Hypertriglyceridemia, Metabolic Syndrome, and Cardiovascular Disease in HIV-Infected Patients: Effects of Antiretroviral Therapy and Adipose Tissue Distribution

The use of combination antiretroviral therapy (CART) in HIV-infected patients has resulted in a dramatic decline in AIDS-related mortality. However, mortality due to non-AIDS conditions, particularly cardiovascular disease (CVD) seems to increase in this population. CART has been associated with several metabolic risk factors, including insulin resistance, low HDL-cholesterol, hypertriglyceridemia and postprandial hyperlipidemia. In addition, HIV itself, as well as specific antiretroviral agents, may further increase cardiovascular risk by interfering with endothelial function. As the HIV population is aging, CVD may become an increasingly growing health problem in the future. Therefore, early diagnosis and treatment of cardiovascular risk factors is warranted in this population. This paper reviews the contribution of both, HIV infection and CART, to insulin resistance, postprandial hyperlipidemia and cardiovascular risk in HIV-infected patients. Strategies to reduce cardiovascular risk are also discussed

Cost-Effectiveness of Lower Extremity Nerve Decompression Surgery in the Prevention of Ulcers and Amputations:A Markov Analysis

Background: The costs and health effects associated with lower extremity complications in diabetes mellitus are an increasing burden to society. In selected patients, lower extremity nerve decompression is able to reduce symptoms of neuropathy and the concomitant risks of diabetic foot ulcers and amputations. To estimate the health and economic effects of this type of surgery, the cost-effectiveness of this intervention compared to current nonsurgical care was studied. Methods: To estimate the incremental cost-effectiveness of lower extremity nerve decompression over a 10-year period, a Markov model was developed to simulate the onset and progression of diabetic foot disease in patients with diabetes and neuropathy who underwent lower extremity nerve decompression surgery, compared to a group undergoing current nonsurgical care. Mean survival time, health-related quality of life, presence or risk of lower extremity complications, and in-hospital costs were the outcome measures assessed. Data from the Rotterdam Diabetic Foot Study were used as current care, complemented with information from international studies on the epidemiology of diabetic foot disease, resource use, and costs, to feed the model. Results: Lower extremity nerve decompression surgery resulted in improved life expectancy (88,369.5 life-years versus 86,513.6 life-years), gain of quality-adjusted life-years (67,652.5 versus 64,082.3), and reduced incidence of foot complications compared to current care (490 versus 1087). The incremental cost-effectiveness analysis was -euro59,279.6 per quality-adjusted life-year gained, which is below the Dutch critical threshold of less than euro80,000 per quality-adjusted life-year. Conclusions: Decompression surgery of lower extremity nerves improves survival, reduces diabetic foot complications, and is cost saving and cost-effective compared with current care, suggesting considerable socioeconomic benefit for society

(Cost-)effectiveness of lower extremity nerve decompression surgery in subjects with diabetes:the DeCompression (DECO) trial-study protocol for a randomised controlled trial

Introduction The peripheral nerves of patients with diabetes are often pathologically swollen, which results in entrapment at places of anatomical narrowing. This results in nerve dysfunction. Surgical treatment of compression neuropathies in the lower extremities (lower extremity nerve decompression (LEND)) results in relief of symptoms and gain in peripheral nerve function, which may lead to less sensory loss (short term) and less associated detrimental effects including foot ulceration and amputations, and lower costs (long term). The aim of the DeCompression trial is to evaluate the effectiveness and (cost-)effectiveness of surgical decompression of compressed lower extremity nerves (LEND surgery) compared with patients treated with conventional (non-surgical) care. Methods and analysis A stratified randomised (1 to 1) controlled trial comparing LEND surgery (intervention) with conventional non-surgical care (control strategy) in subjects with diabetes with problems of neuropathy due to compression neuropathies in the lower extremity. Randomisation is stratified for participating hospital (n=11) and gender. Patients and controls have the same follow-up at 1.5, 3, 6, 9, 12, 18, 24 and 48 months. Participants (n=344) will be recruited in 12 months and enrolled in all affiliated hospitals in which they receive both the intervention or conventional non-surgical care and follow-up. Outcome assessors are blinded to group assignment. Primary outcome: disease-specific quality of life (Norfolk Quality of Life Questionnaire-Diabetic Neuropathy). Secondary outcomes: health-related quality of life (EuroQoL 5-dimension 5-level (EQ-5D5L), 36-item Short Form (SF-36)), plantar sensation (Rotterdam Diabetic Foot Test Battery), incidence of ulcerations/amputations, resource use and productivity loss (Medical Cost Questionnaire, Productivity Cost Questionnaire) during follow-up. The incremental cost-effectiveness ratio will be estimated on the basis of the collected empirical data and a cost-utility model. Ethics and dissemination Ethics approval has been granted by the Medical Research Ethics Committee of Utrecht University Medical Center (reference: NL68312.041.19v5, protocol number: 19-335/M). Dissemination of results will be via journal articles and presentations at national and international conferences

Corrosion evaluation of austenitic and duplex stainless steels in molten carbonate salts at 600 °C for thermal energy storage

Next-generation concentrated solar power (CSP) plants are required to operate at temperatures as high as possible to reach a better energy efficiency. This means significant challenges for the construction materials in terms of corrosion resistance, among others. In the present work, the corrosion behavior in a molten eutectic ternary Li2CO3-Na2CO3-K2CO3 mixture at 600 °C was studied for three stainless steels: an austenitic grade AISI 301LN (SS301) and two duplex grades, namely 2205 (DS2205) and 2507 (DS2507). Corrosion tests combined with complementary microscopy, microanalysis and mechanical characterization techniques were employed to determine the corrosion kinetics of the steels and the oxide scales formed on the surface. The results showed that all three materials exhibited a corrosion kinetics close to a parabolic law, and their corrosion rates increased in the following order: DS2507 < SS301 < DS2205. The analyses of the oxide scales evidenced an arranged multilayer system with LiFeO2, LiCrO2, FeCr2O4 and NiO as the main compounds. While the Ni-rich inner layer of the scales presented a good adhesion to the metallic substrate, the outer layer formed by LiFeO2 exhibited a higher concentration of porosity and voids. Both the Cr and Ni contents at the inner layer and the defects at the outer layer were crucial for the corrosion resistance for each steel. Among the studied materials, super duplex stainless steel 2507 is found to be the most promising alternative for thermal energy storage of those structural components for CSP plants.Peer ReviewedPostprint (published version

Dyslipidemia in Obesity: Mechanisms and Potential Targets

Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia

The natural history of tarsal tunnel syndrome in diabetic subjects

Introduction: Tibial nerve entrapment is highly prevalent in diabetic subjects, resulting in significantly more neuropathic complaints and concomitant sensory disturbances. The study aim was to assess the impact of tarsal tunnel syndrome (TTS) and sensory loss at baseline on incident diabetic foot ulceration (DFU) in diabetic patients, since decompressing the tibial nerve might change the natural history of the disease. Methods: In this study, 113 subjects with TTS (69 bilateral, 23 left-sided and 21 right-sided) participating in the prospective Rotterdam Diabetic Foot Study were compared to 303 diabetic controls without TTS, regarding incident DFU. Kaplan–Meier analysis and Cox’s regression analysis were used to determine the independent hazard of baseline variables for new DFU. Results: The median observation period was 836.5 days (IQR, 459–1077.8). In bilateral TTS, 17.4% (95% CI: 8.4–26.3%) of subjects experienced DFU versus 8.3% (95% CI: 5.1–11.6%) in controls (left or right) during follow-up (p = 0.0036). In left-sided TTS, no subjects versus 6.2% (95% CI: 3.4–9.0%) in controls had DFUs (p = 0.243). Incident ulceration was seen in 14.3% (95% CI: −0.7% to −29.3%) of right-sided TTS subjects versus 4.1% (95% CI: 1.5–6.3%) in controls (p = 0.034). Besides HbA1c, diminished sensation at the hallux independently increased the risk of ulceration, in patients with (HR: 4.692, p = 0.003) and without (HR: 2.307, p = 0.002) prior DFU. Discussion: Elevated sensory thresholds in TTS render diabetic patients at a higher risk for DFU. With effective surgery, TTS is likely to be an amenable factor to potentially prevent diabetic foot disease and thereby reduce amputation risk. Level of evidence: II

Effects of Metformin on the Regulation of Free Fatty Acids in Insulin Resistance: A Double-Blind, Placebo-Controlled Study

Introduction. Impaired free fatty acid (FFA) metabolism is closely linked to insulin resistance. Our aim was to evaluate plasma FFA changes in insulin resistance in a physiological situation after improvement of insulin sensitivity by metformin. Methods. A double-blind, placebo-controlled intervention with metformin was carried out in patients with insulin resistance. Nineteen patients were randomized to receive metformin 850 mg b.i.d. during 6 weeks or placebo. Participants underwent a mental stress test and an oral glucose tolerance test (OGTT) before and after treatment. Results. Fasting plasma glucose, FFA, and HOMA-IR tended to decrease after metformin, suggesting improved insulin sensitivity. FFA concentrations during the mental stress test showed a similar pattern after metformin, albeit lower at all time points, in contrast to the placebo group. The decrease in fasting plasma FFAs was positively associated to the decrease in HbA1c (; ) and in fasting glucose (; ). The suppression of plasma FFAs during OGTT did not change by metformin or placebo. Conclusion. Metformin in insulin resistance did not lead to improved FFA dynamics despite a trend of improved insulin sensitivity. Metformin most likely decreases plasma FFAs mainly by suppressing fasting FFA concentrations and not by suppression of acute stress-induced lipolysis

AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia

Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG) metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R) gene on postprandial lipemia. Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined. Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39 ± 8.36 mM*h/L) compared to homozygous carriers of the 1166-A allele (2.02 ± 6.20 mM*h/L) (P < 0.05). Postprandial lipemia was similar for the different C573T polymorphisms. Conclusion. The 1166-C allele of the AT1R gene seems to be associated with increased postprandial lipemia. These data confirm the earlier described relationships between the renin-angiotensin axis and triglyceride metabolism

Laparoscopic sleeve gastrectomy with an extensive posterior mobilization: Technique and preliminary results

Background: Laparoscopic sleeve gastrectomy (LSG) is becoming increasingly popular as a stand-alone procedure for the treatment of morbidly obese patients. A direct posterior approach to the angle of His was developed at our department to improve visualization of the difficult dissection of the short gastric vessels and to facilitate proper mobilization of the stomach around the left crus enabling safe realization of a tight sleeve. The technique and its preliminary results are described. Methods: LSG by posterior approach was performed in a consecutive series of 445 (110 male/335 female, age 18-63 years, mean body mass index 46 kg/m2 (range 35-76)) patients between 2007 and 2010. Results: Weight loss defined as mean percent excess weight loss (%EWL) was 71% (±26%) at 1 year, 69% (±25%) at 2 years, and 55% (±27%) at 3 years. Sixteen patients (4%) developed postoperative intra-abdominal hematoma, 8 patients (2%) anastomotic leakage, and 6 patients intra-abdominal abscess (1%), requiring reoperation in 20 patients (4%). Five patients (1%) had pulmonary embolism. Thirty-day mortality rate was 0.2%. Conclusions: LSG by the posterior approach is a safe and effective procedure, enabling a tight sleeve formation leading to satisfactory %EWL results. Since long-term results of LSG are unknown, further studies are needed to define the exact place of the LSG as a stand-alone bariatric proc

Pulmonary Function Testing and Complications of Laparoscopic Bariatric Surgery

__Abstract__ __Background__: Obesity is associated with respiratory symptoms and impaired pulmonary function, which could increase the risk of complications after bariatric surgery. The purpose of this study is to assess the relationship between pulmonary function parameters before, and the risk of complications after, laparoscopic bariatric surgery. Methods: This prospective study included patients (age 18-60, BMI >35 kg/m2), who were eligible for bariatric surgery. Spirometry was performed in all patients. Complications up to 30 days after bariatric surgery were recorded. Results: Four hundred eighty-five patients were included (304 laparoscopic sleeve gastrectomy, 181 laparoscopic gastric bypass). There were 53 complications (8 pulmonary, 27 surgical, 14 infectious, 4 other) in 50 patients (10 %). There were 35 re-admissions (7.2 %), and 17 re-laparoscopies (3.5 %). Subjects with and without complications did not differ significantly with respect to demographics, weight, BMI, abdominal circumference or fat percentage. Subjects with complications had a significantly lower mean FEV1(mean 86.9 % predicted) and FVC (95.6 % predicted) compared to patients without complications (95.9 % predicted, p = 0.005, and 100.1 % predicted, p = 0.045, respectively). After adjustment for age, gender, BMI, and smoking, abnormal spirometry value remained the single predictive covariable of postoperative complications: FEV1/FVC <70 % adjusted OR 3.1 (95%CI 1.4-6.8, p = 0.006) and ΔFEV1≥12 % adjusted OR 2.9 (95 %CI 1.3-6.6, p = 0.010). Conclusions: The risk of pulmonary complications after laparoscopic bariatric surgery is low. However, subjects with abnormal spirometry test results have a threefold risk of complications after laparoscopic bariatric surgery. Preoperative pulmonary function testing might be useful to predict the risk of complications of laparoscopic bariatric surgery