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Frontiers in Pharmacology 2022Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2)... (Review)
Review
Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs). PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4. Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups placebo or standard diabetes therapies (SMD: -1.21; 95% CI: -1.91, -0.52, < 0.001). The effects of CRP (SMD: 0.25; 95% CI: -0.47, -0.03, = 0.02) and leptin (SMD: -0.22; 95% CI: -0.43, -0.01, = 0.04) were reduced, and the effects of adiponectin were improved (SMD: 0.28; 95% CI: 0.15, 0.41, < 0.001) in placebo-controlled studies. PAI-1 levels were significantly reduced in studies controlled for diabetes therapies (SMD: -0.38; 95% CI: -0.61, -0.15, = 0.001). This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.
PubMed: 36467062
DOI: 10.3389/fphar.2022.1045235 -
Journal of Thrombosis and Thrombolysis Feb 2023Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of tenecteplase versus alteplase for acute ischemic stroke: an updated systematic review, pairwise, and network meta-analysis of randomized controlled trials.
Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be investigated. Therefore, we aim to evaluate the safety and efficacy of TNK versus alteplase and to investigate the optimal TNK dosage. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, and PubMed until July 26, 2022. We used the risk ratio (RR) for dichotomous outcomes presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022352038. Nine RCTs with a total of 3,707 patients were included. TNK significantly led to complete recanalization (RR: 1.27 with 95% CI [1.02, 1.57], P = 0.03); however, we found no difference regarding early neurological improvement (RR: 1.07 with 95% CI [0.94, 1.21], P = 0.33) and excellent neurological recovery (RR: 1.03 with 95% CI [0.96, 1.10], P = 0.42). Also, TNK was similar to alteplase regarding mortality (RR: 0.99 with 95% CI [0.82, 1.18], P = 0.88), intracranial haemorrhage (RR: 1.00 with 95% CI [0.85, 1.18], P = 0.99), and parenchymal hematoma (RR: 1.13 with 95% CI [0.83, 1.54], P = 0.44). TNK in the dose of 0.25 mg is a viable candidate to displace alteplase as the standard of care in patients with an AIS within 4.5 h of presentation due to its better rate of early neurological recovery and non-inferiority in terms of safety outcomes. However, the evidence regarding TNK's role in AIS presenting after 4.5 h from symptoms onset, wake-up stroke, and minor stroke/TIA is still lacking, necessitating further double-blinded pragmatic RCTs in this regard.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Network Meta-Analysis; Randomized Controlled Trials as Topic; Stroke; Ischemic Stroke; Treatment Outcome; Brain Ischemia
PubMed: 36449231
DOI: 10.1007/s11239-022-02730-5 -
Journal of Clinical Neuroscience :... Dec 2022Treatment of acute ischemic stroke (AIS) with intravenous tissue-type plasminogen activator is effective in few patients when administered within 4.5 h after symptom... (Meta-Analysis)
Meta-Analysis
High-density lipoprotein level is associated with hemorrhage transformation after ischemic stroke treatment with intravenous thrombolysis: A systematic review and meta-analysis.
BACKGROUND
Treatment of acute ischemic stroke (AIS) with intravenous tissue-type plasminogen activator is effective in few patients when administered within 4.5 h after symptom onset. Hemorrhage transformation (HT) is a major cause of poor prognosis of AIS patients post intravenous rt-PA. Several studies report that high-density lipoprotein (HDL) cholesterol is associated with increased risk of HT. However, various studies report inconsistent results.
OBJECTIVE
The aim of the present study was to explore the association between HDL and HT after treatment of AIS patients by intravenous thrombolysis.
METHODS
A literature search for studies on the relationship between HDL and HT after treatment of AIS by intravenous thrombolysis published before, 28 Mar 2022, was conducted in PubMed, EMBASE, Cochrane, Web of Science, CNKI, CPVIP, Wan fang and SINOMED databases. Fixed effects model was used to estimate the mean differences (MDs) at 95% confidence interval (CI). Heterogeneity was assessed by Cochran's Q statistic and quantified by the I statistic. Analysis of included studies was carried out using Review Manager 5.4 and the publication bias was evaluated using Stata 16.0.
RESULTS
A total of 445 studies were screened and 9 studies met the inclusion criteria and were included in this meta-analysis (n = 3673). The results showed that AIS patients with HT had significantly higher HDL concentrations compared with the AIS patients without HT (pooled mean difference, 0.05; 95% confidence interval (CI), 0.01-0.09; P = 0.008).
CONCLUSION
The findings showed that HDL was associated with HT after treatment of AIS by intravenous thrombolysis, implying that is a potential predictor of the risk of HT.
Topics: Humans; Brain Ischemia; Cerebral Hemorrhage; Cholesterol, HDL; Fibrinolytic Agents; Ischemic Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 36283344
DOI: 10.1016/j.jocn.2022.10.016 -
Journal of Clinical Neuroscience :... Dec 2022Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to less than 2% in low- and middle income countries (LMICs). This is because alteplase is expensive and has been cited as one of the most common barriers to IVT in LMICs. Urokinase (UK) is a thrombolytic agent which is almost 50 times cheaper with easier production and purification than alteplase. UK may become a cost-effective option for IVT in LMICs if it is found to be safe and effective. We conducted this study to assess the existing evidence on the safety and efficacy of UK vs alteplase for IVT in AIS.
METHODS
The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Systematic literature search was done in PubMed, EMBASE, and Google Scholar for English literature published from 2010 to 2021.
RESULTS
A total of 4061 participants in the alteplase and 2062 participants in the UK group were included in the final statistical analysis. After IVT, a good functional outcome at last follow-up was found among 80.57 % of patients in the alteplase group compared to 73.79 % of patients in the UK group (OR: 1.11; 95 % CI: 0.95- 1.31; I = 0 %; P = 0.18). Symptomatic Intracerebral Hemorrhage (sICH) was found among 1.77 % of patients in the alteplase group compared to 2.83 % of patients in the UK group (OR: 0.84; 95 % CI: 0.56- 1.26; I = 0 %; P = 0.41). Similarly, mortality was found among 5.03 % of patients in the alteplase group compared to 5.42 % of patients in the UK group (OR: 0.87; 95 % CI: 0.66-1.14; I = 0 %; P = 0.30).
CONCLUSION
Our meta-analysis found that intravenous UK is not inferior to alteplase in terms of safety and efficacy and can be a viable alternative for IVT in AIS patients in LMICs.
Topics: Humans; Fibrinolytic Agents; Ischemic Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome; Urokinase-Type Plasminogen Activator
PubMed: 36274296
DOI: 10.1016/j.jocn.2022.09.015 -
Neurological Sciences : Official... Feb 2023Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small vessel disease responsible for recurrent ischemic... (Review)
Review
BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small vessel disease responsible for recurrent ischemic strokes, often with a progressive course leading to dementia and disability. On MRI, lacunes, microbleeds, and severe white matter alterations are typical features of the disease. In case of acute stroke, because of the bleeding risk associated with the disease and the doubtful efficacy of fibrinolytic treatment in a disease with poor evidence of thrombosis, the efficacy of intravenous thrombolysis remains unproven. Nevertheless, stroke is a frequent occurrence in CADASIL patients, and clinicians not unlikely may face in the emergency room the situation of a CADASIL patient with an acute stroke within the time window for thrombolysis.
OBJECTIVE
We report on two CADASIL patients treated with intravenous alteplase for acute ischemic stroke, and we present a review of literature aimed to report epidemiological data, efficacy and safety of intravenous thrombolysis in CADASIL patients.
METHODS
We performed a systematic review of medical literature published until August 2, 2022. Case reports and series in English language reporting on CADASIL patients and acute stroke were included.
RESULTS
Both patients were treated with intravenous thrombolysis without complications and had a good clinical outcome. The systematic review identified three case reports of CADASIL patients who were treated with intravenous alteplase for acute ischemic stroke; no bleedings complications were described.
CONCLUSIONS
Available data on intravenous thrombolysis in CADASIL patients are scarce but suggest that this treatment can be taken into consideration for these patients.
Topics: Humans; CADASIL; Tissue Plasminogen Activator; Ischemic Stroke; Stroke; Magnetic Resonance Imaging; Thrombolytic Therapy; Receptor, Notch3
PubMed: 36255541
DOI: 10.1007/s10072-022-06449-2 -
World Neurosurgery Jan 2023Thrombolysis (rTPA) and mechanical thrombectomy (MT) are cost-effective treatments for ischemic stroke. However, little is known about the impact of different types of...
BACKGROUND
Thrombolysis (rTPA) and mechanical thrombectomy (MT) are cost-effective treatments for ischemic stroke. However, little is known about the impact of different types of health systems (HSs) on the outcome and cost of ischemic stroke.
METHODS
Literature search was performed on PubMed/OVID for studies without time limits. The year of publication, type of HS, cost of intervention treatment (rTPA/MT), cost of control strategy (conservative treatment or rTPA), quality-adjusted life years (QALYs) gained, and percentage of gross domestic product spent on health were recorded. The inclusion criteria were English literature, cost-effectiveness, and cost-utility analyses. The exclusion criterion was the absence of geographic coherence between the derived QALYs and the costs. The costs were inflated to 2021 and then converted to US dollar/euro. An analysis of variance or Kruskal-Wallis test was used to compare the percentage of cost reduction and the QALYs gained. Gross domestic product percentage was correlated with the QALYs gained.
RESULTS
Thirty-five studies were analyzed. No significant differences in the percentage of cost reduction were found among the different types of HS (Beveridge -14.74% [95% confidence interval {CI} -57.94/53.08] vs. Bismarck -2.27% [95% CI -122.73/118.18] vs. national insurance -0.015% [95% CI -16.96/51.00] vs. private insurance -4.05% [95% CI -32.62/13.18]). No differences were found in QALYs gained among the different HS (Beveridge 1021 [95% CI -36.37/1705.04] vs. Bismarck 440 [95% CI -2290.68/3870.68] vs. national insurance 643 [95% CI -137.54/2366.21] vs. private insurance 550 [95% CI 131.54/1128.06]). No differences were found among the QALYs gained between rTPA/conservative treatment versus rTPA/MT and rtPA + MT/MT. The percentage of gross domestic product spent on health did not correlate with the QALYs gained (rho = -0.16; P = 0.56).
CONCLUSIONS
MT and rTPA are independently cost-effective among different HS.
Topics: Humans; Stroke; Cost-Benefit Analysis; Thrombectomy; Tissue Plasminogen Activator; Ischemic Stroke; Thrombolytic Therapy; Mechanical Thrombolysis; Treatment Outcome
PubMed: 36202340
DOI: 10.1016/j.wneu.2022.09.127 -
CNS & Neurological Disorders Drug... 2023A circadian pattern for the onset of acute ischemic stroke (AIS) has been described, with a higher risk in the early morning and a lower risk during nighttime. However,...
BACKGROUND
A circadian pattern for the onset of acute ischemic stroke (AIS) has been described, with a higher risk in the early morning and a lower risk during nighttime. However, data assessing the circadian distribution of hemorrhagic transformation after intravenous thrombolysis (ivT) are still incongruent.
OBJECTIVES
This review aimed to evaluate whether the time interval based on AIS onset or ivT time could influence the occurrence of intracranial hemorrhage (ICH) related to ivT and if the circadian rhythm of endogenous production of tissue plasminogen activator (t-PA) favors ICH occurrence.
METHODS
We conducted a systematic review following the PRISMA guidelines, searching PubMed and Embase for articles in English using the keywords: 'stroke', 'thrombolysis', and 'circadian'. Articles investigating the AIS onset or ivT time effects on circadian variations of ICH in AIS adult patients treated with ivT were included. Based on ICH's incidence and odds ratio, time intervals associated with higher risk and time intervals associated with lower risk were defined. The Newcastle-Ottawa Scale was used to assess the risk of bias. The resulting data were reported in a qualitative narrative synthesis.
RESULTS
From the 70 abstracts returned by electronic literature search, six studies with 33,365 patients fulfilled the inclusion criteria, out of which three were retrospective analysis studies, one case-control study, one prospective study, and one post hoc analysis of a multicentre trial. Some studies assessed the relationship between ICH occurrence and circadian rhythm depending on AIS onset time (n = 2), treatment time (n = 2), or both (n = 4). All studies investigated the patients' comorbidities as confounding variables for the circadian pattern of symptomatic ICH (sICH). Two studies found no association between AIS onset or ivT time and patient risk factors, but the other four found several differences and used multivariate logistic regression models to balance these covariates. The overall score of the Newcastle- Ottawa scale was 83.3%, which might be interpreted as overall high quality.
CONCLUSION
ICH occurred after ivT seems to follow a circadian pattern; the 18:00-00:00 time frame was the safest one, and patients with AIS onset or ivT time between these hours had the lowest incidence of any ICH, including sICH. The 06:00-12:00 block was associated with the highest incidence of ICH and sICH. However, the analysis is limited by the small number of included studies and the heterogeneous findings reported. Further homogenized studies using comparable time frames and sICH definitions are needed to demonstrate this circadian pattern. The review protocol was registered in the OSF database under reference UHNF, doi:10.17605/OSF.IO/UHNF6.
Topics: Humans; Tissue Plasminogen Activator; Fibrinolytic Agents; Ischemic Stroke; Retrospective Studies; Case-Control Studies; Prospective Studies; Brain Ischemia; Thrombolytic Therapy; Stroke; Intracranial Hemorrhages; Circadian Rhythm; Treatment Outcome; Multicenter Studies as Topic
PubMed: 36200200
DOI: 10.2174/1871527322666221004113752 -
Journal of Neurology Feb 2023Hemorrhagic transformation (HT) is a common complication of alteplase treatment. However, the prevalence rate, risk factors, and clinical outcomes of remote... (Meta-Analysis)
Meta-Analysis Review
Prevalence, risk factors, and clinical outcomes of remote intracerebral hemorrhage after intravenous thrombolysis in acute ischemic stroke: a systematic review and meta-analysis.
BACKGROUND
Hemorrhagic transformation (HT) is a common complication of alteplase treatment. However, the prevalence rate, risk factors, and clinical outcomes of remote intracerebral hemorrhage (rICH) after intravenous thrombolysis in acute ischemic stroke are not well understood.
METHODS
Following a previously registered protocol, the PubMed, Web of Science, and Embase databases were systematically searched to identify relevant literature up to June 2022. Cohort studies reporting thrombolysis-related rICH in patients with acute ischemic stroke were included. Random effects models were used to calculate pooled prevalence rate, mean difference (MD) or odds ratio (OR) with corresponding 95% confidence interval (CI).
RESULTS
Fourteen studies with 52,610 patients were included in this meta-analysis. The pooled rICH prevalence was 3.2% (95% CI 3.1-3.4%). Compared to patients without intracerebral hemorrhage (ICH), those with rICH were older, more likely to be female, and had a higher proportion of prior stroke, chronic heart failure and cardioembolism, and higher diastolic blood pressure. Small vessel disease markers (e.g., white matter hyperintensities and cerebral microbleeds) were strongly associated with rICH. The presence of rICH decreased the likelihood of favorable outcomes (OR 0.36, 95% CI 0.31-0.41) and increased the risk of mortality (OR 4.37, 95% CI 2.86-6.67).
CONCLUSIONS
Although rICH is uncommon after intravenous thrombolysis, its presence can lead to worse functional outcomes and higher mortality in acute ischemic stroke. Patients at high risk of rICH must be identified based on potential risk factors.
Topics: Female; Humans; Male; Brain Ischemia; Cerebral Hemorrhage; Fibrinolytic Agents; Ischemic Stroke; Prevalence; Risk Factors; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 36198828
DOI: 10.1007/s00415-022-11414-2 -
Journal of Neurology Jan 2023This study investigated clinical outcomes after direct endovascular thrombectomy (EVT) compared to bridging therapy (EVT with prior intravenous alteplase) in acute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
This study investigated clinical outcomes after direct endovascular thrombectomy (EVT) compared to bridging therapy (EVT with prior intravenous alteplase) in acute stroke within 4.5 h after onset.
METHODS
PubMed and Embase were searched for eligible randomized controlled trials. The primary outcome was the rates of neurological functional independence defined as modified Rankin scale score 0-2 at 90 days, whose non-inferiority margin was set at - 15%, - 10%, - 6.5%, - 5%, and - 1.3% for its risk difference (RD).
RESULTS
We included six studies enrolling 2334 participants. The crude cumulative rates of functional independence were 49.0% with direct EVT vs 50.9% with bridging therapy, without significant difference (Odd ratio [OR] = 0.93, 95% confidence interval [CI] 0.79-1.09) between two groups, where the pooled RD was - 2% (95% CI - 6 to 2%) whose lower 95% CI bound fell within non-inferiority margins of - 15%, - 10%, -6.5%, but not - 5% and - 1.3%. Between the two groups, no significant difference was found in excellent function rate (30.2% vs 30.6%, OR = 0.99, 95% CI 0.82-1.18) with RD of 0% (95% CI - 3 to 4%), mortality rate (16.0% vs 15.0%, OR = 1.08, 95% CI 0.86-1.35) with RD of 1% (95% CI - 2 to 4%), and symptomatic intracranial hemorrhage rate (4.3% vs 5.0%, OR = 0.86, 95% CI 0.58-1.27) with RD of 0% (95% CI - 2 to 1%).
CONCLUSIONS
No statistical difference was found in functional and safety outcomes between direct EVT and bridging therapy groups in acute stroke within 4.5 h after symptom onset. EVT alone was non-inferior to bridging therapy for several, but not the more stringent, non-inferiority margins.
Topics: Humans; Tissue Plasminogen Activator; Fibrinolytic Agents; Thrombolytic Therapy; Treatment Outcome; Endovascular Procedures; Randomized Controlled Trials as Topic; Stroke; Thrombectomy; Brain Ischemia
PubMed: 36197568
DOI: 10.1007/s00415-022-11413-3 -
Seminars in Thrombosis and Hemostasis Jul 2023Observational studies indicate a relationship between vitamin D deficiency and an increased risk of venous and arterial thrombotic events, but the underlying mechanisms...
Observational studies indicate a relationship between vitamin D deficiency and an increased risk of venous and arterial thrombotic events, but the underlying mechanisms behind this association are uncertain. This systematic review explores if there is an association between decreased vitamin D levels and a prothrombotic profile. The systematic literature search initially identified 3,214 studies (published until December 21, 2021) investigating the relationship between vitamin D and numerous hemostatic parameters. After the screening process, 18 observational and intervention studies fulfilled the inclusion criteria and were included in this systematic review. Parameters of primary hemostasis, secondary hemostasis, and fibrinolysis were investigated in six, thirteen, and fifteen of these studies, respectively. Most of the eligible studies did not identify significant associations between decreased vitamin D levels and hemostatic parameters. Some conflicting results were found between decreased vitamin D levels and thrombin generation parameters and the tissue factor pathway inhibitor. Conflicting results were also found between decreased vitamin D levels and fibrinolytic parameters, although the evidence may point toward weak associations with some regulators of fibrinolysis, mostly decreased tissue type plasminogen activator. Overall, our systematic review did not identify any definitive link between vitamin D deficiency and a prothrombotic profile, which might otherwise help explain the observed association between vitamin D deficiency and increased risk of thrombotic events. Moreover, there is no clinical evidence to confirm or refute a possible antithrombotic effect of vitamin D. Larger high-quality randomized controlled trials are needed to better elucidate the link between vitamin D deficiency and a prothrombotic risk profile.
Topics: Humans; Fibrinolysis; Hemostasis; Vitamin D Deficiency; Thrombosis; Vitamin D; Hemostatics
PubMed: 36174611
DOI: 10.1055/s-0042-1756701