Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

Prasugrel Monotherapy After Percutaneous Coronary Intervention for Chronic Coronary Syndrome: Insights From ASET Pilot Studies.

Background: The ASET (Acetyl-Salicylic Elimination Trial) pilot studies recently investigated P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) in Brazil and Japan. Objectives: This comparative analysis of the 2 ASET pilot studies aimed to summarize clinical outcomes and assess geographic and ethnic differences in baseline demographics and procedures. Methods: Patients undergoing successful platinum-chromium everolimus-eluting stent implantation for chronic coronary syndrome were included. Following the index PCI, patients received prasugrel monotherapy with a maintenance dose of 10 mg/day in Brazil and 3.75 mg/day in Japan. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding at up to 3 months. Results: Of 409 enrollments, 3-month follow-up was completed in 406 patients. Mean age was 64.3 ± 8.4 years, and 73% were men. Overall, post-TIMI flow grade 3 was achieved in 99.8%. Intravascular imaging for poststent optimization was used in 16.8% and 99.6% of treated lesions in Brazil and Japan, respectively. The primary ischemic and bleeding endpoints occurred in the same patient (0.2%). No stent thrombosis events occurred. Conclusions: Prasugrel monotherapy following PCI was safe and feasible in selected low-risk chronic coronary syndrome patients after optimal platinum-chromium everolimus-eluting stent implantation regardless of the ethnic and geographic differences in baseline demographics, procedures, and prasugrel dosage. Randomized controlled trials will be needed to compare P2Y12 inhibitor monotherapy without aspirin with the current standard of care.

Viral shedding of SARS-CoV-2 in body fluids associated with sexual activity: a systematic review and meta-analysis.

OBJECTIVE: To identify and summarise the evidence on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection and persistence in body fluids associated with sexual activity (saliva, semen, vaginal secretion, urine and faeces/rectal secretion). ELIGIBILITY: All studies that reported detection of SARS-CoV-2 in saliva, semen, vaginal secretion, urine and faeces/rectal swabs. INFORMATION SOURCES: The WHO COVID-19 database from inception to 20 April 2022. RISK OF BIAS ASSESSMENT: The National Institutes of Health tools. SYNTHESIS OF RESULTS: The proportion of patients with positive results for SARS-CoV-2 and the proportion of patients with a viral duration/persistence of at least 14 days in each fluid was calculated using fixed or random effects models. INCLUDED STUDIES: A total of 182 studies with 10 023 participants. RESULTS: The combined proportion of individuals with detection of SARS-CoV-2 was 82.6% (95% CI: 68.8% to 91.0%) in saliva, 1.6% (95% CI: 0.9% to 2.6%) in semen, 2.7% (95% CI: 1.8% to 4.0%) in vaginal secretion, 3.8% (95% CI: 1.9% to 7.6%) in urine and 31.8% (95% CI: 26.4% to 37.7%) in faeces/rectal swabs. The maximum viral persistence for faeces/rectal secretions was 210 days, followed by semen 121 days, saliva 112 days, urine 77 days and vaginal secretions 13 days. Culturable SARS-CoV-2 was positive for saliva and faeces. LIMITATIONS: Scarcity of longitudinal studies with follow-up until negative results. INTERPRETATION: SARS-CoV-2 RNA was detected in all fluids associated with sexual activity but was rare in semen and vaginal secretions. Ongoing droplet precautions and awareness of the potential risk of contact with faecal matter/rectal mucosa are needed. PROSPERO REGISTRATION NUMBER: CRD42020204741.

Recovery markers in elite climbers after the national boulder climbing championship.

This study aimed to investigate recovery markers among elite climbers following the National Boulder Championship. We assessed maximum isometric hand grip strength (HS), forearm swelling (circumference), delayed soreness in forearm muscles, tiredness, and exercise readiness at several time points: pre-competition, immediately post-competition (within 4 min after their last effort), and 12, 24, 48, and 60 h post-competition. Maximum isometric hand grip strength decreased by 6.38 ± 1.32% (p = 0.006) post-12 h, returning to pre-competition values post-24 h (all p > 0.05). Forearm circumference (FC) increased 1.78 ± 1.77% (p < 0.001) post-competition, returning to pre-competition values post-12 h (all p > 0.05). Forearm pain (FP) increased post-competition (p = 0.002) and post-12 h (p < 0.001), returning to pre-competition values post-24 h (all p > 0.05). Tiredness increased post-competition (p < 0.001), post-12 h (p < 0.001), and post-24 h (p < 0.001), returning to pre-competition values post-48 h (all p > 0.05). Climbing readiness was reduced post-competition (p < 0.001), post-12 h (p < 0.001), post-24 h (p < 0.001), and post-48 h (p = 0.005), only returning to pre-competition values post-60 h (p = 0.189). Visual analysis of individual data pointed out a relatively small variability in the HS and FC markers, while FP, tiredness, and readiness exhibited larger individual variations. These findings indicate that different recovery patterns exist for the analyzed markers, suggesting that athletes may require up to 60 h after a competition to fully recover and regain their ability to face new competitive challenges.

Geographic disparity of pathophysiological coronary artery disease characteristics: Insights from ASET trials.

BACKGROUND: The geographical disparity in the pathophysiological pattern of coronary artery disease (CAD) among patients undergoing percutaneous coronary intervention (PCI) is unknown. OBJECTIVES: To elucidate the geographical variance in the pathophysiological characteristics of CAD. METHODS: Physiological indices derived from angiography-based fractional flow reserve pullbacks from patients with chronic coronary syndrome enrolled in the ASET Japan (n = 206) and ASET Brazil (n = 201) studies, which shared the same eligibility criteria, were analysed. The pathophysiological patterns of CAD were characterised using Murray law-based quantitative flow ratio (µQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the µQFR pullback pressure gradient index. RESULTS: Significant functional stenoses pre-PCI (µQFR ≤0.80) were more frequent in ASET Japan compared to ASET Brazil (89.9% vs. 67.5%, p < 0.001), as were rates of a post-PCI µQFR <0.91 (22.1% vs. 12.9%, p = 0.013). In the multivariable analysis, pre-procedural µQFR and diffuse disease were independent factors for predicting a post-PCI µQFR <0.91, which contributed to the different rates of post-PCI µQFR ≥0.91 between the studies. Among vessels with a post-PCI µQFR <0.91, a consistent diffuse pattern of CAD pre- and post-PCI occurred in 78.3% and 76.7% of patients in ASET Japan and Brazil, respectively; only 6.3% (Japan) and 10.0% (Brazil) of vessels had a major residual gradient. Independent risk factors for diffuse disease were diabetes mellitus in ASET Japan, and age and male gender in Brazil. CONCLUSIONS: There was geographic disparity in pre-procedural angiography-based pathophysiological characteristics. The combined pre-procedural physiological assessment of vessel µQFR and diffuseness of CAD may potentially identify patients who will benefit most from PCI.

The Stilbene Synthase Family in Arachis: A Genome-Wide Study and Functional Characterization in Response to Stress.

Peanut (Arachis hypogaea) and its wild relatives are among the few species that naturally synthesize resveratrol, a well-known stilbenoid phytoalexin that plays a crucial role in plant defense against biotic and abiotic stresses. Resveratrol has received considerable attention due to its health benefits, such as preventing and treating various human diseases and disorders. Chalcone (CHS) and Stilbene (STS) Synthases are plant-specific type III Polyketide Synthases (PKSs) that share the same substrates and are key branch enzymes in the biosynthesis of flavonoids and stilbenoids, respectively. Although resveratrol accumulation in response to external stimulus has been described in peanut, there are no comprehensive studies of the CHS and STS gene families in the genus Arachis. In the present study, we identified and characterized 6 CHS and 46 STS genes in the tetraploid peanut and an average of 4 CHS and 22 STS genes in three diploid wild species (Arachis duranensis, Arachis ipaënsis and Arachis stenosperma). The CHS and STS gene and protein structures, chromosomal distributions, phylogenetic relationships, conserved amino acid domains, and cis-acting elements in the promoter regions were described for all Arachis species studied. Based on gene expression patterns of wild A. stenosperma STS genes in response to different biotic and abiotic stresses, we selected the candidate AsSTS4 gene, which is strongly induced by ultraviolet (UV) light exposure, for further functional investigation. The AsSTS4 overexpression in peanut hairy roots significantly reduced (47%) root-knot nematode infection, confirming that stilbene synthesis activation in transgenic plants can increase resistance to pathogens. These findings contribute to understanding the role of resveratrol in stress responses in Arachis species and provide the basis for genetic engineering for improved production of valuable secondary metabolites in plants.

An ex vitro hairy root system from petioles of detached soybean leaves for in planta screening of target genes and CRISPR strategies associated with nematode bioassays.

MAIN CONCLUSION: The ex vitro hairy root system from petioles of detached soybean leaves allows the functional validation of genes using classical transgenesis and CRISPR strategies (e.g., sgRNA validation, gene activation) associated with nematode bioassays. Agrobacterium rhizogenes-mediated root transformation has been widely used in soybean for the functional validation of target genes in classical transgenesis and single-guide RNA (sgRNA) in CRISPR-based technologies. Initial data showed that in vitro hairy root induction from soybean cotyledons and hypocotyls were not the most suitable strategies for simultaneous performing genetic studies and nematode bioassays. Therefore, an ex vitro hairy root system was developed for in planta screening of target molecules during soybean parasitism by root-knot nematodes (RKNs). Applying this method, hairy roots were successfully induced by A. rhizogenes from petioles of detached soybean leaves. The soybean GmPR10 and GmGST genes were then constitutively overexpressed in both soybean hairy roots and tobacco plants, showing a reduction in the number of Meloidogyne incognita-induced galls of up to 41% and 39%, respectively. In addition, this system was evaluated for upregulation of the endogenous GmExpA and GmExpLB genes by CRISPR/dCas9, showing high levels of gene activation and reductions in gall number of up to 58.7% and 67.4%, respectively. Furthermore, morphological and histological analyses of the galls were successfully performed. These collective data validate the ex vitro hairy root system for screening target genes, using classical overexpression and CRISPR approaches, directly in soybean in a simple manner and associated with nematode bioassays. This system can also be used in other root pathosystems for analyses of gene function and studies of parasite interactions with plants, as well as for other purposes such as studies of root biology and promoter characterization.

Papel de discentes de enfermagem na prevenção de parasitoses intestinais para crianças de uma comunidade rural ribeirinha do Amazonas, 2019

Objetivos: Descrever as vivências dos discentes de enfermagem na realização de atividades de educação em saúde sobre prevenção de parasitoses para crianças de uma comunidade rural do Amazonas. Método: Estudo descritivo, contendo relato de experiência realizada no mês de dezembro de 2019, na comunidade rural Esperança I, no município de Coari, Amazonas. Participaram da ação 119 pessoas, incluindo 42 crianças. O estudo foi desenvolvido em quatro etapas: análise do território; realização do planejamento e elaboração do projeto educativo; execução; e avaliação da atividade. As informações foram produzidas e analisadas de forma sistematizada por meio de um diário de campo reflexivo. Resultados: A estratégia de análise do território subsidiou a identificação do problema, discussão dos possíveis fatores e determinantes, a teorização, as hipóteses de solução e propiciou a implementação das intervenções geradas no processo educativo, com destaque à peça teatral e à higiene corporal. Posteriormente, foi feita a avaliação da intervenção. Conclusão: Os participantes, através desta ação educativa, puderam construir o saber e o fazer acerca das parasitoses intestinais e temáticas afins, com o compromisso de vivenciar no cotidiano as medidas de prevenção e de controle dessa doença.

The association of myocardial strain with cardiac magnetic resonance and clinical outcomes in patients with acute myocarditis.

Introduction: The role of myocardial strain in risk prediction for acute myocarditis (AMC) patients, measured by cardiac magnetic resonance (CMR), deserves further investigation. Our objective was to evaluate the association between myocardial strain measured by CMR and clinical events in AMC patients. Material and methods: This was a prospective single-center study of patients with AMC. We included 100 patients with AMC with CMR confirmation. The primary outcome was the composite of all-cause mortality, heart failure and AMC recurrence in 24 months. A subgroup analysis was performed on a sample of 36 patients who underwent a second CMR between 6 and 18 months. The association between strain measures and clinical events or an increase in left ventricular ejection fraction (LVEF) was explored using Cox regression analysis. Global peak radial, circumferential and longitudinal strain in the left and right ventricles was assessed. ROC curve analysis was performed to identify cutoff points for clinical event prediction. Results: The mean follow-up was 18.7 ± 2.3 months, and the composite primary outcome occurred in 26 patients. The median LVEF at CMR at baseline was 57.5% (14.6%). LV radial strain (HR = 0.918, 95% CI: 0.858-0.982, p = 0.012), LV circumferential strain (HR = 1.177, 95% CI: 1.046-1.325, p = 0.007) and LV longitudinal strain (HR = 1.173, 95% CI: 1.031-1.334, p = 0.015) were independently associated with clinical event occurrence. The areas under the ROC curve for clinical event prediction were 0.80, 0.79 and 0.80 for LV radial, circumferential, and longitudinal strain, respectively. LV longitudinal strain was independently correlated with prognosis (HR = 1.282, CI 95%: 1.022-1.524, p = 0.007), even when analyzed together with ejection fraction and delayed enhancement. LV and right ventricle (RV) strain were not associated with an increase in LVEF. Finally, when the initial CMR findings were compared with the follow-up CMR findings, improvements in the measures of LV and RV myocardial strain were observed. Conclusion: Measurement of myocardial strain by CMR can provide prognostic information on AMC patients. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients.

P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS.

P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial.

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).

A novel soybean hairy root system for gene functional validation.

Agrobacterium rhizogenes-mediated transformation has long been explored as a versatile and reliable method for gene function validation in many plant species, including soybean (Glycine max). Likewise, detached-leaf assays have been widely used for rapid and mass screening of soybean genotypes for disease resistance. The present study combines these two methods to establish an efficient and practical system to generate transgenic soybean hairy roots from detached leaves and their subsequent culture under ex vitro conditions. We demonstrated that hairy roots derived from leaves of two (tropical and temperate) soybean cultivars could be successfully infected by economically important species of root-knot nematodes (Meloidogyne incognita and M. javanica). The established detached-leaf method was further explored for functional validation of two candidate genes encoding for cell wall modifying proteins (CWMPs) to promote resistance against M. incognita through distinct biotechnological strategies: the overexpression of a wild Arachis α-expansin transgene (AdEXPA24) and the dsRNA-mediated silencing of an endogenous soybean polygalacturonase gene (GmPG). AdEXPA24 overexpression in hairy roots of RKN-susceptible soybean cultivar significantly reduced nematode infection by approximately 47%, whereas GmPG downregulation caused an average decrease of 37%. This novel system of hairy root induction from detached leaves showed to be an efficient, practical, fast, and low-cost method suitable for high throughput in root analysis of candidate genes in soybean.

Measuring discrimination experienced by people with a mental illness: replication of the short-form DISCUS in six world regions.

BACKGROUND: The Discrimination and Stigma Scale (DISC) is a patient-reported outcome measure which assesses experiences of discrimination among persons with a mental illness globally. METHODS: This study evaluated whether the psychometric properties of a short-form version, DISC-Ultra Short (DISCUS) (11-item), could be replicated in a sample of people with a wide range of mental disorders from 21 sites in 15 countries/territories, across six global regions. The frequency of experienced discrimination was reported. Scaling assumptions (confirmatory factor analysis, inter-item and item-total correlations), reliability (internal consistency) and validity (convergent validity, known groups method) were investigated in each region, and by diagnosis group. RESULTS: 1195 people participated. The most frequently reported experiences of discrimination were being shunned or avoided at work (48.7%) and discrimination in making or keeping friends (47.2%). Confirmatory factor analysis supported a unidimensional model across all six regions and five diagnosis groups. Convergent validity was confirmed in the total sample and within all regions [ Internalised Stigma of Mental Illness (ISMI-10): 0.28-0.67, stopping self: 0.54-0.72, stigma consciousness: -0.32-0.57], as was internal consistency reliability (α = 0.74-0.84). Known groups validity was established in the global sample with levels of experienced discrimination significantly higher for those experiencing higher depression [Patient Health Questionnaire (PHQ)-2: p < 0.001], lower mental wellbeing [Warwick-Edinburgh Well-being Scale (WEMWBS): p < 0.001], higher suicidal ideation [Beck Hopelessness Scale (BHS)-4: p < 0.001] and higher risk of suicidal behaviour [Suicidal Ideation Attributes Scale (SIDAS): p < 0.001]. CONCLUSIONS: The DISCUS is a reliable and valid unidimensional measure of experienced discrimination for use in global settings with similar properties to the longer DISC. It offers a brief assessment of experienced discrimination for use in clinical and research settings.

Engineering Resistance against Sclerotinia sclerotiorum Using a Truncated NLR (TNx) and a Defense-Priming Gene.

The association of both cell-surface PRRs (Pattern Recognition Receptors) and intracellular receptor NLRs (Nucleotide-Binding Leucine-Rich Repeat) in engineered plants have the potential to activate strong defenses against a broad range of pathogens. Here, we describe the identification, characterization, and in planta functional analysis of a novel truncated NLR (TNx) gene from the wild species Arachis stenosperma (AsTIR19), with a protein structure lacking the C-terminal LRR (Leucine Rich Repeat) domain involved in pathogen perception. Overexpression of AsTIR19 in tobacco plants led to a significant reduction in infection caused by Sclerotinia sclerotiorum, with a further reduction in pyramid lines containing an expansin-like B gene (AdEXLB8) potentially involved in defense priming. Transcription analysis of tobacco transgenic lines revealed induction of hormone defense pathways (SA; JA-ET) and PRs (Pathogenesis-Related proteins) production. The strong upregulation of the respiratory burst oxidase homolog D (RbohD) gene in the pyramid lines suggests its central role in mediating immune responses in plants co-expressing the two transgenes, with reactive oxygen species (ROS) production enhanced by AdEXLB8 cues leading to stronger defense response. Here, we demonstrate that the association of potential priming elicitors and truncated NLRs can produce a synergistic effect on fungal resistance, constituting a promising strategy for improved, non-specific resistance to plant pathogens.

River Winds and Transport of Forest Volatiles in the Amazonian Riparian Ecoregion.

Volatile organic compounds (VOCs) emitted from forests are important chemical components that affect ecosystem functioning, atmospheric chemistry, and regional climate. Temperature differences between a forest and an adjacent river can induce winds that influence VOC fate and transport. Quantitative observations and scientific understanding, however, remain lacking. Herein, daytime VOC datasets were collected from the surface up to 500 m over the "Rio Negro" river in Amazonia. During time periods of river winds, isoprene, α-pinene, and ß-pinene concentrations increased by 50, 60, and 80% over the river, respectively. The concentrations at 500 m were up to 80% greater compared to those at 100 m because of the transport path of river winds. By comparison, the concentration of methacrolein, a VOC oxidation product, did not depend on river winds or height. The differing observations for primary emissions and oxidation products can be explained by the coupling of timescales among emission, reaction, and transport. This behavior was captured in large-eddy simulations with a coupled chemistry model. The observed and simulated roles of river winds in VOC fate and transport highlight the need for improved representation of these processes in regional models of air quality and chemistry-climate coupling.

Desempenho Diagnóstico da Angiotomografia Computadorizada e da Avaliação Seriada de Troponina Cardíaca Sensível em Pacientes com Dor Torácica e Risco Intermediário para Eventos Cardiovasculares / Diagnostic Performance of Coronary Tomography Angiography and Serial Measurements of Sensitive Cardiac Troponin in Patients With Chest Pain and Intermediate Risk for Cardiovascular Events

Resumo Fundamento A angiotomografia coronária (ATC) tem sido usada para avaliação de dor torácica principalmente em pacientes de baixo risco, e poucos dados existem com pacientes em risco intermediário. Objetivo Avaliar o desempenho de medidas seriadas de troponinas sensíveis e de ATC em pacientes de risco intermediário. Métodos Um total de 100 pacientes com dor torácica, TIMI score 3 ou 4 e troponina negativa foram prospectivamente incluídos. Todos os pacientes foram submetidos à ATC, e aqueles com obstruções ≥ 50% foram encaminhados à cineangiocoronariografia. Pacientes com lesões < 50% recebiam alta hospitalar, receberam alta e foram contatados 30 dias depois por telefonema para avaliação dos desfechos clínicos. Os desfechos foram hospitalização, morte, e infarto agudo do miocárdio em 30 dias. A comparação entre os métodos foi realizada pelo teste de concordância kappa. O desempenho das medidas de troponina e da ATC na detecção de lesões coronárias significativas e desfechos clínicos foi calculado. Os resultados foram considerados estatisticamente significativos quando p <0,05. Resultados Estenose coronária ≥ 50% na ATC foi encontrada em 38% dos pacientes e lesões coronárias significativas na angiografia coronária foram encontradas em 31 pacientes. Dois eventos clínicos foram observados. A análise de concordância Kappa mostrou baixa concordância entre as medidas de troponina e ATC na detecção de lesões coronárias significativas (kappa = 0,022, p = 0,78). O desempenho da ATC para detectar lesões coronárias significativas na angiografia coronária ou para prever eventos clínicos em 30 dias foi melhor que as medidas de troponina sensível (acurácia de 91% versus 60%). Conclusão ATC teve melhor desempenho que as medidas seriadas de troponina na detecção de doença coronariana significativa em pacientes com dor torácica e risco intermediário para eventos cardiovasculares.

Abstract Background Coronary tomography angiography (CTA) has been mainly used for chest pain evaluation in low-risk patients, and few data exist regarding patients at intermediate risk. Objective To evaluate the performance of serial measures of sensitive troponin and CTA in intermediate-risk patients. Methods A total of 100 patients with chest pain, TIMI risk scores of 3 or 4, and negative troponin were prospectively included. All patients underwent CTA and those with coronary stenosis ≥ 50% were referred to invasive coronary angiography. Patients with coronary lesions <50% were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Outcomes were hospitalization, death, and myocardial infarction at 30 days. The comparison between methods was performed by Kappa agreement test. The performance of troponin measures and CTA for detecting significant coronary lesions and clinical outcomes was calculated. Results were considered statistically significant when p < 0.05. Results Coronary stenosis ≥ 50% on CTA was found in 38% of patients and significant coronary lesions on coronary angiography were found in 31 patients. Two clinical events were observed. Kappa agreement analysis showed low agreement between troponin measures and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The performance of CTA for detecting significant coronary lesions on coronary angiography or for predicting clinical events at 30 days was better than sensitive troponin measures (accuracy of 91% versus 60%). Conclusion CTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.

Effect of Alirocumab on Incidence of Atrial Fibrillation After Acute Coronary Syndromes: Insights from the ODYSSEY OUTCOMES Trial.

BACKGROUND: Using data from the ODYSSEY OUTCOMES trial (NCT01663402), we sought to identify factors associated with the development of incident atrial fibrillation in patients with recent acute coronary syndrome without prior atrial fibrillation and to determine whether alirocumab treatment influenced risk of incident atrial fibrillation. METHODS: ODYSSEY OUTCOMES compared alirocumab treatment with placebo in 18,924 patients with recent acute coronary syndrome and dyslipidemia despite high-intensity or maximum-tolerated statin therapy. The primary outcome of major adverse cardiovascular events (MACE) comprised death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischemic stroke, or unstable angina requiring hospitalization. Patients were classified as having previous atrial fibrillation (present prior to or at randomization) or no previous atrial fibrillation. A multivariable model was used to determine factors associated with incident atrial fibrillation. RESULTS: Among 18,262 participants without prior atrial fibrillation at baseline, 499 (2.7%) had incident atrial fibrillation during follow-up. Older age, history of heart failure or myocardial infarction, and higher body mass index were significantly associated with incident atrial fibrillation. Treatment with alirocumab or placebo did not influence the cumulative incidence of atrial fibrillation (hazard ratio 0.91; 95% confidence interval, 0.77-1.09). Patients with vs without a history of atrial fibrillation had a higher incidence of MACE (8.8 vs 3.7 events per 100 patient-years), without significant interaction between atrial fibrillation and randomized treatment on risk of MACE (Pinteraction = .78). CONCLUSIONS: While alirocumab did not modify risk of incident atrial fibrillation after acute coronary syndrome, it did reduce the risk of MACE, regardless of prior atrial fibrillation history. History of atrial fibrillation is an independent predictor of recurrent cardiovascular events after acute coronary syndrome.

Diagnostic Performance of Coronary Tomography Angiography and Serial Measurements of Sensitive Cardiac Troponin in Patients With Chest Pain and Intermediate Risk for Cardiovascular Events. / Desempenho Diagnóstico da Angiotomografia Computadorizada e da Avaliação Seriada de Troponina Cardíaca Sensível em Pacientes com Dor Torácica e Risco Intermediário para Eventos Cardiovasculares.

BACKGROUND: Coronary tomography angiography (CTA) has been mainly used for chest pain evaluation in low-risk patients, and few data exist regarding patients at intermediate risk. OBJECTIVE: To evaluate the performance of serial measures of sensitive troponin and CTA in intermediate-risk patients. METHODS: A total of 100 patients with chest pain, TIMI risk scores of 3 or 4, and negative troponin were prospectively included. All patients underwent CTA and those with coronary stenosis ≥ 50% were referred to invasive coronary angiography. Patients with coronary lesions <50% were discharged and contacted 30 days later by a telephone call to assess clinical outcomes. Outcomes were hospitalization, death, and myocardial infarction at 30 days. The comparison between methods was performed by Kappa agreement test. The performance of troponin measures and CTA for detecting significant coronary lesions and clinical outcomes was calculated. Results were considered statistically significant when p < 0.05. RESULTS: Coronary stenosis ≥ 50% on CTA was found in 38% of patients and significant coronary lesions on coronary angiography were found in 31 patients. Two clinical events were observed. Kappa agreement analysis showed low agreement between troponin measures and CTA in the detection of significant coronary lesions (kappa = 0.022, p = 0.78). The performance of CTA for detecting significant coronary lesions on coronary angiography or for predicting clinical events at 30 days was better than sensitive troponin measures (accuracy of 91% versus 60%). CONCLUSION: CTA performed better than sensitive troponin measures in the detection of significant coronary disease in patients with chest pain and intermediate risk for cardiovascular events.

FUNDAMENTO: A angiotomografia coronária (ATC) tem sido usada para avaliação de dor torácica principalmente em pacientes de baixo risco, e poucos dados existem com pacientes em risco intermediário. OBJETIVO: Avaliar o desempenho de medidas seriadas de troponinas sensíveis e de ATC em pacientes de risco intermediário. MÉTODOS: Um total de 100 pacientes com dor torácica, TIMI score 3 ou 4 e troponina negativa foram prospectivamente incluídos. Todos os pacientes foram submetidos à ATC, e aqueles com obstruções ≥ 50% foram encaminhados à cineangiocoronariografia. Pacientes com lesões < 50% recebiam alta hospitalar, receberam alta e foram contatados 30 dias depois por telefonema para avaliação dos desfechos clínicos. Os desfechos foram hospitalização, morte, e infarto agudo do miocárdio em 30 dias. A comparação entre os métodos foi realizada pelo teste de concordância kappa. O desempenho das medidas de troponina e da ATC na detecção de lesões coronárias significativas e desfechos clínicos foi calculado. Os resultados foram considerados estatisticamente significativos quando p <0,05. RESULTADOS: Estenose coronária ≥ 50% na ATC foi encontrada em 38% dos pacientes e lesões coronárias significativas na angiografia coronária foram encontradas em 31 pacientes. Dois eventos clínicos foram observados. A análise de concordância Kappa mostrou baixa concordância entre as medidas de troponina e ATC na detecção de lesões coronárias significativas (kappa = 0,022, p = 0,78). O desempenho da ATC para detectar lesões coronárias significativas na angiografia coronária ou para prever eventos clínicos em 30 dias foi melhor que as medidas de troponina sensível (acurácia de 91% versus 60%). CONCLUSÃO: ATC teve melhor desempenho que as medidas seriadas de troponina na detecção de doença coronariana significativa em pacientes com dor torácica e risco intermediário para eventos cardiovasculares.

Transcriptome Responses of Wild Arachis to UV-C Exposure Reveal Genes Involved in General Plant Defense and Priming.

Stress priming is an important strategy for enhancing plant defense capacity to deal with environmental challenges and involves reprogrammed transcriptional responses. Although ultraviolet (UV) light exposure is a widely adopted approach to elicit stress memory and tolerance in plants, the molecular mechanisms underlying UV-mediated plant priming tolerance are not fully understood. Here, we investigated the changes in the global transcriptome profile of wild Arachis stenosperma leaves in response to UV-C exposure. A total of 5751 differentially expressed genes (DEGs) were identified, with the majority associated with cell signaling, protein dynamics, hormonal and transcriptional regulation, and secondary metabolic pathways. The expression profiles of DEGs known as indicators of priming state, such as transcription factors, transcriptional regulators and protein kinases, were further characterized. A meta-analysis, followed by qRT-PCR validation, identified 18 metaDEGs as being commonly regulated in response to UV and other primary stresses. These genes are involved in secondary metabolism, basal immunity, cell wall structure and integrity, and may constitute important players in the general defense processes and establishment of a priming state in A. stenosperma. Our findings contribute to a better understanding of transcriptional dynamics involved in wild Arachis adaptation to stressful conditions of their natural habitats.