[Show abstract][Hide abstract] ABSTRACT: Biliopancreatic diversion (BPD) is a complex bariatric operation requiring meticulous surveillance which has impeded its broad adoption. Improvements in surgical care and technique, better teaching programs, and stringent norms for follow-up have contributed to increased safety of BPD for patients with BMI <50, achieving better long-term results than other bariatric operations. Here we report 20-year outcomes of 2615 consecutive patients (median 8) having open BPD with duodenal switch (DS) between 1992 and 2010.
Chart of 92 % of patients with complete clinical, biochemical, and physical examinations completed before 2013 was reviewed. The research was conducted at Academic Medical Center, Quebec City.
There was total mortality of 4.7 %, equivalent to that of the general population of Quebec. Incident diabetes (38.8 %) was cured in 93.4 % (blood glucose <6 mmol/l; HbA1c <6.5 %) with 4 % relapse rate after mean 9.6 years with no new cases. Dyslipidemia (24.2 %) was cured in 80 %. Hypertension (60 %) was cured in 64 % and improved in 31 %. Mean weight loss of 55.3 kg (71 % excess weight loss (EWL); 20 BMI units) was maintained for 5 to 20 years. Operative mortality was reduced from 1.3 % in 1992 to 0.2 % during 2005-2010, with cumulated rate surgical mortality of 0.5, revision rate 3, and reoperations in 13 %. Nutritional deficiencies were present in 2 % for calcium, iron, and vitamin A. Side effects were considered minor by the great majority of patients, rating global satisfaction as 4.5/5 (91 % "satisfied").
BPD deserves more consideration as a primary procedure for eligible patients in experienced centers with sufficient resources for delivering high-quality care and long-term follow-up.
[Show abstract][Hide abstract] ABSTRACT: Whole-genome genotyping and gene expression analyses in blood of 22 BMS and 23 AMS offspring from 19 mothers were conducted using Illumina HumanOmni-5-Quad and HumanHT-12 v4 Expression BeadChips, respectively. Using PLINK we analyzed interactions between offspring gene variations and maternal surgical status on offspring gene expression levels. Altered biological functions and pathways were identified and visualized using DAVID and Ingenuity Pathway Analysis.
Significant interactions (p ≤ 1.22x10-12) were found for 525 among the 16,060 expressed transcripts: 1.9% of tested SNPs were involved. Gene function and pathway analysis demonstrated enrichment of transcription and of cellular metabolism functions and overrepresentation of cellular stress and signaling, immune response, inflammation, growth, proliferation and development pathways.
We suggest that impaired maternal gestational metabolic fitness interacts with offspring gene variations modulating gene expression levels, providing potential mechanisms explaining improved cardiometabolic risk profiles of AMS offspring related to ameliorated maternal lipid and carbohydrate metabolism.
[Show abstract][Hide abstract] ABSTRACT: Glucagon-like peptide-1 (GLP-1) regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1), and body mass index (BMI) in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profiles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing effects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues.
[Show abstract][Hide abstract] ABSTRACT: Objective:
The wide-ranging manipulations to the cardiovascular system that frequently occur during cardiac surgery can expose the brain to variations in its blood supply that could prove deleterious. As a first step to developing a resource suitable for monitoring such changes, we detected the hemodynamic events induced in the brain of a primate model, using high-density near-infrared spectroscopy combined with tomographic reconstruction methods and validated the findings using established radiologic and histologic techniques.
Continuous monitoring of the relative changes in the components of the cerebral hemoglobin signal was performed using high-density near-infrared spectroscopy (270 source-detector channel array) in anesthetized bonnet macaques with the brain exposed to induced ischemia and other acute events. A comparative analysis (exact binomial test) applied to reconstructed 3-dimensional images before and after the events and between cerebral hemispheres, combined with postprocedure magnetic resonance imaging, and postmortem histopathologic examination of the macaques' brains was performed to document and validate the spatial features revealed by the optical findings.
Relative changes in the measured and calculated components of the hemoglobin signal, in response to the performed manipulations, revealed substantial concurrence among the reconstructed 3-dimensional images, magnetic resonance imaging of the macaques' brains, and postmortem histopathologic examination findings. Concurrence was seen when the manipulated hemoglobin concentration and associated oxygenation levels were either increased or decreased, and whether they were bilateral or restricted to a specified hemisphere.
Continuous near-infrared spectroscopy tomography has been shown to accurately capture and localize cerebral ischemia, vasodilatation, and hemorrhage in primates in real time. These findings are directly applicable to clinical intraoperative functional cerebral monitoring.
No preview · Article · Jul 2014 · Journal of Thoracic and Cardiovascular Surgery
[Show abstract][Hide abstract] ABSTRACT: Background:
The choice of first-stage operation in bilio-pancreatic diversion with duodenal switch (BPD-DS) is controversial. There are no published long-term comparisons of one- and two-stage BPD-DS outcomes.
During 2001-2009, among 1,762 patients scheduled for BPD-DS 48 had duodenal switch (DS) and 53 sleeve gastrectomy (SG) as first-stage procedures. We compared prospectively updated outcomes of 42 DS (100 % open) and 49 SG (88 % laparoscopic), 13 of whom completed their second stage, to a control group of 91 patients with open one-stage BPD-DS.
One-year mean percent excess weight loss (%EWL) was greater after SG than DS (47 ± 19 vs. 39 ± 13 SD; p = 0.01) with earlier nadir (16 ± 10 vs. 45 ± 30 months; p < 0.0001) but more rapid significant weight regain. After 5 years, %EWL was 12 ± 35 for 9 SG, 45 ± 19 for 30 DS (p < 0.0006), and 70 ± 18 for the first-stage BPD-DS (p < 0.0001). Weight loss was less after two- than one-stage procedures (p < 0.02). Comorbidities improved progressively between SG, DS and BPD-DS (p < 0.001 for trend). HbA1C decreased by 10, 19, and 31 %, respectively (p < 0.0001). Dyslipidemia was cured in 41, 82, and 100 %, respectively. Systolic and diastolic blood pressure decreased only after DS (12 %; p < 0.0002). Patient satisfaction was similar for SG and DS but greater after BPD-DS overall (p = 0.04).
SG and DS independently contribute to beneficial metabolic outcomes after BPD-DS. Long-term weight loss and correction of metabolic abnormalities were better after DS favoring its use as first stage in BPD-DS; one-stage BPD-DS outcomes were superior to two-staged.
[Show abstract][Hide abstract] ABSTRACT: The 'obesity paradox' refers to observations that run counter to the thesis that normal weight (BMI 18.5-24.9 kg/m(2)) provides the lowest mortality and higher weight is associated with greater mortality. We argue that the weight of lowest mortality is influenced by aging and chronic disease, with mortality advantage extending into the overweight and even class I obese ranges under some circumstances. A focus on quality nutrition, physical activity, fitness, and maintaining function in these weight ranges may be preferable to a focus on intentional weight loss, which has uncertain effects. The 'obesity paradox' is no 'paradox' if one defines and interprets 'ideal' weight appropriately.International Journal of Obesity accepted article peview online, 15 April 2014. doi:10.1038/ijo.2014.59.
Full-text · Article · Apr 2014 · International journal of obesity (2005)
[Show abstract][Hide abstract] ABSTRACT: Body weight support (WS) during treadmill exercise is used to rehabilitate orthopedic/neurological patients. WS lowers musculoskeletal strain and load. It compresses the lower body and increases intrathoracic volume. We studied short-term effects of WS on wave reflection indices using applanation tonometry during progressive WS of 25%, 50%, and 75% of body weight in 25 healthy men. WS decreased mean heart rate from 79 to 69 beats/min (P < .001). Peripheral and central mean arterial, systolic, and pulse pressures (PP) remained unchanged. There was a trend toward lower peripheral and central diastolic pressure. PP amplification ratio decreased significantly (P = .005). Reflected wave characteristics: Augmented pressure and index increased in a stepwise manner with WS (both P < .001). Both ejection duration and systolic duration of the reflected pressure wave (Ätr) increased progressively (both P < .001). The round-trip travel time (Δtp) was unchanged. Left ventricular workload and oxygen demand: Left ventricular wasted pressure energy increased (P < .001), and the subendocardial viability ratio decreased (P = .005), whereas the tension time index remained unchanged. In normal men, WS acutely decreases the PP amplification ratio, increases the amplitude and duration of the reflected aortic pressure wave, and increases measures of wasted left ventricular pressure energy and oxygen demand.
No preview · Article · Mar 2014 · Journal of the American Society of Hypertension (JASH)
[Show abstract][Hide abstract] ABSTRACT: We previously demonstrated an inverse relationship between both dentate gyrus neurogenesis - a form of neuroplasticity - and expression of the antiapoptotic gene marker, BCL-2 and adult macaque body weight. We therefore explored whether a similar inverse correlation existed in humans between body mass index (BMI) and hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity and putatively, neuroplasticity. We also studied the relationship of a potentially neurotoxic process, worry, to hippocampal NAA in patients with generalized anxiety disorder (GAD) and control subjects (CS).
We combined two previously studied cohorts of GAD and control subjects. Using proton magnetic resonance spectroscopy imaging ((1)H MRSI) in medication-free patients with GAD (n = 29) and a matched healthy control group (n = 22), we determined hippocampal concentrations of (1) NAA (2) choline containing compounds (CHO), and (3) Creatine + phosphocreatine (CR). Data were combined from 1.5 T and 3 T scans by converting values from each cohort to z-scores. Overweight and GAD diagnosis were used as categorical variables while the Penn State Worry Questionnaire (PSWQ) and Anxiety Sensitivity Index (ASI) were used as dependent variables.
Overweight subjects (BMI ≥ 25) exhibited lower NAA levels in the hippocampus than normal-weight subjects (BMI < 25) (partial Eta-squared = 0.14) controlling for age, sex and psychiatric diagnosis, and the effect was significant for the right hippocampus in both GAD patients and control subjects. An inverse linear correlation was noted in all subjects between right hippocampal NAA and BMI. High scores on the PSWQ predicted low hippocampal NAA and CR. Both BMI and worry were independent inverse predictors of hippocampal NAA.
Overweight was associated with reduced NAA concentrations in the hippocampus with a strong effect size. Future mechanistic studies are warranted.
Full-text · Article · Jan 2014 · Clinical neuroimaging
[Show abstract][Hide abstract] ABSTRACT: Near-infrared (NIR) optical techniques, using large-area sensing arrays that provide for transcranial measures of cortical function, are finding increasing use for functional assessment of brain activity. In this chapter, we review current capabilities of these methodologies and describe their application to an in vivo large animal model, Bonnet macaque, for the purpose of imaging hemodynamic responses to clinically significant events, including detection of cerebral ischemia and hemorrhage. The described methodology outlines the technology and method of high-density diffuse optical tomography (DOT), as explored using recently developed analysis resources whose accuracy is independently validated. Also discussed are solutions to commonly encountered problems related to data collection and analysis.
[Show abstract][Hide abstract] ABSTRACT: Background. Maternal obesity, excess weight gain and overnutrition during pregnancy increase risks of obesity, type 2 diabetes mellitus, and cardiovascular disease in the offspring. Maternal biliopancreatic diversion is an effective treatment for severe obesity and is beneficial for offspring born after maternal surgery (AMS). These offspring exhibit lower severe obesity prevalence and improved cardiometabolic risk factors including inflammatory marker compared to siblings born before maternal surgery (BMS). Objective. To assess relationships between maternal bariatric surgery and the methylation/expression of genes involved in the immune and inflammatory pathways. Methods. A differential gene methylation analysis was conducted in a sibling cohort of 25 BMS and 25 AMS offspring from 20 mothers. Following differential gene expression analysis (23 BMS and 23 AMS), pathway analysis was conducted. Correlations between gene methylation/expression and circulating inflammatory markers were computed. Results. Five immune and inflammatory pathways with significant overrepresentation of both differential gene methylation and expression were identified. In the IL-8 pathway, gene methylation correlated with both gene expression and plasma C-reactive protein levels. Conclusion. These results suggest that improvements in cardiometabolic risk markers in AMS compared to BMS offspring may be mediated through differential methylation of genes involved in immune and inflammatory pathways.
[Show abstract][Hide abstract] ABSTRACT: Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2-25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring.
No preview · Article · May 2013 · Proceedings of the National Academy of Sciences
[Show abstract][Hide abstract] ABSTRACT: Populations of many countries are becoming increasingly overweight and obese, driven largely by excessive calorie intake and reduced physical activity; greater body mass is accompanied by epidemic levels of comorbid metabolic diseases. At the same time, individuals are living longer. The combination of aging and the increased prevalence of metabolic disease is associated with increases in aging-related comorbid diseases such as Alzheimer's disease, cerebrovascular dementia, and sarcopenia. Here, correlative and causal links between diseases of overnutrition and diseases of aging and cognition are explored.
Full-text · Article · May 2013 · Annals of the New York Academy of Sciences