RBP4 increases lipolysis in human adipocytes and is associated with increased lipolysis and hepatic insulin resistance in obese women.

Retinol-binding protein-4 (RBP4) is elevated in serum and adipose tissue (AT) in obesity-induced insulin resistance and correlates inversely with insulin-stimulated glucose disposal. But its role in insulin-mediated suppression of lipolysis, free fatty acids (FFA), and endogenous glucose production (EGP) in humans is unknown. RBP4 mRNA or protein levels were higher in liver, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in morbidly obese subjects undergoing Roux-en-Y gastric bypass surgery compared to lean controls undergoing elective laparoscopic cholecystectomy. RBP4 mRNA expression in SAT correlated with the expression of several macrophage and other inflammation markers. Serum RBP4 levels correlated inversely with glucose disposal and insulin-mediated suppression of lipolysis, FFA, and EGP. Mechanistically, RBP4 treatment of human adipocytes in vitro directly stimulated basal lipolysis. Treatment of adipocytes with conditioned media from RBP4-activated macrophages markedly increased basal lipolysis and impaired insulin-mediated lipolysis suppression. RBP4 treatment of macrophages increased TNFα production. These data suggest that elevated serum or adipose tissue RBP4 levels in morbidly obese subjects may cause hepatic and systemic insulin resistance by stimulating basal lipolysis and by activating macrophages in adipose tissue, resulting in release of pro-inflammatory cytokines that impair lipolysis suppression. While we have demonstrated this mechanism in human adipocytes in vitro, and correlations from our flux studies in humans strongly support this, further studies are needed to determine whether this mechanism explains RBP4-induced insulin resistance in humans.

Changes in glycemic control and body weight after explantation of the duodenal-jejunal bypass liner.

BACKGROUND AND AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device that induces weight loss and improves glycemic control in patients with type 2 diabetes mellitus (T2DM). The aim of the current study was to assess the effects of DJBL explantation on glycemic control and body weight. METHODS: This prospective, observational study included only patients with T2DM who had the DJBL implanted for at least 6 months and had a follow-up of at least 12 months after explantation. The primary endpoints were changes in glycosylated hemoglobin A1c (HbA1c) and body weight during the 12 months after explantation. Secondary endpoints were changes in fasting plasma glucose, blood pressure, and plasma lipid levels. RESULTS: In total, 59 patients completed the 12-month follow-up after explantation. During this period body weight increased by 5.6 (standard deviation, 6.4) kg (P < .001) and HbA1c rose from 65 (SD 17) to 70 (SD 20) mmol/mol (P < .001). However, body weight remained 8.0 (SD 8.6) kg (P < .001) lower than before implantation, that is, corresponding to a net total body weight loss of 7.4% (SD 7.6) (P < .001). Although HbA1c was significantly higher 12 months after explantation compared with baseline and the mean daily dose of insulin used was comparable, the number of patients on insulin remained significantly lower than before implantation. CONCLUSIONS: Explantation of the DJBL is associated with weight gain and worsening of glycemic control, although some beneficial effects remained detectable 12 months after explantation. A change in strategy is needed to preserve the beneficial effects of DJBL treatment. (Clinical trial registration number: 746∖100111.).

A short or a long Roux limb in gastric bypass surgery: does it matter?

BACKGROUND: The Roux-en-Y gastric bypass (RYGB) still remains the gold standard in bariatric surgery. However, no consensus exists on the optimal limb lengths to induce maximum weight reduction. The aim of the present study was to assess the effect of a longer alimentary limb (AL) length on weight reduction after RYGB. METHODS: A retrospective analysis of a prospectively collected database of patients who underwent a primary laparoscopic RYGB between January 2001 and March 2011 was performed. Patients received a short AL (SAL; 100 cm) or a long AL (LAL; 150 cm). Primary outcome was weight loss, and secondary outcomes were short- and long-term complication rates. RESULTS: A total of 768 patients received a RYGB during the study period. Of these, 730 consecutive patients were included for long-term analysis and had a mean follow-up (FU) of 37 ± 26 [range 0-120] months; 360 (47 %) patients received a SAL RYGB. Overall %TBWL was 33 ± 9 % after 2 years (FU 74 %) and 28 ± 12 % after 5 years (FU 20 %). No significant differences in %TBWL were found between SAL RYGB and LAL RYGB during the study period. The 30-day mortality rate was 0.13, 9 % overall short-term complication rate and 19 % cumulative long-term complication rate. No differences in complications were found between SAL and LAL RYGB patients. CONCLUSION: Lengthening of the alimentary limb from 100 to 150 cm did not affect post-RYGB weight loss. Overall complication rates were low and comparable in this series of RYGB patients.

Weight reduction and improvement in diabetes by the duodenal-jejunal bypass liner: a 198 patient cohort study.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is an endoscopic treatment for patients with type 2 diabetes mellitus (T2DM) and (morbid) obesity. The aim of the current study was to determine its efficacy and safety profile. METHODS: Inclusion criteria for treatment with a DJBL were: age 18-70 years, BMI 28-45 kg/m2, and T2DM with a HbA1c > 48 mmol/mol. Primary outcomes were changes in HbA1c and body weight. Secondary outcomes included changes in blood pressure, lipids, and anti-diabetic medication. Predictive factors for success of treatment with the DJBL were determined. RESULTS: Between 2011 and 2014, 185 out of 198 patients successfully underwent a DJBL implantation procedure, with an intended implantation time of 12 months. In these 185 patients, body weight decreased by 12.8 ± 8.0 kg (total body weight loss of 11.9 ± 6.9 %, p < 0.001), HbA1c decreased from 67 to 61 mmol/mol (p < 0.001) despite a reduction in anti-diabetic medication, and blood pressure and serum lipid levels all decreased. In total, 57 (31 %) DJBLs were explanted early after a median duration of 33 weeks. Adverse events occurred in 17 % of patients. C-peptide ≥1.0 nmol/L and body weight ≥107 kg at screening were independent predictive factors for success. CONCLUSIONS: Treatment with the DJBL in T2DM patients with (morbid) obesity results in improvement in glucose control, a reduction in anti-diabetic medication, and significant weight loss. The largest changes are observed within the first 3-6 months. Initial C-peptide levels and body weight may help to select patients with the greatest chance of success.

Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.

BACKGROUND & AIMS: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA alters hepatic expression of many genes. However, no data are available on the effects of OCA in the human liver. Here we generated gene expression profiles in human precision cut liver slices (hPCLS) after treatment with OCA. METHODS: hPCLS were incubated with OCA for 24 h. Wild-type or FXR(-/-) mice received OCA or vehicle by oral gavage for 7 days. RESULTS: Transcriptomic analysis showed that well-known FXR target genes, including NR0B2 (SHP), ABCB11 (BSEP), SLC51A (OSTα) and SLC51B (OSTß), and ABCB4 (MDR3) are regulated by OCA in hPCLS. Ingenuity pathway analysis confirmed that 'FXR/RXR activation' is the most significantly changed pathway upon OCA treatment. Comparison of gene expression profiles in hPCLS and mouse livers identified 18 common potential FXR targets. ChIP-sequencing in mouse liver confirmed FXR binding to IR1 sequences of Akap13, Cgnl1, Dyrk3, Pdia5, Ppp1r3b and Tbx6. CONCLUSIONS: Our study shows that hPCLS respond to OCA treatment by upregulating well-known FXR target genes, demonstrating its suitability to study FXR-mediated gene regulation. We identified six novel bona-fide FXR target genes in both mouse and human liver. Finally, we discuss a possible explanation for changes in high or low density lipoprotein observed in NASH and primary biliary cholangitis patients treated with OCA based on the genomic expression profile in hPCLS.

Small bites versus large bites for closure of abdominal midline incisions (STITCH): a double-blind, multicentre, randomised controlled trial.

BACKGROUND: Incisional hernia is a frequent complication of midline laparotomy and is associated with high morbidity, decreased quality of life, and high costs. We aimed to compare the large bites suture technique with the small bites technique for fascial closure of midline laparotomy incisions. METHODS: We did this prospective, multicentre, double-blind, randomised controlled trial at surgical and gynaecological departments in ten hospitals in the Netherlands. Patients aged 18 years or older who were scheduled to undergo elective abdominal surgery with midline laparotomy were randomly assigned (1:1), via a computer-generated randomisation sequence, to receive small tissue bites of 5 mm every 5 mm or large bites of 1 cm every 1 cm. Randomisation was stratified by centre and between surgeons and residents with a minimisation procedure to ensure balanced allocation. Patients and study investigators were masked to group allocation. The primary outcome was the occurrence of incisional hernia; we postulated a reduced incidence in the small bites group. We analysed patients by intention to treat. This trial is registered at Clinicaltrials.gov, number NCT01132209 and with the Nederlands Trial Register, number NTR2052. FINDINGS: Between Oct 20, 2009, and March 12, 2012, we randomly assigned 560 patients to the large bites group (n=284) or the small bites group (n=276). Follow-up ended on Aug 30, 2013; 545 (97%) patients completed follow-up and were included in the primary outcome analysis. Patients in the small bites group had fascial closures sutured with more stitches than those in the large bites group (mean number of stitches 45 [SD 12] vs 25 [10]; p<0·0001), a higher ratio of suture length to wound length (5·0 [1·5] vs 4·3 [1·4]; p<0·0001) and a longer closure time (14 [6] vs 10 [4] min; p<0·0001). At 1 year follow-up, 57 (21%) of 277 patients in the large bites group and 35 (13%) of 268 patients in the small bites group had incisional hernia (p=0·0220, covariate adjusted odds ratio 0·52, 95% CI 0·31-0·87; p=0·0131). Rates of adverse events did not differ significantly between groups. INTERPRETATION: Our findings show that the small bites suture technique is more effective than the traditional large bites technique for prevention of incisional hernia in midline incisions and is not associated with a higher rate of adverse events. The small bites technique should become the standard closure technique for midline incisions. FUNDING: Erasmus University Medical Center and Ethicon.

The impact of PPARα activation on whole genome gene expression in human precision cut liver slices.

BACKGROUND: Studies in mice have shown that PPARα is an important regulator of lipid metabolism in liver and key transcription factor involved in the adaptive response to fasting. However, much less is known about the role of PPARα in human liver. METHODS: Here we set out to study the function of PPARα in human liver via analysis of whole genome gene regulation in human liver slices treated with the PPARα agonist Wy14643. RESULTS: Quantitative PCR indicated that PPARα is well expressed in human liver and human liver slices and that the classical PPARα targets PLIN2, VLDLR, ANGPTL4, CPT1A and PDK4 are robustly induced by PPARα activation. Transcriptomics analysis indicated that 617 genes were upregulated and 665 genes were downregulated by PPARα activation (q value < 0.05). Many genes induced by PPARα activation were involved in lipid metabolism (ACSL5, AGPAT9, FADS1, SLC27A4), xenobiotic metabolism (POR, ABCC2, CYP3A5) or the unfolded protein response, whereas most of the downregulated genes were involved in immune-related pathways. Among the most highly repressed genes upon PPARα activation were several chemokines (e.g. CXCL9-11, CCL8, CX3CL1, CXCL6), interferon γ-induced genes (e.g. IFITM1, IFIT1, IFIT2, IFIT3) and numerous other immune-related genes (e.g. TLR3, NOS2, and LCN2). Comparative analysis of gene regulation by Wy14643 between human liver slices and primary human hepatocytes showed that down-regulation of gene expression by PPARα is much better captured by liver slices as compared to primary hepatocytes. In particular, PPARα activation markedly suppressed immunity/inflammation-related genes in human liver slices but not in primary hepatocytes. Finally, several putative new target genes of PPARα were identified that were commonly induced by PPARα activation in the two human liver model systems, including TSKU, RHOF, CA12 and VSIG10L. CONCLUSION: Our paper demonstrates the suitability and superiority of human liver slices over primary hepatocytes for studying the functional role of PPARα in human liver. Our data underscore the major role of PPARα in regulation of hepatic lipid and xenobiotic metabolism in human liver and reveal a marked immuno-suppressive/anti-inflammatory effect of PPARα in human liver slices that may be therapeutically relevant for non-alcoholic fatty liver disease.

Safety experience with the duodenal-jejunal bypass liner: an endoscopic treatment for diabetes and obesity.

BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is a new, device-based endoscopic treatment for type 2 diabetes mellitus (T2DM) and obesity. OBJECTIVE: To report serious safety events of subjects treated with the DJBL while offering a simple guideline to mitigate risk. DESIGN: Single-center observational study. SETTING: Tertiary referral center. PATIENTS: For commercial use, patients were eligible for implantation of the DJBL when they met the following criteria: age 18 to 65 years, body mass index 28 to 45 kg/m(2), T2DM, and negative serum Helicobacter pylori test. INTERVENTIONS: Endoscopic implantation of the DJBL. MAIN OUTCOME MEASUREMENTS: Adverse events, serious adverse events, early explantation. RESULTS: Between October 2007 and January 2014, 152 of 165 planned implantations (92%) and 94 explantations were performed in our center. Significant weight loss and improvement in T2DM and other cardiovascular parameters were achieved. Early removal of the device occurred because of persistent GI symptoms in 16 patients (11%). Serious adverse events were observed in a subset of patients: 7 GI bleeds, 5 of which required early removal; 2 cases of pancreatitis; 1 case of hepatic abscess; and 1 obstruction of the sleeve. Explantation resulted in an esophageal tear in 2 cases. LIMITATIONS: Single-center study. CONCLUSION: The DJBL improves glycemic control while causing weight loss. The safety profile of the DJBL demonstrates a reasonable tolerability profile. However, serious safety adverse events can occur. Patient selection, expert use of the device at placement and removal, and the supportive care of an experienced multidisciplinary team are key for safe and effective use of the DJBL.

The effect of the endoscopic duodenal-jejunal bypass liner on obesity and type 2 diabetes mellitus, a multicenter randomized controlled trial.

OBJECTIVE: Investigate the safety and efficacy of 6 months' duodenal-jejunal bypass liner (DJBL) treatment in comparison with dietary intervention for obesity and type 2 diabetes mellitus (T2DM). BACKGROUND: The DJBL is a bariatric procedure involving an impermeable sleeve that is delivered endoscopically in the proximal intestine. This procedure not only is less invasive than conventional surgical techniques but also has beneficial effects on obesity and T2DM. METHODS: A multicenter randomized controlled trial was conducted. Seventy-seven patients with obesity and T2DM were included. Thirty-eight patients were randomized to 6 months' DJBL treatment in combination with dietary intervention (34 successfully implanted, 31 completed the study), 39 patients received only dietary intervention (controls, 35 completed the study). Total study duration for both groups was 12 months, including 6 months of post-DJBL removal follow-up. RESULTS: After 6 months, just before DJBL removal, the DJBL group had lost 32.0% [22.0%-46.7%] of their excess weight versus 16.4% [4.1%-34.6%] in the control group (P < 0.05). Glycated hemoglobin A1c levels improved to 7.0% [6.4%-7.5%] in the DJBL group and to 7.9% [6.6%-8.3%] in the control group (P < 0.05). In addition, 85.3% of DJBL patients showed decreased postprandial glucose excursions versus 48.7% of control patients (P < 0.05). At 12 months, excess weight loss of the DJBL group was 19.8% [10.6%-45.0%] versus 11.7% [1.4%-25.4%] in the control group (P < 0.05). HbA1c was 7.3% [6.6%-8.0%] versus 8.0% [6.8%-8.8%], DJBL versus control respectively (P = ns). CONCLUSIONS: The DJBL is a safe and effective alternative to invasive bariatric procedures. Six months of DJBL treatment combined with diet leads to superior weight loss and improvement of T2DM when compared with diet alone.

Calorie restriction is a major determinant of the short-term metabolic effects of gastric bypass surgery in obese type 2 diabetic patients.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) and restrictive weight loss interventions, such as gastric banding (GB) and very-low-calorie diets (VLCD) directly impact glucose metabolism, possibly by calorie restriction and/or altered secretion of gut hormones. We aimed to establish the direct endocrine and metabolic effects of RYGB compared to restrictive interventions in obese glucose-tolerant (NGT) subjects and subjects with type 2 diabetes (T2DM). DESIGN: Controlled, nonrandomized observational trial. PATIENTS AND MEASUREMENTS: Four groups of obese females received a mixed meal at baseline and 3 weeks after intervention; NGT-GB (n = 11), NGT-RYGB (n = 16), T2DM-RYGB (n = 15) and T2DM-VLCD (n = 12). Normal weight controls (n = 12) were studied once. RESULTS: At baseline, all obese subjects were hyperinsulinemic. T2DM was associated with hyperglycaemia and decreased GLP-1 levels. RYGB and VLCD reduced glucose levels to a similar extent in T2DM, insulin levels decreased only after VLCD. Comparison of restrictive intervention vs RYGB showed a more pronounced decrease in glucose and insulin AUC after restriction. In NGT and T2DM subjects, RYGB increased GLP-1 and PYY levels and decreased ghrelin levels, whereas VLCD and GB only increased GIP levels. CONCLUSIONS: These data indicate that deterioration of glucose metabolism in T2DM is associated with a decline of GLP-1 levels. Calorie restriction facilitates glucose metabolism and blunts hyperinsulinemia in obese (diabetic) humans. Additional duodenal exclusion through RYGB induces gut hormone release and hyperinsulinemia but does not improve postprandial glucose levels any further. Our data thus strongly suggest that calorie restriction underlies the short-term metabolic benefits of RYGB in obese T2DM patients.

Calorie restriction and Roux-en-Y gastric bypass have opposing effects on circulating FGF21 in morbidly obese subjects.

OBJECTIVE: To study the effect of different weight loss strategies on levels of the metabolic regulator FGF21 in morbidly obese females with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM). DESIGN: Observational intervention trial. PATIENTS AND MEASUREMENTS: Weight reduction was achieved by Gastric Banding (GB, n = 11) or Roux-en-Y Gastric Bypass (RYGB, n = 16) in subjects with NGT, and by RYGB (n = 15) or a very-low-calorie diet (VLCD, n = 12) in type 2 diabetics. Fasted and/or postprandial levels of FGF21, FGF19 (an FGF21-related postprandial hormone) and bile salts (implicated in regulation of FGF21 and FGF19 expression) were measured before, and 3 and 12 weeks after intervention. RESULTS: Fasted FGF21 levels were elevated in T2DM subjects. Calorie restriction by either GB or VLCD lowered bile salt and FGF21 levels. In contrast, RYGB surgery was associated with elevated bile salt and FGF21 levels. CONCLUSIONS: Calorie restriction and RYGB have opposite effects on serum bile salt and FGF21 levels. Calorie restriction results in FGF21 approaching nonobese control levels, suggesting that this intervention is effective in reducing the "nutritional crisis" that appears to underly FGF21 elevation in obesity. FGF21 elevation after RYGB may contribute to the beneficial effect of this procedure.

Hepatic steatosis in morbidly obese patients undergoing gastric bypass surgery: assessment with open-system 1H-MR spectroscopy.

OBJECTIVE: The purpose of this study was to assess, with histopathologic control, the use of open-system 1-T (1)H MR spectroscopy for the evaluation of hepatic steatosis in morbidly obese patients undergoing gastric bypass surgery. SUBJECTS AND METHODS: Patients underwent (1)H MR spectroscopy (MRS) for the assessment of steatosis before and 3 months after surgery. Liver biopsy was performed during surgery. Hepatic steatosis was expressed as the ratio of fat peak area to cumulative water and fat peak areas. Histopathologic percentage of steatosis was graded as none (0-5%), mild (5-33%), moderate (33-66%), or severe (> 66%). The accuracy of (1)H-MRS and Spearman correlation coefficient were calculated. Differences between groups were assessed with the Wilcoxon signed rank and Mann-Whitney tests. RESULTS: The study included 38 patients (median age, 45.5 years; median body mass index, 47.7). Before surgery, median steatosis measured with (1)H-MRS was 5.8%. The accuracy of (1)H-MRS was 89% (32/36), and the (1)H-MRS findings correlated with the histopathologic assessment of steatosis (r = 0.85, p < 0.001). With (1)H-MRS, no steatosis was discriminated from mild steatosis (p = 0.011), mild was discriminated from moderate steatosis (p < 0.001), and moderate was discriminated from severe steatosis (p = 0.021). Three months after surgery, steatosis had decreased to 3.1% (p < 0.001). The prevalence of hepatic steatosis measured with (1)H-MRS decreased from 53% to 32%. CONCLUSION: In the care of morbidly obese patients undergoing assessment of hepatic steatosis and changes in steatosis after gastric bypass surgery, (1)H-MRS with an open 1-T MRI system is feasible. Measurements of hepatic fat with (1)H-MRS are accurate and correlate with clinical and histopathologic results.

The True Story on Deficiencies After Sleeve Gastrectomy: Results of a Double-Blind RCT.

BACKGROUND: Since a few years, the laparoscopic sleeve gastrectomy (SG) has become the most performed bariatric operation worldwide. However, as with all bariatric procedures, SG also leads to vitamin and mineral deficiencies post-operatively and standard multivitamin supplements are probably not sufficient. OBJECTIVE: The present study evaluates the effectiveness of a specialized multivitamin supplement for SG patients (WLS Optimum 1.0, FitForMe, Rotterdam, the Netherlands), compared to a standard multivitamin supplement (sMVS). DESIGN: A double-blind randomized controlled trial was performed. For 12 months, patients in the intervention group received WLS Optimum, containing elevated doses of multiple vitamins and minerals. Patients in the control group were provided with sMVS, containing 100% of the recommended dietary allowance. RESULTS: In total, 139 patients were available for analysis (WLS Optimum, n = 69; sMVS, n = 70). Intention-to-treat analyses revealed more folic acid deficiencies and higher serum vitamin B1 levels in the WLS Optimum group. Per protocol analyses showed that in patients using WLS Optimum, serum folic acid and vitamin B1 levels were higher, serum PTH levels were lower, and only one patient (2.6%) was anemic compared to 11 patients (17.5%) using a sMVS (p < 0.05 for all). No differences were found in prevalence of deficiencies for iron, vitamin B12, vitamin D, and other vitamins and minerals. CONCLUSIONS: This optimized multivitamin supplement only affected serum levels of folic acid, PTH and vitamin B1, and anemia rates compared to a sMVS. There is a clear need to further optimize multivitamin supplementation for SG patients. Besides, non-compliance with multivitamin supplements remains an important issue that should be dealt with. CLINICAL TRIAL REGISTRY: The study protocol was registered at the clinical trials registry of the National Institutes of Health (ClinicalTrials.gov; identifier NCT01609387).

A randomized controlled trial comparing oral and intravenous iron supplementation after Roux-en-Y gastric bypass surgery.

BACKGROUND: Iron deficiency (ID) is one of the most common postoperative deficiencies that may develop after Roux-en-Y gastric bypass (RYGB). The optimal mode of treatment is uncertain. AIM: To compare the efficacy of oral ferrous fumarate (FF), oral ferrous gluconate (FG), and a single intravenous infusion of ferric carboxymaltose (FCM) in women with ID after RYGB. METHODS: Multicenter randomized controlled trial including 120 women with a serum ferritin <20 µg/l during follow-up after RYGB. They were randomized into three groups: 41 patients were treated with FF 200 mg three times a day (total daily dose: 195 mg elemental iron), 39 received FG 695 mg twice a day (total daily dose: 160 mg elemental iron) for three months, and 39 patients were treated with a single intravenous dose of FCM (1000 mg elemental iron). Serum ferritin levels were measured at six weeks, and three, six and twelve months after the start of supplementation. RESULTS: At three months, persistence of ID was observed in 29.4% and 42.4% of the patients treated with FF and FG, respectively, but in none of those treated with FCM (p < 0.001). Over the next nine months, recurrence of ID was observed in 56.5% of patients treated with FF, in 52.9% treated with FG, and in 27.8% of those treated with FCM. Adverse effects were most common during oral treatment. CONCLUSION: In women developing ID after RYGB, a single dose of intravenous FCM is more effective and better tolerated than the standard treatment with either FF or FG. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: The study was registered at clinicaltrials.gov under number NCT02271997.

Correction to: Adequate Multivitamin Supplementation after Roux-En-Y Gastric Bypass Results in a Decrease of National Health Care Costs: a Cost-Effectiveness Analysis.

In the original article, there are some incorrect data in the "Results" section of the Abstract.

Adequate Multivitamin Supplementation after Roux-En-Y Gastric Bypass Results in a Decrease of National Health Care Costs: a Cost-Effectiveness Analysis.

INTRODUCTION: Patients with morbid obesity undergoing metabolic surgery are prone to develop vitamin and mineral deficiencies, which may worsen in time. In order to prevent these deficiencies after metabolic surgery, all patients are advised to take daily multivitamin supplementation. The aim of the study was to assess the cost-effectiveness of specially developed multivitamins (WLS Forte®) for metabolic surgery and over-the-counter (standard) multivitamin supplementation (sMVS). METHODS: This cost-effectiveness analysis was preformed alongside an RCT for the Netherlands. Between June 2011 and March 2012, a total of 148 patients were randomized to one tablet daily of either WLS Forte® or sMVS. The patients were followed for 12 months. Data on costs within the health sector and outside the health sector were collected. The primary outcome is financial and logistic advantages, in terms of less patient visits to the outpatient department and the relevant costs to the employer due to absenteeism. RESULTS: In total, 10 (14%) patients in the WLS Forte® group versus 23 (30%) patients in the sMVS group developed a deficiency. The costs for the WLS forte® supplement were €38 versus €23 for sMVS. Additional return visits and associated costs for medical staff were the largest costs, up to 43% in the sMVS group. Total costs for supplementation with sMVS were €243 versus €134 for WLS Forte®. CONCLUSION: Preventing deficiencies with WLS Forte® seem initially more expensive than sMVS. However, treatment with WLS Forte® resulted in less vitamin and mineral deficiencies, which eventually resulted in less overall costs.

Genetic analysis in the bariatric clinic; impact of a PTEN gene mutation.

BACKGROUND: Pathogenic PTEN gene mutations are known to cause PTEN tumor hamartoma syndrome. Recent studies also suggest a role for PTEN mutations in the pathogenesis of obesity. No PTEN mutations have been reported among bariatric surgery patients and obesity treatment results are unknown. Since preventive screening for associated tumors is offered to patients with molecular proven PTEN hamartoma tumor syndrome, recognition of this condition in the bariatric surgery clinic is important. METHOD: We present a patient with morbid obesity who carries a known pathogenic PTEN mutation, identified at the bariatric surgery clinic using an obesity gene panel consisting of 52 obesity-associated genes. We analyzed the weight loss response during the first 3 years after Sleeve Gastrectomy. RESULTS: At 1, 2 and 3 years after surgery, the patient achieved a Total Body Weight Loss of 39.4%, 48.8% and 44.9%, respectively. This corresponds to the results of a control group of 18 female patients with normal genetic test results. CONCLUSION: Our patient illustrates the importance of recognizing this serious genetic condition for which preventive cancer screening options are available. The positive weight loss results after Sleeve Gastrectomy suggest that this could be a successful treatment option for obesity patients with PTEN mutations.

A novel abdominal wall entry suction device to increase Veress needle safety: A prospective cohort pilot study.

BACKGROUND: In laparoscopic surgery, the Veress needle technique is most often used to initiate a pneumoperitoneum. Although low, entry-related injuries of the intestines and major vascular structures occur in 0.04-0.1% of cases. Up to 50% of these injuries remain undiagnosed at the time of surgery, resulting in mortality rates between 2.5 and 30%. In an effort to minimize such injuries we objectively assessed a novel abdominal wall entry suction device (AWESD) that was hypothesized to lift the abdominal wall and create an additional post-peritoneum safe margin for safer Veress needle introduction. MATERIALS AND METHODS: A prospective pilot study was conducted in which CT-scans with and without AWESD application (centered above the umbilicus) were assessed to determine its effect on the distance from the linea alba to the intestines, vena cava and abdominal aorta. Paired measurements were subjected to the Wilcoxon signed rank test. RESULTS: Twelve participants were included. The AWESD significantly increased the median distance towards the intestines in the axial and sagittal plane (P = 0.01 and P = 0.006) from 0.93 (Inter Quartile Range (IQR): 0.33-1.51) and 0.85 (IQR: 0.32-1.47) to 1.35 (IQR: 0.39-2.27) and 1.25 (IQR: 0.42-2.10) centimeters, respectively. Similarly, for the median axial distances towards the vena cava and abdominal aorta (both P = 0.002) that were increased from 10.00 (IQR: 7.18-11.12) and 9.33 (IQR: 6.55-10.28) to 13.23 (IQR: 11.76-14.31) and 12.49 (IQR: 10.98-13.32) centimeters, respectively. CONCLUSION: The AWESD significantly increased the distances between the peritoneum and main intra-abdominal structures. However, conclusions on subsequent increased safety cannot be drawn as high-volume studies are required to determine its clinical relevance.

Long-term nutritional status in patients following Roux-en-Y gastric bypass surgery.

BACKGROUND & AIMS: Roux-en-Y gastric bypass (RYGB) is an effective treatment for obesity. However, it also leads to multiple nutritional deficiencies. Much is known about the short term prevalence, but hardly any long term data is available on deficiencies. The aim of this study was to assess the long term outcome of nutritional status after RYGB. METHODS: We performed a retrospective analysis of prospectively collected data obtained from 51 morbidly obese patients who underwent a primary laparoscopic RYGB. Primary outcomes were iron, vitamin B12 and vitamin D deficiencies. Secondary outcomes were deficiencies of other vitamins and minerals and compliance of the patients to multivitamin use. RESULTS: The mean follow-up was 81 ± 27 months. A total of 35%, 16% and 55% of the patients had deficiencies for iron, vitamin B12 and vitamin D respectively. Sixty-nine percent of patients used a (nonspecific) multivitamin supplement on a daily basis. Patients with multivitamin usage had a lower rate of iron deficiency (26% vs. 56%, p = 0.034), vitamin B12 (11% vs. 25%, p = 0.46) and vitamin D (46% vs. 75%, p = 0.07), compared to non-compliant patients. CONCLUSIONS: Nutritional deficiencies are common after a RYGB operation. Therefore, strict follow-up by a bariatric surgeon, endocrinologist or general practitioner is required, both short and long term.