Feasibility and reproducibility of free fatty acid profiling in abdominal adipose tissue with 1H-magnetic resonance spectroscopy at 3 T: differences between lean and obese individuals.

PURPOSE: To evaluate the feasibility and reproducibility of free fatty acid (FFA) measurement for diagnosing adipose tissue dysfunction by (1)H-magnetic resonance spectroscopy ((1)H-MRS) in different abdominal adipose tissue depots in healthy obese and lean subjects. MATERIALS AND METHODS: Polyunsaturated fatty acids (PUFA), total unsaturated fatty acids (TUFA), triglycerides (TG), and their ratios were determined in three adipose tissue depots of 12 obese and 13 lean subjects. Subjects underwent two separate examinations to assess reproducibility. RESULTS: In lean subjects, 44% of measurements failed due to inclusion of nonadipose tissue in the spectroscopy voxel, as opposed to 23% in obese subjects. Reproducibility of PUFA, TUFA, and TG was moderate to good in obese subjects (intraclass correlation coefficients [ICCs] 0.18-0.75), and poor to moderate in lean subjects (ICCs -1.04-0.55) in subcutaneous and omental adipose tissue. In the perirenal adipose tissue, ICCs were poor in both lean and obese subjects (-0.794-0.013). PUFA/TUFA and PUFA/TG were higher in omental adipose tissue in obese vs. lean subjects (35*10(-3) vs. 0.16*10(-3), P = 0.01 and 2.05*10(-3) vs. 0.01*10(-3), P = 0.02, respectively). CONCLUSION: (1)H-MRS is a feasible and reproducible method for FFA profiling in abdominal adipose tissue in abdominally obese individuals. (1)H-MRS has potential as diagnostic tool for noninvasive identification of adipose tissue dysfunction.

Tailored anticoagulant treatment after a first venous thromboembolism: protocol of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study - cohort-based randomised controlled trial.

INTRODUCTION: Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks. METHODS AND ANALYSIS: The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences. TRIAL REGISTRATION NUMBER: NCT06087952.

EUS-guided endoscopic transgastric necrosectomy in patients with infected necrosis in acute pancreatitis.

BACKGROUND: Infected pancreatic and peripancreatic necrosis in acute pancreatitis is potentially lethal, with mortality rates up to 35%. Therefore, there is growing interest in minimally invasive treatment options, such as (EUS-guided) endoscopic transgastric necrosectomy. METHODS: Retrospective cohort study on EUS-guided endoscopic transgastric necrosectomy in patients with infected necrosis in acute pancreatitis. RESULTS: 8 patients (age 38-75, mean 50 years) with documented infected peripancreatic or pancreatic necrosis were included. Median time to first intervention was 33 days (range 17-62) after onset of symptoms. At the time of first intervention 2 patients had organ failure. All patients were managed on the patient ward. Initial endoscopic drainage was successful in all patients, a median of 4 (range 2-6) subsequent endoscopic necrosectomies were needed to remove all necrotic tissue. Two patients needed additional surgical intervention because of pneumoperitoneum (n = 1) and insufficient endoscopic drainage (n = 1). Six patients recovered, with 1 mild relapse during follow-up (median 12, range 8-60 months). One patient died. CONCLUSION: EUS-guided endoscopic transgastric necrosectomy of infected necrosis in acute pancreatitis appears to be a feasible and relatively safe treatment option in patients who are not critically ill. Further randomized comparison with the current 'gold standard' is warranted to determine the place of this treatment modality.

The relation between body fat distribution, plasma concentrations of adipokines and the metabolic syndrome in patients with clinically manifest vascular disease.

Introduction We evaluated the relationship between adipokine plasma concentrations and body fat distribution and the metabolic syndrome. Methods In a cohort of 1215 patients with clinically manifest vascular disease the relation between subcutaneous adipose tissue, visceral adipose tissue, waist circumference, body mass index and plasma concentrations of adipsin, chemerin, monocyte chemoattractant protein-1, migration inhibitory factor, nerve growth factor, resistin, plasma amyloid A1, adiponectin, leptin, plasminogen activator inhibitor-1 and hepatic growth factor were cross-sectionally assessed with linear regression and adjusted for age and gender. The relation between adipokines and the metabolic syndrome was cross-sectionally evaluated using logistic regression. An adipokine profile was developed to measure the effect of combined rather than single adipokines. Results Adiposity was related to higher nerve growth factor, hepatic growth factor, migration inhibitory factor, leptin and adipsin and with lower chemerin, plasminogen activator inhibitor-1, resistin, plasma amyloid A1 and adiponectin. The strongest positive relations were between body mass index and adipsin (ß 0.247; 95% CI 0.137-0.356) and leptin (ß 0.266; 95% CI 0.207-0.324); the strongest negative relations were between body mass index and plasma amyloid A1 (ß -0.266; 95% CI -0.386 to -0.146) and visceral adipose tissue and adiponectin (ß -0.168; 95% CI -0.226 to -0.111). There was no relation between subcutaneous adipose tissue and adipokines. Odds for the metabolic syndrome were higher with each 1 SD higher hepatic growth factor (OR 1.21; 95% CI 1.06-1.38) and leptin (OR 1.26; 95% CI 1.10-1.45) and lower with each 1 SD higher adiponectin (OR 0.73; 95% CI 0.64-0.83) and resistin (OR 0.85; 95% CI 0.74-0.97). The adipokine profile was related to the metabolic syndrome (OR 1.03; 95% CI 1.00-1.06). Conclusion Plasma concentrations of adipokines are related to obesity and body fat distribution. The relation between adipokine concentrations and the metabolic syndrome is independent of visceral adipose tissue.

Identifying treatment response to antihypertensives in patients with obesity-related hypertension.

BACKGROUND: In patients with obesity-related hypertension (ORH), reaction to antihypertensive medication is likely influenced by patientcharacteristics. METHODS: Effects of aliskiren, moxonidine and hydrochlorothiazide on 24-h blood pressure (BP) were compared to placebo. Linear mixed effect models were used to analyze the effect of patient characteristics on BP levels and treatment response. RESULTS: Systolic BP response to aliskiren was higher in patients with a BMI > 30.7 kg/m2 compared to patients with a BMI ≤ 30.7 kg/m2 (-21 mmHg versus -4 mmHg). In patients with a hsCRP > 1.8 mg/L the systolic BP response to aliskiren was higher than in patients with a low hsCRP (-15 mmHg versus -7 mmHg). Hydrochlorothiazide (HCTZ) treatment effect on systolic BP was -13 mmHg when heart rate > 71 beats/min compared to -3 mmHg when heart rate was ≤ 71 beats/min. CONCLUSION: In patients with ORH, BP response to aliskiren is positively related to BMI and hsCRP. Systolic BP response to HCTZ is positively related to heart rate and negatively to renin levels. TRIAL REGISTRATION: NCT01138423. Registered June 4th, 2010.

Differential effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension: a double-blind, placebo-controlled cross-over trial.

OBJECTIVES: The objective of this study is to determine the effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension. METHODS: A randomized, four-way, double-blind, crossover study in 31 adults with previously untreated obesity-related hypertension, in which the effects of 8 weeks' inhibition of the renin-angiotensin-aldosterone system (using aliskiren 300 mg), sympathoinhibition (using moxonidine 0.4 mg), diuretic therapy (using hydrochlorothiazide 25 mg) or placebo on flow-mediated dilation and 24-h blood pressure were compared. RESULTS: The median flow-mediated dilation during placebo was 4.0% [interquartile range (IQR) 2.9-5.5%] and was increased by aliskiren [0.81%, 95% confidence interval (CI) 0.02-1.79], but not by moxonidine (0.20%, 95% CI -0.46 to 1.03) or hydrochlorothiazide (0.39%, 95%CI -0.31%-1.26%). Similarly, compared with placebo, mean 24-h blood pressure was most reduced by aliskiren (-9.8/-6.3 mmHg) and to a lesser degree by hydrochlorothiazide (-5.9/-2.6 mmHg). Moxonidine did not significantly affect blood pressure despite reduction of muscle sympathetic nerve activity. Insulin sensitivity deteriorated during hydrochlorothiazide treatment and was unaffected by aliskiren or moxonidine. Unlike aliskiren and moxonidine, hydrochlorothiazide reduced urinary 8-iso-prostaglandin F2α-VI, a marker of oxidative stress. Vascular stiffness, systemic inflammation, leptin, adiponectin and other oxidative stress markers (plasma malondialdehyde, myeloperoxidase activity and urinary 8-hydroxydeoxyguanosine) were unaffected by treatment. CONCLUSION: Renin inhibition, but not sympathoinhibition or diuretic therapy, improves endothelial function and results in larger reductions of 24-h, office, and central blood pressure in obesity-related hypertension. This adds weight to the hypothesis that inhibition of the renin-angiotensin-aldosterone system is an effective first step in the treatment of obesity-related hypertension.