Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study.

BACKGROUND: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. METHODS: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. RESULTS: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31). CONCLUSIONS: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.

Glucagon-like peptide-1 receptor agonists and stroke: A systematic review and meta-analysis of cardiovascular outcome trials.

BACKGROUND: In patients surviving stroke, approximately 15% and 60% exhibit concurrent diabetes mellitus and overweight/obesity, respectively, necessitating heightened secondary prevention efforts. Despite glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrating improved outcomes for those with diabetes mellitus or obesity, their underutilization persists among eligible individuals. This systematic review and meta-analysis investigated the impact of GLP-1 RAs on stroke risk. The findings aim to optimize the implementation of this therapeutic strategy in patients surviving stroke with diabetes mellitus or obesity. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we systematically reviewed MEDLINE and Scopus until 15 November 2023. Eligible studies included randomized cardiovascular outcome trials (CVOTs) with individuals, with or without type 2 diabetes, randomized to either GLP-1 RA or placebo. The outcomes were total strokes, non-fatal strokes, and fatal strokes. Analyses were conducted using RevMan 5.4.1. RESULTS: Among 1369 screened studies, 11 were eligible, encompassing 82,140 participants (34.6% women) with a cumulative follow-up of 247,596 person-years. In the GLP-1 RAs group, the stroke rate was significantly lower compared to placebo (RR: 0.85, 95% CI: 0.77-0.93; NNT: 200), showing no heterogeneity or interaction with administration frequency (daily vs weekly). In addition, the GLP-1 RAs group exhibited a significantly lower rate of non-fatal strokes compared to placebo (RR: 0.87, 95% CI: 0.79-0.95; NNT: 250), with no heterogeneity or interaction based on administration frequency, route (oral vs subcutaneous), or diabetes presence. CONCLUSION: In this meta-analysis of 11 CVOTs with 82,140 participants, GLP-1 RAs demonstrated a 16% relative reduction in stroke risk compared to placebo. This finding may increase implementation of GLP-1 RAs by stroke specialists in individuals with stroke and comorbid diabetes mellitus or obesity. DATA ACCESS STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Efficacy and safety of direct oral anticoagulants vs vitamin K antagonists in patients with atrial fibrillation and end-stage renal disease on hemodialysis: A systematic review and meta-analysis.

BACKGROUND: The prevalence of atrial fibrillation (AF) in individuals with end-stage renal disease (ESRD) on chronic hemodialysis is increasing. The optimal anticoagulant choice in this population is unclear since these patients were excluded from the pivotal randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) in the general AF population. We aimed to assess the efficacy and safety of DOACs vs. VKAs in patients with AF and ESRD on chronic hemodialysis through a systematic review and meta-analysis of all available evidence. PATIENTS/METHODS: We performed a systematic search in MEDLINE and Scopus for RCTs or observational studies of patients with AF and ESRD on chronic hemodialysis who were treated with DOACs or VKAs. The outcomes of interest included ischemic stroke, the composite of ischemic stroke or systemic embolism, major bleeding, gastrointestinal bleeding, minor bleeding events and all-cause mortality. RESULTS: Among 397 studies identified from the literature search, six studies (three RCTs and three observational studies) were included in the meta-analysis. Compared with VKA-treated patients, those treated with DOACs had similar risk of ischemic stroke (RR:0.76, 95% CI:0.41-1.41), ischemic stroke or systemic embolism (RR:0.65, 95% CI:0.38-1.10), major bleeding (RR:0.79, 95% CI:0.49-1.28) and all-cause death (RR:0.79, 95% CI:0.56-1.12). The risk of gastrointestinal bleeding was lower in DOAC- vs VKA-treated patients in three eligible observational studies (RR:0.73, 95% CI: 0.54-0.99, I2 = 79%) but this was not confirmed in two eligible RCTs (RR:0.69, 95% CI: 0.33-1.43, I2 = 0%). CONCLUSIONS: Among AF patients with ESRD on chronic hemodialysis, the risk of ischemic stroke, ischemic stroke or systemic embolism, minor bleeding, major bleeding, and all-cause mortality is similar in patients treated with DOACs compared to VKAs. Given that the meta-analysis of RCTs on gastrointestinal bleeding did not confirm the results of the meta-analysis of the observational studies, it cannot be concluded that gastrointestinal bleeding is lower among DOAC-treated patients. PROTOCOL REGISTRATION: PROSPERO CRD42023391966.

Argatroban as an Add-On to rtPA in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Current treatment options for acute ischemic stroke, including intravenous thrombolysis (IVT) and mechanical thrombectomy, have undoubtedly revolutionized stroke care. The need for additional treatment options has brought into the light direct thrombin inhibitors (DTIs) and, specifically, argatroban as a promising candidate. However, there is uncertainty regarding the safety of adding argatroban to IVT, mainly due to the increased hemorrhagic risk. In this study, we performed a systematic review and meta-analysis examining the safety and efficacy of argatroban as an add-on treatment for IVT. The following databases were searched from inception until the 14th of May 2023: Pubmed/MEDLINE, ClinicalTrials.gov, the EU Clinical Trials Register, EMBASE/Scopus, and the Cochrane Library. Only randomized clinical trials (RCTs) enrolling patients with acute ischemic stroke who underwent IVT evaluating the add-on use of any DTIs were selected for the systematic review and further meta-analysis. The PRISMA guidelines were followed at all stages. Four studies with argatroban were included in the final analysis. Analysis of risk ratio and relative risk shows that the add-on therapy with argatroban seems to be effective and favors a good clinical outcome (mRS 0-2) at 90 days, similar to that of alteplase. All studies showed a low pooled incidence of symptomatic intracerebral hemorrhage (5%), parenchymal hematoma (3%), and other major bleeding (1%). Argatroban as an add-on treatment to IVT seems not to be associated with excessive bleeding risk; however, its efficacy remains unproven. According to this synopsis of the currently available evidence, it is premature to use argatroban as an add-on to IVT treatment outside the current clinical trial setting.

Sodium-glucose cotransporter-2 inhibitors in heart failure patients across the range of body mass index: a systematic review and meta-analysis of randomized controlled trials.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in patients with heart failure, with or without diabetes. We sought to assess whether there is an interaction of these effects with body mass index (BMI). A systematic review of the MEDLINE and Scopus databases (last search: November 15th, 2022) was performed according to the PRISMA statement. Studies eligible for this review were randomized control trials (RCTs) with patients with chronic heart failure with either preserved or reduced ejection fraction randomly assigned to SGLT2 inhibitors or placebo. Data were extracted independently by two reviewers. BMI was classified according to the WHO classification into under/normal weight (BMI: < 25 kg/m2), overweight (BMI: 25-29.9 kg/m2), obesity class I (BMI: 30-34.9 kg/m2), and obesity classes II/III (BMI: ≥ 35 kg/m2). All analyses were performed using RevMan 5.4. Among 1461 studies identified in the literature search, 3 were eligible and included in the meta-analysis. Among 14,737 patients (32.2% were women), 7,367 were randomized to an SGLT2 inhibitor (dapagliflozin or empagliflozin) and 7,370 to placebo. There were significantly fewer hospitalizations for HF (OR: 0.70, 95%CI: 0.64-0.76), cardiovascular deaths (OR:0.86, 95%CI: 0.77-0.97) and all-cause deaths (OR:0.90, 95%CI: 0.82-0.98) in the SGLT2 inhibitors group compared to the placebo group, without any interaction with BMI group (test for subgroup differences: x2 = 1.79, p = 0.62; x2 = 0.27, p = 0.97; x2 = 0.39, p = 0.94, respectively). There is no interaction between the efficacy of SGLT2 inhibitors and BMI in patients with HF with either preserved or reduced ejection fraction. SGLT2 inhibitors are associated with improved outcomes regardless of the BMI.Trial registration: PROSPERO ID: CRD42022383643.

Risk Stratification Tools to Guide a Personalized Approach for Cardiac Monitoring in Embolic Stroke of Undetermined Source.

Current recommendations support a personalized sequential approach for cardiac rhythm monitoring to detect atrial fibrillation after embolic stroke of undetermined source. Several risk stratification scores have been proposed to predict the likelihood of atrial fibrillation after embolic stroke of undetermined source. This systematic review aimed to provide a comprehensive overview of the field by identifying risk scores proposed for this purpose, assessing their characteristics and the cohorts in which they were developed and validated, and scrutinizing their predictive performance. We identified 11 risk scores, of which 4 were externally validated. The most frequent variables included were echocardiographic markers and demographics. The areas under the curve ranged between 0.70 and 0.94. The 3 scores with the highest area under the curve were the Decryptoring (0.94 [95% CI, 0.88-1.00]), newly diagnosed atrial fibrillation (0.87 [95% CI, 0.79-0.94]), and AF-ESUS (Atrial Fibrillation in Embolic Stroke of Undetermined Source) (0.85 [95% CI, 0.80-0.87]), of which only the latter was externally validated. Risk stratification scores can guide a personalized approach for cardiac rhythm monitoring after embolic stroke of undetermined source.

Interleukin-6 inhibitors reduce mortality in coronavirus disease-2019: An individual patient data meta-analysis from randomized controlled trials.

OBJECTIVE: To assess the efficacy of IL-6 inhibitors compared to standard of care (SOC) in COVID-19 patients. DATA SOURCES: A systematic review of the MEDLINE and Scopus databases (last search: October 8th, 2021) was performed according to the PRISMA statement. STUDY SELECTION: Randomized control trials (RCTs) comparing IL-6 inhibitors to SOC in hospitalized COVID-19 patients were deemed eligible. DATA EXTRACTION AND SYNTHESIS: Individual patient data were extracted from the Kaplan-Meier curves or were obtained from authors of included studies. Additionally, the reviewers independently abstracted data and assessed study quality of each eligible report. RESULTS: Eleven studies were identified, incorporating 7467 patients (IL-6 inhibitors: 4103, SOC: 3364). IL-6 inhibitors were associated with decreased risk for death compared to SOC at the one-stage meta-analysis (Hazard Ratio [HR]: 0.75, 95% Confidence interval [CI]: 0.69-0.82, p<0.0001) and the two-stage meta-analysis (HR: 0.85, 95%CI: 0.77-0.93, p<0.001, I2 = 0.0%). Meta-regression analysis revealed that the difference in OS between the two groups was not influenced by the mean age of patients. At secondary meta-analyses, IL-6 inhibitors were associated with decreased odds for intubation OR:0.74, 95%CI:0.65-0.85, p<0.001, I2=0.0%). IL-6 inhibitors were associated with increased odds for discharge compared to SOC (OR:1.28, 95% CI:1.15-1.42, p<0.001, I2=0.0%). CONCLUSIONS AND RELEVANCE: This meta-analysis of individual patient data from randomized trials shows that IL-6 inhibitors significantly reduce the risk of death compared to SOC. IL-6 inhibitors are also associated with better outcomes in terms of intubation and discharge rates compared to SOC.

Self-reported risk of obstructive sleep apnea syndrome, and awareness about it in the community of 4 insular complexes comprising 41 Greek Islands.

Obstructive Sleep Apnea Syndrome (OSAS) is a chronic disease that significantly increases morbidity and mortality of the affected population. There is lack of data concerning the OSAS prevalence in the insular part of Greece. The purpose of this study was to investigate the self-reported prevalence of OSAS in 4 Greek insular complexes comprising 41 islands, and to assess the awareness of the population regarding OSAS and its diagnosis. Our study comprised 700 participants from 41 islands of the Ionian, Cyclades, Dodecanese and Northeast Aegean island complexes that were studied by means of questionnaires via a telephone randomized survey (responsiveness rate of 25.74%). Participants were assessed by the Berlin Questionnaire (BQ) for evaluation of OSA risk, by the Epworth Sleepiness Scale (ESS) for evaluation of excessive daytime sleepiness, and by 3 questions regarding the knowledge and diagnosis of OSAS. The percentage of participants at high risk according to BQ was 27.29% and the percentage of people who were at high risk according to ESS was 15.43%. A percentage of 6.29% of the population was at high risk for OSAS (high risk both in BQ and ESS). A high percentage of 73.43%, were aware of OSAS as a syndrome however a significantly less percentage (28.00%) was aware of how a diagnosis of OSAS is established. The community prevalence of OSAS in Greek islands in combination with the low-level awareness of the OSAS diagnostic methods highlights the need for development of health promotion programs aiming at increasing the detection of patients at risk while increasing the awareness of OSAS.

Probing the whole ore chalcopyrite-bacteria interactions and jarosite biosynthesis by Raman and FTIR microspectroscopies.

The whole ore chalcopyrite-bacteria interaction and the formation of the extracellular polymeric substances (EPS) during the bioleaching process by microorganisms found in the mine of Hellenic Copper Mines in Cyprus were investigated. Raman and FTIR microspectroscopies have been applied towards establishing a direct method for monitoring the formation of secondary minerals and the newly found vibrational marker bands were used to monitor the time evolution of the formation of covellite, and the K(+) and NH4(+)-jarosites from the chalcopyrite surfaces. The Raman data indicate that the formation of K(+)-jarosite is followed by the formation of NH4(+)-jarosite. The variation in color in the FTIR imaging data and the observation of the amide I vibration at 1637cm(-1) indicate that the microorganisms are attached on the mineral surface and the changes in the frequency/intensity of the biofilm marker bands in the 900-1140cm(-1) frequency range with time demonstrate the existence of biofilm conformations.