MiR-146a Contributes to Thromboinflammation and Recurrence in Young Patients with Acute Myocardial Infarction

Studies on older patients have established notable conceptual changes in the etiopathogenesis of acute coronary syndrome (ACS), but little is known about this disease in young patients (<45 years). Of special interest is thromboinflammation, key at onset, evolution and therapy of cardiovascular pathology. Therefore, we explored whether ACS at an early age is a thromboinflammatory disease by analyzing NETs and rs2431697 of miR-146a (a miRNA considered as a brake of TLR/NF-kB pathway), elements previously related to higher rates of recurrence in atrial fibrillation and sepsis. We included 359 ACS patients (<45 years) and classified them for specific analysis into G1 (collected during the hospitalization of the first event), G2 and G3 (retrospectively collected from patients with or without ACS recurrence, respectively). cfDNA and citH3–DNA were quantified, and rs2431697 was genotyped. Analysis in the overall cohort showed a moderate but significant correlation between cfDNA and citH3–DNA and Killip–Kimball score. In addition, patients with citH3–DNA > Q4 more frequently had a history of previous stroke (6.1% vs. 1.6%). In turn, rs2431697 did not confer increased risk for the onset of ACS, but T carriers had significantly higher levels of NET markers. By groups, we found that cfDNA levels were similarly higher in all patients, but citH3–DNA was especially higher in G1, suggesting that in plasma, this marker may be attenuated over time. Finally, patients from G2 with the worst markers (cfDNA and citH3–DNA > Q2 and T allele) had a two-fold increased risk of a new ischemic event at 2-year follow-up. In conclusion, our data confirm that ACS is younger onset with thromboinflammatory disease. In addition, these data consolidate rs2431697 as a silent proinflammatory factor predisposing to NETosis, and to a higher rate of adverse events in different cardiovascular diseases

The Use of Insecticide-Treated Curtains for Control of Aedes aegypti and Dengue Virus Transmission in “Fraccionamiento” Style Houses in México

Dengue, chikungunya, yellow fever, and Zika viruses transmitted by Aedes aegypti mosquitoes are major public health threats in the tropical and subtropical world. In México, construction of large tracts of “fraccionamientos” high density housing to accommodate population growth and urbanization has provided fertile ground for Ae. aegypti-transmitted viruses. We investigated the utility of pyrethroid-treated window curtains to reduce both the abundance of Ae. aegypti and to prevent dengue virus (DENV) transmission in fraccionamiento housing. Windows and doors of fraccionamiento homes in urban/suburban areas, where Ae. aegypti pyrethroid resistance associated with the Ile1016 knock down resistance (kdr) mutation in the voltage gated sodium channel gene was high, and in rural areas, where kdr resistance was low, were fitted with either insecticide-treated curtains (ITCs) or non-treated curtains (NTCs). The homes were monitored for mosquito abundance and DENV infection. ITCs reduced the indoor abundance of Ae. aegypti and the number of DENV-infected mosquitoes in homes in rural but not in urban/suburban study sites. The presence of non-treated screens also was associated with reduced numbers of mosquitoes in homes. “Super-infested” homes, yielding more than 50 mosquitoes, including DENV-infected mosquitoes, provide a significant public health risk to occupants, visitors, and people in neighboring homes

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Agencia Española del Medicamento; Consejería de Salud de Andalucía.Background & Aims: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. Methods: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. Results: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). Conclusions: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. Lay summary: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes