Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

AIMS: Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg-1 min-1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. CONCLUSIONS: These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.

The Impact of Different Surgical Techniques on Outcomes in Laparoscopic Sleeve Gastrectomies: The First Report from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP).

OBJECTIVE: Questions remain regarding best surgical techniques to use for a laparoscopic sleeve gastrectomy (LSG) including the use of staple line reinforcement (SLR), bougie size (BS), and distance from the pylorus (DP) where the staple line is initiated. Our objectives were to assess the impact of these techniques on 30-day outcomes and to evaluate the impact of these techniques on weight loss and comorbidities at 1 year. METHODS: Using the MBSAQIP data registry, univariate analyses and hierarchical logistical regression models were developed to analyze outcomes for techniques of LSG at patient and surgeon-level. RESULTS: A total of 189,477 LSG operations were performed by 1634 surgeons at 720 centers from 2012 to 2014. Eighty percent of surgeons used SLR, 20% did not. SLR cases were associated with higher leak rates (0.96% vs 0.65%, odds ratio [OR] 1.20 95% confidence interval [CI] 1.00-1.43) and lower bleed rates (0.75% vs 1.00%, OR 0.74 95% CI 0.63-0.86) compared to no SLR at patient level. At the surgeon level, leak rates remained significant, but bleeding events became nonsignificant. BS ≥38 was associated with significantly lower leak rates compared to BS <38 at patient and surgeon level (patient level: 0.80% vs 0.96%, OR 0.72, 95% CI 0.62-0.94; surgeon level: 0.84% vs 0.95%, OR 0.90, 95% CI 0.80-0.99). BS ≥40 was associated with increased weight loss. DP had no impact on leaks or bleeds but showed an increase in weight loss with increasing DP. CONCLUSION: LSG is a safe procedure with a low morbidity rate. SLR is associated with increased leak rates. A surgeon should consider risks, benefits, and costs of these surgical techniques when performing a LSG and selectively utilize those that, in their hands, minimize morbidity while maximizing clinical effectiveness.

Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.

Early weight regain after gastric bypass does not affect insulin sensitivity but is associated with elevated ghrelin.

OBJECTIVES: We sought to determine: (1) if early weight regain between 1 and 2 years after Roux-en-Y gastric bypass (RYGB) is associated with worsened hepatic and peripheral insulin sensitivity, and (2) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB. METHODS: Hepatic and peripheral insulin sensitivity and ghrelin and leptin plasma levels were assessed longitudinally in 45 subjects before RYGB and at 1 month, 6 months, 1 year, and 2 years postoperatively. Weight regain was defined as ≥5% increase in body weight between 1 and 2 years after RYGB. RESULTS: Weight regain occurred in 33% of subjects, with an average increase in body weight of 10 ± 5% (8.5 ± 3.3 kg). Weight regain was not associated with worsening of peripheral or hepatic insulin sensitivity. Subjects with weight regain after RYGB had higher preoperative and postoperative levels of ghrelin compared to those who maintained or lost weight during this time. Conversely, the trajectories of leptin levels corresponded with the trajectories of fat mass in both groups. CONCLUSIONS: Early weight regain after RYGB is not associated with a reversal of improvements in insulin sensitivity. Higher preoperative ghrelin levels might identify patients that are more susceptible to weight regain after RYGB.

Prevalence and predictors of atrial fibrillation among patients undergoing bariatric surgery.

BACKGROUND: While AF is a disease of the elderly, it can occur earlier in the presence of risk factors such as obesity. Bariatric surgery patients are significantly younger and more obese than previously described populations with AF. Therefore, it remains to be determined whether current estimates of the prevalence and predictors for AF remain true in the bariatric surgery population. METHODS: We performed a cross-sectional analysis of 1,341 consecutive patients who underwent bariatric surgery from January 2008 to October 2012. Baseline characteristics were compared between patients with and without AF. For additional comparison, 176 patients with AF and body mass index (BMI) >40 kg/m(2) were identified from the Vanderbilt AF Registry. A multivariable logistic regression was performed to identify predictors of AF within the bariatric surgery cohort. RESULTS: The prevalence of AF in the bariatric surgery cohort was 1.9 % (25/1,341). Patients with AF were older (median 56 years (interquartile range [52-64) vs.46 [38-56] years, p < 0.001), were more often male (48 vs. 23 %, p = 0.004), had more comorbidities, but had no difference in BMI (50 kg/m(2) [44-58] vs. 48 [43-54], p = 0.4). In multivariable analysis, the odds of AF increased 2.2-fold by age per decade (95 % CI, 1.4-3.5; p < 0.001) and 2.4-fold by male gender (1.1-5.4, p = 0.03) when adjusted for BMI. BMI was not independently associated with AF (OR 1.15 [95 % CI, 0.98-1.41], p = 0.09). CONCLUSIONS: The prevalence of AF is 1.9 % among patients undergoing bariatric surgery. Risk of AF was found to increase with age and male gender, but not with higher BMI.

Internal hernia after laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: The goal of this study was to determine the impact of mesenteric defect closure and Roux limb position on the rate of internal hernia after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: A retrospective review was conducted of all LRYGB patients from 2001 to 2011 who had all internal hernia (IH) defects closed (DC) or all defects not closed (DnC). RESULTS: Of 914 patients, 663 (72.5 %) had DC vs. 251 (27.5 %) with DnC, and 679 (74.3 %) had an ante-colic vs. 235 (25.7 %) with a retro-colic Roux limb. Forty-six patients (5 %) developed a symptomatic IH. Of these, 25 (3.8 %) were in the DC vs. 21 (8.4 %) in the DnC group (p = 0.005), and 26 (3.8 %) were in the ante-colic vs. 20 (8.5 %) in the retro-colic Roux limb position (p = 0.005). Data from 45 patients were available for further analysis. The most common symptom was chronic postprandial abdominal pain (53.4 %). All patients underwent CT scan consistent with IH in 26 patients (57.5 %), suggestive in 7 (15.6 %), showing small bowel obstruction in 4 (8.9 %), and negative in 8 (17.8 %). CONCLUSIONS: Closure of mesenteric defects and ante-colic Roux limb position result in a significantly lower IH rate. Furthermore, a high index of suspicion must be maintained since symptoms may be nonspecific and imaging may be negative in nearly 20 % of patients.

Laparoscopic Roux-en-Y gastric bypass: long term clinical outcomes.

BACKGROUND: Bariatric surgery remains the most effective treatment for morbid obesity, and laparoscopic Roux-en-Y gastric bypass (LRYGB) continues to be the preferred operation. However, data for long-term outcomes are lacking. Our goal was to determine the long-term clinical outcomes after LRYGB. METHODS: Retrospective review of a prospectively maintained database was conducted on all patients who underwent LRYGB from 2001-2006. Only patients who had postoperative clinic visits both at ≤2 and ≥5 years were included. Data collected included patient demographics and postoperative clinical outcomes, including percent excess weight loss (%EWL), complications, and improvement or resolution of preoperative comorbidities (type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and hyperlipidemia). Data were analyzed by using SAS (version 9.2) and SPSS (version 16) statistical software. RESULTS: There were 770 patients who underwent LRYGB at UAB from 2001-2006. Of these, 172 patients met inclusion criteria (148 women and 24 men) with a median age of 41 years and median body mass index of 46 kg/m(2). Median short- and long-term follow-up was 12 and 75 months, respectively. Mean %EWL was 69% for short-term and 65% for long-term follow-up (P = 0.0032). Of 172 patients, 66 experienced 81 complications at a median of 26 months after operation. The improvement or resolution of comorbidities was maintained in the long-term, and there was no statistically significant difference compared with improvement or resolution in the short-term. CONCLUSIONS: Although there was a statistically significant difference in %EWL between short- and long-term follow-up, both arms showed a clinically relevant %EWL (69 and 65%) and both were statistically significant compared with preoperative values. The improvement or resolution of comorbidities achieved with LRYGB was maintained in long-term follow-up. Thus, LRYGB resulted in significant improvement in clinical outcomes that were durable in the long term.

Effectiveness of thoracoscopic truncal vagotomy in the treatment of marginal ulcers after laparoscopic Roux-en-Y gastric bypass.

Marginal ulcer is a significant complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). Most marginal ulcers resolve with medical management, but nonhealing ulcers may require revision of the gastrojejunostomy, a procedure with significant morbidity and mortality. Traditionally, surgical therapy for refractory peptic ulcers includes a vagotomy. The current study evaluates the effectiveness of thoracoscopic truncal vagotomy (TTV) in the management of refractory marginal ulcers. All patients at two institutions with an intractable marginal ulcer after LRYGB treated with TTV between 2003 and 2010 were reviewed. Data were collected from chart review and telephone interview. Seventeen patients (mean age, 39 ± 13 years; 16 females) were diagnosed with marginal ulceration a median of 18 months after LRYGB and proceeded to TTV at a mean of 39 ± 43 weeks (range, 1 to 114 weeks) after the diagnosis. The median operative time was 89 ± 65 minutes (range, 45 to 318 minutes). Four patients had a complication (sympathetic contralateral pleural effusion, pneumothorax, operative bleeding, and readmission for emesis). Eleven patients had follow-up of 3 months to 6 years (median, 7 months). Nine patients (82%) had symptomatic improvement and/or endoscopic resolution, whereas two (18%) did not. No patient had endoscopic evidence of persistent or recurrent marginal ulcer. TTV achieves symptomatic improvement and/or endoscopic resolution of intractable marginal ulcers in over 80 per cent of patients status post gastric bypass and therefore offers a less morbid alternative to revision of the gastrojejunostomy.

Reduction in inflammatory gene expression in skeletal muscle from Roux-en-Y gastric bypass patients randomized to omentectomy.

OBJECTIVES: To examine the effects of Roux-en-Y gastric bypass (RYGB) surgery with and without laparoscopic removal of omental fat (omentectomy) on the temporal gene expression profiles of skeletal muscle. DESIGN: Previously reported were the whole-body metabolic effects of a randomized, single-blinded study in patients receiving RYGB surgery stratified to receive or not receive omentectomy. In this follow up study we report on changes in skeletal muscle gene expression in a subset of 21 patients, for whom biopsies were collected preoperatively and at either 6 months or 12 months postoperatively. METHODOLOGY/PRINCIPAL FINDINGS: RNA isolated from skeletal muscle biopsies of 21 subjects (8 without omentectomy and 13 with omentectomy) taken before RYGB or at 6 and 12 months postoperatively were subjected to gene expression profiling via Exon 1.0 S/T Array and Taqman Low Density Array. Robust Multichip Analysis and gene enrichment data analysis revealed 84 genes with at least a 4-fold expression difference after surgery. At 6 and 12 months the RYGB with omentectomy group displayed a greater reduction in the expression of genes associated with skeletal muscle inflammation (ANKRD1, CDR1, CH25H, CXCL2, CX3CR1, IL8, LBP, NFIL3, SELE, SOCS3, TNFAIP3, and ZFP36) relative to the RYGB non-omentectomy group. Expressions of IL6 and CCL2 were decreased at all postoperative time points. There was differential expression of genes driving protein turnover (IGFN1, FBXW10) in both groups over time and increased expression of PAAF1 in the non-omentectomy group at 12 months. Evidence for the activation of skeletal muscle satellite cells was inferred from the up-regulation of HOXC10. The elevated post-operative expression of 22 small nucleolar RNAs and the decreased expression of the transcription factors JUNB, FOS, FOSB, ATF3 MYC, EGR1 as well as the orphan nuclear receptors NR4A1, NR4A2, NR4A3 suggest dramatic reorganizations at both the cellular and genetic levels. CONCLUSIONS/SIGNIFICANCE: These data indicate that RYGB reduces skeletal muscle inflammation, and removal of omental fat further amplifies this response. TRIAL REGISTRATION: ClinicalTrials.gov NCT00212160.

The effects of an amino acid supplement on glucose homeostasis, inflammatory markers, and incretins after laparoscopic gastric bypass.

BACKGROUND: Protein supplements are routinely used after a laparoscopic gastric bypass (LGB). The aim of this study was to evaluate the impact of an amino acid supplement on glucose homeostasis and hormonal and inflammatory markers after LGB. STUDY DESIGN: Thirty patients undergoing LGB were randomized to receive or not 24 g of an oral supplement containing a leucine metabolite, glutamine, and arginine twice daily. Changes in weight, glucose, insulin, C-peptide, insulin sensitivity, interleukin (IL) 6, C-reactive protein (CRP), leptin, insulin-like growth factor (IGF) 1, ghrelin, and incretins were assessed preoperatively and 2 weeks and 8 weeks postoperatively. RESULTS: Thirty patients (96.7% female, age 46.9 ± 8.4 years, body mass index 43.3 ± 4.1 kg/m(2)) were randomized. The experimental (n = 14) and control (n = 16) groups were not significantly different at baseline. Weight loss was similar for the 2 groups. Fasting glucose decreased significantly at 2 and 8 weeks compared with base line (p < 0.0001) with no difference between the experimental and control groups (p = 0.8), but insulin and calculated insulin sensitivity, which were similar at baseline, became significantly worse in the experimental group 8 weeks after surgery (p = 0.02 for insulin; p = 0.04 for the homeostasis model assessment of insulin resistance). CRP and IL-6, which were similar at baseline, were found to be significantly higher at 8 weeks in the experimental group (p = 0.018 and p = 0.05, respectively). Leptin and IGF-1 levels decreased significantly from baseline at 2 and 8 weeks (p < 0.0001), but there was no difference between the 2 groups. No significant changes in GLP-1, ghrelin, or gastric inhibitory polypeptide were noticed after 8 weeks. CONCLUSIONS: An amino acid supplement had no effect on the early postoperative incretins after LGB. It may have a negative influence on glucose kinetics and degree of inflammation. Future studies are needed to clarify these effects.

Laparoscopic versus open insertion of the peritoneal catheter in ventriculoperitoneal shunt placement: review of 810 consecutive cases.

OBJECT: Traditional ventriculoperitoneal (VP) shunt surgery involves insertion of the distal catheter by minilaparotomy. However, minilaparotomy may be a significant source of morbidity during shunt surgery. Laparoscopic insertion of the distal catheter is an alternative technique that may simplify and improve the safety of shunt surgery. METHODS: The authors performed a retrospective review of hospital records of all patients undergoing new VP shunt insertion at a tertiary care center between 2004 and 2009. Patient characteristics and outcomes were compared between patients undergoing open or laparoscopic insertion of the distal catheter. Independent variables in the analysis included age, sex, race, body mass index, surgical technique, previous VP shunt placement, previous abdominal procedures, American Society of Anesthesiology (ASA) score, and indication for shunt placement. Dependent variables included the occurrence of shunt failure, cause of shunt failure, complications, length of stay (LOS), LOS after shunt placement, estimated blood loss, and operative time. RESULTS: The authors identified 810 patients who met the inclusion criteria; open or laparoscopic distal catheter insertion was performed in 335 and 475 patients, respectively. There were no significant differences between the groups regarding age, race, ASA score, or indication for shunt placement. The most common indication was hydrocephalus due to subarachnoid hemorrhage, followed by tumor-associated hydrocephalus, normal pressure hydrocephalus (NPH), and hydrocephalus due to trauma. The incidence of shunt failure was not statistically different between cohorts, occurring in 20.0% of laparoscopic and 20.9% of open catheter placement cases (p = 0.791). With analysis of causes of shunt failure, shunt obstruction occurred significantly more often in the open surgery cohort (p = 0.012). In patients with a known cause shunt obstruction, distal obstruction occurred in 35.7% of the open cohort obstructions and 4.8% of the laparoscopic cohort obstructions (p = 0.014). The relative risk of distal obstruction in open cases compared with laparoscopic cases was 7.50. Infections occurred in 8.2% of laparoscopic cases compared with 6.6% of open cases (p = 0.419). Within the NPH subgroup, the laparoscopically treated patients had significantly more overdrainage (p = 0.040), whereas those in the open cohort experienced significantly more shunt obstructions (p = 0.034). Laparoscopically treated patients had shorter operative times (p < 0.0005), inpatient LOS (p < 0.001), and inpatient LOS after VP shunt placement (p = 0.01) as well as less blood loss (p = 0.058). CONCLUSIONS: To our knowledge this is the largest reported comparison of distal VP shunt catheter insertion techniques. Compared with minilaparotomy, the laparoscopic approach was associated with decreased time in the operating room and a decreased LOS. Moreover, laparoscopy was associated with fewer distal shunt obstructions. Laparoscopic shunt surgery is a viable alternative to traditional shunt surgery.

Effects of virtual reality simulator training method and observational learning on surgical performance.

BACKGROUND: Virtual reality (VR) simulators and Web-based instructional videos are valuable supplemental training resources in surgical programs, but it is unclear how to optimally integrate them into minimally invasive surgical training. METHODS: Medical students were randomized to proficiency-based training on VR laparoscopy and endoscopy simulators by two different methods: proctored training (automated simulator feedback plus human expert feedback) or independent training (simulator feedback alone). After achieving simulator proficiency, trainees performed a series of laparoscopic and endoscopic tasks in a live porcine model. Prior to their entry into the animal lab, all trainees watched an instructional video of the procedure and were randomly assigned to either observe or not observe the actual procedure before performing it themselves. The joint effects of VR training method and procedure observation on time to successful task completion were evaluated with Cox regression models. RESULTS: Thirty-two students (16 proctored, 16 independent) completed VR training. Cox regression modeling with adjustment for relevant covariates demonstrated no significant difference in the likelihood of successful task completion for independent versus proctored training [Hazard Ratio (HR) 1.28; 95% Confidence Interval (CI) 0.96-1.72; p=0.09]. Trainees who observed the actual procedure were more likely to be successful than those who watched the instructional video alone (HR 1.47; 95% CI 1.09-1.98; p=0.01). CONCLUSIONS: Proctored VR training is no more effective than independent training with respect to surgical performance. Therefore, time-consuming human expert feedback during VR training may be unnecessary. Instructional videos, while useful, may not be adequate substitutes for actual observation when trainees are learning minimally invasive surgical procedures.

Nutritional effect of oral supplement enriched in beta-hydroxy-beta-methylbutyrate, glutamine and arginine on resting metabolic rate after laparoscopic gastric bypass.

BACKGROUND: Weight regain that begins 12-18 months after laparoscopic gastric bypass has been attributed to changes in resting metabolic rate (RMR), which is largely determined by lean body mass (LBM). An oral supplement containing beta-hydroxy-beta-methylbutyrate, glutamine, and arginine (HMB/Glu/Arg) has helped to restore LBM in cachexia due to cancer and in critically ill trauma patients. The objective of this study was to evaluate the effect of oral HMB/Glu/Arg on LBM and RMR following laparoscopic gastric bypass (LGB). METHODS: Patients who underwent LGB were randomized to receive 24 g of HMB/Glu/Arg dissolved in water twice daily for 8 weeks or to receive no supplement. Weight loss, LBM, and RMR were assessed preoperatively, 2 and 8 weeks postoperatively. LBM was determined by dual emission x-ray absorptiometry (DXA) and RMR was measured by indirect calorimetry. RESULTS: Thirty patients were enrolled: 80% white; 20% African American; 96.7% women; mean age 46.9±8.4 years; mean weight 113.4±11.6 kg; and mean body mass index (BMI) 43.3±4.1 kg/m2. The experimental and control groups included 14 and 16 patients, respectively, and there was no difference in baseline demographics and characteristics between the two groups. At 8 weeks, weight, BMI, LBM, and RMR significantly decreased by 15.7±2.5 kg, 6.0±1.0 kg/m2, 7.8±4.0 kg, and 290.6±234.9 kcal/day, respectively (P<0.0001 for each variable). However, when comparing these changes between the two groups, no statistical significance was observed. CONCLUSIONS: There is a significant decrease in weight, BMI, LBM, and RMR in all subjects after LGB, and these changes were not affected by the use of HMB/Glu/Arg. Potential preservation of LBM as a result of HMB/Glu/Arg requires further investigation. However, its consumption (78 calories per serving) did not adversely affect weight loss in the experimental group.

Comparative evaluation of whole body and hepatic insulin resistance using indices from oral glucose tolerance test in morbidly obese subjects with nonalcoholic Fatty liver disease.

Nonalcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a marker of Insulin Resistance (IR). Euglycemic-hyperinsulinemic clamp is the gold standard for measuring whole body IR (hepatic + peripheral IR). However, it is an invasive and expensive procedure. Homeostasis Model Assessment Index for Insulin Sensitivity (HOMA-IS), Quantitative Insulin Sensitivity Check Index (QUICKI) for hepatic IR and Insulin Sensitivity Index (ISI(0,120)), and Whole Body Insulin Sensitivity Index (WBISI) for whole body IR are the indices calculated after Oral Glucose Tolerance Test (OGTT). We used these indices as noninvasive methods of IR (inverse of insulin sensitivity) estimation and compared hepatic/peripheral components of whole body IR in NAFLD. Methods. 113 morbidly obese, nondiabetic subjects who underwent gastric bypass surgery and intraoperative liver biopsy were included in the study. OGTT was performed preoperatively and the indices were calculated. Subjects were divided into closely matched groups as normal, fatty liver (FL) and Non-Alcoholic Steatohepatitis (NASH) based on histology. Results. Whole body IR was significantly higher in both FL and NASH groups (NAFLD) as compared to Normal, while hepatic IR was higher only in NASH from Normal. Conclusions. FL is a manifestation of peripheral IR but not hepatic IR.

Inflammation anergy in human intestinal macrophages is due to Smad-induced IkappaBalpha expression and NF-kappaB inactivation.

Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3-TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon beta, which together mediate all TLR MyD88-dependent and -independent NF-kappaB signaling, did not phosphorylate NF-kappaB p65 or Smad-induced IkappaBalpha, and did not translocate NF-kappaB into the nucleus. Importantly, transforming growth factor-beta released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-kappaB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-beta-induced dysregulation of NF-kappaB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages.

Cognitive performance of morbidly obese patients seeking bariatric surgery.

Bariatric surgery is efficacious for the treatment of severe obesity; however, little empirical research exists describing the demographic, psychosocial, and cognitive characteristics of patients presenting for the surgery. One hundred and sixty-nine morbidly obese patients seeking bariatric surgery underwent a presurgical psychological assessment, including cognitive testing. Morbidly obese individuals seeking bariatric surgery were similar in education, income status, and IQ compared with normative data. IQ was average, did not correlate with body mass index, and reflected a normal distribution. As a group, bariatric surgery patients endorsed minimal levels of depression and low levels of psychopathology. Obese individuals did demonstrate specific cognitive deficits on tests of executive function (e.g., problem solving and planning) when compared with normative data. This data suggests that bariatric surgery patients differ very little from other surgical populations on most demographic and psychosocial variables. The data does provide evidence for specific cognitive deficits in the area of executive functions at baseline in morbidly obese adults seeking bariatric surgery.

Laparoscopy-assisted transjejunal ERCP in a patient with Roux-en-Y reconstruction following partial gastrectomy.

In this article, we report a patient with a history of partial gastrectomy and Roux-en-Y reconstruction who presented with abdominal pain due to sphincter of Oddi dysfunction. After failed endoscopic retrograde cholangiopancreatography (ERCP) through the anatomic route, the procedure was successfully performed with laparoscopy assistance through an enterotomy into the biliopancreatic limb. An internal hernia was diagnosed incidentally and treated appropriately. Laparoscopy-assisted ERCP is a viable option in patients with Roux-en-Y anatomy, even when the gastric remnant and duodenum are not available.

Dendritic cells transmit HIV-1 through human small intestinal mucosa.

To dissect the early events in the transmission of HIV-1 from mother to child, we investigated whether DCs participate in HIV-1 entry into human small intestinal mucosa. We isolated human MNLs from jejunal lamina propria and identified a subpopulation of CD11c(+)HLA-DR(+) MNLs that expressed DC-SIGN, CD83, CD86, CD206, and CCR7, indicating a DC phenotype. Jejunal DCs also expressed the HIV-1 receptor CD4 and coreceptors CCR5 and CXCR4 and in suspension rapidly took up cell-free HIV-1. HIV-1 inoculated onto the apical surface of explanted jejunum was transported by lamina propria DCs through the mucosa and transmitted in trans to blood and intestinal lymphocytes. These findings indicate that in addition to intestinal epithelial cells, which we showed previously transcytose infectious HIV-1 to indicator cells, intestinal DCs play an important role in transporting HIV-1 through the intestinal mucosa and the subsequent transmission to T cells.