model, we found that SG significantly exacerbates both colitis and colitis-associated CRC. Using a germ-free (GF) microbiota transplant model, we found that the post-SG microbiota, when transplanted into GF mice, is capable of independently recapitulating the tumor-promoting phenotype of SG. Our results suggest that the postsurgical microbiome plays a key causal role in the increased risk for CRC after SG. This finding represents the first step in our understanding of this complex relationship that is at the intersection of two rising public health threats.

During the COVID-19 pandemic, deferral of inpatient elective surgical procedures served as a primary mechanism to increase surge inpatient capacity. Given the benefit of bariatric surgery on treating obesity and associated comorbidities, decreased access to bariatric surgery may have long-term public health consequences. Understanding the extent of the disruption of the COVID-19 pandemic to bariatric surgery will help health systems plan for appropriate access.This is an observational cohort study using the PINC AI Healthcare Database from 1/1/2019-6/31/2021. A Poisson regression model with patient characteristics and hospital-fixed effects was used to assess the relative monthly within-hospital reduction in surgical encounters, variations by race and ethnicity, and shift from inpatient to outpatient procedures. A multivariate linear probability model was used to assess the change in 30-day readmissions from 2020 and 2021 compared to 2019.Among 309 hospitals, there were 46,539 bariatric procedures conducted in 2019 with a 14.8% reduction in volume to 39,641 procedures in 2020. There were 22,642 bariatric procedures observed from January to June of 2021. The most pronounced decrease in volume occurred in April with an 89.7% relative reduction from 2019. Black and Hispanic patients were more likely to receive bariatric surgery after the height of the pandemic compared to white patients. A clinically significant shift from inpatient to outpatient bariatric surgical procedures was not observed. Relative to 2019, there were no significant differences in bariatric surgical readmission rates.During the pandemic there was a sizable decrease in bariatric surgical volume. There did not appear to be disparities in access to bariatric surgery for minority patients. We did not observe a meaningful shift toward outpatient bariatric surgical procedures. Post-pandemic, monitoring is needed to assess if hospitals have been able to meet the demand for bariatric surgical procedures.

Bariatric surgery, the most effective treatment for obesity and type 2 diabetes, is associated with increased levels of the incretin hormone glucagon-like peptide-1 (GLP-1) and changes in levels of circulating bile acids. The levels of individual bile acids in the gastrointestinal (GI) tract after surgery have, however, remained largely unstudied. Using ultra-high performance liquid chromatography-mass spectrometry-based quantification, we observed an increase in an endogenous bile acid, cholic acid-7-sulfate (CA7S), in the GI tract of both mice and humans after sleeve gastrectomy. We show that CA7S is a Takeda G-protein receptor 5 (TGR5) agonist that increases Tgr5 expression and induces GLP-1 secretion. Furthermore, CA7S administration increases glucose tolerance in insulin-resistant mice in a TGR5-dependent manner. CA7S remains gut restricted, minimizing off-target effects previously observed for TGR5 agonists absorbed into the circulation. By studying changes in individual metabolites after surgery, the present study has revealed a naturally occurring TGR5 agonist that exerts systemic glucoregulatory effects while remaining confined to the gut.

There are currently few pre-operative predictors of initial and long-term weight loss following bariatric surgery. We evaluated the role of pre-operative patient characteristics and baseline gut and adipose-derived hormones in predicting maximal total body weight loss (WLmax) and risk of weight regain (WR) after Roux-en-Y gastric bypass (RYGB) surgery. One hundred five adult patients undergoing primary RYGB were prospectively recruited. Baseline demographics were recorded and fasting plasma glucose, glycosylated hemoglobin (A1C), insulin, glucagon, leptin, active ghrelin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured on day of surgery. Our cohort had a mean age of 44.4 ± 13.0 years, and initial BMI (body mass index) of 45.1 ± 6.7 kg/m2 with mean post-operative follow-up of 40 months. Eighty patients were female and 26 had type 2 diabetes mellitus (T2D). Average WLmax was 35.3 ± 7.4%. On univariate analysis, higher baseline fasting ghrelin, lower age, lower CRP (C-reactive protein), lower A1C, and negative T2D status were associated with greater WLmax (p

Background Recurrence rates after ventral hernia repair vary widely and evidence about risk factors for recurrence are conflicting. There is little evidence for risk factors for long-term recurrence. Methods Patients who underwent ventral hernia repair at our institution and were captured in the American College of Surgeons-National Surgical Quality Improvement Program database between 2002 and 2015 were included. We reviewed all demographic, procedural, and hernia-specific data. Results Six hundred and thirty patients were included for analysis with a median follow-up of 4.9 years (inter-quartile range, 2–7.3 years). By univariate analysis, index hernia repairs were more likely to recur if defect size was ≥4 cm (P = .019), no mesh was used (P = .026), or if the repair was for a recurrent hernia (P = .001). Five-year cumulative incidence of recurrence and reoperation was 24.3% and 16.0%, respectively. Patients with a perioperative surgical site occurrence, which included superficial, deep-incisional, and organ space surgical site infections as well as wound disruption, had a 5-year cumulative incidence of recurrence of 54.9% compared with 22.6% for those without surgical site occurrence. By multivariable analysis, non-primary hernia repair (hazard ratio 1.7, 95% confidence interval 1.2–2.4, P = .005) and any postoperative surgical site occurrence (hazard ratio 1.9, 95% confidence interval 1.1–3.6, P = .02) were the only risk factors predictive of recurrence. Patient body mass index had no independent effect on recurrence. Conclusion 1 in 4 patients undergoing an open ventral hernia repair will have a recurrence after 5 years, and this risk is doubled among patients who experience any perioperative surgical site occurrence. After controlling for patient comorbidities, including body mass index, hernia size, and mesh position, the most significant risk factor for recurrence after ventral hernia repair was a non-primary hernia and surgical site occurrence.

Recent data describing gastrointestinal (GI) symptoms experienced by patients after bariatric surgery is lacking, and previous studies in sleeve gastrectomy patients have been limited in scope of follow-up time or extent of GI symptoms examined. We sought to characterize the prevalence and time course of patient-reported eating-related symptoms in sleeve gastrectomy patients.From July 2020 to July 2021, sleeve gastrectomy patients seen at three Boston area hospitals received electronic surveys and prospectively reported GI symptoms using the BODY-Q eating-related symptoms scale. Descriptive analyses were performed for patient demographics and symptom prevalence. Chi-square tests were used to compare prevalence of eating-related symptoms between follow-up time intervals.491 sleeve gastrectomy patients completed postoperative surveys with mean follow-up time of 1.9 years. Mean age was 46.6 years, and 81.3% were female. The most reported GI symptoms overall included constipation (56.6%), bloating (54.0%), heartburn when standing (41.5%), and heartburn when lying down (39.9%) while the least commonly reported symptoms were palpitations (16.3%), low blood sugar (15.7%), and emesis (15.1%). At greater than 12 months, the most reported symptoms similarly included bloating (60.3%), constipation (53.2%), and heartburn while standing (46.0%). When comparing prevalence of eating-related symptoms across follow-up time intervals from 1 to 12 months, patients reported a significant decrease in constipation, abdominal pain, and nausea over time (p = 0.012, p .0001, p = 0.03, respectively).Patients experience both upper and lower GI symptoms following sleeve gastrectomy, and symptoms, including bloating, constipation, and heartburn may persist through long-term follow-up. These patient-centered measures add value by guiding preoperative counseling, informing postoperative expectations, and providing real-time clinical feedback for bariatric surgery patients.

Surgical patients with limited digital literacy may experience reduced telemedicine access. We investigated racial/ethnic and socioeconomic disparities in telemedicine compared with in-person surgical consultation during the coronavirus disease 2019 (COVID-19) pandemic.Retrospective analysis of new visits within the Division of GeneralGastrointestinal Surgery at an academic medical center occurring between March 24 through June 23, 2020 (Phase I, Massachusetts Public Health Emergency) and June 24 through December 31, 2020 (Phase II, relaxation of restrictions on healthcare operations) was performed. Visit modality (telemedicine/phone vs in-person) and demographic data were extracted. Bivariate analysis and multivariable logistic regression were performed to evaluate associations between patient characteristics and visit modality.During Phase I, 347 in-person and 638 virtual visits were completed. Multivariable modeling demonstrated no significant differences in virtual compared with in-person visit use across racial/ethnic or insurance groups. Among patients using virtual visits, Latinx patients were less likely to have video compared with audio-only visits than White patients (OR, 0.46; 95% CI 0.22-0.96). Black race and insurance type were not significant predictors of video use. During Phase II, 2,922 in-person and 1,001 virtual visits were completed. Multivariable modeling demonstrated that Black patients (OR, 1.52; 95% CI 1.12-2.06) were more likely to have virtual visits than White patients. No significant differences were observed across insurance types. Among patients using virtual visits, race/ethnicity and insurance type were not significant predictors of video use.Black patients used telemedicine platforms more often than White patients during the second phase of the COVID-19 pandemic. Virtual consultation may help increase access to surgical care among traditionally under-resourced populations.

Background: Breast cancer is the most common cancer among women worldwide and 14.2% of deaths in Iranian women were due to breast cancer. Objectives: The present study aimed at investigating the survival of females with breast cancer diagnosed over 14 years and its related factors in Kerman Province. Methods: This is a longitudinal study. Information about 2851 females diagnosed with breast cancer was inquired from the Cancer Registry of Kerman University of Medical Sciences from March 2001 to March 2015. Data analysis was performed by Stata 14 and SPSS 22. Results: Totally, 8511 women diagnosed with breast cancer were enrolled in this study. The median survival time among patients with grade 3 at diagnosis was 0.51 of patients with grade 1 (P = 0.016). The median survival time among patients with stage 4 at diagnosis was 0.11 of patients with stages 0 and 1 (P < 0.001). The median survival time among post-menopause patients at diagnosis was 0.65 of pre-menopause patients (P = 0.014). The median survival time among patients with secondary metastasis was 0.22 of patients without it (P < 0.001) and the median survival time among patients with hormonotherapy was 1.52 of patients without this treatment (P = 0.013). Conclusions: Early diagnosis can improve the survival of patients with breast cancer. Periodic checkups especially in menopause ages are recommended. Hormone therapy has been successful in increasing patients’ survival.

Adrenal metastasectomy is associated with increased survival in non-small cell lung cancer (NSCLC) with isolated adrenal metastases. Although clinical use of adrenal metastasectomy has expanded, indications remain poorly defined. The aim of this study was to evaluate the clinical benefit of adrenal metastasectomy for all lung cancer subtypes.We performed a retrospective cohort study of patients who underwent adrenal metastasectomy for metastatic lung cancer at six institutions between 2001 and 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Cox proportional hazards regressions and Kaplan-Meier survival analysis were performed.For 122 patients, the mean age was 60.5 years and 49.2% were female. Median time to detection of the metastasis was 11 months, and 41.8% were ipsilateral to the primary lung cancer. Median DFS was 40 months (1 year: 64.8%; 5 year: 42.9%). Factors associated with longer DFS included primary tumor resection [hazard ratio (HR): 0.001; p = 0.005], longer time to adrenal metastasis (HR: 0.94; p = 0.005), and ipsilateral metastases (HR: 0.13; p = 0.004). Shorter DFS corresponded with older age (HR: 1.11; p = 0.01), R1 resection (HR: 8.94; p = 0.01), adjuvant radiation (HR: 9.45; p = 0.02), and open adrenal metastasectomy (HR: 10.0; p = 0.03). Median OS was 47 months (1 year: 80.2%; 5 year: 35.2%). Longer OS was associated with ipsilateral metastasis (HR: 0.55; p = 0.02) and adjuvant chemotherapy (HR: 0.35; p = 0.02). Shorter OS was associated with extra-adrenal metastases at adrenalectomy (HR: 3.52; p = 0.007), small cell histology (HR: 15.0; p = 0.04), and lung radiation (HR: 3.37; p = 0.002).Durable survival was observed in patients undergoing adrenal metastasectomy and should be considered for isolated adrenal metastases of NSCLC. Small cell histology and extra-adrenal metastases are relative contraindications to adrenal metastasectomy.

Background: Post-operative changes in eating behavior, eating-related distress and eating-related symptoms play an important role in the lives of bariatric surgery patients. However, there are no studies that assess these outcomes using a specifically designed patient-reported outcome measure (PROM) for patients undergoing bariatric surgery. We use our newly developed and validated scales as part of the well-established BODY-Q PROMs to compare laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass patients (LRYGB). Methods: We analyzed data from an international multi-center prospective cohort study of patients over 18 who underwent bariatric surgery. We used multivariable linear regression models to assess the difference between LRYGB and LSG for the new BODY-Q scales, which include eating behavior, eating-related distress and eating-related symptoms. All analyses were corrected for significant confounding variables. Results: Out of 1420 patients, 920 underwent LRYGB and 500 underwent LSG. The LRYGB group had a higher percentage total weight loss (p < 0.001). There was no significant difference in eating behavior (e.g., stop eating before feeling full, avoiding unhealthy snacks, etc.) or eating-related distress (e.g., feeling ashamed or out of control after eating). Patients who underwent LSG scored significantly better on the post-prandial eating-related symptoms scale (e.g., vomiting, reflux; p < 0.001). Symptoms more prevalent in the LRYGB patients were related to dumping syndrome whereas symptoms more prevalent in LSG patients were related to reflux. Conclusion: Patients who underwent LRYGB had a significantly better weight loss after surgery, but they scored worse on post-prandial symptoms in comparison to LSG patients. This information may be relevant for patients in the pre-operative counseling setting, as it may influence their decision for surgical procedure selection.

Purpose: The BODY-Q is a rigorously developed patient-reported outcome measure (PROM) for patients seeking treatment for obesity and body contouring surgery. A limitation of the uptake of the BODY-Q in weight management treatments is the absence of scales designed to measure eating-specific concerns. We aimed to develop and validate 5 new BODY-Q scales measuring weight loss expectations, eating behaviors, distress, symptoms, and work life. Material and Methods: In phase 1 (qualitative), patient and expert input was used to develop and refine the new BODY-Q scales. In phase 2 (quantitative), the scales were field-tested in bariatric and weight management clinics in the United States (US), The Netherlands, and Denmark between June 2019 and January 2020. Data were also collected in the US and Canada in September 2019 through a crowdworking platform. Rasch measurement theory (RMT) analysis was used for item reduction and to examine reliability and validity. Results: The new BODY-Q scales were refined through qualitative input from 17 patients and 20 experts (phase 1) and field-tested in 4004 participants (phase 2). All items showed ordered thresholds and good fit to the Rasch model. The RMT analysis provided evidence of reliability, with PSI values ≥0.72, Cronbach alpha values ≥0.83, and test-retest values ≥0.79. Better scores on 4 scales (exception expectations scale) correlated with lower BMI, with the strongest correlation between the eating-related distress scale scores and BMI (r= −0.249, P < 0.001). Conclusion: The new BODY-Q scales can be used in research and clinical practice to assess weight loss treatments from the patient perspective. Graphical abstract: [Figure not available: see fulltext.].

This experiment was designed to study the effects of a hydroalcoholic fruit extract from

Obesity has grown to become a global pandemic, leading to higher medical costs and a lower quality of life. Progressively, there is a growing consensus that bariatric surgery is the optimal treatment option for individuals who are clinically morbidly obese and have failed medical treatment. It has proved to be effective in sustaining weight loss, providing remission of obesity-related comorbidities, improving quality of life and prolonging life expectancy. The number of bariatric surgery procedures have gradually increased over the past years. This not only attributed to the increasing global prevalence of obesity with the need for weight loss surgery but also in addition to the global increasing acknowledgement of the metabolic health benefits associated with it. With its recognition over the past decade, bariatric surgery has evolved tremendously, with most of these procedures are now performed laparoscopically. The minimally invasive techniques lower surgical risks and complications, providing minimal postoperative pain, faster recovery and therefore shorter hospital stays. At present, approximately 1% of eligible population with severe obesity receive bariatric surgery. Undoubtedly, better understanding of the mechanisms and the effects of bariatric surgery would aid physicians to select the optimal surgical approach for each patient. Herein, this review will summarize the historic and contemporary bariatric surgical techniques (Roux-en-Y gastric bypass, vertical sleeve gastrectomy and adjustable gastric banding) and their impact on obesity related metabolic diseases.

Bariatric surgery rapidly induces improvements in type 2 diabetes (T2D) in concert with reduction in systemic markers of inflammation. The impact of bariatric surgery on local intestinal immunity is not known. We hypothesize that sleeve gastrectomy (SG) and gastric bypass (RYGB) surgeries resolve obesity-induced intestinal inflammation, thereby promoting T2D resolution. SG and RYGB, or control surgery was performed in SD rats (n = 4–6/group). Key cytokines involved in insulin resistance (TNF-α, IFN-γ), inflammasome activation (IL-1β, IL-18), inflammation resolution (IL-10, IL-33), and Th17 cell responses (IL-17, IL-23) were measured by qPCR in mucosal scrapings of jejunum at 4 weeks post-surgery. Intestinal cytokine expressions were correlated with weight change, systemic and portal glucose, and insulin levels in response to an enteral glucose load. SG downregulated IL-17 and IL-23 in both proximal and distal jejunum, and IFN-γ was reduced only in distal jejunum (p

Diabetes is a worldwide health problem. Roux-en-Y gastric bypass (RYGB) leads to rapid resolution of type 2 diabetes (T2D). Decreased hepatic insulin resistance is key, but underlying mechanisms are poorly understood. We hypothesized that changes in intestinal function and subsequent changes in portal venous milieu drive some of these postoperative benefits. We therefore aimed to evaluate postoperative changes in portal milieu. Two rat strains, healthy [Sprague-Dawley (SD)] and obese diabetic [Zucker diabetic fatty (ZDF)] rats, underwent RYGB or control surgery. After 4 wk, portal and systemic blood was sampled before and during an intestinal glucose bolus to investigate changes in intestinal glucose absorption (Gabsorp) and utilization (Gutil), and intestinal secretion of incretins and glucagon-like peptide-2 (GLP-2). Hepatic activity of dipeptidyl peptidase-4 (DPP4), which degrades incretins, was also measured. RYGB decreased Gabsorp in both rat strains. Gutil increased in SD rats and decreased in ZDF rats. In both strains, there was increased expression of intestinal hexokinase and gluconeogenesis enzymes. Systemic incretin and GLP-2 levels also increased after RYGB. This occurred without an increase in secretion. Hepatic DPP4 activity and expression were unchanged. RYGB perturbs multiple intestinal pathways, leading to decreased intestinal glucose absorption and increased incretin levels in both healthy and diabetic animals. In diabetic rats, intestinal glucose balance shifts toward glucose release. The portal vein as the gut-liver axis may integrate these intestinal changes to contribute to rapid changes in hepatic glucose and hormone handling. This fresh insight into the surgical physiology of RYGB raises the hope of less invasive alternatives. NEW & NOTEWORTHY Portal milieu after gastric bypass surgery is an underinvestigated area. Roux-en-Y gastric bypass perturbs multiple intestinal pathways, reducing intestinal glucose absorption and increasing incretin levels. In diabetic rats, the intestine becomes a net releaser of glucose, increasing portal glucose levels. The portal vein as the gut-liver axis may integrate these intestinal changes to contribute to changes in hepatic glucose handling. This fresh insight raises the hope of less invasive alternatives.

Bariatric surgery is associated with a reduced risk of developing certain malignancies, particularly in women. However, the impact of bariatric surgery on tumor characteristics, cancer treatment, and oncologic outcomes is unknown. In a retrospective cohort study, 42 subjects diagnosed with breast cancer after bariatric surgery (1989–2014) were matched to 84 subjects with breast cancer (1984–2012) who did not undergo bariatric surgery, based on age, body mass index (BMI), and menopausal status at the time of breast cancer diagnosis, as well as the date of cancer diagnosis. Medical records were reviewed for cancer and bariatric endpoints. Statistical analysis was performed using mixed effects regression models, generalized estimating equation, conditional logistic regression, and Fisher’s exact tests. Women who developed breast cancer after bariatric surgery presented at an earlier stage compared to non-operated, obese controls. In the bariatric surgery group, there were fewer tumors with human epidermal growth factor receptor 2 overexpression (HER2+) (OR 0.16 (0.03–0.76); p = 0.02), with no significant differences seen in estrogen and progesterone receptor positivity. No HER2+ cancers were found in patients who underwent Roux-en-Y gastric bypass (OR 0.00 (0.00–0.43); p = 0.002). On multivariate analysis, bariatric surgery status remained associated with reduced HER2+ breast cancers (OR 0.18 (0.03–0.99); p

Surgery in neutropenic patients is challenging due to both atypical manifestations of common conditions and higher perioperative risk. We sought to describe the outcomes of neutropenic patients undergoing abdominal surgery and to identify factors contributing to morbidity and mortality. A retrospective chart review was performed for all patients neutropenic in the 24-hours prior to an abdominal operation at our institution between 1998 and 2017. The primary and secondary outcomes were 30-day mortality and morbidity, respectively. The chi-square test and two-tailed Student’s t test were used for univariable comparisons (non-parametric tests used when appropriate). To determine the optimal threshold of absolute neutrophil count (ANC) to discriminate 30-day mortality, we maximized the Youden index (J). Amongst 237 patients, mortality was 11.8% (28/237) and morbidity 54.5% (130/237). Absolute neutrophil count

Background:Obesity is widespread and linked to various co-morbidities. Bariatric surgery has been identified as the only effective treatment, promoting sustained weight loss and the remission of co-morbidities.Methods:Metabolic profiling was performed on diet-induced obese (DIO) mice, lean mice, and DIO mice that underwent sleeve gastrectomies (SGx). In addition, mice were subjected to intraperitoneal (i.p.) injections with taurodeoxycholic acid (TDCA) and valine. Indirect calorimetry was performed to assess food intake and energy expenditure. Expression of appetite-regulating hormones was assessed through quantification of isolated RNA from dissected hypothalamus tissue. Subsequently, i.p. injections with a melanin-concentrating hormone (MCH) antagonist and intrathecal administration of MCH were performed and weight loss was monitored.Results:Mass spectrometric metabolomic profiling revealed significantly reduced systemic levels of TDCA and L-valine in DIO mice. TDCA and L-valine levels were restored after SGx in both human and mice to levels comparable with lean controls. Systemic treatment with TDCA and valine induced a profound weight loss analogous to effects observed after SGx. Utilizing indirect calorimetry, we confirmed reduced food intake as causal for TDCA/valine-mediated weight loss via a central inhibition of the MCH.Conclusions:In summary, we identified restored TDCA/valine levels as an underlying mechanism of SGx-derived effects on weight loss. Of translational relevance, TDCA and L-valine are presented as novel agents promoting weight loss while reversing obesity-associated metabolic disorders.Funding:This work has been supported in part by a grant from NIH (UO-1 A1 132898 to S.G.T., DP and MA). M.Q. was supported by the IFB Integrated Research and Treatment Centre Adiposity Diseases (Leipzig, Germany) and the German Research Foundation (QU 420/1-1). J.I. was supported by the Biomedical Education Program (BMEP) of the German Academic Exchange Service (DAAD). T.H. (HE 7457/1-1) and F.K. (KR 4362/1-1) were supported by the German Research Foundation (DFG). H.R.C.B. was supported the Swiss Society of Cardiac Surgery. Y.N. was supported by the Chinese Scholarship Council (201606370196) and Central South University. H.U., T.M. and R.M. were supported by the Osaka Medical Foundation. C.S.F. was supported by the German Research Foundation (DFG, SFB738, B3).

The worsening obesity epidemic has driven a parallel increase in incidence of type-2 diabetes (T2D) found in 13% of the adult US population. Roux-en-Y gastric bypass surgery (RYGB) is the golden standard surgical treatment for obesity-related T2D. However, over 70% of T2D patient do not meet the NIH criteria for surgery, and many that do, are reluctant to consider such an invasive intervention. Mechanisms behind the antidiabetic effect of RYGB are not clearly understood, but isolation of proximal bowel from nutrient exposure plays a critical role. In this study, we tested the impact of daily administration of an oral gut coating agent, LuCI (Luminal Coating of the Intestine), in controlling weight and insulin resistance. LuCI is not systemically absorbed and provides a transient coating of the proximal intestines and excludes the coated bowel from nutrient contact, thus mimicking the effects of RYGB. We demonstrate that LuCI results in weight loss and improved insulin sensitivity in a rat DIO model. LuCI also appears to replicate hormonal changes seen after RYGB, by increasing post-prandial GLP-1 and GIP levels. LuCI has the potential to replicate the metabolic benefit of surgery and be a novel therapeutic strategy for obesity associated T2D.

Bariatric and metabolic surgery has evolved from simple experimental procedures for a chronic problem associated with significant morbidity into a sophisticated multidisciplinary treatment modality rooted in biology and physiology. Although the complete mechanistic narrative of bariatric surgery cannot yet be written, significant advance in knowledge has been made in the past 2 decades. This article provides a brief overview of the most studied hypotheses and their supporting evidence. Ongoing research, especially in frontier areas, such as the microbiome, will continue to refine, and perhaps even revise, current mechanistic understanding.

Obesity is widespread and linked to various co-morbidities. Bariatric surgery has been identified as the only effective treatment, promoting sustained weight loss and the remission of co-morbidities.We performed sleeve-gastrectomies (SGx) in a pre-clinical mouse model of diet-induced obesity (DIO), delineating the effects on long-term remission from obesity. SGx resulted in sustained weight loss and improved glucose tolerance. Mass-spectrometric metabolomic profiling revealed significantly reduced systemic levels of taurodeoxycholic acid (TDCA) and L-valine in DIO mice. Notably, TDCA and L-Valine levels were restored after SGx in both human and mice to levels comparable with lean controls.Strikingly, combined systemic treatment with TDCA and valine induced a profound weight loss in DIO mice analogous to effects observed after SGx. Utilizing indirect calorimetry, we confirmed reduced food intake as causal for TDCA/valine-mediated weight loss via a central inhibition of the melanin-concentrating hormone.In summary, we identified restored TDCA/valine levels as an underlying mechanism of SGx-derived effects on weight loss. Of translational relevance, TDCA and L-valine are presented as novel agents promoting weight loss while reversing obesity-associated metabolic disorders.

Obesity is a well-established risk factor for endometrial cancer and is thought to adversely affect outcomes. The impact of significant and sustained weight loss as achieved by bariatric surgery for women with endometrial cancer is not well understood.We performed an institutional retrospective review of patients who underwent bariatric surgery and were diagnosed with premalignant or malignant uterine disease from 1989 to 2019 (n=171). We compared tumor characteristics and cancer-specific outcomes in patients diagnosed with uterine disease before ("PRE" group) or after ("POST" group) undergoing bariatric surgery and in a BMI- and age-matched cohort who did not undergo bariatric surgery.Of the 171 patients, 120 were in the PRE group and 51 in the POST group. The POST group was more likely to have adenocarcinoma (68.6 vs 45.0%, p=0.012) and more likely to have a minimally invasive hysterectomy (80.9 vs 46.2%, p0.001). Post-bariatric surgery weight loss was similar between the two groups. In women with malignant disease, tumor grade and pathology were similar in the PRE and POST groups. The 5-year overall survival was 98% in the PRE group and 77.8% in the POST group (p=0.016). However, 5-year overall survival was statistically similar in both PRE and POST groups compared to a matched cohort who did not undergo bariatric surgery.In this study, we did not detect an impact of bariatric surgery on endometrial cancer pathology or disease survival. Larger, multi-center studies are needed to investigate the relationship between bariatric surgery status and cancer outcomes.

Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed bariatric surgical procedure. Little is known about how surgeon training background influences the learning curve of this procedure. We examined operating times (OT), weight loss outcomes, and 30-day complications between surgeons with and without fellowship training in LSG. We hypothesize that post-residency training specific to LSG influences learning curves.Surgeons from a single institution were split into two groups: those who had not completed fellowship training in LSG (NF, n = 3), and those who had completed LSG specific training in fellowship (SGF, n = 3). OTs, BMI changes at 1 year, and 30-day readmissions, reoperations, and complications were extracted for the first 100 LSG cases of each surgeon. Data were analyzed in bins of 20 cases. Comparisons were made between cohorts within a bin and between adjacent bins of the same surgeon cohort. Logistic regression analyses were performed of OT and weight loss outcomes.SGF surgeons showed no difference in OTs over their first 100 cases. NF surgeons had statistically significant increased OTs compared to SGF surgeons during their first 60 cases and progressively shortened OTs during that interval (109 min to 78 min, p 0.001 for NF surgeons vs. 73 min to 69 min, SGF surgeons). NF surgeons had a significantly steeper slope for improvement in OT over case number. There was no correlation between case number and weight loss outcomes in either group, and no differences in 30-day outcomes between groups.Surgeons who trained to perform LSG in fellowship demonstrate faster and consistent OR times on their initial independent LSG cases compared to surgeons who did not, with no correlation between case number and weight loss outcomes or safety profiles for either group. This suggests that learning curves for LSG are achieved during formal case-specific fellowship training.