BackgroundThe development of insulin resistance (IR) in mouse models of obesity and type 2 diabetes mellitus (DM) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue inflammation via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose inflammation and investigated the role of Tregs in IR/obesity through coordinated studies in mice and humans.Methods and Findings Foxp3-green fluorescent protein (GFP) “knock-in” mice were randomized to a high-fat diet intervention for a duration of 12 weeks to induce DIO/IR. Morbidly obese humans without overt type 2 DM (n = 13) and lean controls (n = 7) were recruited prospectively for assessment of visceral adipose inflammation. DIO resulted in increased CD3+CD4+, and CD3+CD8+ cells in visceral adipose with a striking decrease in visceral adipose Tregs. Treg numbers in visceral adipose inversely correlated with CD11b+CD11c+ adipose tissue macrophages (ATMs). Splenic Treg numbers were increased with up-regulation of homing receptors CXCR3 and CCR7 and marker of activation CD44. In-vitro differentiation assays showed an inhibition of Treg differentiation in response to conditioned media from inflammatory macrophages. Human visceral adipose in morbid obesity was characterized by an increase in CD11c+ ATMs and a decrease in foxp3 expression.ConclusionsOur experiments indicate that obesity in mice and humans results in adipose Treg depletion. These changes appear to occur via reduced local differentiation rather than impaired homing. Our findings implicate a role for Tregs as determinants of adipose inflammation.

This study provides level 1 data, suggesting that elimination of intraperitoneal drainage in all cases of PD increases the frequency and severity of complications.

TF was an effective treatment for patients with GERD symptoms, particularly in those with persistent regurgitation despite PPI therapy, based on evaluation 6 months after the procedure. Clinicaltrials.gov no: NCT01136980.

The variables associated with gastroesophageal reflux (GER) after peroral endoscopic myotomy (POEM) are largely unknown. This study aimed to: 1) identify the prevalence of reflux esophagitis and asymptomatic GER in patients who underwent POEM, and 2) evaluate patient and intraprocedural variables associated with post-POEM GER. All patients who underwent POEM and subsequent objective testing for GER (pH study with or without upper gastrointestinal [GI] endoscopy) at seven tertiary academic centers (one Asian, two US, four European) were included. Patients were divided into two groups: 1) DeMeester score ≥ 14.72 (cases) and 2) DeMeester score of< 14.72 (controls). Asymptomatic GER was defined as a patient with a DeMeester score ≥ 14.72 who was not consuming proton pump inhibitor (PPI). A total of 282 patients (female 48.2 %, Caucasian 84.8 %; mean body mass index 24.1 kg/m) were included. Clinical success was achieved in 94.3 % of patients. GER evaluation was completed after a median follow-up of 12 months (interquartile range 10 - 24 months). A DeMeester score of ≥ 14.72 was seen in 57.8 % of patients. Multivariable analysis revealed female sex to be the only independent association (odds ratio 1.69, 95 % confidence interval 1.04 - 2.74) with post-POEM GER. No intraprocedural variables were associated with GER. Upper GI endoscopy was available in 233 patients, 54 (23.2 %) of whom were noted to have reflux esophagitis (majority Los Angeles Grade A or B). GER was asymptomatic in 60.1 %. Post-POEM GER was seen in the majority of patients. No intraprocedural variables were identified to allow for potential alteration in procedural technique.

Augmentation of the lower esophageal sphincter with a magnetic device provides significant and sustained control of reflux, with minimal side effects or complications. No new safety risks emerged over a 5-year follow-up period. These findings validate the long-term safety and efficacy of the magnetic sphincter augmentation device for patients with GERD. ClinicalTrials.gov no: NCT00776997.

BACKGROUND Intraoperative cholangiography (IOC) is the current gold standard for biliary imaging during laparoscopic cholecystectomy (LC). However, utilization of IOC remains low. Near Infrared Fluorescence Cholangiography (NIRF-C) is a novel, noninvasive method for real-time, intraoperative biliary mapping. Our aims were to assess the safety and efficacy of NIRF-C for identification of biliary anatomy during LC. METHODS Patients were administered indocyanine green (ICG) prior to surgery. NIRF-C was used to identify extrahepatic biliary structures before, and after partial and complete dissection of Calot's triangle. Routine IOC was performed in each case. Identification of biliary structures using NIRF-C and IOC, and time required to complete each procedure were collected. RESULTS Eighty-two patients underwent elective LC with NIRF-C and IOC. Mean age and BMI were 42.6±13.7 years and 31.5±8.2 kg/m2, respectively. ICG was administered 73.8±26.4 minutes prior to incision. NIRF-C was significantly faster than IOC (1.9±1.7 vs. 11.8±5.3 minutes, p<0.001). IOC was unobtainable in 20 (24.4%) patients while NIRF-C did not visualize biliary structures in 4 (4.9%) patients. After complete dissection, the rates of visualization of the cystic duct, common bile duct, and common hepatic duct using NIRF-C were 95.1%, 76.8%, and 69.5%, respectively, compared to 72.0%, 75.6%, and 74.3% for IOC. In 20 patients where IOC could not be obtained, NIRF-C successfully identified biliary structures in 80% of the cases. Higher BMI was not a deterrent to visualization of anatomy with NIRF-C. No adverse events were observed with NIRF-C. CONCLUSIONS NIRF-C is a safe and effective alternative to IOC for imaging extrahepatic biliary structures during LC. This technique should be evaluated further under a variety of acute and chronic gallbladder inflammatory conditions to determine its usefulness in biliary ductal identification.

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Radiofrequency ablation of the lower esophageal sphincter produces significant improvement in reflux symptoms and may represent an alternative to medical treatment and surgical fundoplication in select patients.