CVEs, mainly those confined to the heart, complicate the course of almost one-third of patients hospitalized for CAP. More importantly, the occurrence of CVEs is associated with a 5-fold increase in CAP-associated 30-day mortality.

Quantifying the importance of the key sites on haemagglutinin in determining the selection advantage of influenza virus: Using A/H3N2 as an example Dear Editor , Authors' contributionsSZ and MHW conceived the study. SZ carried out the analysis, and drafted the first manuscript. SZ and MHW discussed the results. All authors read, revised the manuscript, and gave final approval for publication. Declaration of Competing InterestMHW is a shareholder of Beth Bioinformatics Co., Ltd, and BCYZ is a shareholder of Beth Bioinformatics Co., Ltd and Health View Bioanalytics Ltd. Declarations Ethics approval and consent to participateThe ethical approval or individual consent was not applicable. Availability of data and materialsAll influenza viruses sequence data were collected via the influenza virus database (IVD) of the National center for Biotechnology Information (NCBI). Please see the online supporting information for details. Consent for publicationNot applicable.

BackgroundThe optimal timing to administer non–vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention.Methods and ResultsRecurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA 2 DS 2‐VASc score >4 and less reduced renal function. Thirty‐two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke.ConclusionsIn patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.

Background In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3–8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0–6.0) of those without HT ; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24–2.35). Conclusions In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

Metabolomics and lipidomics have been used in several studies to define the biochemical alterations induced by COVID-19 in comparison with healthy controls. Those studies highlighted the presence of a strong signature, attributable to both metabolites and lipoproteins/lipids. Here, 1H NMR spectra were acquired on EDTA-plasma from three groups of subjects: i) hospitalized COVID-19 positive patients (≤21 days from the first positive nasopharyngeal swab); ii) hospitalized COVID-19 positive patients (>21 days from the first positive nasopharyngeal swab); iii) subjects after 2–6 months from SARS-CoV-2 eradication. A Random Forest model built using the EDTA-plasma spectra of COVID-19 patients ≤21 days and Post COVID-19 subjects, provided a high discrimination accuracy (93.6%), indicating both the presence of a strong fingerprint of the acute infection and the substantial metabolic healing of Post COVID-19 subjects. The differences originate from significant alterations in the concentrations of 16 metabolites and 74 lipoprotein components. The model was then used to predict the spectra of COVID-19>21 days subjects. In this group, the metabolite levels are closer to those of the Post COVID-19 subjects than to those of the COVID-19≤21 days; the opposite occurs for the lipoproteins. Within the acute phase patients, characteristic trends in metabolite levels are observed as a function of the disease severity. The metabolites found altered in COVID-19≤21 days patients with respect to Post COVID-19 individuals overlap with acute infection biomarkers identified previously in comparison with healthy subjects. Along the trajectory towards healing, the metabolome reverts back to the “healthy” state faster than the lipoproteome.

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Community acquired pneumonia (CAP) is a common reason for hospitalization and death in elderly people. Many predictors of in-hospital outcome have been studied in the general population with CAP. However, data are lacking on the prognostic significance of conditions unique to older patients, such as delirium and the coexistence of multiple comorbidities. The aim of this study was to evaluate predictors of in-hospital outcome in elderly patients hospitalized for CAP. In this retrospective study, consecutive patients with CAP aged ≥65 years were enrolled between January 2011 and June 2012 in two general wards. Clinical and laboratory characteristics were collected from electronic medical records. The end-point of the study was the occurrence of in-hospital death. 443 patients (mean age 81.8 ± 7.5, range 65-99 years) were enrolled. More than 3 comorbidities were present in 31 % of patients. Mean confusion, blood urea nitrogen, respiratory rate, blood pressure and age ≥65 years (CURB-65) score was 2.5 ± 0.7 points. Mean length of stay was 7.6 ± 5.7 days. In-hospital death occurred in 54 patients (12.2 %). At multivariate analysis, independent predictors of in-hospital death were: chronic obstructive pulmonary disease (COPD) (OR 6.21, p = 0.005), occurrence of at least one episode of delirium (OR 5.69, p = 0.017), male sex (OR 5.10, p < 0.0001), and CURB-65 score (OR 3.98, p < 0.0001). Several predictors of in-hospital death (COPD, male gender, CURB-65) in patients with CAP older than 65 years are similar to those of younger patients. In this cohort of elderly patients, the occurrence of delirium was highly prevalent and represented a distinctive predictor of death.

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