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BackgroundBariatric surgery is endorsed by multiple societies as the most effective treatment for obesity. Psychosocial functioning has also been noted to improve for most patients after bariatric surgery. However, some studies have shown an increase in post-operative suicide risk. The aim of this study was to review the published literature and evaluate the association of bariatric surgery with suicide events and suicide/self-harm attempts in patients who have undergone weight loss surgery.MethodsMEDLINE and Embase were searched from inception through January 2018 for retrospective or prospective studies reporting mortality outcomes and self-harm or suicide rates after bariatric procedures. The primary outcome was the pooled event rate with 95% confidence interval (95% CI) for suicide. Secondary outcomes were suicide/self-harm attempts after bariatric surgery compared to same population prior to surgery and to matched control subjects, with the respective calculated odds ratios (OR) and 95% CI.ResultsFrom 227 citations, 32 studies with 148,643 subjects were eligible for inclusion. The patients were predominantly females (76.9%). Roux-en-Y gastric bypass (RYGB) was the most commonly performed procedure (58.9%). The post-bariatric suicide event rate was 2.7/1000 patients (95% CI 0.0019–0.0038), while the suicide/self-harm attempt event rate was 17/1000 patients (95% CI 0.01–0.03). The self-harm/suicide attempt risk was higher after bariatric surgery within the same population with OR of 1.9 (95% CI 1.23–2.95), and compared to matched control subjects, OR 3.8 (95% CI, 2.19–6.59).ConclusionsPost-bariatric surgery patients had higher self-harm/suicide attempt risk compared to age-, sex-, and BMI-matched controls. Various pre- and post-surgical psychosocial, pharmacokinetic, physiologic, and medical factors may be involved.

BackgroundRoux-en-Y gastric bypass (RYGB) is an effective treatment for diabetes. Glucagon-like peptide-1 (GLP-1) is a gut hormone that is important to glucose homeostasis.ObjectiveThis study aimed to assess GLP-1 level and its predictors after RYGB.MethodsThe study design was a meta-analysis. The data sources were MEDLINE, EMBASE, Web of Science, and the Cochrane Databases. The study selection composed of studies with pre- and post-RYGB levels. The main outcomes were as follows: Primary outcome was the change in postprandial GLP-1 levels after RYGB. Secondary outcomes included the changes in fasting glucose, fasting insulin, and fasting GLP-1 levels after RYGB. Meta-regression to determine predictors of changes in GLP-1 levels was performed. Outcomes were reported using Hedge’s g.ResultsTwenty-four studies with 368 patients were included. Postprandial GLP-1 levels increased after RYGB (Hedge’s g = 1.29, p < 0.0001), while fasting GLP-1 did not change (p = 0.23). Peak postprandial GLP-1 levels gave the most consistent results (I2 = 9.11). Fasting glucose and insulin levels decreased after RYGB (p < 0.0001).Roux limb length was a significant predictor for amount of GLP-1 increase (β = − 0.01, p = 0.02). Diabetes status, amount of weight loss, length of biliopancreatic limb, and time of measurement were not significant predictors (p > 0.05).ConclusionPostprandial GLP-1 levels increase after RYGB, while fasting levels remain unchanged. Shorter Roux limb length is associated with greater increase in postprandial GLP-1, which may lead to better glycemic control in this population.

The AspireAssist System (AspireAssist) is an endoscopic weight loss device that is comprised of an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage of about 30% of the calories consumed in a meal, in conjunction with lifestyle (diet and exercise) counseling. In this 52-week clinical trial, 207 participants with a body-mass index (BMI) of 35.0-55.0 kg/m were randomly assigned in a 2:1 ratio to treatment with AspireAssist plus Lifestyle Counseling (n=137; mean BMI was 42.2±5.1 kg/m ) or Lifestyle Counseling alone (n=70; mean BMI was 40.9±3.9 kg/m ). The co-primary end points were mean percent excess weight loss and the proportion of participants who achieved at least a 25% excess weight loss. At 52 weeks, participants in the AspireAssist group, on a modified intent-to-treat basis, had lost a mean (±s.d.) of 31.5±26.7% of their excess body weight (12.1±9.6% total body weight), whereas those in the Lifestyle Counseling group had lost a mean of 9.8±15.5% of their excess body weight (3.5±6.0% total body weight) (P<0.001). A total of 58.6% of participants in the AspireAssist group and 15.3% of participants in the Lifestyle Counseling group lost at least 25% of their excess body weight (P<0.001). The most frequently reported adverse events were abdominal pain and discomfort in the perioperative period and peristomal granulation tissue and peristomal irritation in the postoperative period. Serious adverse events were reported in 3.6% of participants in the AspireAssist group. The AspireAssist System was associated with greater weight loss than Lifestyle Counseling alone.

Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included Desulfovibrio fairfieldensis and Clostridium hylemonae. To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. Bacteroides ovatus and Phocaeicola dorei were positively correlated with unconjugated bile acids. Bifidobacterium adolescentis, Collinsella aerofaciens, and Faecalibacterium prausnitzii were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation.

Chlamydia trachomatis is an obligate intracellular human pathogen that exhibits stage-specific gene transcription throughout a biphasic developmental cycle. The mechanisms that control modulation in transcription and associated phenotypic changes are poorly understood. This study provides evidence that a switch-protein kinase regulatory network controls availability of σ66, the main sigma subunit for transcription in Chlamydia. In vitro analysis revealed that a putative switch-protein kinase regulator, RsbW, is capable of interacting directly with σ66, as well as phosphorylating its own antagonist, RsbV1, rendering it inactive. Conversely, the putative PP2C-like phosphatase domain of chlamydial RsbU was capable of reverting RsbV1 into its active state. Recent advances in genetic manipulation of Chlamydia were employed to inactivate rsbV1, as well as to increase the expression levels of rsbW or rsbV1, in vivo. Representative σ66-dependent gene transcription was repressed in the absence of rsbV1 or upon increased expression of RsbW, and increased upon elevated expression of RsbV1. These effects on housekeeping transcription were also correlated to several measures of growth and development. A model is proposed where the relative levels of active antagonist (RsbV1) and switch-protein anti-sigma factor (RsbW) control the availability of σ66 and subsequently act as a molecular 'throttle' for Chlamydia growth and development.

ObjectiveEndoscopic submucosal dissection (ESD) allows for en bloc resection of superficial gastrointestinal neoplasms; however, US experience has been limited. We aimed to evaluate our clinical outcomes in colorectal ESD.DesignThis prospective study included consecutive patients undergoing colorectal ESD at a major US center. Demographics, lesion and technical characteristics, outcomes, adverse events, and pathological diagnoses were recorded. Factors affecting resection outcomes and procedure time were evaluated.Results77 patients who underwent colorectal ESD were analyzed. Mean colorectal lesion diameter was 49.4 mm. Mean procedure time was 104.7 min, and 97.4% of patients were discharged home on the same day. En bloc, complete, and curative resection was achieved in 97.4%, 97.4%, and 93.5% of colorectal ESD cases. Microperforation and delayed bleeding rates were 1.3% and 3.9%. On univariable analysis, the presence of tattoo adversely affected en bloc resection (p = 0.002), complete resection (p = 0.002), and curative resection (p = 0.008). Prior EMR attempts adversely affected en bloc resection (p = 0.028), complete resection (p = 0.028), and procedure time (p = 0.008). On multivariable analysis, the presence of tattoo predicted failure to achieve curative resection (OR 0.13; 95% CI 0.02–0.98; p = 0.048). Lesion size > 50 mm (OR 3.89; 95% CI 1.13–13.41; p = 0.031), presence of tattoo (OR 9.38; 95% CI 1.05–83.83; p = 0.045), and prior EMR attempts (OR 7.13; 95% CI 1.76–28.90; p = 0.006) predicted procedure time ≥ 90 min. A scoring system was created to predict prolonged ESD procedure time and was externally validated, with AUC 0.78 (95% CI 0.73–0.83).ConclusionThis study demonstrates the effects of multiple risk factors on resection outcomes and procedure time in colorectal ESD. Tattoo placement and attempted EMR should be avoided for lesions being considered for ESD.

BackgroundEUS-guided gastroenterostomy (EUS-GE) is a novel procedure for palliation of malignant gastric outlet obstruction (GOO); however, data comparing EUS-GE to enteral stent placement are limited. We aimed to compare clinical outcomes between EUS-GE and enteral stent placement in the palliation of malignant GOO.MethodsRetrospective analysis of a prospectively collected database on patients who underwent EUS-GE or enteral stent placement for palliation of malignant GOO from 2014 to 2017 was conducted. Primary outcome was the rate of stent failure requiring repeat intervention. Secondary outcomes included technical and clinical success, time to repeat intervention, length of hospital stay, and adverse events.ResultsA total of 100 consecutive patients (mean age 65.9 ± 11.9 years, 44.0% female) were identified, of which 78 underwent enteral stent placement, and 22 underwent EUS-GE. Rate of stent failure requiring repeat intervention was higher in the enteral stent group than the EUS-GE group (32.0% vs. 8.3%, p = 0.021). Technical success was achieved in 100% in both groups. Higher initial clinical success was attained in the EUS-GE group than the enteral stent group (95.8% vs. 76.3%, p = 0.042). Mean length of hospital stay following stent placement was similar between groups (p = 0.821). The enteral stent group trended towards increased adverse events (40.2% vs. 20.8%, p = 0.098). Kaplan–Meier analysis showed decreased stent function in the enteral stent group (p = 0.013).ConclusionCompared to enteral stent placement, EUS-GE has a higher rate of initial clinical success and lower rate of stent failure requiring repeat intervention. EUS-GE may be offered for selected patients with malignant GOO in centers with extensive experience.

Background: An education system for narrow band imaging (NBI) interpretation requires sufficient exposure to key features. However, access to didactic lectures by experienced teachers is limited in the United States. Aim: To develop and assess the effectiveness of a colorectal lesion identification tutorial. Methods: In the image analysis pretest, subjects including 9 experts and 8 trainees interpreted 50 white light (WL) and 50 NBI images of colorectal lesions. Results were not reviewed with subjects. Trainees then participated in an online tutorial emphasizing NBI interpretation in colorectal lesion analysis. A post-test was administered and diagnostic yields were compared to pre-education diagnostic yields. Results: Under the NBI mode, experts showed higher diagnostic yields (sensitivity 91.5% [87.3–94.4], specificity 90.6% [85.1–94.2], and accuracy 91.1% [88.5–93.7] with substantial interobserver agreement [κ value 0.71]) compared to trainees (sensitivity 89.6% [84.8–93.0], specificity 80.6% [73.5–86.3], and accuracy 86.0% [82.6–89.2], with substantial interobserver agreement [κ value 0.69]). The online tutorial improved the diagnostic yields of trainees to the equivalent level of experts (sensitivity 94.1% [90.0–96.6], specificity 89.0% [83.0–93.2], and accuracy 92.0% [89.3–94.7], p < 0.001 with substantial interobserver agreement [κ value 0.78]). Conclusions: This short, online tutorial improved diagnostic performance and interobserver agreement.

The obligate intracellular pathogen , along with its close species relatives, is known to be strictly dependent upon the availability of iron. Deprivation of iron induces an aberrant morphological phenotype termed \"persistence.\" This persistent phenotype develops in response to various immunological and nutritional insults and may contribute to the development of sub-acute -associated chronic diseases in susceptible populations. Given the importance of iron to , relatively little is understood about its acquisition and its role in gene regulation in comparison to other iron-dependent bacteria. Analysis of the genome sequences of a variety of chlamydial species hinted at the involvement of unconventional mechanisms, being that lack many conventional systems of iron homeostasis that are highly conserved in other bacteria. Herein we detail past and current research regarding chlamydial iron biology in an attempt to provide context to the rapid progress of the field in recent years. We aim to highlight recent discoveries and innovations that illuminate the strategies involved in chlamydial iron homeostasis, including the vesicular mode of acquiring iron from the intracellular environment, and the identification of a putative iron-dependent transcriptional regulator that is synthesized as a fusion with a ABC-type transporter subunit. These recent findings, along with the noted absence of iron-related homologs, indicate that have evolved atypical approaches to the problem of iron homeostasis, reinvigorating research into the iron biology of this pathogen.

PurposeWeight regain after Roux-en-Y gastric bypass (RYGB) is associated with worsening of liver outcomes. However, the effect of transoral outlet reduction (TORe) on liver fibrosis in RYGB patients with weight regain and possible advanced fibrosis remains unknown.Materials and MethodsThis was a retrospective analysis of prospectively collected data of RYGB patients who underwent TORe for weight regain. Only patients with possible advanced fibrosis were included. TORe was performed using either an endoscopic suturing device (S-TORe) or plication device (P-TORe) to reduce the gastrojejunal anastomosis (GJA) and pouch sizes. Primary outcomes included changes in non-invasive tests (NITs) for fibrosis at 6–12 months. Secondary outcomes included weight loss and changes in insulin resistance and lipid profile at 6–12 months.ResultsFifty RYGB patients were included. Baseline age and BMI were 55 ± 11 years and 40.1 ± 7.3 kg/m2. Baseline GJA and pouch sizes were 20 ± 7 mm and 5 ± 2 cm, respectively. Thirty patients (60%) underwent S-TORe and 20 patients (40%) underwent P-TORe. At 12 months following TORe, there were statistically significant improvements in NITs for fibrosis, including ALT, AST and FIB-4. There was a trend towards significant improvement in liver stiffness measurement on transient elastography. Patients experienced 8.8 ± 11.2% total weight loss (TWL) (p < 0.0001), with 60% experiencing at least 10% TWL. Additionally, there was a significant improvement in HbA1c and a trend toward significant improvement in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), suggestive of improved insulin sensitivity.ConclusionTORe is associated with an improvement in hepatic fibrosis in patients with NAFLD and possible advanced fibrosis.