Peripheral Obesity Research Articles

Association between community greenness and obesity in urban-dwelling Chinese adults

Living in greener places may protect against obesity, but epidemiological evidence is inconsistent and mainly comes from developed nations. We aimed to investigate the association between greenness and obesity in Chinese adults and to assess air pollution and physical activity as mediators of the association. We recruited 24,845 adults from the 33 Communities Chinese Health Study in 2009. Central and peripheral obesity were defined by waist circumference (WC) and body mass index (BMI), respectively, based on international obesity standards. The Normalized Difference Vegetation Index (NDVI) was used to quantify community greenness. Two-level logistic and generalized linear mixed regression models were used to evaluate the association between NDVI and obesity, and a conditional mediation analysis was used also performed. In the adjusted models, an interquartile range increase in NDVI500-m was significantly associated with lower odds of peripheral 0.80 (95% confidence interval [CI]: 0.74–0.87) and central obesity 0.88 (95% CI: 0.83–0.93). Higher NDVI values were also significantly associated with lower BMI. Age, gender, and household income significantly modified associations between greenness and obesity, with stronger associations among women, older participants, and participants with lower household incomes. Air pollution mediated 2.1–20.8% of the greenness-obesity associations, but no mediating effects were observed for physical activity. In summary, higher community greenness level was associated with lower odds of central and peripheral obesity, especially among women, older participants, and those with lower household incomes. These associations were partially mediated by air pollutants. Future well-designed longitudinal studies are needed to confirm our findings.

The Relationship of Chemotherapy-Induced Peripheral Neuropathy and Obesity: A Systematic Review

Background:Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting neurotoxic effect of chemotherapy that affects many survivors. Obesity is also known to have a negative effect on neuropathy. This review aimed to determine what relationship, if any, obesity might have with the incidence and severity of CIPN.Methods:Electronic databases PubMed, PEDro (Physiotherapy Evidence Database), CENTRAL (Cochrane Central Register of Controlled Trials), Ovid, and EBSCO were systematically searched from January 2008 to March 2019. All types of studies, data collections, and review articles were included in the adult population.Results:Twelve articles describing relationships between overweight/obesity and presence of CIPN were included in the review. Associations between body mass index (BMI), body surface area (BSA), and sarcopenic obesity and CIPN incidence and severity were described in patients who had received taxane therapy, platinum compound therapy, or bortezomib. Eleven of the 12 studies indicated an increased incidence of CIPN with higher BMI or BSA or sarcopenic obesity, and the 2 studies that analyzed severity of symptoms found an increase in those who were overweight/obese.Limitations:The number of studies specifically analyzing the relationship between overweight/obesity is limited. Also limiting comparison between studies is the categorization of obesity and the methods used to define CIPN.Conclusions:Overall, being overweight or obese would put one at a higher risk for development of CIPN. Clinicians should encourage healthy lifestyles to help decrease or control symptoms and/or limit dose reductions of chemotherapy. Further research regarding changes in severity of CIPN with weight loss or gain is needed.

Patients with lower extremity dialysis access have poor primary patency and survival

ObjectiveLower extremity arteriovenous (AV) access is an alternative when upper extremity access options have been exhausted. Our goal was to assess short- and medium-term outcomes of lower extremity hemodialysis access. MethodsThe Vascular Quality Initiative was reviewed for all lower extremity AV hemodialysis cases. Patient and case details were recorded. Multivariable analysis was used to analyze outcomes. ResultsWe identified 463 lower extremity AV access cases in the VQI registry. There were 56 AVF (12.1%) and 407 AVG (87.9%). The mean age was 56 ± 15 years, 46.9% were male, and 40.7% were Caucasian. The majority (90%) had a previous upper extremity AV access and 25.4% had a prior lower extremity access. More than one-half (57.9%) had a tunneled line at the time of the procedure. Patients undergoing an AVF vs AVG creation were younger, more often ambulatory, and less often with peripheral arterial disease. For AVF, the superficial femoral artery was more often used for access inflow (76.8% vs 49.4%; P < .001), compared with AVG, and there was no difference in using femoral vein as the main outflow (78.6% vs 82.6%; P = .466). For AVF, compared with AVG, there was no difference in wound infection (12.5% vs 9.6%; P = .571), ischemic steal (5% vs 2.2%; P = .273), or leg swelling (2.5% vs 3.3%; P = .99) at 6 months. Kaplan-Meier analysis of the overall cohort showed that freedom from loss of primary patency at 6 months was 52.9%, freedom from any reintervention at 6 months was 75.3%, and the 1-year survival was 81.9%. Survival at 5 years was 65.5%. Multivariable analysis showed no significant association of access type (AVF vs AVG) with primary patency loss or death (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.36-1.5; P = .4), any reintervention or death (HR, 1.65; 95% CI, 0.82-3.33; P = .163), or mortality (HR, 1.94; 95% CI, 0.71-5.33; P = .197). Factors independently associated with primary patency loss or death included peripheral arterial disease (HR, 1.6; 95% CI, 1.06-2.42; P = .03) and obesity (HR, 1.5; 95% CI, 1.1-2.05; P = .01). Any reintervention or death was associated with obesity (HR, 1.67; 95% CI, 1.09-2.56; P = .015). Mortality was associated with congestive heart failure (HR, 1.82; 95% CI, 1.13-2.94; P = .015) and white race (HR, 1.71; 95% CI, 1.08-2.73; P = .023). ConclusionsIn our contemporary multicenter analysis, patients undergoing lower extremity AV access creation have low primary access patency and almost 20% mortality at 1 year. These results should be considered when suggesting a lower extremity dialysis access, as well as other dialysis alternatives when available.

Role of Inflammation in Control of Hepatic Lipid Metabolism—New Insights to the Pathogenesis of NASH

Non‐alcoholic fatty liver disease (NAFLD) is a common metabolic disorder whose incidence among US adults exceeds 30%. While NAFLD manifests as benign hepatic steatosis in most patients, in about 20% of patients it assumes a much more aggressive form – non‐alcoholic steatohepatitis (NASH). The mechanisms that control the switch from benign steatosis to NASH are poorly understood, but were suggested to depend on ER stress. To query the role of ER stress in NASH development and establish a proper mouse model for studying the disease, we fed high‐fat diet (HFD) to MUP‐uPA mice, which are prone to liver ER stress due to hepatocyte‐specific urokinase plasminogen activator (uPA) expression. Placing these mice on HFD triggered full‐blown NASH within 3–4 months and most of the NASH‐afflicted mice progressed to develop hepatocellular carcinoma (HCC), the most common form of liver cancer whose incidence and development rates greatly increase with steatohepatitis. Both NASH and HCC development in MUP‐uPA mice depend on ER stress and are associated with persistent activation of sterol response element binding proteins (SREBP) 1 and 2. SREBP1 activation drives de novo lipogenesis (DNL) and cholesterol biosynthesis in HFD‐fed MUP‐uPA mice remains elevated without any sign of feedback inhibition mechanisms that control SREBP2 activation in tissue culture cells. DNL and cholesterol synthesis are also chronically elevated in NASH patients and the hepatic accumulation of free cholesterol was suggested to be a key switch from simple steatosis to NASH. While investigating the mechanism by which ER stress leads to persistent SREBP activation, we uncovered a previously unknown pathway in which caspase‐2 (Casp2) leads to constitutive activation of site 1 protease (S1P), which initiates SREBP cleavage activating protein (SCAP)‐independent SREBP activation. Of note, genetic ablation or pharmacological inhibition of Casp2 in MUP‐uPA mice blocks NASH development by preventing hepatic steatosis. Casp2 ablation in both MUP‐uPA and BL6 mice also prevents HFD‐induced adipocyte hypertrophy and increases energy consumption. None of the effects of Casp2 on liver lipid metabolism are related to cell death. The NAFLD/NASH epidemic was also suggested to be associated with increased consumption of fructose, which is a major constituent of high‐fructose corn syrup (HFCS), the main sweetener and a general food additive in the US. Increased consumption of HFCS has been linked to elevated risk of developing HCC, pancreatic and colon cancer. Indeed, feeding MUP‐uPA mice a high‐fructose diet (HFrD) results in NASH and HCC development even without the peripheral obesity that accompanies HFD consumption. Although fructose was believed to give rise to hepatic steatosis through preferential uptake and direct incorporation into the glycolytic pathway in hepatocytes, recent results indicate that the first site of fructose metabolism is the small intestine. Correspondingly, we found that fructose gives rise to NASH and HCC by first disrupting the intestinal epithelial barrier, evoking an inflammatory response that drives both NASH and HCC development.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Female infertility: which role for obesity?

Obesity is associated with infertility in women through multiple and complex mechanisms. Briefly, the adipose tissue through the production of many factors, such as leptin, free fatty acids (FFA), and cytokines may affect both ovarian and endometrium functions, with a final alteration in oocyte maturation and endometrial epithelium receptivity. In addition, through the development of peripheral insulin resistance obesity produces a condition of functional hyperandrogenism and hyperestrogenism that contribute to produce anovulation and to reduce endometrial receptivity and, therefore participate to cause infertility. Weight loss is able to restore fertility in most cases, but there are no practical indications to guide the clinician to choice the best method among increased physical activity, diet, drugs, and bariatric surgery.

Evaluation of a clinical score for predicting atrial fibrillation in cryptogenic stroke patients with insertable cardiac monitors: results from the CRYSTAL AF study.

Background:The HAVOC score was previously developed to predict the risk of atrial fibrillation (AF) after cryptogenic stroke (CS) or transient ischemic attack (TIA). The purpose of this study was to apply the HAVOC score to patients who received insertable cardiac monitors (ICMs) in the CRYSTAL AF study.Methods:All patients from the CRYSTAL AF study who received an ICM were included. HAVOC score (one point each for peripheral vascular disease and obesity with body mass index >30, two points each for hypertension, age ⩾ 75, valvular heart disease, and coronary artery disease, 4 points for congestive heart failure) was computed for all patients. The primary endpoint was AF detection by 12 months of ICM monitoring.Results:A total of 214 patients who received ICM were included. AF was detected in 40 patients while the remaining 174 patients were AF negative. The HAVOC score was significantly higher among patients with AF [median 3.0 with interquartile range (IQR) 2–4] than those without AF [median 2.0 (IQR 0–3)], p = 0.01. AF increased significantly across the three HAVOC score groups: 11% in Group A (score 0–1), 18% in Group B (score 2–3), and 32 % in Group C (score ⩾ 4) with p = 0.02.Conclusions:The HAVOC score was shown in this post hoc analysis of CRYSTAL AF to successfully stratify AF risk post CS or TIA. The 11% AF rate in the lowest HAVOC score group highlights the significance of nontraditional contributors to AF and ischemic stroke.

THE CORRELATION BETWEEN EPICARDIAL FAT THICKNESS BASED ON MULTI SLICE COMPUTED-TOMOGRAPHY SCAN THORAX WITH WAIST CIRCUMFERENCE AND BODY MASS INDEX ON DYSLIPIDEMIA NON-DIABETES MELLITUS SUBJECT

Introduction : Epicardial fat is visceral fat that plays a role in cardiovascular disease. Dyslipidemia non-diabetes mellitus can be found in both obese and non-obese patients. Measurement of waist circumference and BMI can assess central and peripheral obesity. The study aims to finding out the correlation between epicardial fat thickness based on MSCT scan Thorax with waist circumference and BMI on dyslipidemia non-diabetes mellitus subject. Method: There were 57 research samples of 28 to 70 years old who had dysfunction lipid profile. The most samples were found in the age group of 45-64 years with epicardial fat ranges from 2.80 to 10.80 mm and mean of 6.37 mm. Data were analysed by Mann-Whitney and Spearman correlation test. Result: There was a significant correlation between waist circumference and epicardial fat (r = 0.286, p = 0,031). There was no difference in mean of epicardial fat thickness by sex. There was no correlation between sex, and BMI with epicardial fat. Conclusion: There is a correlation between waist circumference and epicardial fat that may be affected by several factors in patients with dyslipidemia non-diabetes mellitus.

Prospective Study of Central versus Peripheral Obesity in Total Knee Arthroplasty.

PurposeBody mass index (BMI) is often used to predict surgical difficulty in patients receiving total knee arthroplasty (TKA); however, BMI neglects variation in the central versus peripheral distribution of adipose tissue. We sought to examine whether anthropometric factors, rather than BMI alone, may serve as a more effective indication of surgical difficulty in TKA.Materials and MethodsWe prospectively enrolled 67 patients undergoing primary TKA. Correlation coefficients were used to evaluate the associations of tourniquet time, a surrogate of surgical difficulty, with BMI, pre- and intraoperative anthropometric measurements, and radiographic knee alignment. Similarly, Knee Injury and Osteoarthritis Outcome Score (KOOS) was compared to BMI.ResultsTourniquet time was significantly associated with preoperative inferior knee circumference (p=0.025) and ankle circumference (p=0.003) as well as the intraoperative depth of incision at the quadriceps (p=0.014). BMI was not significantly associated with tourniquet time or any of the radiographic parameters or KOOS scores.ConclusionsInferior knee circumference, ankle circumference, and depth of incision at the quadriceps (measures of peripheral obesity) are likely better predictors of surgical difficulty than BMI. Further study of alternative surgical indicators should investigate patients that may be deterred from TKA for high BMI, despite relatively low peripheral obesity.

Excess in Atherosclerotic and Inflammametabolic Diseases Are Differentially Expressed in Myelodysplasia and Are Highly Dependent on Age, R-IPSS and Ethnicity

Background Myelodysplastic syndrome (MDS) is an inflammatory heterogeneous group of myeloid disorders with variable risk for acute myeloid leukemia (AML) conversion. Recent reports highlight that mutations [i.e. TET2, DNMT3A, AXSL1] configurate not only risk for malignant conversion in “healthy elderly individuals” but also ‘directly’ participate in coronary artery disease [CAD] development. TET2 clonal hematopoiesis [TET2 CHIP] accelerates atherosclerosis in mice via monocytic inflammatory amplification. Indeed, germ-line DNMT3A human disease phenocopy obesity and neurocognitive abnormalities suggesting that a more complex, but still poorly characterized cardiometabolic risk, probably originates from patient predisposition and somatic mutation acquisition. We seek to originate a cross-sectional “proof of concept” for quantifying the association between myelodysplasia [a clonal disorder initiated by CHIP mutations] and several systemic inflammatory conditions [i.e. CAD, peripheral vascular disease (PVD), obesity, depression and COPD].Methods: A cross-sectional analysis of a nationally-representative sample of inpatient hospitalizations in the United States between 2007 and 2015 [750,249 MDS-related hospitalizations, or 83,361 hospitalizations per year] was performed to identify co-occurring inflammatory diseases during hospitalizations in patients older than 35 years, in which MDS was documented. Given the inflammatory nature of the disease, subgroups were defined to investigate the prevalence of individual inflammatory domains (per 1,000 MDS-related hospitalizations) according to Revised-International Prognostic Score System [R-IPSS]. Subgroup analysis was performed for patients based on age (above and below 65 years), and race/ethnicity. Prevalence and confidence intervals [CI] were obtained for each inflammatory condition. “Relevant” inflammatory domains were considered statistically significant based on non-overlapping 95% CIs.Results: In examined admissions, prevalence for CAD in (Low-risk) LR- MDS age <> 65 was 12.2 vs 24.7, PVD 21.8 vs 60.2, [Fig 1 A and B] obesity 88.1 vs 51.7, major depression 14.6 vs 5.3, COPD 42.1 vs 70.7, p=0.0001 for all comparisons [Fig 1 B and C]. Conversely, prevalence for CAD in (High-risk) HR MDS age <> 65 was 9.1 vs 17.3, p=0.04; PVD 14.5 vs 43.2, p=0001; obesity 73.7 vs 42.2, p=0.003 major depression 5.1 vs 6.9, p=0.04 and COPD 23.0 vs 34.6, p=0.05. Differential prevalence expression for CAD was observed between non-Hispanic Whites (W) and Hispanics (H) [22 vs 28, p=0.02]. PVD was more prevalent, in both W vs H [64.6 and 52.2, p= 0.0002] and NH-Blacks/African Americans (AA) vs H [63.1 vs 52.2, p= 0.009]. Obesity was more prevalent among AA and H [64.1 and 62.9, respectively] than in W [51.9, p=0.009 for W vs AA and p=0.0002 for W vs H]. Similar expression for diabetes was observed between H vs W [404 vs 282, p<0.0001], H vs AA [404 vs 364, p=0.0001], and AA vs W [364 vs 282, p=<0.0001]. COPD was dominant among W and AA [73.8 and 78.4] as compared with H [50.4, p=0.0001 for H vs W and H vs AA]. Idiopathic pulmonary fibrosis was dominant in W and H [1.8 and 1.9] in comparison to AA [0.9, p=0.04 AA vs H and p=0.02 AA vs W]. Major depression prevalence was observed in AA, W and H in 5.4 vs 9.5 vs 14.3, respectively, p=0.0001 H vs AA and H vs W].Conclusions. Prevalence of systemic inflammatory diseases in MDS are associated with age, disease biology [Low vs High risk] and ethnicity. Cardiopulmonary complications, such as PVD+ COPD are dominant in W and AA. Lower prevalence for PVD and COPD, but high rates for CAD, depression, diabetes and IPF in H vs W and AA suggest that ethnicity could differentially drive cardiometabolic and inflammametabolic phenotypes when co-occurring with clonal hemopoietic disorders such as MDS. DisclosuresNo relevant conflicts of interest to declare.

Impact of Immune Thrombocytopenia in Patients Admitted with Coronary Artery Disease: Results from National Inpatient Sample 2009-2011

BackgroundPatients with immune thrombocytopenia (ITP) may be at increased risk of thromboembolism related to different causes, including the use of thrombopoietin receptor agonists and splenectomy. Patients with ITP who develop coronary artery disease (CAD) can be a further challenge given their risk of both thromboembolism and bleeding, which may significantly increase the risk of mortality and length of stay (LOS) compared to patients who do not have ITP. We aimed to study the impact of ITP in hospital outcomes of patients with CAD.MethodsWe utilized the National Inpatient Sample database from years 2009 - 2011. We selected non-pregnant inpatients over the age of 18 with history of CAD. We selected patients with CAD and ITP based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). We used STATA version 13.0 (College Station, TX) for database analysis.ResultsA total of 4,777 cases of ITP with CAD were identified compared to 2,614,008 without ITP (Table 1). Logistic multivariable analyses found that patients with ITP had higher in-hospital mortality (95% CI: 1.21 to 1.55, p=0.0001) and LOS (95% CI: 1.32 to 1.72, p<0.0001) after adjustment for age, sex, race, smoking, obesity, dyslipidemia, diabetes, hypertension, chronic kidney disease, peripheral vascular disease, smoking, obesity, stroke, and Charlson comorbidity index (Table 2).Conclusion: Our study shows that in patients with coronary artery disease-associated ITP, adjusted LOS and mortality was significantly higher compared to patients without ITP. DisclosuresNo relevant conflicts of interest to declare.

Are risk factors of cerebral small vessel disease differ from those in patients with high atherothrombotic risk without cerebrovascular disease?

Knowledge of risk factors for cerebral small vessel disease (CSVD) may generate hypothesis regarding possible targets for prevention. Our aim was to evaluate if atherothrombotic risk factors differ between patients with CSVD and with subjects without cerebrovascular disease but with high cardiovascular (CVD) risk. A single-center, cohort study was performed in consecutive patients with different CSVD manifestations. The study group consisted of 205 patients: 52 with lacunar stroke (LS), 20 with subcortical hemorrhagic stroke (HS), 50 with vascular dementia (VaD), 28 with vascular parkinsonism (VaP) and 55 controls (CG) with high CVD risk (35 with atherosclerotic CVD, 20 with 10-year risk of CVD with SCORE?5). Logistic regression was used to analyze the influence of clinical and laboratory data on the occurrence of CSVD. Mean age, sex distribution, prevalence of smoking, hyperlipidemia, peripheral artery disease and obesity were similar in CSVD and CG. The factors significantly associated with CSVD compared to controls were diabetes mellitus, polymetabolic syndrome, elevated systolic blood pressure, low levels of eGFR, HDL, albumin and high uric acid, fibrinogen, fasting glucose, HbA1c and intima medic thickness (p&lt;0.05). Hypertension, chronic kidney disease and elevated fasting blood glucose were related to LS and HS (p&lt;0.1). Diabetes was significantly associated with LS and VaD while smoking and low total cholesterol were related to HS (p&lt;0.1). The study confirms that risk factors profile for CSVD differs from subjects with proatherogenic profile without history of cerebrovascular disease. Our results also support that unique risk factors profiles exist for different manifestations of the CSVD.

Influence of Childhood and Adulthood Obesity on Arterial Stiffnes and Central Blood Pressure in Men

Aim. To study the effect of obesity in childhood and adulthood on the indices of arterial stiffness, central aortic pressure in the population sample of men 42 to 43 years. Methods. The study is part of a 32-year prospective cohort monitoring of males, beginning with childhood (11-12 years). 303 (30.1%) of the representatives of the initial population sample (n=1005) were examined after 32 years. 290 people are included into the analysis. The average age of men at the time of the examination was 42.9 years. The study included a survey on a standard questionnaire, measurement of anthropometric indicators, blood pressure (BP), pulse counting. The stiffness of the arterial wall and central pressure was measured by the applanation tonometry. Results. Normal body weight was found in 95 of 290 men (32.8%) at the age of 43 years, weight gain – in 111 (38.3%) and obesity – in 84 (28.9%). Men with obesity and overweight in adulthood had a statistically significant increase in body weight as early as in childhood. Central aortic BP (CBP), as a surrogate vascular rigidity index, was statistically significantly higher in obesity and overweight groups. A statistically significant positive relationship between the indicators characterizing childhood obesity (the Quetelet index, the thickness of skin folds), and the level of blood pressure in childhood was found in the correlation analysis. A positive correlation between the thickness of skin folds in childhood with CBP in adulthood, as well as a weak positive relationship between peripheral systolic BP (pSBP) in childhood and central systolic BP (cSBP) in adulthood have been found. From potential predictors evaluated at the age of 12 years and included in the regression model only the thickness of the skin fold under the scapula affected cSBP at the age of 43. The increase in the thickness of skin fold under the scapula in childhood at1 mmis associated with an increase in сSBP by0.4 mmHg in the adult state. Among the predictors evaluated in adulthood, pSBP, peripheral diastolic BP (pDBP), and the Quetelet index have a statistically significant effect on the level of cSBP. The thickness of the skin fold on the abdomen at the age of 12 influenced central diastolic BP (cDBP) level at the age of43. Astatistically significant effect on the cDBP level was provided by pDBP, obesity rates among potential predictors evaluated in adulthood. Conclusion. Central aortic pressure in adulthood is maximally dependent on increased peripheral blood pressure and obesity. Only obesity was important among children's predictors (12 years of age).

Coronary artery bypass surgery in Syrian refugees. Outcomes in a Turkish tertiary center.

Objectives:To assess outcomes of Syrian refugees undergoing coronary artery bypass surgery in a tertiary hospital in Turkey.Methods:We sought for in-hospital mortality and one year all-cause mortality as the main outcomes. We reviewed records of 67 Syrian and 427 Turkish patients undergoing isolated coronary bypass surgery between 2015 January and 2017 January retrospectively.Results:History of coronary, peripheral and carotid artery diseases and obesity were more frequent in Syrian patients. C-reactive protein levels were higher in Syrian patients whereas lipid profiles and systolic functions of the 2 groups were similar. Syrian patients more frequently presented with the acute coronary syndrome (26.9% versus 15.5%, p<0.001). SYNTAX I (Synergy between PCI with Taxus and Cardiac Surgery) and SYNTAX II-PCI were higher in Syrian patients whereas SYNTAX II-CABG was similar with Turkish patients. Extubation time was longer and amount of the hemorrhage was greater in Syrian patients; however, bleeding revision was not increased. Although wound infection was more frequent in Syrian patients, postoperative complications were similar between groups. In-hospital mortality and one year all-cause mortality did not differ between Syrian (n=1; 1.5% versus n=13; 13.1%) (p=0.476) and Turkish patients (n=3; 4.5% versus n=25; 5.9%) (p=0.63).Conclusion:Syrian patients had higher SYNTAX I and SYNTAX II PCI scores, but not SYNTAX II CABG score compared with Turkish patients. Intraoperative and postoperative complications were similar. In-hospital mortality and one year all-cause mortality of Syrian patients were similar with Turkish patients. Surgical outcomes of Syrian patients were acceptable. Primary prevention of obesity must be provided. Aggressive secondary preventive measures must be taken due to increased severity of coronary artery disease.

Peripheral Lymphocytes, Obesity, and Metabolic Syndrome in Young Adults: An Immunometabolism Study.

Obesity is characterized by a low-intensity chronic inflammatory process in which immune system cells interact in a complex network, which affects systemic metabolic processes. This raises interest in analyzing possible changes in the proportions of immune system cells in individuals with obesity with and without metabolic syndrome (MS), in relation to their body composition. Circulating cells were analyzed with flow cytometry in young adults: monocytes, granulocytes, lymphocytes (T, B, and natural killer [NK]), TCD4+CD62-, TCD8+CD28-, and naive and memory cells of TCD3+ and TCD4+. Body composition was obtained by bioelectrical impedance analysis and dual-energy X-ray absorptiometry, and metabolic parameters. A total of 169 persons were evaluated: 20% presented normal body mass index (BMI); 49% was overweight, and 31% had obesity; 28% had MS. It was observed that with an increase in BMI and visceral adipose tissue increase (VATI), body composition and biochemical variables were negatively altered. With regard to cell subpopulations, total lymphocytes increased and granulocytes and NK lymphocytes decreased in patients with MS and VATI. Memory cells increased with BMI and VATI. In individuals with MS, monocytes, and NK lymphocytes comprised a negative association with VAT, fat mass, and skeletal muscle mass (SMM). In individuals with MS and VATI, a negative correlation was observed between monocytes and SMM. Significant changes were detected in the subpopulations of lymphocytes, suggesting that weight gain, SMM, and VAT accumulation gave rise to immunological changes at the peripheral level, and the presence of increased memory cells could be related to low-intensity chronic inflammation.

The roles of early surgery and comorbid conditions on outcomes of severe necrotizing soft-tissue infections.

Severe necrotizing soft-tissue infections (NSTIs) require immediate early surgical treatment to avoid adverse outcomes. This study aims to determine the impact of early surgery and comorbid conditions on the outcomes of NSTIs. A retrospective cohort study was performed on all subjects presenting with NSTI at an academic medical center between 2005 and 2016. Patients were identified based on ICD codes. Those under the age of 18 or with intraoperative findings not consistent with NSTI diagnosis were excluded. There were 115 patients with a confirmed diagnosis of NSTI with a mean age of 55 ± 18 years; 41% were females and 55% were diabetics. Thirty percent of patients underwent early surgery (< 6h). There were no significant differences between groups in baseline characteristics. The late group (≥ 6h) had prolonged hospital stay (38 vs. 23 days, p < 0.008) in comparison to the early group (< 6h). With every 1h delay in time to surgery, there is a 0.268day increase in length of stay, adjusted for these other variables: alcohol abuse, number of debridements, peripheral vascular disease, previous infection and clinical necrosis. Mortality was 16.5%. Multivariable analysis revealed that alcohol abuse, peripheral vascular disease, diabetes, obesity, hypothyroidism, and presence of COPD were associated with an increase in mortality. Early surgical intervention in patients with severe necrotizing soft-tissue infections reduces length of hospital stay. Presence of comorbid conditions such as alcohol abuse, peripheral vascular disease, diabetes, obesity and hypothyroidism were associated with increased mortality.

F235. DIFFERENTIAL EFFECTS OF ANTIPSYCHOTICS ON NEUROINFLAMMATION AND ENERGY SENSING IN A HYPOTHALAMIC CELL LINE

BackgroundAntipsychotics (AP)s are the cornerstone of treatment for schizophrenia but cause serious metabolic side-effects. The hypothalamus is the primary brain region responsible for whole body energy regulation and disruptions in energy sensing (e.g. insulin signaling) and inflammation in this brain region have been implicated in the development of peripheral insulin resistance and obesity. Thus, it is possible that hypothalamic inflammation and disturbed energy sensing could be involved in AP-induced metabolic disturbances. Data in relation to AP-associated changes in inflammatory markers in schizophrenia has been inconsistent, owing in part to confounds of illness-related factors (e.g. diet, smoking) and secondary effects of weight gain. To our knowledge, direct effects of APs on hypothalamic cells in relation to insulin signaling and inflammation have not been examined.MethodsTo examine direct, molecular effects of APs in the hypothalamus, an immortalized rat hypothalamic cell line, rHypoE-19, was treated with olanzapine (dose range between 0.25–100 uM), clozapine (2.5–100 uM) or aripiprazole (5–20 uM). Western blotting was used to detect changes in the energy sensing protein AMPK, components of the insulin signaling pathway (AKT, GSK3B), and components of the mitogen activated-protein kinase (MAPK) pathway (ERK1/2, JNK, p38), the latter which are linked to inflammation. Quantitative real-time PCR was performed to determine changes in the mRNA expression of interleukin (IL)-6, IL-10 and brain derived neurotrophic factor (BDNF).ResultsBoth olanzapine (100 uM) and clozapine (100 uM) significantly increased pERK1/2 and pJNK protein expression, while aripiprazole (20 uM) only increased pJNK. Clozapine (100 uM) and aripiprazole (5 and 20 uM) significantly increased AMPK phosphorylation and inhibited insulin-induced phosphorylation of AKT. Olanzapine (100 uM) treatment caused a significant increase in IL-6 while aripiprazole (20 uM) significantly decreased IL-10. Olanzapine (100 uM) and aripiprazole (20 uM) increased BDNF expression.DiscussionAll the APs studied upregulated pJNK, along with olanzapine-associated increases in IL-6, and aripiprazole-associated decreases in IL-10, together suggesting AP-mediated upregulation of pro-inflammatory pathways in rHypoE-19 neurons. Aripiprazole and clozapine (but not olanzapine) inhibited insulin-stimulated AKT, suggesting impaired hypothalamic insulin action by some, but not all, APs. Clozapine additionally increased AMPK phosphorylation (activation), an orexigenic energy sensor, which would also be expected to disrupt energy homeostasis. Conversely, olanzapine and aripiprazole increased BDNF, a factor linked to the underlying etiology of schizophrenia, suggesting BDNF upregulation may be a mechanism of therapeutic action. Taken together, our findings suggest differential and pleotropic effects of APs on neuroinflammation and energy sensing in the hypothalamus, which do not necessarily align consistently with known metabolic liability of these agents (i.e. clozapine = olanzapine > aripiprazole). Our data warrants further exploration into the mechanism of these effects, including replication of these effects in an in vivo model.

Oxidative stress and cardiovascular disease: new insights.

The role of oxidative stress in the onset and progression of atherosclerosis and its impact on the development of cardiovascular events has been widely described. Thus, increased oxidative stress has been described in several atherosclerotic risk factors, such as hypertension, dyslipidaemia, peripheral artery disease, metabolic syndrome, diabetes, and obesity. Among others, specific oxidative pathways involving both pro-oxidant and antioxidant enzymes seem to play a major role in the production of reactive oxidant species (ROS), such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, myeloperoxidase, superoxide dismutase, and glutathione peroxidase. In this review, we will discuss: 1) the most relevant enzyme systems involved in the formation and detoxification of ROS, 2) the relationship between oxidative stress and cardiovascular risk, and 3) therapeutic implications to modulate oxidative stress.

Prevalence of obesity and ethno-geographic variation in body sizes of Nigerians with type 2 diabetes mellitus - A multi-centre study

BACKGROUND : Excess weight gain is common in people with type 2 diabetes mellitus (DM) but little is known about its ethno-geographic variation among the Nigerian populace. We aimed to report the prevalence and regional variation of overweight/obesity among subjects with type 2 DM in all the six geo-political regions of Nigeria. METHOD : Basic demographic and anthropometric data were consecutively collected from patients with type 2 DM attending out-patient clinics of seven designated teaching hospitals in the six geographic regions of the country using a pre-agreed method of measurement of anthropometry including waist circumference. The study was hospital-based descriptive cross-sectional in design. Body Mass Index (BMI) was categorised using the WHO criteria. Based on recommendations of the International Diabetes Federation (IDF) cut-off values for waist circumference, values >94 cm and > 80 cm were taken as abnormal for men and women respectively. RESULTS : A total of 709 subjects with DM comprising 378 (53.3%) females and 331 (46.7%) males (female: male ratio 1:1.14) with an overall mean age (SD) of 51.9 (13.9) years were evaluated. The prevalence of excess body weight among Nigerian subjects with type 2 DM was: peripheral (417 or 58.8%) and abdominal obesity (449 or 63.3%). Also, there was a significant wide variation in excess weight gain (both peripheral and central) across ethno-geographic regions (p=0.001) and between both sexes (p=0.001). In both peripheral and abdominal obesities, whether intra or inter centres, the female subjects with type 2 DM demonstrated relatively higher proportions of anthropometric measures. Generally, subjects from south-south and south-east Nigeria had higher BMI and abdominal obesity compared to those from south-west who had the lowest. The female subjects with type 2 DM were heavier peripherally and centrally compared to their male counterparts. CONCLUSION : The prevalence of peripheral and central obesity among Nigerians living with type 2 DM (especially the female subjects) is unacceptably high. Additionally, there is a wide variation in the proportion and absolute values of both peripheral and central obesity across different parts of Nigeria. KEY WORDS : Obesity, Prevalence, Ethno-Geographic Variation, Nigerians, Type 2 Diabetes Mellitus

Panniculectomy Outcomes in Patients with End-Stage Renal Disease in Preparation for Renal Transplant.

End-stage renal disease (ESRD) is associated with increased cardiovascular risk factors, electrolyte imbalances, and iron deficiency anemia. These factors may increase the risk of adverse outcomes in patients undergoing panniculectomy. There is a paucity of data regarding outcomes in patients with ESRD undergoing panniculectomy. The purpose of this study is to investigate whether ESRD is associated with increased rate of complications following a panniculectomy. The Nationwide Inpatient Sample database (2006-2011) was used to identify patients who underwent a panniculectomy. Among this cohort, patients diagnosed with end-stage renal disease were identified. Patients excluded from the study were emergency admissions, pregnant women, patients less than 18years old, and patients with concurrent nephrectomy or kidney transplants. Demographic factors, comorbidities, and postoperative complications were evaluated. Chi-squared and risk-adjusted multivariate logistic regression analyses were performed to determine whether end-stage renal disease was associated with increased rate of postoperative complications. A total of 34,779 panniculectomies were performed during the study period. Of these, 613 (1.8%) were diagnosed with ESRD. Patients with ESRD were older (mean age 58.9 vs. 49.3, p<0.01) and more likely to have Medicare (63.5 vs. 18.4%, p<0.01). They had higher rates of comorbidities, including diabetes, hypertension, congestive heart failure, chronic lung disease, chronic anemia, liver disease, peripheral artery disease, obesity, and coagulopathies (p<0.01). The procedure was more likely to occur at a large, teaching hospital (p<0.01). Postoperatively, patients with ESRD had a higher rate of death (3.3 vs. 0.2%, p<0.01), wound complications (10.6 vs. 6.2%, p<0.01), venous thromboembolism (4.9 vs. 0.8%, p<0.01), blood transfusions (25.3% vs. 7.0%, p<0.01), non-renal major medical complications (40.0% vs. 8.4%), and longer hospital stay (9.2 vs. 3.8days, p<0.01). Multivariate logistic regression analysis controlling for age, race, sex, hospital location/teaching hospital, payer, and all comorbidities demonstrated that ESRD was independently associated with increased venous thromboembolisms (OR 2.38, 95% CI 1.48-3.83) and non-renal major medical complications (OR 1.51, 95% CI 1.19-1.91). ESRD was not independently associated with increased rate of wound complications or transfusions. Patients with ESRD are at increased risk of VTE and non-renal major medical complications following panniculectomy. Moreover, patients with ESRD have longer hospital stays and higher rates of mortality. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prevalence of factors leading to obesity among school children (aged 15–18 years) in Giza governorate, Egypt

Objective The aim of this study was to determine the prevalence of obesity and the factors leading to it among adolescents in Giza governorate. Participants and methods A cross-sectional study was conducted among 1021 adolescents (between 15 and 18 years of age) of both sexes. They were recruited from different schools of Giza governorate, Egypt, through convenience sampling. The ‘Obesity Questionnaire Survey Sheet’ was administered to the selected students and they were assessed for height, weight, and body composition using InBody120. The frequencies and percentages were reported for categorical variables. Results The results revealed that 58% of the adolescents had normal BMI, whereas 36.5% were overweight and obese. It is also interesting to find out that 78.1% had high percent body fat and 69.5% had peripheral obesity. Furthermore, 77.9% of students had trunk obesity. As regards fast food consumption, 79% of adolescents consumed it occasionally. It is also interesting that 40.4% of participants had positive family history. In addition, 54.9% of students never participated in any physical activity. Conclusion Our study concluded that the major risk factor for obesity in 15–18-year-old adolescents is lack of physical activity. However, consumption of fast food is also increasing in this age group. Furthermore, genetic predisposition cannot be ignored.