Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial

Effective prevention and risk prediction are important for peripheral artery disease (PAD) due to its poor prognosis and the huge disease burden it produces. Circulating amino acids (AA) and their metabolites may serve as biomarkers of PAD risk, but they have been scarcely investigated. The objective was to prospectively analyze the associations of baseline levels of plasma AA (and their pathways) with subsequent risk of PAD and the potential effect modification by a nutritional intervention with the Mediterranean diet (MedDiet). A matched case-control study was nested in the PREDIMED trial, in which participants were randomized to three arms: MedDiet with tree nut supplementation group, MedDiet with extra-virgin olive oil (EVOO) supplementation group or control group (low-fat diet). One hundred and sixty-seven PAD cases were matched with 250 controls. Plasma AA was measured with liquid chromatography/mass spectrometry at the Broad Institute. Baseline tryptophan, serine and threonine were inversely associated with PAD (ORfor 1 SD increase = 0.78 (0.61–0.99); 0.67 (0.51–0.86) and 0.75 (0.59–0.95), respectively) in a multivariable-adjusted conditional logistic regression model. The kynurenine/tryptophan ratio was directly associated with PAD (ORfor 1 SD increase = 1.50 (1.14–1.98)). The nutritional intervention with the MedDiet+nuts modified the association between threonine and PAD (p-value interaction = 0.018) compared with the control group. However, subjects allocated to the MedDiet+EVOO group were protected against PAD independently of baseline threonine. Plasma tryptophan, kynurenine/tryptophan ratio, serine and threonine might serve as early biomarkers of future PAD in subjects at a high risk of cardiovascular disease. The MedDiet supplemented with EVOO exerted a protective effect, regardless of baseline levels of threonine

Plasma lipidome and risk of atrial fibrillation: results from the PREDIMED trial

The potential role of the lipidome in atrial fibrillation (AF) development is still widely unknown. We aimed to assess the association between lipidome profiles of the Prevenci\uf3n con Dieta Mediterr\ue1nea (PREDIMED) trial participants and incidence of AF. We conducted a nested case–control study (512 incident centrally adjudicated AF cases and 735 controls matched by age, sex, and center). Baseline plasma lipids were profiled using a Nexera X2 U-HPLC system coupled to an Exactive Plus orbitrap mass spectrometer. We estimated the association between 216 individual lipids and AF using multivariable conditional logistic regression and adjusted the p values for multiple testing. We also examined the joint association of lipid clusters with AF incidence. Hitherto, we estimated the lipidomics network, used machine learning to select important network-clusters and AF-predictive lipid patterns, and summarized the joint association of these lipid patterns weighted scores. Finally, we addressed the possible interaction by the randomized dietary intervention. Forty-one individual lipids were associated with AF at the nominal level (p < 0.05), but no longer after adjustment for multiple-testing. However, the network-based score identified with a robust data-driven lipid network showed a multivariable-adjusted ORper+1SD of 1.32 (95% confidence interval: 1.16–1.51; p < 0.001). The score included PC plasmalogens and PE plasmalogens, palmitoyl-EA, cholesterol, CE 16:0, PC 36:4;O, and TG 53:3. No interaction with the dietary intervention was found. A multilipid score, primarily made up of plasmalogens, was associated with an increased risk of AF. Future studies are needed to get further insights into the lipidome role on AF. Current Controlled Trials number, ISRCTN35739639

Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Adherence to the Mediterranean diet and risk of stroke and stroke subtypes

Several meta-analyses including a small number of cohorts showed inverse associations between the Mediterranean Diet (MedDiet) and risk of stroke. However, it remains unclear whether such a relation varies by region of the study population or by major subtypes of stroke. We searched PubMed and EMBASE databases for relevant studies and we further included unpublished results from the Singapore Chinese Health Study (N = 57,078) and the Seguimiento Universidad de Navarra (SUN) study (N = 12,670). We used a random-effects model to calculate summary relative risk (RR) with 95% confidence intervals (CI) of stroke for each 4-point increment of the MedDiet score, roughly corresponding to the difference between extreme quintiles of the MedDiet score among participants of the included studies. The final analyses included 20 prospective cohort studies involving 682,149 participants and 16,739 stroke cases. The summary RRs for each 4-point increment of the MedDiet score were 0.84 (95% CI 0.81\u20130.88; I 2 = 11.5%) for all combined, 0.76 (95% CI 0.65\u20130.89) for studies in Mediterranean populations and 0.86 (95% CI 0.83\u20130.89) for those in non-Mediterranean populations. Lower risk of stroke associated with higher MedDiet score also was observed in the analyses stratified by study population and methodological characteristics including study risk of bias, version of the MedDiet index, and definition of moderate alcohol consumption. The MedDiet was similarly associated with lower risk of ischemic stroke (RR 0.86, 95% CI 0.81\u20130.91; nine studies) and hemorrhagic stroke (RR 0.83, 95% CI 0.74\u20130.93; eight studies). Our meta-analysis suggests that adhering to the Mediterranean diet was associated with lower risk of stroke in both Mediterranean and non-Mediterranean populations, and for both ischemic stroke and hemorrhagic stroke risk

Range extensions of amphibians and reptiles in the southeastern part of the Lacandona rainforest, Mexico

AbstractThe Lacandona rainforest represents one of the most diverse Mexican tropical wet forests. Although some studies have described the amphibians and reptiles of the region, most herpetological lists come from the northern part of the Lacandona, and there are no confirmed records for many of the expected species. We reviewed databases of scientific collections, taxonomy, and published herpetological lists to produce the most recent updated list of amphibian and reptile species in the region (35 amphibians and 90 reptiles). Furthermore, based on recent inventories (2007–2013) we establish 40 range extensions of 8 amphibians and 32 reptiles for the southeastern part of the Lacandona rainforest. Four out of these 40 records confirmed the occurrence of Dermophis mexicanus, Eleutherodactylus leprus, Pantherophis flavirufus, and Bothriechis schlegelii in the region

Prophecy Matters: Nahum and Nineveh\u27s Fall

Relative Risk of Cardiovascular Disease, according to quartiles of toenail mercury, among case participants and matched controls in the PREDIMED trial, restricted to those who were not diagnosed with cardiovascular disease within one year of follow-up. Table S2. Relative Risk of Cardiovascular Disease, according to quartiles of toenail mercury, among case participants and matched controls in the PREDIMED trial, restricted to those who were diagnosed with cardiovascular disease within 5 years of toenail collection. Table S3. Relative Risk of Cardiovascular Disease, according to quartiles of toenail mercury, among case participants and matched controls in the PREDIMED trial, restricted to participants who were below the 90th percentile of toenail selenium. Table S4. Relative Risk of Cardiovascular Disease, according to quartiles of toenail mercury, among case participants and matched controls in the PREDIMED trial, stratified by baseline median fish intake (below/above the median). Table S5. Relative Risk of Cardiovascular Disease, according to quartiles of toenail mercury, among case participants and matched controls in the PREDIMED trial, restricted to participants who were at very high risk of cardiovascular disease. Table S6. Relative Risk of Cardiovascular Disease, according to quartiles of toenail mercury, among case participants and matched controls in the PREDIMED trial, stratified by baseline aspirin use (yes/no). Table S7. Bias analysis (simulation study). Sensitivity analysis to assess the degree of plausible bias due to residual confounding, assuming an unknown binary confounder (n-3 PUFA consumption; dichotomized at median) with different prevalence among exposed (highest quartile of mercury) and unexposed (lowest quartile of mercury) controls and with a relatively strong association (even after adjusting for the known and measured confounders) with cardiovascular disease. This correction was applied to our observed OR=0.66 for the highest versus lowest quartile of mercury exposure. (DOC 153 kb