Pioglitazone Decreases Plasma Cholesteryl Ester Transfer Protein Mass, Associated With a Decrease in Hepatic Triglyceride Content, in Patients With Type 2 Diabetes

Thiazolidinediones reduce hepatic steatosis and increase HDL cholesterol levels. In mice with human-like lipoprotein metabolism (APOE*3-Leiden.CETP transgenic mice), a decrease in hepatic triglyceride content is associated with a decrease in plasma cholesteryl ester transfer protein (CETP) mass and an increase in HDL levels. Therefore, the aim of the present study was to assess the effects of pioglitazone on CETP mass in patients with type 2 diabetes. We included 78 men with type 2 diabetes (aged 56.5 +/- 0.6 years; HbA1c 7.1 +/- 0.1%) who were randomly assigned to treatment with pioglitazone (30 mg/day) or metformin (2000 mg/day) and matching placebo, in addition to glimepiride. At baseline and after 24 weeks of treatment plasma HDL cholesterol levels and CETP mass were measured, and hepatic triglyceride content was assessed by proton magnetic resonance spectroscopy. RESULTS Pioglitazone decreased hepatic triglyceride content (5.9 [interquartile range 2.6-17.4] versus 4.1 [1.9-12.3]%, P <0.05), decreased plasma CETP mass (2.33 +/- 0.10 vs. 2.06 +/- 0.10 microg/ml, P <0.05), and increased plasma HDL cholesterol level (1.22 +/- 0.05 vs. 1.34 +/- 0.05 mmol/l, P <0.05). Metformin did not significantly change any of these parameters. A decrease in hepatic triglyceride content by pioglitazone is accompanied by a decrease in plasma CETP mass and associated with an increase in HDL cholesterol levels. These results in patients with type 2 diabetes fully confirm recent findings in mic

Study Protocol PROMETHEUS:Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma

Purpose: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan–Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. Discussion: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands

Purpose The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. Participants The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. Findings to date By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. Future plans The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes

Progressive caloric restriction induces dose-dependent changes in myocardial triglyceride content and diastolic function in healthy men

In animal experiments, high plasma concentrations of free fatty acids (FFAs) are associated with increased triglyceride (TG) stores in liver and heart, and impaired cardiac function. In humans caloric restriction increases plasma FFA levels. Our objective was to assess the effects of progressive caloric restriction on myocardial and hepatic TG content and myocardial function. This was a prospective intervention study. This study included 10 lean healthy men. Three-day partial (471 kcal/d) and complete starvation was performed. Plasma levels of FFA, myocardial and hepatic TG content, and myocardial function were calculated. Plasma FFA increased from 0.6 +/- 0.4 mmol/liter to 1.2 +/- 0.4 and to 1.9 +/- 0.7 mmol/liter, after partial and complete starvation, respectively (P <0.001). Myocardial TG content increased from 0.35 +/- 0.14% to 0.59 +/- 0.27%, and 1.26 +/- 0.49%, respectively (P <0.01). The ratio between the early diastole and atrial contraction decreased from 2.2 +/- 0.4 to 2.1 +/- 0.4 (P = 0.7) and 1.8 +/- 0.4, respectively (P <0.01), and diastolic early deceleration from 3.4 +/- 0.7 ml/sec(2) x 10(-3) to 2.9 +/- 0.5 and 2.8 +/- 0.9 ml/sec(2) x 10(-3), respectively (P <0.05). Hepatic TG content decreased after partial starvation (from 2.23 +/- 2.24% to 1.43 +/- 1.33%; P <0.05) but did not change upon complete starvation. Progressive caloric restriction induces a dose-dependent increase in myocardial TG content and a dose-dependent decrease in diastolic function in lean healthy men. Hepatic TG content showed a differential response to progressive caloric restriction, indicating that redistribution of endogenous TG stores is tissue specifi

Learning Curve Analysis of Complex Endovascular Aortic Repair

Background: When introducing new techniques, attention must be paid to learning curve. Besides quantitative outcomes, qualitative factors of influence should be taken into consideration. This retrospective cohort study describes the quantitative learning curve of complex endovascular aortic repair (EVAR) in a nonhigh-volume academic center and provides qualitative factors that were perceived as contributors to this learning curve. With these factors, we aim to aid in future implementation of new techniques. Methods: All patients undergoing complex EVAR in the Leiden University Medical Center (LUMC) between July 2013 and April 2021 were included (n = 90). Quantitative outcomes were as follows: operating time, blood loss, volume of contrast, hospital stay, major adverse events (MAE), 30-day mortality, and complexity. Patients were divided into 3 temporal groups (n = 30) for dichotomous outcomes. Regression plots were used for continuous outcomes. In 2017, the treatment team was interviewed by an external researcher. These interviews were reanalyzed for factors that contributed to successful implementation. Results: Length of hospital stay (P = 0.008) and operating time (P = 0.010) decreased significantly over time. Fewer cardiac complications occurred in the third group (3: 0% vs. 2: 17% vs. 1: 17%, P = 0.042). There was a trend of increasing complexity (P = 0.076) and number of fenestrations (P = 0.060). No significant changes occurred in MAE and 30-day mortality. Qualitative factors that, according to the interviewees, positively influenced the learning curve were as follows: communication, mutual trust, a shared sense of responsibility and collective goals, clear authoritative structures, mutual learning, and team capabilities. Conclusions: In addition to factors previously identified in the literature, new learning curve factors were found (mutual learning and shared goals in the operating room (OR)) that should be taken into account when implementing new techniques.</p

Changes in body fat and lipid metabolism in testicular cancer patients undergoing curative chemotherapy.

Cardiovascular Aspects of Radiolog