Federico J. Serrot

Risk for Hospital Readmission following Bariatric Surgery

Background and Objectives Complications resulting in hospital readmission are important concerns for those considering bariatric surgery, yet present understanding of the risk for these events is limited to a small number of patient factors. We sought to identify demographic characteristics, concomitant morbidities, and perioperative factors associated with hospital readmission following bariatric surgery. Methods We report on a prospective observational study of 24,662 patients undergoing primary RYGB and 26,002 patients undergoing primary AGB at 249 and 317 Bariatric Surgery Centers of Excellence (BSCOE), respectively, in the United States from January 2007 to August 2009. Data were collected using standardized assessments of demographic factors and comorbidities, as well as longitudinal records of hospital readmissions, complications, and mortality. Results The readmission rate was 5.8% for RYGB and 1.2% for AGB patients 30 days after discharge. The greatest predictors for readmission following RYGB were prolonged length of stay (adjusted odds ratio [OR], 2.3; 95% confidence interval [CI], 2.0–2.7), open surgery (OR, 1.8; CI, 1.4–2.2), and pseudotumor cerebri (OR, 1.6; CI, 1.1–2.4). Prolonged length of stay (OR, 2.3; CI, 1.6–3.3), history of deep venous thrombosis or pulmonary embolism (OR, 2.1; CI, 1.3–3.3), asthma (OR, 1.5; CI, 1.1–2.1), and obstructive sleep apnea (OR, 1.5; CI, 1.1–1.9) were associated with the greatest increases in readmission risk for AGB. The 30-day mortality rate was 0.14% for RYGB and 0.02% for AGB. Conclusion Readmission rates are low and mortality is very rare following bariatric surgery, but risk for both is significantly higher after RYGB. Predictors of readmission were disparate for the two procedures. Results do not support excluding patients with certain comorbidities since any reductions in overall readmission rates would be very small on the absolute risk scale. Future research should evaluate the efficacy of post-surgical managed care plans for patients at higher risk for readmission and adverse events.

Increased adipose protein carbonylation in human obesity

Insulin resistance is associated with obesity but mechanisms controlling this relationship in humans are not fully understood. Studies in animal models suggest a linkage between adipose reactive oxygen species (ROS) and insulin resistance. ROS oxidize cellular lipids to produce a variety of lipid hydroperoxides that in turn generate reactive lipid aldehydes that covalently modify cellular proteins in a process termed carbonylation. Mammalian cells defend against reactive lipid aldehydes and protein carbonylation by glutathionylation using glutathione‐S‐transferase A4 (GSTA4) or carbonyl reduction/oxidation via reductases and/or dehydrogenases. Insulin resistance in mice is linked to ROS production and increased level of protein carbonylation, mitochondrial dysfunction, decreased insulin‐stimulated glucose transport, and altered adipokine secretion. To assess protein carbonylation and insulin resistance in humans, eight healthy participants underwent subcutaneous fat biopsy from the periumbilical region for protein analysis and frequently sampled intravenous glucose tolerance testing to measure insulin sensitivity. Soluble proteins from adipose tissue were analyzed using two‐dimensional gel electrophoresis and the major carbonylated proteins identified as the adipocyte and epithelial fatty acid‐binding proteins. The level of protein carbonylation was directly correlated with adiposity and serum free fatty acids (FFAs). These results suggest that in human obesity oxidative stress is linked to protein carbonylation and such events may contribute to the development of insulin resistance.

Comparative effectiveness of bariatric surgery and nonsurgical therapy in adults with type 2 diabetes mellitus and body mass index <35 kg/m2

BACKGROUND Outcomes of bariatric surgery in patients with a body mass index (BMI) <35 kg/m(2) have been an active area of investigation. We examined the comparative effectiveness of Roux-en-Y gastric bypass (RYGB) to routine medical management (nonsurgical controls; NSCs) in achieving appropriate targets defined by the American Diabetes Association for type 2 diabetes mellitus (T2DM) in patients with class I obesity (BMI 30.0-34.9 kg/m(2)) T2DM at 1 year. METHODS We identified patients undergoing RYGB (N = 17) with both class I obesity and T2DM and compared them to similar NSC (N = 17) treated in the Primary Care Center. Data were collected at baseline and 1 year for systolic blood pressure (SBP), as well as blood levels for low-density lipoprotein (LDL) cholesterol and hemoglobin A1c (HbA1c). RESULTS After RYGB, BMI decreased from 34.6 ± 0.8 kg/m(2) to 25.8 ± 2.5 kg/m(2) (P < .001) and HbA1c decreased from 8.2 ± 2.0% to 6.1 ± 2.7% (P < .001). The NSC cohort had no significant change in either BMI or HbA1c. SBP and LDL did not significantly change in either group. The RYGB group had a decrease in medication use compared to the NSC group (P < .001). The RYGB group ceased the use of antihypertensive and antihyperlipidemia medications by 1 year despite abnormal values. CONCLUSION RYGB can be performed in patients with both a BMI <35 kg/m(2) and T2DM with better weight loss, glycemic control, and fewer antihyperglycemic medications than NSC. Inappropriate cessation of medications may partially explain the persistent increase in both SBP and LDL after RYGB.

Benefits and complications of the duodenal switch/biliopancreatic diversion compared to the Roux-en-Y gastric bypass

BACKGROUND Despite providing superb excess weight loss and increased resolution of comorbid diseases, such as type 2 diabetes mellitus, compared to other bariatric procedures, the duodenal switch/ biliopancreatic diversion (DS/BD) has not gained widespread acceptance among patients and physicians. In this study, we investigated outcomes, symptoms and complications among postsurgical DS patients compared to RYGB patients. METHODS We used propensity scores to retrospectively match patients who underwent DS/BD between 2005 and 2010 to comparable Roux-en-Y gastric bypass (RYGB) patients. We then reviewed patient charts, and surveyed patients using the University of Minnesota Bariatric Surgery Outcomes Survey tool to track outcomes, comorbid illnesses and complications. RESULTS One hundred ninety consecutive patients underwent primary DS/BD between 2005 and 2010 at the University of Minnesota Medical Center. There were 178 patients available for follow-up (93.7%) who were matched to 139 RYGB patients. Type 2 diabetes, hypertension, and hyperlipidemia all significantly improved in each group. Improvements were significantly higher in the DS/BD group. Percent total weight loss was not different between groups. Loose stools and bloating symptoms were more frequently reported among DS/BD patients. With the exception of increased emergency department visits among DS/BD patients (P < .01), overall complication rates were not significantly different between DS/BD and RYGB. There was no difference in mortality rates between the groups. CONCLUSION The DS/BD is a robust procedure that engenders both superior weight loss and improvement of major comorbidities. Complication and adverse event rates are similar to those of RYGB.

Case-matched outcomes in bariatric surgery for treatment of type 2 diabetes in the morbidly obese patient.

Objective: To compare the relative efficacy of medical management, the duodenal switch (DS), and the laparoscopic adjustable gastric band (LAGB) to the Roux-en-Y gastric bypass (RYGB) for treatment of type 2 diabetes mellitus (T2DM). Background: The RYGB resolves T2DM in a high proportion of patients and is considered the standard operation for T2DM resolution in morbidly obese patients. However, no data exist comparing the efficacy of medical management and other bariatric operations to the RYGB for treatment of T2DM in comparable patient populations. Methods: We performed a retrospective case-matched study of morbidly obese patients with T2DM who had undergone medical management (nonsurgical controls [NSC]; N = 29), LAGB (N = 30), or DS (N = 27) and were compared with matched T2DM patients who had undergone RYGB. Matching was performed with respect to age, sex, body mass index, and hemoglobin A1C (HbA1C). Outcomes assessed were changes in body mass index, HbA1C, and diabetes medication scores at 1 year. Results: The Roux-en-Y gastric bypass produced greater weight loss, HbA1C normalization, and medication score reduction compared to both NSC and LAGB-matched cohorts. Duodenal switch produced greater reductions in HbA1C and medication score than RYGB, despite no greater weight loss at 1 year. Surgical complications were rarely life threatening. Conclusions: This study provides an important perspective about the comparative efficacy of LAGB, DS, and NSC to the RYGB for treatment of T2DM among obese patients. After 1 year of follow-up, RYGB is superior to NSC and LAGB with respect to weight loss and improvement in diabetes whereas DS is superior to RYGB in reducing HbA1C and medication score.

Routine upper gastrointestinal imaging is superior to clinical signs for detecting gastrojejunal leak after laparoscopic roux-en-y gastric bypass

BACKGROUND There are myriad symptoms and signs of gastrojejunal leak; prompt recognition is essential. Many surgeons use clinical predictors to guide selective use of upper gastrointestinal imaging (UGI). The appropriate practice remains undefined. STUDY DESIGN A review of patients who underwent primary laparoscopic Roux-en-Y gastric bypass between January 2002 and December 2008 was conducted. All underwent routine UGI studies on postoperative day 1. Actual gastrojejunal leak within 7 days of surgery (actual leak [AL], radiologic leaks), operative reports, patient charts, and postoperative vital signs were retrospectively reviewed. RESULTS There were 2,099 operations. Eight ALs (0.43%) occurred without associated mortality. UGI was positive in 7 AL patients and falsely positive in 6 patients. The AL patients underwent laparoscopy on postoperative days 1 and 3 (n = 5 and n = 1, respectively), laparotomy on postoperative day 3 (n = 1), and peritoneal drainage (n = 1). False-positive UGIs prompted laparoscopy (n = 3) and close observation (n = 3). Pulse was 100 to 120 beats per minute in 2 patients and fever (>38.5°C) was present in 0 AL patients. AL patients had osteogenesis imperfecta (n = 1), macronodular cirrhosis (n = 1), positive bubble test (n = 3), and concomitant splenectomy (n = 1). No jejunojejunostomy leaks were identified. CONCLUSIONS Routine UGI after laparoscopic Roux-en-Y gastric bypass has greater sensitivity than clinical signs for detecting gastrojejunal leak. Delay in the diagnosis of leakage can impact mortality, and this suggests that indications for routine UGI might still exist. Tachycardia is not a reliable early marker of leak. There might be risk factors for leak in addition to vital signs, including patient medical history or intraoperative events, which should prompt routine UGI on postoperative day 1.

Bile Acids Increase Independently From Hypocaloric Restriction After Bariatric Surgery.

Objectives: To measure changes in the composition of serum bile acids (BA) and the expression of Takeda G-protein-coupled receptor 5 (TGR5) acutely after bariatric surgery or caloric restriction. Summary Background Data: Metabolic improvement after bariatric surgery occurs before substantial weight loss. BA are important metabolic regulators acting through the farnesoid X receptor and TGR5 receptor. The acute effects of surgery on BA and the TGR5 receptor in subcutaneous white adipose tissue (WAT) are unknown. Methods: A total of 27 obese patients with type 2 diabetes mellitus were randomized to Roux-en-Y gastric bypass (RYGB) or to hypocaloric diet (HC diet) restriction (NCT 1882036). A cohort of obese patients with and without type 2 diabetes mellitus undergoing vertical sleeve gastrectomy was also recruited (n = 12) as a comparison. Results: After vertical sleeve gastrectomy, the level of BA increased [total: 1.17 ± 1.56 &mgr;mol/L to 4.42 ± 3.92 &mgr;mol/L (P = 0.005); conjugated BA levels increased from 0.99 ± 1.42 &mgr;mol/L to 3.59 ± 3.70 &mgr;mol/L (P = 0.01) and unconjugated BA levels increased from 0.18 ± 0.24 &mgr;mol/L to 0.83 ± 0.70 &mgr;mol/L (P = 0.009)]. With RYGB, there was a trend toward increased BA [total: 1.37 ± 0.97 &mgr;mol/L to 3.26 ± 3.01 &mgr;mol/L (P = 0.07); conjugated: 1.06 ± 0.81 &mgr;mol/L to 2.99 ± 3.02 &mgr;mol/L (P = 0.06)]. After HC diet, the level of unconjugated BA decreased [0.92 ± 0.55 &mgr;mol/L to 0.32 ± 0.43 &mgr;mol/L (P = 0.05)]. The level of WAT TGR5 gene expression decreased after surgery, but not in HC diet. Protein levels did not change. Conclusions: The levels of serum BA increase after bariatric surgery independently from caloric restriction, whereas the level of WAT TGR5 protein is unaffected.

Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery

Background:Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined.Materials and Methods:Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, β-oxidation, lipolysis and cysteine oxidation.Results:Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery.Conclusions:These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.