Weight recurrence after Sleeve Gastrectomy versus Roux-en-Y gastric bypass: a propensity score matched nationwide analysis.

BACKGROUND: Literature remains scarce on patients experiencing weight recurrence after initial adequate weight loss following primary bariatric surgery. Therefore, this study compared the extent of weight recurrence between patients who received a Sleeve Gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) after adequate weight loss at 1-year follow-up. METHODS: All patients undergoing primary RYGB or SG between 2015 and 2018 were selected from the Dutch Audit for Treatment of Obesity. Inclusion criteria were achieving ≥ 20% total weight loss (TWL) at 1-year and having at least one subsequent follow-up visit. The primary outcome was ≥ 10% weight recurrence (WR) at the last recorded follow-up between 2 and 5 years, after ≥ 20% TWL at 1-year follow-up. Secondary outcomes included remission of comorbidities at last recorded follow-up. A propensity score matched logistic regression analysis was used to estimate the difference between RYGB and SG. RESULTS: A total of 19.762 patients were included, 14.982 RYGB and 4.780 SG patients. After matching 4.693 patients from each group, patients undergoing SG had a higher likelihood on WR up to 5-year follow-up compared with RYGB [OR 2.07, 95% CI (1.89-2.27), p < 0.01] and less often remission of type 2 diabetes [OR 0.69, 95% CI (0.56-0.86), p < 0.01], hypertension (HTN) [OR 0.75, 95% CI (0.65-0.87), p < 0.01], dyslipidemia [OR 0.44, 95% CI (0.36-0.54), p < 0.01], gastroesophageal reflux [OR 0.25 95% CI (0.18-0.34), p < 0.01], and obstructive sleep apnea syndrome (OSAS) [OR 0.66, 95% CI (0.54-0.8), p < 0.01]. In subgroup analyses, patients who experienced WR after SG but maintained ≥ 20%TWL from starting weight, more often achieved HTN (44.7% vs 29.4%), dyslipidemia (38.3% vs 19.3%), and OSAS (54% vs 20.3%) remission compared with patients not maintaining ≥ 20%TWL. No such differences in comorbidity remission were found within RYGB patients. CONCLUSION: Patients undergoing SG are more likely to experience weight recurrence, and less likely to achieve comorbidity remission than patients undergoing RYGB.

The endothelial function biomarker soluble E-selectin is associated with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Plasma soluble E-selectin (sE-selectin) is a frequently used biomarker of systemic endothelial dysfunction. The present study explored the relationship between nonalcoholic fatty liver disease (NAFLD) and plasma sE-selectin levels. METHODS: Expression of E-selectin in liver, visceral adipose tissue (VAT) and muscle was studied in relation to plasma sE-selectin in severely obese individuals (n = 74). The course of hepatic E-selectin expression in relation to hepatic steatosis and inflammation was examined in C57BL/6J LDLR-/- mice on a Western-type diet. The relationship between biomarkers of NAFLD, that is, plasma aminotransferase (ALT) and NAFLD susceptibility genes (rs738409 [PNPLA3] and rs1260326 [GCKR]), and plasma sE-selectin was studied in the combined CODAM (n = 571) and Hoorn (n = 694) studies. RESULTS: E-selectin expression in liver, not VAT or muscle, was associated with plasma sE-selectin in severely obese individuals (ß = 0.26; 95% CI: 0.05-0.47). NAFLD severity was associated with hepatic E-selectin expression (P = .02) and plasma sE-selectin (P = .003). LDLR-/- mice on a Western-type diet displayed increased hepatic E-selectin expression that followed the same course as hepatic inflammation, but not steatosis. In the CODAM study, plasma ALT was associated with plasma sE-selectin, independent of potential confounders (ß = 0.25; 95% CI: 0.16-0.34). Both rs738409 and rs1260326 were associated with higher plasma sE-selectin in the combined CODAM and Hoorn studies (P = .01 and P = .004 respectively). CONCLUSIONS: NAFLD and related markers are associated with higher expression of hepatic E-selectin and higher levels of plasma sE-selectin. Further studies are required to investigate the role of E-selectin in the pathogenesis of NAFLD and the applicability of sE-selectin as a plasma biomarker of NAFLD/NASH.

Measuring quality of life in bariatric surgery: a multicentre study.

BACKGROUND: Current studies mainly focus on total weight loss and comorbidity reduction. Only a few studies compare Quality of Life (QoL) after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). This study was conducted to examine the extent of improvement in QoL on different domains after primary bariatric surgery and compare these results to Dutch reference values. METHODS: The study included prospectively collected data from patients who underwent primary bariatric surgery in five Dutch hospitals. The RAND-36 questionnaire was used to measure the patient's QoL; preoperatively and twelve months postoperatively. Postoperative scores were compared to Dutch reference values, standardized for age, using t-test. A difference of more than 5% was considered a minimal important difference. A multivariate linear regression analysis was used to compare SG and RYGB on the extent of improvement, adjusted for case-mix factors. RESULTS: In total, 4864 patients completed both the pre- and postoperative questionnaire. Compared with Dutch reference values, patients postoperatively reported clinically relevant better physical functioning (RYGB + 6.8%), physical role limitations (SG + 5.6%; RYGB + 6.2%) and health change (SG + 77.1%; RYGB + 80.0%), but worse general health perception (SG - 22.8%; RYGB - 17.0%). Improvement in QoL was similar between SG and RYGB, except for physical functioning (ß 2.758; p-value 0.008) and general health perception (ß 2.607; p-value < 0.001) for which RYGB patients improved more. CONCLUSIONS: SG and RYGB patients achieved a better postoperative score in physical functioning, physical role limitations and health change compared to Dutch reference values, and a worse score in general health perception.

The first consensus statement on revisional bariatric surgery using a modified Delphi approach.

BACKGROUND: Revisional bariatric surgery (RBS) constitutes a possible solution for patients who experience an inadequate response following bariatric surgery or significant weight regain following an initial satisfactory response. This paper reports results from the first modified Delphi consensus-building exercise on RBS. METHODS: We created a committee of 22 recognised opinion-makers with a special interest in RBS. The committee invited 70 RBS experts from 27 countries to vote on 39 statements concerning RBS. An agreement amongst ≥ 70.0% experts was regarded as a consensus. RESULTS: Seventy experts from twenty-seven countries took part. There was a consensus that the decision for RBS should be individualised (100.0%) and multi-disciplinary (92.8%). Experts recommended a preoperative nutritional (95.7%) and psychological evaluation (85.7%), endoscopy (97.1%), and a contrast series (94.3%). Experts agreed that Roux-Y gastric bypass (RYGB) (94.3%), One anastomosis gastric bypass (OAGB) (82.8%), and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) (71.4%) were acceptable RBS options after gastric banding (84.3%). OAGB (84.3%), bilio-pancreatic diversion/duodenal switch (BPD/DS) (81.4%), and SADI-S (88.5%) were agreed as consensus RBS options after sleeve gastrectomy. lengthening of bilio-pancreatic limb was the only consensus RBS option after RYGB (94.3%) and OAGB (72.8%). CONCLUSION: Experts achieved consensus on a number of aspects of RBS. Though expert opinion can only be regarded as low-quality evidence, the findings of this exercise should help improve the outcomes of RBS while we develop robust evidence to inform future practice.

Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice.

OBJECTIVE: Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c+ proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development. DESIGN: vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr-/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH. RESULTS: Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c+ and CD11c- macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c+ ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes. CONCLUSION: ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment.

A liver-specific long noncoding RNA with a role in cell viability is elevated in human nonalcoholic steatohepatitis.

Hepatocyte apoptosis in nonalcoholic steatohepatitis (NASH) can lead to fibrosis and cirrhosis, which permanently damage the liver. Understanding the regulation of hepatocyte apoptosis is therefore important to identify therapeutic targets that may prevent the progression of NASH to fibrosis. Recently, increasing evidence has shown that long noncoding (lnc) RNAs are involved in various biological processes and that their dysregulation underlies a number of complex human diseases. By performing gene expression profiling of 4,383 lncRNAs in 82 liver samples from individuals with NASH (n = 48), simple steatosis but no NASH (n = 11), and healthy controls (n = 23), we discovered a liver-specific lncRNA (RP11-484N16.1) on chromosome 18 that showed significantly elevated expression in the liver tissue of NASH patients. This lncRNA, which we named lnc18q22.2 based on its chromosomal location, correlated with NASH grade (r = 0.51, P = 8.11 × 10-7 ), lobular inflammation (r = 0.49, P = 2.35 × 10-6 ), and nonalcoholic fatty liver disease activity score (r = 0.48, P = 4.69 × 10-6 ). The association of lnc18q22.2 to liver steatosis and steatohepatitis was replicated in 44 independent liver biopsies (r = 0.47, P = 0.0013). We provided a genetic structure of lnc18q22.2 showing an extended exon 2 in liver. Knockdown of lnc18q22.2 in four different hepatocyte cell lines resulted in severe phenotypes ranging from reduced cell growth to lethality. This observation was consistent with pathway analyses of genes coexpressed with lnc18q22.2 in human liver or affected by lnc18q22.2 knockdown. CONCLUSION: We identified an lncRNA that can play an important regulatory role in liver function and provide new insights into the regulation of hepatocyte viability in NASH. (Hepatology 2017;66:794-808).

Nε-(carboxymethyl)lysine-receptor for advanced glycation end product axis is a key modulator of obesity-induced dysregulation of adipokine expression and insulin resistance.

OBJECTIVE: Dysregulation of inflammatory adipokines by the adipose tissue plays an important role in obesity-associated insulin resistance. Pathways leading to this dysregulation remain largely unknown. We hypothesized that the receptor for advanced glycation end products (RAGE) and the ligand N(ε)-(carboxymethyl)lysine (CML) are increased in adipose tissue and, moreover, that activation of the CML-RAGE axis plays an important role in obesity-associated inflammation and insulin resistance. APPROACH AND RESULTS: In this study, we observed a strong CML accumulation and increased expression of RAGE in adipose tissue in obesity. We confirmed in cultured human preadipocytes that adipogenesis is associated with increased levels of CML and RAGE. Moreover, CML induced a dysregulation of inflammatory adipokines in adipocytes via a RAGE-dependent pathway. To test the role of RAGE in obesity-associated inflammation further, we constructed an obese mouse model that is deficient for RAGE (ie, RAGE(-/-)/Leptr(Db-/-) mice). RAGE(-/-)/Leptr(Db-/-) mice displayed an improved inflammatory profile and glucose homeostasis when compared with RAGE(+/+)/Leptr(Db-/-) mice. In addition, CML was trapped in adipose tissue in RAGE(+/+)/Leptr(Db-/-) mice but not in RAGE(-/-)/Leptr(Db-/-). RAGE-mediated trapping in adipose tissue provides a mechanism underlying CML accumulation in adipose tissue and explaining decreased CML plasma levels in obese subjects. Decreased CML plasma levels in obese individuals were strongly associated with insulin resistance. CONCLUSIONS: RAGE-mediated CML accumulation in adipose tissue and the activation of the CML-RAGE axis are important mechanisms involved in the dysregulation of adipokines in obesity, thereby contributing to the development of obesity-associated insulin resistance.

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.

Prophylactic intraperitoneal mesh placement to prevent incisional hernia after stoma reversal: a feasibility study.

BACKGROUND: Incisional hernias in old stoma wounds occur in one-third of former stoma patients and pose a significant clinical problem. Parastomal hernias can be prevented by prophylactic mesh placement; however, no trial results are available for incisional hernia prevention after stoma reversal. In this feasibility study, we explore the safety of placing an intraperitoneal mesh to prevent incisional herniation after temporary stoma reversal. METHODS: Ten patients who underwent a low anterior resection with a deviating double-loop stoma for rectal cancer received an intraperitoneal parastomal mesh at the time of stoma formation. At stoma reversal, laparoscopy was performed and adhesions were scored. After reversal, the mesh defect was closed. Mesh and stoma complications were closely monitored. Incisional herniation was assessed at the 2-year follow-up after stoma reversal using ultrasonography. RESULTS: No infections occurred after mesh placement. After a median of 6 months, stomas were reversed. Laparoscopy could be performed in seven patients; all patients had adhesions (median of 25 % of mesh surface). In three patients, the bowel was involved; one required a laparotomy for bowel mobilization during stoma reversal. No adhesion-related morbidity was noted at any time. Except for one superficial wound infection after stoma reversal, no infectious complications were observed. After a median follow-up of 26 months, no incisional herniations were demonstrated. CONCLUSIONS: Prophylactic mesh placement in temporary stoma formations seems safe and feasible and prevents incisional herniation 2 years after stoma reversal.

The Impact of Longer Biliopancreatic Limb Length on Weight Loss and Comorbidity Improvement at 5 Years After Primary Roux-en-Y Gastric Bypass Surgery: A Population-Based Matched Cohort Study.

INTRODUCTION: Different limb lengths are used in Roux-en-Y gastric bypass (RYGB) surgery, as there is no consensus which limb length strategy has the best outcomes. The biliopancreatic limb (BPL) is thought to play an important role in achieving weight loss and associated comorbidity resolution. The objective of this study was to assess the impact of a longer BPL on weight loss and comorbidity improvement at 5 years after primary RYGB. METHODS: All patients aged ≥ 18 years undergoing primary RYGB between 2014-2017 with registered follow-up 5 years after surgery were included. Long BPL was defined as BPL ≥ 100 cm and short BPL as BPL < 100 cm. The primary outcome was achieving at least 25% total weight loss (TWL) at 5 years. Secondary outcomes included absolute %TWL and improvement of comorbidities. A propensity score matched logistic and linear regression was used to estimate the difference in outcomes between patients with long and short BPL. RESULTS: At 5 years, long BPL had higher odds to achieve ≥ 25% TWL (odds ratio (OR) 1.19, 95% confidence interval (CI) [1.01 - 1.41]) and was associated with 1.26% higher absolute TWL (ß = 1.26, 95% CI [0.53 - 1.99]). Furthermore, long BPL was more likely to result in improved diabetes mellitus (OR = 2.17, 95% CI [1.31 - 3.60]) and hypertension (OR = 1.45, 95% CI [1.06 - 1.99]). CONCLUSION: Patients undergoing RYGB with longer BPL achieved higher weight loss and were more likely to achieve improvement of comorbidities at 5 years.

Optimizing Hospital Performance Evaluation in Total Weight Loss Outcomes After Bariatric Surgery: A Retrospective Analysis to Guide Further Improvement in Dutch Hospitals.

INTRODUCTION: Bariatric surgery aims for optimal patient outcomes, often evaluated through the percentage total weight loss (%TWL). Quality registries employ funnel plots for outcome comparisons between hospitals. However, funnel plots are traditionally used for dichotomous outcomes, requiring %TWL to be dichotomized, potentially limiting feedback quality. This study evaluates whether a funnel plot around the median %TWL has better discriminatory performance than binary funnel plots for achieving at least 20% and 25% TWL. METHODS: All hospitals performing bariatric surgery were included from the Dutch Audit for Treatment of Obesity. A funnel plot around the median was constructed using 5-year %TWL data. Hospitals positioned above the 95% control limit were colored green and those below red. The same hospitals were plotted in the binary funnel plots for 20% and 25% TWL and colored according to their performance in the funnel plot around the median. We explored the hospital's procedural mix in relation to %TWL performance as possible explanatory factors. RESULTS: The median-based funnel plot identified four underperforming and four outperforming hospitals, while only one underperforming and no outperforming hospitals were found with the binary funnel plot for 20% TWL. The 25% TWL binary funnel plot identified two underperforming and three outperforming hospitals. The proportion of sleeve gastrectomies performed per hospital may explain part of these results as it was negatively associated with median %TWL (ß = - 0.09, 95% confidence interval [- 0.13 to - 0.04]). CONCLUSION: The funnel plot around the median discriminated better between hospitals with significantly worse and better performance than funnel plots for dichotomized %TWL outcomes.

Weight Loss and Glycemic Control After Bariatric Surgery in Adolescents With Severe Obesity: A Randomized Controlled Trial.

PURPOSE: Bariatric surgery is regarded as a valuable treatment option for adolescents with severe obesity. However, high-quality evidence of its superiority over prolonged conservative treatment with multidisciplinary lifestyle intervention (MLI) is limited. This study investigated the efficacy and safety of bariatric surgery in adolescents without sufficient weight loss after MLI for severe obesity. METHODS: A two-group randomized controlled trial was designed to assess one-year health effects of bariatric surgery in adolescents with severe obesity. The participants were referred by pediatricians after completing MLI without sufficient effects. Eligible for participation were adolescents aged 14-16 years with severe obesity (age- and sex-adjusted body mass index (BMI) using the International Obesity Task Force cutoffs: BMI ≥40 kg/m2, or ≥35 kg/m2 in combination with comorbidity). Participants were assigned to MLI combined with laparoscopic adjustable gastric banding (n = 29) versus only MLI (n = 30). Participants were included from 2011 to 2019. Main outcomes were weight change and sex- and age-specific BMI loss. Additionaly, glucose metabolism, blood pressure and lipid profile were analysed. RESULTS: 53 patients completed the 12-months follow-up (89.8%). Mean (±standard deviation [SD]) weight loss in the surgery group was 11.2 ± 7.8% after 12 months, compared to a weight gain of 1.7 ± 8.1% in the control group. The fasting insulin, insulin resistance score and lipid profile improved significantly in the surgery group. DISCUSSION: Bariatric surgery was associated with substantial weight loss and improvements in glucose and lipid metabolism after 12 months compared to conservative treatment in adolescents with severe obesity.

Convincing 10-Year Follow-up Results of the Banded Roux-en-Y Gastric Bypass.

INTRODUCTION: Several studies have shown the positive effect on weight loss of the banded Roux-en-Y gastric bypass (BRYGB). Thus far, studies describing the 10-year post-operative results are scarce. Therefore, the aim of this study was to describe the weight loss results, effect on associated medical problems, and complication rates during 10 years of follow-up after BRYGB. METHOD: Data were collected from patients who underwent laparoscopic BRYGB with a non-adjustable silicone gastric ring between January 2011 and March 2013. All patients were included when found to be eligible according to the IFSO criteria. RESULTS: One hundred forty-nine patients were included, 110 received a primary BRYGB and 39 received a conversional BRYGB. The primary BRYGB group consisted of 68% female patients with a mean BMI of 44.5 kg/m2 and a mean age of 46 years old. The conversional group consisted of 77% females and had a mean BMI of 34.8 kg/m2 and a mean age of 48 years. At 10-year follow-up, 67.1% of the data was available. Ten-year post-operative 30% total weight loss was seen in the primary group, and 7% in the conversional group. In 10 years, 23% of the patients had complications of which half were ring-related. CONCLUSION: The addition of a silicon ring to the Roux-en-Y gastric bypass may result in substantial and stable weight loss maintenance 10 years post-operative. Furthermore, the number of patients with long-term complications was low and the number of associated medical problems was significantly reduced.

Non-alcoholic steatohepatitis: a non-invasive diagnosis by analysis of exhaled breath.

BACKGROUND & AIMS: Histological evaluation of a liver biopsy is the current gold standard to diagnose non-alcoholic steatohepatitis (NASH), but the procedure to obtain biopsies is associated with morbidity and high costs. Hence, only subjects at high risk are biopsied, leading to underestimation of NASH prevalence, and undertreatment. Since analysis of volatile organic compounds in breath has been shown to accurately identify subjects with other chronic inflammatory diseases, we investigated its potential as a non-invasive tool to diagnose NASH. METHODS: Wedge-shaped liver biopsies from 65 subjects (BMI 24.8-64.3 kg/m(2)) were obtained during surgery and histologically evaluated. The profile of volatile organic compounds in pre-operative breath samples was analyzed by gas chromatography-mass spectrometry and related to liver histology scores and plasma parameters of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). RESULTS: Three exhaled compounds were sufficient to distinguish subjects with (n=39) and without NASH (n=26), with an area under the ROC curve of 0.77. The negative and positive predictive values were 82% and 81%. In contrast, elevated ALT levels or increased AST/ALT ratios both showed negative predictive values of 43%, and positive predictive values of 88% and 70%, respectively. The breath test reduced the hypothetical percentage of undiagnosed NASH patients from 67-79% to 10%, and of misdiagnosed subjects from 49-51% to 18%. CONCLUSIONS: Analysis of volatile organic compounds in exhaled air is a promising method to indicate NASH presence and absence. In comparison to plasma transaminase levels, the breath test significantly reduced the percentage of missed NASH patients and the number of unnecessarily biopsied subjects.

Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex.

Nutritional stimulation of the cholecystokinin-1 receptor (CCK-1R) and nicotinic acetylcholine receptor (nAChR)-mediated vagal reflex was shown to reduce inflammation and preserve intestinal integrity. Mast cells are important early effectors of the innate immune response; therefore modulation of mucosal mast cells is a potential therapeutic target to control the acute inflammatory response in the intestine. The present study investigates intestinal mast cell responsiveness upon nutritional activation of the vagal anti-inflammatory reflex during acute inflammation. Mucosal mast cell degranulation was induced in C57/Bl6 mice by administration of Salmonella enterica LPS. Lipid-rich enteral feeding prior to LPS significantly decreased circulatory levels of mouse mast cell protease at 30 min post-LPS compared with isocaloric low-lipid nutrition or fasting. CCK-1R blockage reversed the inhibitory effects of lipid-rich feeding, whereas stimulation of the peripheral CCK-1R mimicked nutritional mast cell inhibition. The effects of lipid-rich nutrition were negated by nAChR blockers chlorisondamine and α-bungarotoxin and vagal intestinal denervation. Accordingly, release of ß-hexosaminidase by MC/9 mast cells following LPS or IgE-ovalbumin complexes was dose dependently inhibited by acetylcholine and nicotine. Application of GSK1345038A, a specific agonist of the nAChR α7, in bone marrow-derived mast cells from nAChR ß2-/- and wild types indicated that cholinergic inhibition of mast cells is mediated by the nAChR α7 and is independent of the nAChR ß2. Together, the present study reveals mucosal mast cells as a previously unknown target of the nutritional anti-inflammatory vagal reflex.

Endoscopic duodenal-jejunal bypass liner rapidly improves plasma parameters of nonalcoholic fatty liver disease.

Bariatric surgery reduces nonalcoholic fatty liver disease (NAFLD). We investigated the effects of duodenal-jejunal bypass liner (DJBL), nonsurgical bariatric device, on plasma parameters of NAFLD. Seventeen obese subjects with type 2 diabetes received the DJBL for 24 weeks. Before, during, and after DJBL implantation, we determined plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (γ-GT), albumin, caspase-cleaved cytokeratin-18 (CK-18), and liver fatty acid-binding protein (L-FABP). At baseline, subjects had increased levels of AST (35 ± 4 IU/L), ALT (54 ± 5 IU/L), and γ-GT (66 ± 14 IU/L), compared with healthy individuals; subjects' mean concentrations of caspase-cleaved CK-18 and L-FABP were 214.4 ± 35.6 U/L and 29.3 ± 2.6 ng/mL, respectively. Three months after implantation of DJBL, all NAFLD-related parameters had decreased from baseline (AST, 28 ± 3 IU/L; ALT, 32 ± 2 IU/L; γ-GT, 44 ±7 IU/L; caspase-cleaved CK-18, 140.6 ± 16.3U/L; and L-FABP, 18.2 ± 1.5 ng/mL; all P < .05). After 6 months, levels of ALT and γ-GT had further decreased (ALT, 28 ± 2 IU/L and γ-GT, 35 ± 5 IU/L), whereas levels of AST, caspase-cleaved CK-18, and L-FABP had stabilized (P = not significant). Six months after DJBLs were removed, levels of ALT (37 ± 3 IU/L), γ-GT (42 ± 5 IU/L), and caspase-cleaved CK-18 (124.5 ± 12.5U/L) were still reduced (P < .05), whereas AST and L-FABP had returned to near baseline levels (P = not significant). Therefore, in obese subjects, DJBL reduces plasma parameters of NAFLD. ClinicalTrials.gov, Number: NCT00985114.

Prevention of hemolysis-induced organ damage by nutritional activation of the vagal anti-inflammatory reflex*.

OBJECTIVES: Acute hemolysis is associated with organ damage, inflammation, and impaired vascular function. Stimulation of the cholecystokinin-1 receptor-dependent vagal anti-inflammatory reflex with lipid-rich enteral nutrition was demonstrated to prevent tissue damage and attenuate inflammation. This study investigates the effects of nutritional activation of the vagal anti-inflammatory reflex on organ integrity, systemic inflammation, and microcirculation during hemolysis. DESIGN: Prospective randomized controlled study. SETTING: University research unit. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Intravascular hemolysis was simulated by infusion of prelysed erythrocytes. Animals were fasted or received lipid-rich enteral nutrition. Pegylated (PEG)-CCK9A, A70104 (a cholecystokinin-1 receptor antagonist), and chlorisondamine (a nicotinic acetylcholine receptor antagonist) were applied to investigate involvement of the vagal reflex. MEASUREMENTS AND MAIN RESULTS: Nutritional intervention reduced hemolysis-related renal tubular cell damage, hepatocyte damage, ileal leakage of horseradish peroxidase, and bacterial translocation compared with food deprivation (all p < 0.05). Also circulating interleukin (IL)-6 levels were decreased by enteral nutrition (p < 0.05). Blockage of the cholecystokinin-1 receptor or the nicotinic acetylcholine receptor reversed the protective nutritional effects compared with vehicle (p < 0.05), whereas PEG-CCK9 mimicked the impact of enteral feeding in fasted animals (p < 0.05). Furthermore, nutritional intervention increased renal, hepatic, and intestinal blood flow compared with fasting (all p < 0.05), as evaluated using fluorescent microspheres. CONCLUSIONS: Nutritional activation of the vagal anti-inflammatory reflex preserves tissue integrity and attenuates systemic inflammation in a rodent model of acute hemolysis. In addition, lipid-rich nutrition improves renal, hepatic, and intestinal microcirculation. These findings implicate stimulation of the autonomic nervous system by nutritional means as a potential therapy to prevent complications of acute hemolysis. (Crit Care Med 2013; 41:e361-e367).

Coated meshes for hernia repair provide comparable intraperitoneal adhesion prevention.

BACKGROUND: Laparoscopic incisional hernia repair with intraperitoneal mesh is associated with a certain degree of adhesion formation to the mesh. This experimental study examined the efficacy of several coated meshes for adhesion reduction. METHODS: Five commercially available meshes with a layered coating were placed intraperitoneally in rats and followed up for 90 days: polypropylene and polyester meshes, both coated with absorbable collagen (Parietene Composite and Parietex Composite, respectively), and three polypropylene meshes respectively coated with absorbable omega-3 fatty acids (C-Qur Edge), absorbable cellulose (Sepramesh IP), and nonabsorbable expanded polytetrafluoroethylene (Intramesh T1). Uncoated polypropylene and collagen meshs (Parietene and Permacol, respectively) served as the control condition. Adhesions, incorporation, and tissue reaction were evaluated macro- and microscopically. Additionally, the development of the neoperitoneum was examined. RESULTS: All the coated meshes performed equally well in terms of adhesion reduction. The collagen mesh performed comparably, but the uncoated polypropylene mesh performed significantly worse. The different coatings led to very differing degrees of inflammation. Ingrowth was observed only at the place of suture but was comparable for all the meshes except C-Qur Edge, which showed the weakest incorporation. Development of a neoperitoneum on the mesh surface occurred independently of whether an absorbable or nonabsorbable coating or no coating at all was present. CONCLUSIONS: Commercially available meshes with a layered coating deliver comparable adhesion reduction. The physical presence of a layered coating between the intraperitoneal content and the abdominal wall seems to be more important than the chemical properties of the coating in adhesion formation.

Safety of bariatric surgery in the elderly: results from the Dutch National Registry.

BACKGROUND: The increased human life expectancy and prevalence of obesity lead to more elderly people with obesity. As the popularity of bariatric surgery continues to grow, more elderly persons apply for bariatric surgery. However, because of the potentially higher surgical risk in elderly patients, bariatric surgery has been performed in small numbers. Moreover, the literature so far has shown controversial results. OBJECTIVE: To determine the safety of bariatric surgery in elderly patients in terms of 2-year morbidity and mortality. SETTING: Dutch nationwide mandatory registry for bariatric surgery. METHODS: A population-based retrospective cohort study. Elderly patients (aged ≥65 years) who received primary bariatric surgery between January 2015 and January 2020 were compared with the general bariatric surgical population (aged 18-65 years). RESULTS: Of 49,553 patients, 838 elderly patients (1.7%) were included. An intraoperative complication was registered in 1.2% of the elderly patients and 1.1% of the nonelderly patients (P = .814). A severe short-term complication (≤30 days) was registered in 38 elderly patients (4.5%) and 1071 nonelderly patients (2.2%) (P < .001). The short-term mortality rates were .2% and .1%, respectively (P = .173). Bleeding was the most reported short-term complication. Significantly more nonelderly patients had a follow-up visit; 560 elderly patients (66.8%) versus 34,975 nonelderly patients (71.8%) (P = .002). The severe midterm complication rate (>30 days to ≤2 years) was significantly higher in nonelderly patients (3.7% versus 1.6%; P = .008). CONCLUSIONS: Bariatric surgery in elderly patients is safe in terms of perioperative outcome, mortality, and midterm complication rate. However, elderly patients experienced twice as many severe short-term complications. Bariatric surgery in elderly patients should be recommended on a case-by-case basis.

Laparoscopic Conversion of Vertical Banded Gastroplasty to Roux-en-Y Gastric Bypass Gives Better Result Compared to an Open Approach.

BACKGROUND: Vertical banded gastroplasty (VBG) has a relatively high failure rate in the long run, requiring revisional surgery in 30-65%. A common conversion option is to Roux-en-Y gastric bypass (RYGB), which can be performed laparoscopically or open. Current literature contains small cohorts and inconclusive results. Therefore, we set out to compare our series of open and laparoscopic VBG to RYGB conversions. METHODS: All conversions performed between 1996 and 2020 were included. Patients were divided into 3 groups based on conversion indication: weight recurrence (group 1), excessive weight loss (group 2), and eating/pouch difficulties (group 3). The primary outcome was postoperative complications according to the Clavien-Dindo (CD) classification. Secondary outcome was %total weight loss (%TWL) 1 to 5 years after revisional surgery. RESULTS: We included 205 patients (84.9% female) of whom 105 underwent laparoscopic and 100 open VBG to RYGB conversion. Twenty-three short-term complications occurred in the laparoscopic group, with 16 > CD3a. In the open group, 33 complications occurred with 12 > CD3a. Overall complications were 33.3% in laparoscopic and 64% in open patients. There were no significant differences between the laparoscopic and open group in BMI (p = 0.76) and %TWL (p = 0.694) after 5 years. After 5 years, lost to follow-up was 97% in the open group. Twenty-eight percent of patients who reached follow-up in the laparoscopic group had available data. CONCLUSIONS: We demonstrate that the overall complication rate is lower in the laparoscopic group compared to the open group. Regarding BMI, an improvement was achieved in both groups after 5 years.