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Increase in the mediators of asthma in obesity and obesity with type 2 diabetes: reduction with weight loss

Dandona, Paresh; Ghanim, Husam; Monte, Scott V; Caruana, Joseph A; Green, Kelly; Abuaysheh, Sanaa; Lohano, Teekam; Schentag, Jerome; Dhindsa, Sandeep; Chaudhuri, Ajay
OBJECTIVE: To determine whether the expression of key asthma related genes, IL-4, LIGHT, LTBR, MMP-9, CCR-2, and ADAM-33 in mononuclear cells and the plasma concentration of nitric oxide metabolites (NOM) and MMP-9 are increased in the obese, obese type 2 diabetics (T2DM) and in morbidly obese patients prior to and after gastric bypass surgery (RYGB). DESIGN AND METHODS: The expression of these genes in MNC and plasma concentrations of these indices was measured in healthy lean and in obese with and without T2DM and following RYGB in obese T2DM. RESULTS: The expression of IL-4, MMP-9, LIGHT and CCR-2 and plasma NOM concentrations was significantly higher in the obese subjects and in obese T2DM patients than in normal subjects. The expression of IL-4, LIGHT, MMP-9, and CCR-2 expression was related to BMI and HOMA-IR. The expression of IL-4, LIGHT, LTBR, ADAM-33, MMP-9, and CCR-2 fell after RYGB surgery as did plasma concentrations of MMP-9 and NOM. CONCLUSIONS: Obesity with and without T2DM is associated with an increase in the expression of IL-4, LIGHT, MMP-9 and CCR-2; plasma NOM and MMP-9 concentrations are also increased. Following RYGB surgery and weight loss, the expression of these factors in MNC and plasma concentrations falls significantly.
PMID: 23804543
ISSN: 1930-739x
CID: 1646212

Reduction in inflammation and the expression of amyloid precursor protein and other proteins related to Alzheimer's disease following gastric bypass surgery

Ghanim, Husam; Monte, Scott V; Sia, Chang Ling; Abuaysheh, Sanaa; Green, Kelly; Caruana, Joseph A; Dandona, Paresh
OBJECTIVE: Obesity and type 2 diabetes are associated with an increase in the incidence and prevalence of Alzheimer's disease (AD) and an impaired cognitive function. Because peripheral blood mononuclear cells (MNC) express amyloid precursor protein (APP), the precursor of beta-amyloid, which forms the pathognomonic plaques in the brain, we hypothesized that APP expression diminishes after the marked caloric restriction and weight loss associated with Roux-en-Y gastric bypass (RYGB) surgery. RESEARCH DESIGN AND METHODS: Fifteen type 2 diabetic patients with morbid obesity (body mass index, 52.1 +/- 13 kg/m(2)) underwent RYGB, and the expression of inflammatory and AD-related genes was examined before and after 6 months in plasma and in MNC. RESULTS: Body mass index fell to 40.4 +/- 11.1 kg/m(2) at 6 months after RYGB. There was a significant fall in plasma concentrations of glucose and insulin and in homeostasis model of assessment for insulin resistance. The expression of APP mRNA fell by 31 +/- 9%, and that of protein fell by 36 +/- 14%. In addition, there was a reduction in the expression of other AD-related genes including presinilin-2, ADAM-9, GSK-3beta, PICALM, SORL-1, and clusterin (P < 0.05 for all). Additionally, the expression of c-Fos, a subunit of the proinflammatory transcription factor AP-1, was also suppressed after RYGB. These changes occurred in parallel with reductions in other proinflammatory mediators including C-reactive protein and monocyte chemoattractant protein-1. CONCLUSIONS: Thus, the reversal of the proinflammatory state of obesity is associated with a concomitant reduction in the expression of APP and other AD-related genes in MNC. We conclude that obesity and caloric intake modulate the expression of APP in MNC. If indeed, this effect also occurs in the brain, this may have implications for the pathogenesis and the treatment of AD. It is relevant that cognitive function has been shown to improve with weight loss following bariatric surgery.
PMID: 22508715
ISSN: 1945-7197
CID: 1646222

Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus

Monte, Scott V; Caruana, Joseph A; Ghanim, Husam; Sia, Chang Ling; Korzeniewski, Kelly; Schentag, Jerome J; Dandona, Paresh
BACKGROUND: Roux-en-Y gastric bypass (RYGB) results in profound weight loss and resolution of type 2 diabetes mellitus (T2DM). The mechanism of this remarkable transition remains poorly defined. It has been proposed that endotoxin (lipopolysaccharide [LPS]) sets inflammatory tone, triggers weight gain, and initiates T2DM. Because RYGB may diminish LPS from endogenous and exogenous sources, we hypothesized that LPS and the associated cascade of oxidative and inflammatory stress would diminish after RYGB. METHODS: Fifteen adults with morbid obesity and T2DM undergoing RYGB were studied. After an overnight fast, a baseline blood sample was collected the morning of surgery and at 180 days to assess changes in glycemia, insulin resistance, LPS, mononuclear cell nuclear factor (NF)-kappaB binding and mRNA expression of CD14, TLR-2, TLR-4, and markers of inflammatory stress. RESULTS: At 180 days after RYGB, subjects had a significant decrease in body mass index (52.1 +/- 13.0 to 40.4 +/- 11.1), plasma glucose (148 +/- 8 to 101 +/- 4 mg/dL), insulin (18.5 +/- 2.2 mmuU/mL to 8.6 +/- 1.0 mmuU/mL) and HOMA-IR (7.1 +/- 1.1 to 2.1 +/- 0.3). Plasma LPS significantly reduced by 20 +/- 5% (0.567 +/- 0.033 U/mL to 0.443 +/- 0.022 E U/mL). NF-kappaB DNA binding decreased significantly by 21 +/- 8%, whereas TLR-4, TLR-2, and CD-14 expression decreased significantly by 25 +/- 9%, 42 +/- 8%, and 27 +/- 10%, respectively. Inflammatory mediators CRP, MMP-9, and MCP-1 decreased significantly by 47 +/- 7% (10.7 +/- 1.6 mg/L to 5.8 +/- 1.0 mg/L), 15 +/- 6% (492 +/- 42 ng/mL to 356 +/- 26 ng/mL) and 11 +/- 4% (522 +/- 35 ng/mL to 466 +/- 35 ng/mL), respectively. CONCLUSION: LPS, NF-kappaB DNA binding, TLR-4, TLR-2, and CD14 expression, CRP, MMP-9, and MCP-1 decreased significantly after RYGB. The mechanism underlying resolution of insulin resistance and T2DM after RYGB may be attributable, at least in part, to the reduction of endotoxemia and associated proinflammatory mediators.
PMID: 22088821
ISSN: 1532-7361
CID: 1646232

Roux en Y gastric bypass by single-incision mini-laparotomy: outcomes in 3,300 consecutive patients

Caruana, Joseph A; McCabe, Marc N; Smith, Audrey D; Stawiasz, Karen A; Kabakov, Eran; Kabakov, Julia M
BACKGROUND: Although the laparoscopic technique of Roux en Y gastric bypass (LRYGB) has popularized this weight loss procedure, the costs are justifiable if outcomes are superior to the open technique. We report our results with single-incision mini-laparotomy. METHODS: From June 2000 through November 2009, RYGB was performed in 3,300 consecutive patients using a 10-15-cm single-abdominal incision. Established guidelines for patient selection were followed and protocols were developed for patient education and for the prevention of perioperative complications. Weight loss (WL) over time and complications were recorded prospectively. Actual 90-day mortality was compared to that predicted by the Obesity Surgery Mortality Risk Score (OS-MRS). RESULTS: Eighty-four percent of patients were females with a mean body mass index (BMI) of 50 +/- 13. BMI of males was 54 +/- 9. There was a normal distribution of the WL response over 2,000 days. Complications included bleeding (1.4%), leak (1%), pulmonary embolism (0.7%), internal hernia (2.5%), and incisional hernia (5.6%). There were 1,793 Class A, 1,288 Class B, and 219 Class C patients. Eleven patients (0.3%) died within 90 days (one Class A, seven Class B, and three Class C), with mortality rates in all classes less than expected by the OS-MRS. Average hospital charges were $13,000. CONCLUSIONS: Our protocols and operative technique should be reproducible in other centers and may have a special appeal, if the costs of LRYGB limit access to bariatric surgery in qualified patients.
PMID: 21445657
ISSN: 1708-0428
CID: 1646242

The pulmonary embolism risk score system reduces the incidence and mortality of pulmonary embolism after gastric bypass

Caruana, Joseph A; Anain, Paul M; Pham, Dang Tuan
BACKGROUND: Pulmonary embolism (PE) is a leading cause of death after roux-en-Y gastric bypass (RYGB); therefore, current recommendations for prophylaxis may be inadequate. METHODS: We reviewed our first 1,341 patients (controls) who underwent RYGB and weighted factors that may have contributed to PE to arrive at a pulmonary embolism risk score (PERS). We postulated that more aggressive prophylaxis in higher risk patients might have reduced the incidence of PE. We tested our hypothesis by basing prophylaxis on the PERS in 1,652 subsequent RYGB patients (study group). Standard risk patients (PERS <4) were ambulated 2 hours after surgery, had application of intermittent compression devices, and received subcutaneous low-dose, unfractionated heparin (LDUH). Intermediate risk patients (PERS = 4) received standard prophylaxis and 3 weeks of postdischarge LDUH. High-risk patients (PERS >4) had postdischarge LDUH and a preoperative vena cava filter. RESULTS: The 0.36% incidence of PE (6 patients) in the study group was significantly lower (P <.05) than the 1% incidence (13 patients) in the controls. Three of 189 men in the control group died of PE, whereas there were no deaths from PE in 271 men in the study group (P <.05). CONCLUSION: The PERS may be an appropriate scoring system for determining preoperatively the level of risk for postoperative PE in RYGB patients. Basing prophylaxis on the level of risk reduces the incidence and mortality of PE and consumes resources judiciously.
PMID: 19789027
ISSN: 1532-7361
CID: 1646252

Evaluation of bariatric Centers of Excellence Web sites for functionality and efficacy

Kabakov, Julia M; Kabakov, Eran; Caruana, Joseph A
BACKGROUND: The Internet is a valuable method of information sharing and could have important applications for bariatric surgical practices. The purpose of this study was to devise criteria by which Centers of Excellence Web sites could be evaluated. By applying these criteria to the study sample, we hoped to identify specific content that could improve Web site functionality and, thereby, its efficacy. METHODS: We developed an original survey instrument that used specific criteria of Web site content to determine its functionality. The categories of content were Marketing, Interactivity, Education, and Support. Each of these categories was further divided into 3-7 subcategories for more in-depth analysis. From the Surgical Review Committee Web site page, 66 Centers of Excellence Web sites met our inclusion criteria of private, exclusively bariatric surgery practices. We then applied the survey instrument to evaluate their functionality. RESULTS: The survey revealed marketing and education content in all sites, and nearly all were interactive and provided patient support. However, all Web sites had deficiencies in >1 subcategory. CONCLUSION: Many Centers of Excellence have a Web presence. However, the opportunity exists to increase Web site functionality and efficacy by improving content in specific areas and using up-to-date technology.
PMID: 18436485
ISSN: 1550-7289
CID: 1646262

Risk of massive upper gastrointestinal bleeding in gastric bypass patients taking clopidogrel

Caruana, Joseph A; McCabe, Marc N; Smith, Audrey D; Panemanglore, Vishnudas Pai; Sette Camara, Daniel
BACKGROUND: The antiplatelet drug clopidogrel (Plavix) is widely used in patients who have undergone coronary artery stenting or had a stroke. Because morbid obesity is associated with atherosclerosis, some of these patients are candidates for weight loss surgery. We chose to determine the risk of upper gastrointestinal bleeding after gastric bypass in patients taking clopidogrel. METHODS: Patients who took clopidogrel after gastric bypass were identified by specific review of the subset of patients who had had upper gastrointestinal bleeding requiring hospital admission and transfusion. All who bled underwent emergency endoscopy. RESULTS: Of 11 patients taking clopidogrel, 4 (36%) presented with significant upper gastrointestinal bleeding 25-234 days after gastric bypass. All stopped bleeding with discontinuation of the drug and treatment with an intravenous proton pump inhibitor. CONCLUSION: Gastric bypass patients appear to be at high risk of bleeding complications when taking clopidogrel. On the basis of the available published data from another high-risk group (i.e., those with a history of peptic ulcer disease), co-treatment with omeprazole may be indicated when clopidogrel must be continued.
PMID: 17400519
ISSN: 1550-7289
CID: 1646272

Incidence of symptomatic gallstones after gastric bypass: is prophylactic treatment really necessary?

Caruana, Joseph A; McCabe, Marc N; Smith, Audrey D; Camara, Daniel Sette; Mercer, Michele A; Gillespie, John A
BACKGROUND: Because rapid weight loss after bariatric surgery increases gallstone formation, a 6-month treatment regimen with ursodiol has been recommended. Even prophylactic cholecystectomy at the time of gastric bypass in the absence of stones has been proposed. However, the incidence of symptomatic gallstones requiring cholecystectomy in untreated patients after gastric bypass has not yet been established. METHODS: The patients in our study were not treated with ursodiol after open Roux-en-Y gastric bypass. Additional inclusion criteria were no palpable gallstones at bypass, at least 16 months of follow-up after bypass, and continuous coverage by the same health insurance plan extending from the time of the operation to study completion, to track subsequent cholecystectomies by claims paid. RESULTS: A total of 100 females and 25 males met the study inclusion criteria. Follow-up extended from 16 to 48 months. Symptomatic gallstones requiring cholecystectomy developed in 10 patients, all females. Laparoscopic cholecystectomy was performed in 9 of these patients and open cholecystectomy was performed in the remaining patient, between 3 and 21 months after bypass. There were no serious complications from the stones or the cholecystectomy. CONCLUSIONS: Prophylactic cholecystectomy would have been unnecessary in 115 of the 125 patients in the study group. A 6-month course of ursodiol for all 125 patients, at a cost of 56,250 dollars, would have had to decrease the number of cholecystectomies from 10 to 3 to demonstrate a treatment effect (P < .05). Therefore, most newly formed gallstones after gastric bypass are likely asymptomatic, prophylactic cholecystectomy is not indicated, and ursodiol therapy may be better reserved for symptomatic patients who refuse surgery.
PMID: 16925292
ISSN: 1550-7289
CID: 1646282