Fady Moustarah

Weight Loss Interventions in Chronic Kidney Disease: A Systematic Review and Meta-analysis

BACKGROUND AND OBJECTIVES Obesity is an independent risk factor for development and progression of chronic kidney disease (CKD). We conducted a systematic review to assess the benefits of intentional weight loss in patients with non-dialysis-dependent CKD and glomerular hyperfiltration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched MEDLINE, SCOPUS, and conference proceedings for randomized, controlled trials and observational studies that examined various surgical and nonsurgical interventions (diet, exercise, and/or antiobesity agents) in adult patients with CKD. Results were summarized using random-effects model. RESULTS Thirteen studies were included. In patients with CKD, body mass index (BMI) decreased significantly (weighted mean difference [WMD] -3.67 kg/m(2); 95% confidence interval [CI] -6.56 to -0.78) at the end of the study period with nonsurgical interventions. This was associated with a significant decrease in proteinuria (WMD -1.31 g/24 h; 95% CI -2.11 to -0.51) and systolic BP with no further decrease in GFR during a mean follow-up of 7.4 mo. In morbidly obese individuals (BMI >40 kg/m(2)) with glomerular hyperfiltration (GFR >125 ml/min), surgical interventions decreased BMI, which resulted in a decrease in GFR (WMD -25.56 ml/min; 95% CI -36.23 to -14.89), albuminuria, and systolic BP. CONCLUSIONS In smaller, short-duration studies in patients with CKD, nonsurgical weight loss interventions reduce proteinuria and BP and seem to prevent further decline in renal function. In morbidly obese individuals with glomerular hyperfiltration, surgical interventions normalize GFR and reduce BP and microalbuminuria. Larger, long-term studies to analyze renal outcomes such as development of ESRD are needed.

Perioperative complications in a consecutive series of 1000 duodenal switches

BACKGROUND In the past 10 years, most bariatric surgeries have seen an important reduction in the early complication rate, partly associated with the development of the laparoscopic approach. Our objective was to assess the current early complication rate associated with biliopancreatic diversion with duodenal switch (BPD-DS) since the introduction of a laparoscopic approach in our institution, a university-affiliated tertiary care center. METHODS A consecutive series of 1000 patients who had undergone BPD-DS from November 2006 to January 2010 was surveyed. The primary endpoint was the mortality rate. The secondary endpoints were the major 30-day complication rate and hospital stay >10 days. The data are reported as a mean ± SD, comparing the laparoscopic (n = 228) and open (n = 772) groups. RESULTS The mean age of the patients was 43 ± 10 years (40 ± 10 years in the laparoscopy group versus 44 ± 10 years in the open group, P < .01). The preoperative body mass index was 51 ± 8 kg/m(2) (47 ± 7 laparoscopy versus 52 ± 8 kg/m(2) open, P < .01). The conversion rate in the laparoscopy group was 2.6%. There was 1 postoperative death (.1%) from a pulmonary embolism in the laparoscopy group. The mean hospital stay was shorter after laparoscopic surgery (6 ± 6 d versus 7 ± 9 d, P = .01), and a hospital stay >10 days was more frequent in the open group (4.4% versus 7%, P = .04). Major complications occurred in 7% of the patients, with no significant differences between the 2 groups (7% versus 7.4%, P = .1). No differences were found in the overall leak or intra-abdominal abscess rate (3.5% versus 4%, P = .1); however, gastric leaks were more frequent after open surgery (0% versus 2%, P = .02). During a mean 2-year follow-up, 1 additional death occurred from myocardial infarction, 2 years after open BPD-DS. CONCLUSION The early and late mortality rate of BPD-DS is low and comparable to that of other bariatric surgeries.

Pancreatic islet isolation after gastric bypass in a rat model: technique and initial results for a promising research tool

BACKGROUND Roux-en-Y gastric bypass (RYGB) affords a high remission rate of type 2 diabetes mellitus among morbidly obese diabetic patients. We report the use of the isolated islet technique to assess pancreatic function and glucoregulatory mechanisms after RYGB surgery. METHODS A total of 15 adult, male, Sprague Dawley diet-induced obese rats were randomly divided into 3 experimental groups: sham, RYGB, and pair-fed, with 5 rats in each group. The body weight was measured at baseline and every week for 4 weeks. Pancreatic islet function was assessed in vitro according to the amount of insulin secreted from isolated islets incubated in 2 mM and 20 mM glucose for 1 hour at 37 °C. Fasting plasma glucose, insulin, glucagon-like peptide-1, PYY3-36, and glucose-dependent insulinotropic peptide were measured at baseline and 28 days after surgery. RESULTS The baseline body weight was 917 ± 61, 831 ± 42, and 927 ± 43 g for the sham, RYGB, and pair-fed groups, respectively. The RYGB group lost 32% body weight compared with 16% for the sham and 24% for the pair-fed groups. Glucose-stimulated insulin secretion from the isolated islets in the RYGB group was greater than in the comparison groups (P = .04) at 4 weeks after surgery. Fasting plasma glucagon-like peptide-1 and PYY3-36 were significantly increased at 4 weeks in the RYGB group. CONCLUSION Islet isolation and stimulation in the present animal model was feasible, affords a direct measurement of pancreatic islet function, and might provide a useful tool to study the effects of RYGB on pancreatic function and the relationship between islet cell function and incretin production after bariatric surgery.

Characterization of Dedifferentiating Human Mature Adipocytes from the Visceral and Subcutaneous Fat Compartments: Fibroblast-Activation Protein Alpha and Dipeptidyl Peptidase 4 as Major Components of Matrix Remodeling

Mature adipocytes can reverse their phenotype to become fibroblast-like cells. This is achieved by ceiling culture and the resulting cells, called dedifferentiated fat (DFAT) cells, are multipotent. Beyond the potential value of these cells for regenerative medicine, the dedifferentiation process itself raises many questions about cellular plasticity and the pathways implicated in cell behavior. This work has been performed with the objective of obtaining new information on adipocyte dedifferentiation, especially pertaining to new targets that may be involved in cellular fate changes. To do so, omental and subcutaneous mature adipocytes sampled from severely obese subjects have been dedifferentiated by ceiling culture. An experimental design with various time points along the dedifferentiation process has been utilized to better understand this process. Cell size, gene and protein expression as well as cytokine secretion were investigated. Il-6, IL-8, SerpinE1 and VEGF secretion were increased during dedifferentiation, whereas MIF-1 secretion was transiently increased. A marked decrease in expression of mature adipocyte transcripts (PPARγ2, C/EBPα, LPL and Adiponectin) was detected early in the process. In addition, some matrix remodeling transcripts (FAP, DPP4, MMP1 and TGFβ1) were rapidly and strongly up-regulated. FAP and DPP4 proteins were simultaneously induced in dedifferentiating mature adipocytes supporting a potential role for these enzymes in adipose tissue remodeling and cell plasticity.

34 Laparoscopic Malabsorption Procedures: Management of Surgical Complications

In addition to recognized complications after general surgical operations, those related to laparoscopic malabsorptive bariatric procedures are particular and mandate careful attention and follow-up in the postoperative period to maintain surgical benefits and good health of patients. Today, biliopancreatic diversion with duodenal switch represents the most commonly performed malabsorptive weight loss procedure. It is often offered to patients with high body mass indices suffering from advanced severe clinical obesity and its associated cardiovascular, pulmonary, and metabolic comorbidities. Because the number of bariatric procedures involving gastrointestinal reconfiguration has increased dramatically, it is important for primary and emergency care providers, in addition to general and bariatric surgeons, to be prepared for timely recognition and management of potentially serious postoperative complications and emergencies. This chapter reviews important early and late surgical, non-nutritional complications specific to laparoscopic biliopancreatic diversion with or without duodenal switch.

457 Gastric Pacing Can Eliminate Dependency On Supplemental Nutrition and Improve Medically Refractory Gastroparesis

INTRODUCTION: Gastric stimulation has been shown to improve the symptoms of medically refractory gastroparesis. With enough symptomatic improvement, patients should be able to decrease or eliminate their dependency on supplemental nutrition (parenteral or enteral) in the post-operative period. MATERIALS AND METHODS: This is a review of a single surgeons operative experience from 9/02 to 7/08. Patients with a diagnosis of diabetic or idiopathic gastroparesis that had a gastric pacer placed were selected for analysis. Chart review included age, gender, weight, symptom improvement, and the requirement of additional nutritional supplementation at baseline, six, and 12 months. RESULTS: Fifty-two patients had interrogation and programming of the gastric pacer (Enterra) at time of implantation. As part of follow-up, patients were assessed for symptom improvement and were adjusted appropriately if no improvement was seen. Patients included eight males and 44 females. The average age was 38 years (range 20-87). Thirty-one had a pre-operative, 6 month, and 12 month weight recording. Average weight was 151.9 lbs, 153.2 lbs, and 155.1 lbs at those respective times. In 47 patients with a mean follow-up of 19 months, 34 (72%) reported improvement in symptoms, nine (19%) reported no improvement in symptoms, and four had initial resolution of symptoms but return to baseline at last followup. Preoperatively, 10 patients were receiving jejunal feeds (TF) and two were receiving total parenteral nutrition (TPN). Subsequently after device implantation, seven patients at six months and an additional three at one year were off all forms of supplementation and receiving nutrition solely by mouth. No statistically significant weight change was seen in this group. Seven patients had a jejunostomy tube placed at the time of device implantation for subsequent enteral feeds. Three patients at six months had enteral feedings stopped and the remaining four continued tube feeds at one year. No patient in this group had an infectious complication secondary to concomitant gastric stimulator and jejunal tube placement. One Enterra system was replaced due to device malfunction, two revised secondary to generator malposition, and one removed due to lead erosion. CONCLUSIONS: The majority of patients demonstrated weight stability after gastric pacer placement. 72% of patients reported improvement in symptoms. Patients receiving supplemental nutrition preoperatively showed decreased reliance on enteral feeds or TPN after gastric stimulation. Concomitant jejunal tube and gastric pacer placement did not demonstrate a higher infectious complication rate.