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Translational Stroke Research Jun 2021Intravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However,... (Meta-Analysis)
Meta-Analysis
Intravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0-1 and 0-2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29-1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31-2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76-28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%-1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.
Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Ischemic Stroke; Prospective Studies; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 33641037
DOI: 10.1007/s12975-021-00890-9 -
Turkish Neurosurgery Feb 2024Extraventricular drainage (EVD) combined with fibrinolytics may prove effective in reducing morbidity and mortality rates associated with intraventricular cerebral...
INTRODUCTION
Extraventricular drainage (EVD) combined with fibrinolytics may prove effective in reducing morbidity and mortality rates associated with intraventricular cerebral hemorrhage (IVH). This efficacy is primarily attributed to increased drainage capacity and a decreased risk of EVD obstruction when fibrinolytics are employed. This systematic review and meta-analysis aimed to determine the effectiveness of thrombolytics in this context.
METHODS
A literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration number: CRD42022332152). Articles were selected from various sources, including PubMed, Trip Database, LILACS, Cochrane Library, and ScienceDirect. Clinical trials focusing on IVH treatment using EVD and/or fibrinolytics were considered. The Risk of Bias in Non-randomized Studies of Interventions (ROB 2) tool was employed for bias assessment. A fixed-effects regression model was used following heterogeneity analysis. Treatment effectiveness was evaluated based on mortality outcomes.
RESULTS
A total of 531 patients from four studies were included. The use of fibrinolytics significantly decreased IVH mortality compared with a placebo. The odds ratio (OR) for recombinant tissue plasminogen activator (rtPA) or alteplase was 0.54 [0.36; 0.82]. For urokinase (UK), the OR was 0.21 [0.03; 1.54], rendering it statistically non-significant. The overall OR was 0.52 [0.35; 0.78], and the heterogeneity I2 was 0% (indicating low heterogeneity).
CONCLUSION
While EVD alone is a common approach for managing hydrocephalus, its effectiveness is limited by potential blockages and infections. Combining EVD with UK or rtPA demonstrated improved patient outcomes. rtPA stands out as a reliable and effective option, while limited data are available regarding UK\'s effectiveness in reducing IVH mortality.
PubMed: 38874256
DOI: 10.5137/1019-5149.JTN.45919-23.1 -
Hand (New York, N.Y.) May 2022Vascular thrombosis secondary to frostbite can lead to ischemic tissue damage in severe cases. Threatened extremities may be salvaged with thrombolytics to restore...
BACKGROUND
Vascular thrombosis secondary to frostbite can lead to ischemic tissue damage in severe cases. Threatened extremities may be salvaged with thrombolytics to restore perfusion; however, current data are limited to single institution case series. The authors performed a systematic review to determine the efficacy of thrombolytic therapy in treating upper extremity frostbite.
METHODS
PubMed, EBSCO, and Google Scholar were queried using the keywords "thrombolytics," "frostbite," "fibrinolytics," and "tPA." Exclusion criteria were failure to delineate anatomic parts injured, failure to report number of limbs salvaged, animal studies, and non-English language publications. Thrombolytic therapy was defined as intraarterial (IA) or intravenous (IV) administration of tissue plasminogen activator (tPA), alteplase, urokinase, streptokinase, or any tPA derivative.
RESULTS
A total of 42 studies were identified, with 13 satisfying inclusion criteria. Eight studies reported catheter-directed IA thrombolysis, four reported systemic IV administration, and 1 reported both methods. A total of 157 patients received thrombolytics. In all, 73 upper extremity digits were treated by IA route and 136 digits were treated by IV route. Overall upper extremity digit salvage rate was 59%. There was a significantly higher salvage rate in digits treated by the IA route compared to the IV route.
CONCLUSIONS
Thrombolytics, particularly when administered by the intra-arterial route, are emerging as a promising treatment of severe frostbite of the upper extremity, increasing digit salvage rates.
Topics: Fibrinolytic Agents; Frostbite; Humans; Thrombolytic Therapy; Tissue Plasminogen Activator; Upper Extremity
PubMed: 32935578
DOI: 10.1177/1558944720940065 -
Frontiers in Pediatrics 2021Worldwide neonatal hypoxic-ischemic encephalopathy (HIE) is a common cause of mortality and neurologic disability, despite the implementation of therapeutic hypothermia...
Worldwide neonatal hypoxic-ischemic encephalopathy (HIE) is a common cause of mortality and neurologic disability, despite the implementation of therapeutic hypothermia treatment. Advances toward new neuroprotective interventions have been limited by incomplete knowledge about secondary injurious processes such as cerebral hyperperfusion commonly observed during the first 1-5 days after asphyxia. Cerebral hyperperfusion is correlated with adverse neurodevelopmental outcome and it is a process that remains poorly understood. In order to provide an overview of the existing knowledge on the pathophysiology and highlight the gaps in current understanding of cerebral hyperperfusion in term animals and neonates with HIE, we performed a systematic research. We included papers scoping for study design, population, number of participants, study technique and relevant findings. Methodological quality was assessed using the checklist for cohort studies from The Joanna Briggs Institute. Out of 2,690 results, 34 studies were included in the final review-all prospective cohort studies. There were 14 studies of high, 17 moderate and 3 of low methodological quality. Data from the literature were analyzed in two main subjects: (1) Hemodynamic Changes subdivided into macro- and microscopic hemodynamic changes, and (2) Endogenous Pathways which was subdivided into N-methyl-D-aspartate/Mitogen activated protein kinase (NDMA/MAPK), Nitric Oxide (NO), prostanoids and other endogenous studies. Cerebral hyperperfusion in term neonates with HIE was found to be present 10-30 min after the hypoxic-ischemic event and was still present around day 10 and up to 1 month after birth. Cerebral hyperperfusion was also characterized by angiogenesis and cerebral vasodilation. Additionally, cerebral vasodilation was mediated by endogenous pathways such as MAPK through urokinase Plasminogen Activator (uPA), by neuronal NO synthase following NMDA and by prostanoid synthesis. Future research should elucidate the precise role of NMDA, MAPK and prostanoids in cerebral hyperperfusion. Moreover, research should focus on possible interventions and the effect of hypothermia on hyperperfusion. These findings should be taken into account simultaneously with brain imagining techniques, becoming a valuable asset in assessing the impact in neurodevelopmental outcome.
PubMed: 33604320
DOI: 10.3389/fped.2021.631258 -
Medicine Nov 2023Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus,... (Meta-Analysis)
Meta-Analysis
Role of soluble urokinase type plasminogen activator receptor (suPAR) in predicting mortality, readmission, length of stay and discharge in emergency patients: A systematic review and meta analysis.
BACKGROUND
Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus, serves as a useful tool for ED physicians. Our study aims to analyze the efficacy of suPAR in predicting these prognostic markers in ED.
METHODS
We performed a comprehensive search on 6 databases from the inception to 30th November 2022, to select the following eligibility criteria; a) observation or triage trial studies investigating the role of suPAR levels in predicting: 30 day and 90-day mortality, 30-day readmission, early discharge (within 24hr), and LOS in patients coming to AMU.
RESULTS
A total of 13 studies were included, with a population size of 35,178, of which 52.9% were female with a mean age of 62.93 years. Increased risk of 30-day mortality (RR = 10.52; 95% CI = 4.82-22.95; I2 = 38%; P < .00001), and risk of 90-day mortality (RR = 5.76; 95% CI = 3.35-9.91; I2 = 36%; P < .00001) was observed in high suPAR patients. However, a slightly increased risk was observed for 30-day readmission (RR = 1.50; 95% CI = 1.16-1.94; I2 = 54%; P = .002). More people were discharged within 24hr in the low suPAR level group compared to high suPAR group (RR = 0.46; 95% CI = 0.40-0.53; I2 = 41%; P < .00001). LOS was thrice as long in high suPAR level patients than in patients with low suPAR (WMD = 3.20; 95% CI = 1.84-4.56; I2 = 99%; P < .00001).
CONCLUSION
suPAR is proven to be a significant marker in predicting 30-day and 90-day mortality in ED patients.
Topics: Humans; Female; Middle Aged; Male; Receptors, Urokinase Plasminogen Activator; Patient Discharge; Patient Readmission; Length of Stay; Biomarkers; Prognosis
PubMed: 37960735
DOI: 10.1097/MD.0000000000035718 -
Cardiology Journal Sep 2023In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with...
BACKGROUND
In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS.
METHODS
A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used if I² < 50%; otherwise, the random-effects model was performed.
RESULTS
Five studies with 3417 participants were included in the meta-analysis. Pooled analysis showed that mean suPAR levels in the ACS group were statistically significantly higher than in the control group (3.56 ± 1.38 vs. 2.78 ± 0.54 ng/mL, respectively; mean difference: 1.04; 95% confidence interval: 0.64-1.44; I² = 99%; p < 0.001).
CONCLUSIONS
In the context of acute coronary syndrome, suPAR is a potential biomarker for the early identification of medical conditions in individuals who are being treated in emergency rooms.
PubMed: 37772350
DOI: 10.5603/cj.96228 -
Journal of Neuro-ophthalmology : the... Sep 2020Acute nonarteritic central retinal artery occlusion (CRAO) is an eye stroke with poor visual prognosis and no proven effective therapies. Given advances in acute stroke...
BACKGROUND
Acute nonarteritic central retinal artery occlusion (CRAO) is an eye stroke with poor visual prognosis and no proven effective therapies. Given advances in acute stroke care, thrombolysis in CRAO merits critical re-examination. We review the evidence for intravenous (IV) and intra-arterial (IA) tissue plasminogen activator (tPA) in CRAO management.
EVIDENCE ACQUISITION
MEDLINE, Scopus, and Cochrane online databases were systematically searched from 1960 to present, for reports of acute IV or IA therapy with alteplase or tenecteplase in nonarteritic CRAO patients. English language case reports, case series, interventional studies, or randomized controlled trials were included. The study type, age and number of subjects, the regimen administered, the time since symptoms' onset, visual outcome, and safety reports were noted.
RESULTS
Use of IV thrombolysis with alteplase was reported in 7 articles encompassing 111 patients, with 54% of them receiving IV tPA within 4.5 hours of symptom onset, and none developing symptomatic intracranial or ocular hemorrhage. Six studies described IA alteplase administration, with only 18 of a total of 134 patients (13.4%) treated within the first 6 hours after visual loss. The reported adverse events were minimal. Visual outcomes post-IV and IA thrombolysis were heterogeneously reported; however, most studies demonstrated benefit of the respective reperfusion therapies when administered very early. We found no reports of tenecteplase administration in CRAO.
CONCLUSIONS
In 2020, nonarteritic CRAO patients should theoretically receive the same thrombolytic therapies, in the same time window, as patients with acute cerebral ischemia. Eye stroke and teleeye stroke code encounters must include an expert ophthalmologic evaluation to confirm the correct diagnosis and to evaluate for ocular signs that may help guide IV tPA administration or IA management. Future research should focus on developing feasible retinal penumbra imaging studies that, similar to cerebral tissue viability or perfusion imaging, can be incorporated into the thrombolysis decision-making algorithm.
Topics: Fibrinolytic Agents; Humans; Infusions, Intravenous; Retinal Artery Occlusion; Thrombolytic Therapy; Treatment Outcome; Visual Acuity
PubMed: 32739995
DOI: 10.1097/WNO.0000000000001027 -
Frontiers in Neurology 2021Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue...
Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue plasminogen activator (tPA) have proven to be effective treatments, their window-of-efficacy time is very short, leaving many patients with no viable treatment option. Over recent years there has been a growing interest in stimulating the facial nerves or ganglions to treat AIS. Pre-clinical studies have consistently demonstrated an increase in collateral blood flow (CBF) following ganglion stimulation, with positive indications in infarct size and neurological scores. Extensive human trials have focused on trans-oral electrical stimulation of the sphenopalatine ganglion, but have suffered from operational limitations and non-significant clinical findings. Regardless, the potential of ganglion stimulation to treat AIS or elongate the window-of-efficacy for current stroke treatments remains extremely promising. This review aims to summarize results from recent trial publications, highlight current innovations, and discuss future directions for the field. Importantly, this review comes after the release of four important clinical trials that were published in mid 2019.
PubMed: 34867737
DOI: 10.3389/fneur.2021.753182 -
Medicine May 2020Acute ischemic stroke due to large-vessel occlusion is a leading cause of death and disability, and therapeutic time window was limited to 4.5 hour when treated with... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Acute ischemic stroke due to large-vessel occlusion is a leading cause of death and disability, and therapeutic time window was limited to 4.5 hour when treated with intravenous thrombolysis. It has been acknowledged that endovascular treatment (EVT) is superior to general treatment (only medication, including intravenous recombinant tissue plasminogen activator (rt-PA)) in improving the outcome of AIS since 2015. However, the benefits were limited to improvement of functional outcomes and functional independence. Hence, this meta-analysis was conducted to summarize the benefits of EVT for acute ischemic stroke, explore underlying indications of EVT for AIS patients and suggest implications for clinical practice and future research.
METHODS
A search was performed to identify eligible studies in PubMed, Scopus and Web of Science updated to February 5, 2019. Functional outcomes, the modified Rankin Scale (mRS) 0-1, mRS 0-2, all-cause mortality, symptomatic intracerebral hemorrhage and asymptomatic intracerebral hemorrhage (aICH) at 90 days were selected as outcomes. Data was pooled to calculate the odds ratio (OR) and 95% confidence interval (CI). Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were also performed in this meta-analysis.
RESULTS
Eighteen studies comprising 3831 patients were included and analyzed in this meta-analysis. In comparison with general treatment, improved functional outcomes (mRS 0-1: OR = 1.68, 95% CI = 1.43-1.97, inconsistency index [I = 57%, P < .00001; mRS 0-2: OR = 1.78, 95% CI = 1.55-2.03, I = 69%, P < .00001), reduced risk of all-cause mortality (OR = 0.82, 95% CI = 0.70-0.98, I = 27%, P = .03) but higher risk of aICH (OR = 1.43, 95% CI = 1.05-1.95, I = 0%, P = .02) at 90 days were found in AIS patients treated with EVT. Age < 70, National Institutes of Health Stroke Scale ≥20 and maximum delay for invention>5 hours could improve clinical outcomes following EVT. In sensitivity analysis, it showed that 2 studies had a great influence on the pooled ORs. No potential publication bias was found in this meta-analysis.
CONCLUSION
Taken together, EVT, which led to improved functional outcomes and decreased risk of death, is superior to general treatment for AIS patients with age < 70, National Institutes of Health Stroke Scale ≥20 and maximum delay for invention>5 hours. Moreover, it suggests that "with mechanical thrombectomy" is potential favorable factor for improving aICH in comparison with general treatment.
Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Brain Ischemia; Cerebral Hemorrhage; Endovascular Procedures; Female; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Male; Middle Aged; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Stroke; Thrombectomy; Thrombolytic Therapy; Time-to-Treatment; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 32443338
DOI: 10.1097/MD.0000000000020187 -
Orphanet Journal of Rare Diseases Oct 2020Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAEnCI) is associated with skin swellings, abdominal attacks, and the risk of asphyxia due to upper airway...
BACKGROUND
Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAEnCI) is associated with skin swellings, abdominal attacks, and the risk of asphyxia due to upper airway obstruction. Several different gene mutations linked to the HAE phenotype have been identified. Our aim was to qualitatively assess and describe the clinical differentiators of these genetically identified HAEnCI types. To achieve this, we performed a systematic literature review of patients with angioedema symptoms and a genetically confirmed diagnosis of an HAEnCI type.
RESULTS
A systematic literature search, conducted in March 2020, returned 132 records, 43 of which describe patients with symptoms of angioedema and a genetically confirmed diagnosis of an HAEnCI type. Overall, this included 602 patient cases from 220 families. HAEnCI with a mutation in the coagulation factor XII gene (F12) (HAE-FXII) was diagnosed in 446 patients from 185 families (male:female ratio = 1:10). Estrogens (oral contraceptives, hormonal replacement therapy, and pregnancy) negatively impacted the course of disease in most female patients (252 of 277). Asphyxia occurred in 2 of 446 patients. On-demand and/or long-term prophylaxis treatment included C1-INH concentrates, icatibant, progestins, and tranexamic acid. HAEnCI with a specific mutation in the plasminogen gene (HAE-PLG) was diagnosed in 146 patients from 33 families (male:female ratio = 1:3). Estrogens had a negative influence on the course of disease in the minority of female patients (14 of 62). Tongue swelling was an important clinical feature. Asphyxia occurred in 3 of 146 patients. On-demand treatment with icatibant and C1-INH concentrate and long-term prophylaxis with progestins and tranexamic acid were effective. HAEnCI with a specific mutation in the angiopoietin-1 gene (HAE-ANGPT1) was diagnosed in 4 patients from 1 family and HAEnCI with a specific mutation in the kininogen-1 gene (HAE-KNG1) in 6 patients from 1 family.
CONCLUSIONS
A number of clinical differentiators for the different types of HAEnCI have been identified which may support clinicians to narrow down the correct diagnosis of HAEnCI prior to genetic testing and thereby guide appropriate treatment and management decisions. However, confirmation of the causative gene mutation by genetic testing will always be required.
Topics: Angioedema; Angioedemas, Hereditary; Complement C1 Inhibitor Protein; Factor XII; Female; Humans; Male; Mutation; Phenotype; Pregnancy
PubMed: 33059692
DOI: 10.1186/s13023-020-01570-x