ABSTRACT Background Elevated serum free fatty acid (FFA) concentration is associated with insulin resistance and is a hallmark of metabolic syndrome. A pathological feature of insulin resistance is impaired endothelial function. Objective To investigate the effect of FFA reduction with either acipimox, a nicotinic acid derivative that impairs lipolysis, or salsalate, a salicylate that reduces basal and inflammation‐induced lipolysis, on insulin‐mediated endothelium‐dependent vasodilation. Methods This was a post hoc, combined analysis of two randomised, double‐blind, placebo‐controlled crossover trials. Sixteen subjects were recruited (6 with metabolic syndrome and 10 controls) and randomised to acipimox 250 mg orally every 6 h for 7 days or placebo. Nineteen subjects were recruited (13 with metabolic syndrome and 6 controls) and randomised to receive salsalate 4.5 g/day for 4 weeks or placebo. The primary outcome was the association between FFA concentration and insulin‐mediated vasodilation, measured by venous‐occlusion strain‐gauge plethysmography at baseline and following FFA modulation with the study drugs. Results At baseline, FFA concentration ( R = −0.35, p = 0.043) and insulin sensitivity (HOMA‐IR: R = −0.42, p = 0.016, Adipo‐IR: R = −0.39, p = 0.025) predicted insulin‐mediated vasodilation. FFA levels were significantly reduced after drug pretreatment (0.604 vs. 0.491 mmol/L, p = 0.036) while insulin levels, insulin sensitivity and inflammatory markers were unchanged. Despite a reduction in circulating FFA with drug therapy, neither insulin‐stimulated vasodilation nor insulin sensitivity improved. Conclusions Short‐term reduction of FFA concentration does not improve insulin‐stimulated vasodilation in patients with metabolic syndrome. Trial Registration ClinicalTrials.gov identifier: NCT00759291 and NCT00760019 (formerly NCT00762827)
Intravenous sedation and analgesia are important therapies during mechanical ventilation (MV). However, daily interruption of these medications is associated with improved outcomes in mechanically ventilated patients. We tested a clinical pathway for the use of sedation and analgesia during MV in a cardiac intensive care unit (CICU).We evaluated all mechanically ventilated patients in a CICU during two phases: phase 1 prior to pathway implementation (PRE) and phase 2 post-pathway implementation (POST). A total of 198 patients (98 PRE and 100 POST) and 1012 days of intubation (574 PRE and 434 POST) were included in this analysis. We found an increase in the frequency of daily interruptions of sedation post-implementation (49.3% PRE and 58.4% POST, p=0.0041). There was a significant decrease in the mean duration of MV in the POST vs PRE periods (5.0±2.3 vs 6.1±2.8 days, p=0.015). There was also a significant decrease in total neuroimaging studies (9 vs 49, p=0.001) and a trend toward a decrease in tracheostomies (3.0% vs 6.1%, p=0.33). Mean CICU length of stay (LOS) and hospital LOS respectively were 10.4 days and 16.8 days PRE and 10.4 days and 17.9 days POST (p=0.99 and p=0.55). Mortality did not differ (PRE 36.7% vs POST 32.0% p=0.55).Implementation of a pragmatic pathway for sedation and analgesia in a CICU was associated with an increase in the daily interruption of sedation and a corresponding decrease in the duration of MV days and the need for neuroimaging.
Lipedema is a painful connective tissue disease involving excessive subcutaneous adipose tissue (SAT) accumulation in the lower extremities. Lipedema remains poorly recognized as a unique clinical entity and is often misdiagnosed as obesity. Whole-body magnetic resonance imaging (MRI) acquisitions could provide insight into the unique body composition of lipedema, yet methodologies for multi-slice analyses are lacking. In this work, a semi-automated processing workflow was developed to segment and quantify adiposity from whole-leg chemical-shift encoded (CSE) MRI to distinguish lipedema. Patients with lipedema (N=15) and controls (N=13) matched for age and body mass index underwent a CSE MRI exam in eight stacks from the head-to-ankles. Slices from thighs-to-ankles were segmented via Chan-Vese segmentation, clustering, and morphological techniques to separate SAT and skeletal muscle. SAT and muscle volume per slice and the SAT-to-muscle volume ratio were recorded in decades of slices and compared between groups using Mann-Whitney U test with two-sided significance criteria p<0.05. SAT volume was significantly elevated in participants with lipedema in all decades (p<0.001), while muscle volume was not significantly different. SAT-to-muscle volume ratio was elevated in lipedema compared to controls (p<0.001), with the greatest effect size (rrb = 0.74) observed in the eighth decade corresponding to the mid-thigh region. These findings reveal SAT distribution is uniquely elevated throughout the legs of participants with lipedema as discerned from whole-leg CSE MRI. CSE MRI and analysis methods developed herein for SAT quantification could inform the diagnosis of lipedema, which suffers from few objective strategies to differentiate the disease from obesity.
Peripheral artery disease (PAD) is underdiagnosed due to poor patient and clinician awareness. Despite this, no widely accepted PAD screening is recommended.
