Metabolic Footprint, towards Understanding Type 2 Diabetes beyond Glycemia

Type 2 diabetes (T2D) heterogeneity is a major determinant of complications risk and treatment response. Using cluster analysis, we aimed to stratify glycemia within metabolic multidimensionality and extract pathophysiological insights out of metabolic profiling. We performed a cluster analysis to stratify 974 subjects (PREVADIAB2 cohort) with normoglycemia, prediabetes, or non-treated diabetes. The algorithm was informed by age, anthropometry, and metabolic milieu (glucose, insulin, C-peptide, and free fatty acid (FFA) levels during the oral glucose tolerance test OGTT). For cluster profiling, we additionally used indexes of metabolism mechanisms (e.g., tissue-specific insulin resistance, insulin clearance, and insulin secretion), non-alcoholic fatty liver disease (NAFLD), and glomerular filtration rate (GFR). We found prominent heterogeneity within two optimal clusters, mainly representing normometabolism (Cluster-I) or insulin resistance and NAFLD (Cluster-II), at higher granularity. This was illustrated by sub-clusters showing similar NAFLD prevalence but differentiated by glycemia, FFA, and GFR (Cluster-II). Sub-clusters with similar glycemia and FFA showed dissimilar insulin clearance and secretion (Cluster-I). This work reveals that T2D heterogeneity can be captured by a thorough metabolic milieu and mechanisms profiling-metabolic footprint. It is expected that deeper phenotyping and increased pathophysiology knowledge will allow to identify subject's multidimensional profile, predict their progression, and treat them towards precision medicine.publishersversionpublishe

Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade

Background-Angiographic successful reperfusion in acute myocardial infarction has been defined as TIMI 3 flow. However, TIMI 3 flow does not always result in effective myocardial reperfusion. Myocardial blush grade (MBG) is an angiographic measure of myocardial perfusion. We hypothesized that optimal angiographic reperfusion is defined by TIMI 3 flow and MBG 2 or 3. Methods and Results-In 924 consecutive patients with TIMI 3 flow after angioplasty for acute myocardial infarction, we prospectively studied the value of MBG. End points were death, MACE, enzymatic infarct size, and residual left ventricular ejection fraction. Follow-up was 16+/-11 months. Of the 924 patients, 101 (11%) patients had MBG 0 or 1. Mortality was significantly higher in patients with MBG 0 or 1 compared with patients with MBG 2 or 3 (relative risk, 4.7; 95% CI, 2.3 to 9.5; P Conclusions -MBG is a strong angiographic predictor of mortality in patients with TIMI 3 flow after primary angioplasty. Enzymatic infarct size is larger and residual left ventricular ejection fraction is lower in patients with MBG 0 or 1 compared with MBG 2 or 3. Angiographic definition of successful reperfusion should include both TIMI 3 flow as well as MBG 2 or 3

Outcome and Predictors for Mortality in Patients with Cardiogenic Shock:A Dutch Nationwide Registry-Based Study of 75,407 Patients with Acute Coronary Syndrome Treated by PCI

It is important to gain more insight into the cardiogenic shock (CS) population, as currently, little is known on how to improve outcomes. Therefore, we assessed clinical outcome in acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with and without CS at admission. Furthermore, the incidence of CS and predictors for mortality in CS patients were evaluated. The Netherlands Heart Registration (NHR) is a nationwide registry on all cardiac interventions. We used NHR data of ACS patients treated with PCI between 2015 and 2019. Among 75,407 ACS patients treated with PCI, 3028 patients (4.1%) were identified with CS, respectively 4.3%, 3.9%, 3.5%, and 4.3% per year. Factors associated with mortality in CS were age (HR 1.02, 95%CI 1.02-1.03), eGFR (HR 0.98, 95%CI 0.98-0.99), diabetes mellitus (DM) (HR 1.25, 95%CI 1.08-1.45), multivessel disease (HR 1.22, 95%CI 1.06-1.39), prior myocardial infarction (MI) (HR 1.24, 95%CI 1.06-1.45), and out-of-hospital cardiac arrest (OHCA) (HR 1.71, 95%CI 1.50-1.94). In conclusion, in this Dutch nationwide registry-based study of ACS patients treated by PCI, the incidence of CS was 4.1% over the 4-year study period. Predictors for mortality in CS were higher age, renal insufficiency, presence of DM, multivessel disease, prior MI, and OHCA

Comparison of Outcome After Percutaneous Mitral Valve Repair With the MitraClip in Patients With Versus Without Atrial Fibrillation

Percutaneous mitral valve repair with the MitraClip is an established treatment for patients with mitral regurgitation (MR) who are inoperable or at high risk for surgery. Atrial Fibrillation (AF) frequently coincides with MR, but only scarce data of the influence of AF on outcome after MitraClip is available. The aim of the current study was to compare the clinical outcome after MitraClip treatment in patients with versus without atrial fibrillation. Between January 2009 and January 2016, all consecutive patients treated with a MitraClip in 5 Dutch centers were included. Outcome measures were survival, symptoms, MR grade, and stroke incidence. In total, 618 patients were treated with a MitraClip. Patients with AF were older, had higher N-terminal B-type natriuretic peptide levels, more tricuspid regurgitation, less often coronary artery disease and a better left ventricular function. Survival of patients treated with the MitraClip was similar for patients with AF (82%) and without AF (non-AF; 85%) after 1 year (p = 0.30), but significantly different after 5-year follow-up (AF 34%; non-AF 47%; p = 0.006). After 1 month, 64% of the patients with AF were in New York Heart Association class I or II, in contrast to 77% of the patients without AF (p = 0.001). The stroke incidence appeared not to be significantly different (AF 1.8%; non-AF 1.0%; p = 0.40). In conclusion, patients with AF had similar 1-year survival, MR reduction, and stroke incidence compared with non-AF patients. However, MitraClip patients with AF had reduced long-term survival and remained more symptomatic compared with those without AF.</p

Epinephrine and short-term survival in cardiogenic shock : an individual data meta-analysis of 2583 patients

Correction Volume: 44 Issue: 11 Pages: 2022-2023 DOI: 10.1007/s00134-018-5372-9Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients. We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality. Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17-76%) and short-term mortality rate was 49% (21-69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8-3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4-6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0-6.0]). In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death.Peer reviewe

A policy-based framework for the determination of management options to protect vulnerable marine ecosystems under the EU deep-sea access regulations

Vulnerable marine ecosystems (VMEs) are particularly susceptible to bottom-fishing activity as they are easily disturbed and slow to recover. A data-driven approach was developed to provide management options for the protection of VMEs under the European Union “deep-sea access regulations.” A total of two options within two scenarios were developed. The first scenario defined VME closure areas without consideration of fishing activity. Option 1 proposed closures for the protection of VME habitats and likely habitat, while Option 2 also included areas where four types of VME geophysical elements were present. The second scenario additionally considered fishing. This scenario used VME biomass—fishing intensity relationships to identify a threshold where effort of mobile bottom-contact gears was low and unlikely to have caused significant adverse impacts. Achieving a high level of VME protection requires the creation of many closures (> 100), made up of many small (∼50 km2) and fewer larger closures (> 1000 km2). The greatest protection of VMEs will affect approximately 9% of the mobile fleet fishing effort, while closure scenarios that avoid highly fished areas reduce this to around 4–6%. The framework allows managers to choose the level of risk-aversion they wish to apply in protecting VMEs by comparing alternative strategies.En prensa2,27

The influence of implantation techniques on lesion oriented-outcomes in Absorb BVS and Xience EES lesions treated in routine clinical practice at complete three year follow-up: AIDA trial QCA substudy

It has been hypothesized that dedicated optimized Absorb BVS implantation techniques might mitigate the risk of adverse events such as target vessel