Background and aims To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19). Methods We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL. Results We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13–3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively. Conclusions Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

Exacerbations of chronic obstructive pulmonary disease (COPD) are known to increase the risk of cardiovascular (CV) events and mortality. However, the temporal trend of this risk has not fully elucidated. This systematic review and meta-analysis aims to quantify the risk of CV events after COPD exacerbations over different time periods. To assess the temporal association between CV events, including acute coronary syndrome (ACS), heart failure (HF), acute cereberovascular events, arrhythmia and all-cause mortality after the onset of COPD exacerbations in the following timepoints: 1-30 and 31-180 days; 1-7, 8-14, 15-30, 31-180, 181-365 and >365 days. A comprehensive literature search was conducted in PubMed, Embase, Web of Science and Cochrane databases, identifying observational studies that reported CV outcomes following COPD exacerbations. Studies were included if they enrolled adults diagnosed with COPD and compared CV event rates during exacerbation and non-exacerbation periods (PROSPERO, CRD42024561490). Sixteen studies with over 1.8 million participants were included. Our meta-analysis demonstrated a significantly increased risk of ACS, HF, cerebrovascular events and arrhythmia, with the highest magnitude of risk observed in the period 1-30 days following an exacerbation. This increased risk showed a decline in time points 31-180, 181-365 days and remained persistently higher for ACS even one year after an acute exacerbation. Notably, the risk of HF was found to be greater compared to the other CV outcomes. COPD exacerbations significantly increase the risk of acute CV events, particularly within the first 30 days. Optimal strategies to reduce cardiopulmonary risk are needed.

Background: We investigated incidence and outcome of spontaneous intracerebral hemorrhage (ICH) in a population‐based stroke registry and provided data to inform on the figures of the disease in women and in men. Methods and Results: Our prospective population‐based registry included patients with first‐ever ICH occurring from January 2011 to December 2020. Incidence rates were standardized to the 2011 Italian and European population, and incidence rate ratios were calculated. Multivariate hazard ratios for 30‐day and 1‐year fatality were estimated with Cox regression, including components of the ICH score and sex. We included 748 first‐ever ICHs (41.3% women). Women were significantly older than men at ICH onset (78.9±12.6 versus 73.2±13.6 years; P <0.001) and showed higher clinical severity on presentation (median National Institutes of Health Stroke Scale score, 11 [interquartile range, 6–20] versus 9 [interquartile range, 4–15], respectively; P =0.016). The crude annual incidence rate was 20.2 (95% CI, 18.0–22.6) per 100 000 person‐years in women and 30.2 (95% CI, 27.4–33.2) per 100 000 person‐years in men); incidence was lower in women versus men (incidence rate ratio, 0.67 [95% CI, 0.58–0.78]; P <0.001) and did not change over time in both sexes ( P for trend=0.073 and 0.904, respectively). Unadjusted comparison showed higher 1‐year case‐fatality rates in women versus men (48.5% versus 40.1%; P =0.026). After adjusting for components of the ICH score, female sex lost significance as a predictor of mortality. Conclusions: We found lower ICH incidence in women than in men. However, women showed a higher 1‐year case‐fatality rate versus men, which was likely related to older age at ICH onset and higher clinical severity. Identification of factors explaining the reported differences is important to develop targeted interventions.

Background: The COVID-19 pandemic is having major implications for stroke services worldwide. We aimed to study the impact of the national lockdown period during the COVID-19 outbreak on stroke and transient ischemic attack (TIA) care in London, UK.Methods: We retrospectively analyzed data from a quality improvement registry of consecutive patients presenting with acute ischemic stroke and TIA to the Stroke Department, Imperial College Health Care Trust London during the national lockdown period (between March 23rd and 30th June 2020). As controls, we evaluated the clinical reports and stroke quality metrics of patients presenting with stroke or TIA in the same period of 2019.Results: Between March 23rd and 30th June 2020, we documented a fall in the number of stroke admissions by 31.33% and of TIA outpatient referrals by 24.44% compared to the same period in 2019. During the lockdown, we observed a significant increase in symptom onset-to-door time in patients presenting with stroke (median = 240 vs. 160 min, p = 0.020) and TIA (median = 3 vs. 0 days, p = 0.002) and a significant reduction in the total number of patients thrombolysed [27 (11.49%) vs. 46 (16.25%, p = 0.030)]. Patients in the 2020 cohort presented with a lower median pre-stroke mRS (p = 0.015), but an increased NIHSS (p = 0.002). We registered a marked decrease in mimic diagnoses compared to the same period of 2019. Statistically significant differences were found between the COVID and pre-COVID cohorts in the time from onset to door (median 99 vs. 88 min, p = 0.026) and from onset to needle (median 148 vs. 126 min, p = 0.036) for thrombolysis whilst we did not observe any significant delay to reperfusion therapies (door-to-needle and door-to-groin puncture time).Conclusions: National lockdown in the UK due to the COVID-19 pandemic was associated with a significant decrease in acute stroke admission and TIA evaluations at our stroke center. Moreover, a lower proportion of acute stroke patients in the pandemic cohort benefited from reperfusion therapy. Further research is needed to evaluate the long-term effects of the pandemic on stroke care.

Background: Mechanical thrombectomy is the standard of care, in selected patients, for acute ischemic stroke with large vessel occlusion but its use in patients with stroke secondary to infective endocarditis is controversial. We report three cases of acute ischemic stroke treated by mechanical thrombectomy and we propose an extensive review of the literature to evaluate the clinical safety and efficacy of thrombectomy in patients with stroke secondary to infective endocarditis. Methods: A comprehensive literature search was performed following a pre-specified protocol of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Case reports, cases series, cross-sectional studies, case control studies, randomized controlled trials or nonrandomized controlled trials were considered that included endocarditis-related acute ischemic stroke patients who underwent mechanical thrombectomy. Results: The database search yielded 431 relevant records published until January 2020. Nineteen articles fulfilled the eligibility criteria that described thirty patients. After the thrombectomy, 13.3% of the patients experienced intracranial haemorrhage. After the procedure, the median National Institutes of Health Stroke Scale score dropped from 15 (IQR 7) to 2.5 (IQR 5.75). At 90 days, mortality was 23.3% while 46.7% of the patients were functionally independent (mRS ≤ 2). Discussion: Based on our review, the use of mechanical thrombectomy in patients with large vessel occlusion due to endocarditis-associated stroke might improve patient outcome but it should be considered on a case by case base as the safety has not been well established yet. Further research on risk stratification is needed to drive clinician during the decision-making process.