Peri-event plasma PCSK9 and hsCRP after an acute myocardial infarction correlate with early deterioration of left ventricular ejection fraction: a cohort study.

BACKGROUND: It is important to identify patients at increased risk of worsening of left ventricular ejection fraction (LVEF) after a myocardial infarction (MI). We aimed to identify the association of various potential biomarkers with LVEF impairment after an MI in South American patients. METHODS: We studied adult patients admitted to a University Hospital and diagnosed with an acute MI. Plasma concentrations of high-sensitivity C-reactive protein (hsCRP), proprotein convertase subtilisin/kexin type 9 (PCSK9), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and heart-type fatty-acid-binding protein (FABP3) were determined in samples drawn shortly after the event. Participants had a follow-up visit at least 45 days after the event. The primary endpoint was defined as any decline in LVEF at follow-up relative to baseline. RESULTS: The study included 106 patients (77.4% men, 22.6% women), mean age was 64.1, mean baseline LVEF was 56.6, 19% had a prior MI. We obtained a follow-up evaluation in 100 (94.4%) of participants, mean follow-up time was 163 days. There was a significant correlation between baseline PCSK9 and hsCRP (r = 0.39, p < 0.001). Baseline hsCRP concentrations were higher in patients who developed the endpoint than in those who did not (32.1 versus 21.2 mg/L, p = 0.066). After multivariate adjustment, baseline PCSK9, male sex and age were significantly associated with impairment in LVEF. The absolute change in LVEF was inversely correlated with baseline hsCRP (standardized coefficient = - 0.246, p = 0.004). CONCLUSION: High plasma levels of PCSK9 and hsCRP were associated with early decreases in LVEF after an MI in Latin American patients.

Effects of oral contraceptives on metabolic parameters in adult premenopausal women: a meta-analysis.

OBJECTIVE: To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis. PATIENTS AND METHODS: Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, BMI, insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random-effects model. We performed subgroup analyses by study duration (<12 months vs ≥12 months) and polycystic ovary syndrome (PCOS) status. RESULTS: Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel (P < 0.001) to 35.1 mg/dL for chlormadinone (P < 0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, P < 0.001) and drospirenone (+7.4 mg/dL, P < 0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL (P < 0.001). Levonorgestrel (+6.8 mg/dL, P < 0.001) and norgestimate (+11.5 mg/dL, P = 0.003) increased LDLc, while dienogest decreased it (-7.7 mg/dL, P = 0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration. CONCLUSION: Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.

Effectiveness and adverse events of topical and allergen immunotherapy for atopic dermatitis: a systematic review and network meta-analysis protocol.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory chronic condition that affects the skin of children and adults and has an important impact on the quality of life. Treatments for AD are based on environmental controls, topical and systemic therapies, and allergen-specific immunotherapy (AIT). However, it remains unclear the effectiveness and adverse events of AIT and all conventional topical treatments compared with placebo and each other for AD. METHODS: We will search five electronic databases [Central Cochrane register of controlled trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and LILACS] from inception until November 2019 with no language restriction, and we will include experimental studies [randomized controlled trials (RCTs), and quasi-RCTs]. The primary outcome is global and specific skin symptoms assessment. Secondary outcomes are hospital length of stay, quality of life, and adverse events. Reviewers independently will extract data from the studies that meet our inclusion criteria and will assess the risk of bias of individual primary studies. We will conduct random effects pairwise meta-analyses for the observed pairwise comparisons with at least two trials. Then, we will perform random-effects Bayesian network meta-analysis (NMA) to obtain treatment effects for all possible comparisons and to provide a hierarchy of all interventions for each outcome. Possible incoherence between direct and indirect sources of evidence will be investigated locally (if possible) and globally. To investigate sources of statistical heterogeneity, we will perform a series of meta-regression analyses based on pre-specified important effect modifiers. Two authors will appraise the certainty of the evidence for each outcome applying the GRADE's framework for NMA. DISCUSSION: The findings of this systematic review will shed the light on the effectiveness and adverse events of all possible comparisons for treating AD and on the quality of the collated evidence for recommendations. It will also provide critical information to health care professionals to comprehend and manage this disease at different age stages, treatment type, duration, and severity of atopic dermatitis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Protocol ID CRD42019147106.

Cellular Senescence as a Therapeutic Target for Age-Related Diseases: A Review.

Life expectancy has increased substantially over the last few decades, leading to a worldwide increase in the prevalence and burden of aging-associated diseases. Recent evidence has proven that cellular senescence contributes substantially to the development of these disorders. Cellular senescence is a state of cell cycle arrest with suppressed apoptosis and concomitant secretion of multiple bioactive factors (the senescence-associated secretory phenotype-SASP) that plays a physiological role in embryonic development and healing processes. However, DNA damage and oxidative stress that occur during aging cause the accumulation of senescent cells, which through their SASP bring about deleterious effects on multiple organ and systemic functions. Ablation of senescent cells through genetic or pharmacological means leads to improved life span and health span in animal models, and preliminary evidence suggests it may also have a positive impact on human health. Thus, strategies to reduce or eliminate the burden of senescent cells or their products have the potential to impact multiple clinical outcomes with a single intervention. In this review, we touch upon the basics of cell senescence and summarize the current state of development of therapies against cell senescence for human use.