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Cureus Oct 2023High blood pressure (HBP) is usually prominent after the onset of acute ischemic stroke (AIS). Although previous studies have found that about half of patients with... (Review)
Review
High blood pressure (HBP) is usually prominent after the onset of acute ischemic stroke (AIS). Although previous studies have found that about half of patients with AIS have a background of hypertension, there is no clear etiology for HBP in AIS. The literature reveals discrepancies in the relationship between HBP and clinical outcomes of AIS, pointing toward the contested effect of blood pressure (BP) reduction clinical outcomes. Thus, the potential benefits and hazards of HBP treatment were explored in the context of clinical outcomes after AIS. An electronic database and a manual search were carried out to identify all the articles related to this topic and published between 2000 and January 2023. The Review Manager software was also used to perform the meta-analysis and quality appraisal. In analyses related to patients not treated with reperfusion therapies, mortality, and dependency outcomes were categorized as short-term (<3 months) or long-term (≥3 months). Our search strategy yielded 2459 articles, of which only 15 met the inclusion criteria. The results of our meta-analysis demonstrate that in patients not treated with reperfusion therapies, BP lowering had no significant impact on either short-term or long-term mortality (risk ratio (RR): 1.18; 95% confidence interval (CI): 0.81-1.73; p = 0.39, and RR: 1.04; 95% CI: 0.77-1.40; p = 0.81, respectively) and dependency (RR: 1.12; 95% CI: 0.97-1.30; p = 0.11, and RR: 0.98; 95% CI: 0.90-1.07; p = 0.61, respectively). Furthermore, BP lowering prior to reperfusion showed no significant effect on mortality (RR: 0.7; 95% CI: 0.23-2.26; p = 0.58), but it did significantly reduce the risk of dependency (RR: 0.89; 95% CI: 0.85-0.94; p < 0.00001). When the dataset was restricted to patients who had successful reperfusion, intensive BP lowering (target systolic BP <120 mmHg) was found to increase the risk of dependency (RR: 1.23; 95% CI: 1.09-1.39; p = 0.0009). In addition, BP reduction had an insignificant effect on the risk of recurrent strokes and combined vascular events (RR: 1.00; 95% CI: 0.54-1.84; p = 1.00, and RR: 0.99; 95% CI: 0.70-1.41; p = 0.95, respectively). Lowering BP in patients not treated with reperfusion therapies is not beneficial in reducing the risk of either short or long-term mortality and dependency. However, BPR before reperfusion reduces the risk of dependency, while aggressive BPR (target systolic blood pressure (SBP) <120 mmHg) after successful reperfusion increases the risk of dependency. Therefore, we recommend BPR as early as possible for patients undergoing reperfusion therapies but suggest against aggressive BPR in patients who have undergone successful reperfusion.
PubMed: 38021612
DOI: 10.7759/cureus.47729 -
Clinical Neurology and Neurosurgery Jan 2024Acute ischemic stroke (AIS) is a leading cause of death and disability. AIS is caused by an embolus or thrombus that restricts blood flow to the brain tissue. Despite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute ischemic stroke (AIS) is a leading cause of death and disability. AIS is caused by an embolus or thrombus that restricts blood flow to the brain tissue. Despite intravenous thrombolysis and endovascular thrombectomy, a substantial number of patients do not achieve effective reperfusion. Argatroban, a direct thrombin inhibitor, can potentially improve neurological outcomes in AIS patients. However, there are conflicting results in the medical literature regarding the efficacy and safety of argatroban in this context.
OBJECTIVE
This study aims to evaluate the efficacy and safety of argatroban as monotherapy or adjunct therapy for acute ischemic stroke.
METHODS
Five major databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) were searched for randomized controlled trials (RCTs) that compared the efficacy and safety of using argatroban alone or in combination with recombinant tissue plasminogen activator (r-TPA) in the management protocol of the AIS. We used Review Manager Software (RevMan 5.4.1) for data analysis.
RESULTS
We included 1393 patients from eight RCTs (of them, 726 were treated with argatroban alone or combined with r-TPA, while 667 received the placebo, standard therapy (standard treatments based on current guidelines including antihypertensive, antiplatelet agents, and statins) or endovascular r-TPA). Neither argatroban vs control nor argatroban with r-TPA vs r-TPA showed significant difference regarding the activity in daily living; (SMD= 1.69, 95% CI [-0.23, 3.61]; p = 0.09), (SMD= 0.99, 95% CI [-0.88, 2.86]; p = 0.30), respectively. Also, there was no significant difference in the National Institutes of Health Stroke Scale (NIHSS) score at seven days, the number of patients achieving modified Rankin Scale (mRS) of 0-1 or 0-2 at 90 days (p > 0.05). Argatroban did not significantly increase the risk of adverse events or symptomatic intracranial hemorrhage (ICH), or major systemic bleeding compared to control or r-TPA (p > 0.05) CONCLUSIONS: Argatroban does not demonstrate superior efficacy compared to placebo or standard therapy in terms of ADL, NIHSS and mRS outcomes. Importantly, argatroban does not significantly increase the incidence of adverse events, including symptomatic ICH and systemic bleeding.
Topics: Humans; Arginine; Brain Ischemia; Fibrinolytic Agents; Intracranial Hemorrhages; Ischemic Stroke; Pipecolic Acids; Stroke; Sulfonamides; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 38176219
DOI: 10.1016/j.clineuro.2023.108097 -
Heliyon Sep 2023Geniposide, as a pharmacologically bioactive component, is derived from a classic and common Chinese herb, Ellis. Geniposide has been shown to be effective for treating...
Protective effect and possible mechanisms of geniposide for ischemia-reperfusion injury: A systematic review with meta-analysis and network pharmacology of preclinical evidence.
BACKGROUND
Geniposide, as a pharmacologically bioactive component, is derived from a classic and common Chinese herb, Ellis. Geniposide has been shown to be effective for treating I/R injury in recent studies. Current effectively pharmaceutical treatments are scarce, and treatment based on geniposide may become a novel option. As far as we know, this research is the initial systematic evaluation of the protective effects of geniposide in I/R injury.
AIM OF THE STUDY
This study is engrossed in evaluating the mechanism of action of geniposide in I/R injury through a preclinical systematic review with meta-analysis and network pharmacology.
MATERIALS AND METHODS
We built a systematic review which provided a view of effect and mechanism of geniposide for I/R injury. Based on seven databases, an open-ended search from their inception to August 31st, 2022, was conducted. Animal studies on the effects of geniposide in I/R injury were considered. The data was analyzed using Review Manager 5.3, and bias was assessed using the CAMARADES 10-item scale. 13 articles including 279 animals were selected finally. And network pharmacology was joined to elucidate the mechanism.
RESULTS
According to the meta-analysis, in I/R injury, geniposide can attenuate cardiomyocytes viability and the size of MI, decrease the volume of cerebral infraction and neurological score, decrease serum ALT and AST activity, and downregulated serum Cr and BUN. The review found that geniposide protects against I/R injury by inhibiting apoptosis, oxidation, inflammation and improvement of autophagy and mitochondrial respiration, which is consistent with the results of the network pharmacology screening.
CONCLUSION
This preclinical systematic review including meta-analysis and network pharmacology, which was the first one summarizing the relationship between geniposide and ischemia diseases, shows a novel therapy for I/R injury and appears an enticing implication of geniposide in I/R injury, and further research is looked forward. Given the restricted quantity of included researches and the unclear risk of bias of the studies, we should interpret the results with caution.
PubMed: 37809705
DOI: 10.1016/j.heliyon.2023.e20114 -
International Journal of Molecular... Jun 2024Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in... (Meta-Analysis)
Meta-Analysis Review
Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in clinical practice. This meta-analysis aims to assess the effect of IL-10 immunotherapy on renal ischemia-reperfusion injury. Medline, Embase, Cochrane-library, Google Scholar and clinicaltrials.gov were searched up to 31 March 2023. Preclinical and clinical interventional studies investigating IL-10 immunotherapy for renal ischemia-reperfusion were eligible for inclusion. The primary endpoint was renal function (serum creatinine) following ischemia-reperfusion. The secondary endpoints included mitochondrial integrity, cellular proliferation, regulated cell death (TUNEL assay), expression of inflammatory cytokines (TNF-α, IL-6 and IL-1β), M1/M2 macrophage polarization, tissue integrity (tubular injury score), long-term kidney fibrosis (fibrotic area %) and adverse events (pulmonary toxicity, cardiotoxicity hepatotoxicity). The search returned 861 records. From these, 16 full texts were screened and subsequently, seven animal studies, corresponding to a population of 268 mice/rats, were included. Compared to the control treatment, IL-10 immunotherapy reduced serum creatinine more effectively within 24 h of administration (95% CI: -9.177, -5.601, I = 22.42%). IL-10 immunotherapy promoted mitochondrial integrity and cellular proliferation and reduced regulated cell death (95% CI: -11.000, -4.184, I = 74.94%). It decreased the expression of TNF-α, IL-6 and IL-1β, led to M2 polarization of the local macrophages, reduced tubular injury score (95% CI: -8.917, -5.755, I = 22.71%), and long-term kidney fibrosis (95% CI: -6.963, -3.438, I = 0%). No adverse outcomes were captured. In Conclusion, IL-10 immunotherapy safely improves outcomes in animal models of renal ischemia-reperfusion; the translational potential of IL-10 immunotherapy needs to be further investigated in clinical trials.
Topics: Reperfusion Injury; Animals; Interleukin-10; Humans; Immunotherapy; Kidney; Acute Kidney Injury; Mice
PubMed: 38892418
DOI: 10.3390/ijms25116231 -
Clinical Neurology and Neurosurgery Jan 2024We acknowledge that between endovascular treatment (EVT) has emerged as a promising therapeutic approach, with some evidence of benefits observed in clinical trials.... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We acknowledge that between endovascular treatment (EVT) has emerged as a promising therapeutic approach, with some evidence of benefits observed in clinical trials. However, there remains a significant gap in the evidence regarding the real-world application and effectiveness of EVT.The objective of this study was to comprehensively evaluate the safety and efficacy differences between EVT and standard medical treatment (SMT) in patients with basilar artery occlusion(BAO).
METHODS
Real-world studies (RWSs) on patients with BAO who underwent EVT and SMT were identified through searches in EMBASE, PubMed, and Cochrane Library databases. The efficacy outcomes included good clinical outcomes [defined as modified Rankin Scale (mRS) scores of 0-3 at 90 days], excellence clinical outcomes (defined as mRS scores of 0-2 at 90 days), 90-day mortality rate, and reperfusion status. The safety outcome was symptomatic intracranial hemorrhage (sICH). Subgroup analysis was conducted based on study type (prospective and retrospective studies). The relationship between EVT and SMT with the prognosis of BAO patients was expressed using odds ratios (OR) with a 95% confidence interval (95% CI).
RESULTS
The seven studies involved a total of 2885 patients. After conducting sensitivity analysis and excluding articles with high heterogeneity, EVT demonstrated a significant association with good clinical outcomes at 90 days (OR=4.01, 95% CI: 2.60-6.19) and excellence clinical outcomes at 90 days (OR=5.70, 95% CI: 3.18-10.22) compared to SMT. Additionally, EVT showed a lower correlation with 90-day mortality rate compared to the SMT group (OR=0.35, 95% CI: 0.25-0.47). Subgroup analysis based on study type revealed that EVT had higher rates of successful reperfusion (retrospective study group: OR=7.97, 95% CI: 4.83-13.15; prospective study group: OR=51.57, 95% CI: 29.76-89.38) than the SMT group in both subgroups. The presence of sICH was not statistically significant in the retrospective study group (OR=1.20, 95% CI: 0.58-2.48) and showed high heterogeneity. However, in the prospective study group, EVT exhibited a higher risk of bleeding compared to SMT (OR=11.42, 95% CI: 2.65-49.20).
CONCLUSIONS
In summary, our real-world study aligns with the conclusions of recently published randomized controlled trials research. When comparing EVT and SMT in the treatment of BAO, EVT shows a higher correlation with favorable clinical outcomes, higher rates of successful reperfusion, and lower mortality rates. However, it does come with an increased risk of sICH.
Topics: Humans; Stroke; Retrospective Studies; Prospective Studies; Basilar Artery; Treatment Outcome; Arterial Occlusive Diseases; Intracranial Hemorrhages; Endovascular Procedures; Thrombectomy
PubMed: 38181677
DOI: 10.1016/j.clineuro.2023.108096 -
International Journal of Stroke :... Aug 2023Blood-brain barrier permeability (BBBp) is a key process involved in ischemic stroke pathophysiology. However, there is a lack of consensus on how BBBp evolves after the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood-brain barrier permeability (BBBp) is a key process involved in ischemic stroke pathophysiology. However, there is a lack of consensus on how BBBp evolves after the ischemia injury, and its clinical relevance at different timepoints post stroke.
AIMS
The main objective of this study is to assess BBBp evolution through stroke phases and its implications on patient outcomes.
METHODS
We screened PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials up to 31 December 2021. We included research quantitatively using neuroimaging to assess BBBp in stroke patients. BBBp in the different phases was evaluated by a random-effect model based on the standardized mean difference (SMD) between the ipsilateral and contralateral sides of the brain. We performed a subgroup analysis on clinical outcome, reperfusion treatment, haemorrhagic transformation, and imaging method.
RESULTS
We identified 3761 studies, of which 22 (1592 patients and 1787 evaluations) were included in our study. Overall, 17 studies reported BBBp for the hyperacute phase, 8 for the acute, 5 for the subacute, and 2 for the chronic phase. All phases were associated with increased BBBp: 0.74 (0.48-0.99), 1.68 (0.94-2.42), 1.98 (0.96-3.00), and 1.00 (0.45-1.55), respectively. An increase in BBBp was associated with hemorrhagic transformation in the hyperacute phase and with improved functional outcomes in the late subacute phase.
CONCLUSION
BBBp is persistently increased after stroke, peaking in the acute and subacute phases. The degree of BBBp influences patient outcomes depending on stroke phase. Our findings support the clinical relevance of BBBp dynamics in stroke care.
Topics: Humans; Stroke; Blood-Brain Barrier; Tomography, X-Ray Computed; Brain; Permeability
PubMed: 36927176
DOI: 10.1177/17474930231166306 -
Biomedicine & Pharmacotherapy =... May 2024Propofol, a commonly used intravenous anesthetic, has demonstrated potential in protecting against myocardial ischemia/reperfusion injury (MIRI) based on preclinical... (Meta-Analysis)
Meta-Analysis Review
Propofol, a commonly used intravenous anesthetic, has demonstrated potential in protecting against myocardial ischemia/reperfusion injury (MIRI) based on preclinical animal studies. However, the clinical benefits of propofol in this context are subject to debate. We conducted a systematic search across eight databases to identify all relevant animal studies investigating the preventive effects of propofol on MIRI until October 30, 2023. We assessed the methodological quality of the included studies using SYRCLE's bias risk tool. Statistical analysis was performed using STATA 15.1. The primary outcome measures analyzed in this study were myocardial infarct size (IS) and myocardial injury biomarkers. This study presents a comprehensive analysis of 48 relevant animal studies investigating propofol's preventive effects on MIRI. Propofol administration demonstrated a reduction in myocardial IS and decreased levels of myocardial injury biomarkers (CK-MB, LDH, cTnI). Moreover, propofol improved myocardial function parameters (+dp/dtmax, -dP/dtmax, LVEF, LVFS), exhibited favorable effects on inflammatory markers (IL-6, TNF-α) and oxidative stress markers (SOD, MDA), and reduced myocardial cell apoptotic index (AI). These findings suggest propofol exerts cardioprotective effects by reducing myocardial injury, decreasing infarct size, and improving heart function. However, the absence of animal models that accurately represent comorbidities such as aging and hypertension, as well as inconsistent administration methods that align with clinical practice, may hinder its clinical translation. Further robust investigations are required to validate these findings, elucidate the underlying mechanisms of propofol, and facilitate its potential translation into clinical practice.
Topics: Propofol; Animals; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress; Biomarkers; Anesthetics, Intravenous; Humans; Apoptosis
PubMed: 38640712
DOI: 10.1016/j.biopha.2024.116629 -
Frontiers in Neurology 2023Thrombectomy may provide superior results compared to best medical care for acute posterior circulation strokes (PCS). Contact aspiration (CA), stent retriever (SR), and...
OBJECTIVE
Thrombectomy may provide superior results compared to best medical care for acute posterior circulation strokes (PCS). Contact aspiration (CA), stent retriever (SR), and combined SR + CA (SRA) are commonly employed as first-line techniques. However, the optimal strategy and the role of SRA remain uncertain.
METHODS
Systematic searching was conducted in three databases (PubMed, Embase, and Cochrane). Network meta-analyzes were performed using random-effects models. The reperfusion and clinical outcomes were compared. Pooled outcomes were presented as odds ratios (OR) with 95% confidence intervals (CI). Rankograms with surface under the cumulative ranking curve (SUCRA) were calculated.
RESULTS
Seventeen studies were included, involving a total of 645 patients who received first-line CA, 850 patients who received SR, and 166 patients who received SRA. Regarding final recanalization outcomes, both first-line SRA (OR = 3.2, 95%CI 1.4-11.0) and CA (OR = 2.1, 95%CI 1.3-3.7) demonstrated superiority over SR in achieving successful reperfusion [modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3], with values of SUCRA 91.1, 58.5, and 0.4%, respectively. In addition, first-line SRA showed an advantage in achieving final mTICI 2c/3 compared to CA (OR = 3.6, 95%CI 0.99-16.0) and SR (OR = 6.4, 95%CI 1.3-35.0), with SUCRA value of 98.0, 44.7, and 7.2%, respectively. Regarding reperfusion outcome after the first pass, SRA also achieved a higher rate of mTICI 3 than SR (OR = 4.1, 95%CI 1.3-14.0), while CA did not (SUCRA 97.4, 4.6, 48.0%). In terms of safety outcomes, first-line CA was associated with a lower incidence of symptomatic intracranial hemorrhage (sICH) compared to SR (OR = 0.38, 95%CI 0.1-1.0), whereas the SRA technique did not (SUCRA 15.6, 78.6, 55.9%). Regarding clinical prognosis, first-line CA achieved a higher proportion of functional independence (modified Rankin Scale (mRS) 0-2) at 90 days than SR (OR = 1.4, 95%CI 1.1-1.9), whereas SRA did not (SUCRA 90.5, 17.4, 42.1%).
CONCLUSION
For acute PCS, a first-line CA strategy yielded better results in terms of final successful reperfusion and 90-day functional independence compared to SR. As the combined technique, first-line SRA was associated with superior first-pass and final reperfusion outcomes compared to SR. However, no significant difference was observed in functional independence achieved by first-line SRA compared to the other two strategies. Further high-quality studies are warranted.
PubMed: 38020623
DOI: 10.3389/fneur.2023.1279233 -
American Journal of Transplantation :... Aug 2023Intracardiac thrombosis and/or pulmonary thromboembolism (ICT/PE) is a rare but devastating complication during liver transplantation. Its pathophysiology remains poorly... (Meta-Analysis)
Meta-Analysis
Intracardiac thrombosis and/or pulmonary thromboembolism (ICT/PE) is a rare but devastating complication during liver transplantation. Its pathophysiology remains poorly understood, and successful treatment remains a challenge. This systematic review summarizes the available published clinical data regarding ICT/PE during liver transplantation. Databases were searched for all publications reporting on ICT/PE during liver transplantation. Data collected included its incidence, patient characteristics, the timing of diagnosis, treatment strategies, and patient outcomes. This review included 59 full-text citations. The point prevalence of ICT/PE was 1.42%. Thrombi were most often diagnosed during the neohepatic phase, particularly at allograft reperfusion. Intravenous heparin was effective in preventing early-stage thrombus from progressing further and restoring hemodynamics in 76.32% of patients it was utilized for; however, the addition of tissue plasminogen activator or sole use of tissue plasminogen activator offered diminishing returns. Despite all resuscitation efforts, the in-hospital mortality rate of an intraoperative ICT/PE was 40.42%, with nearly half of these patients dying intraoperatively. The results of our systematic review are an initial step for providing clinicians with data that can help identify higher-risk patients. The clinical implications of our results warrant the development of identification and management strategies for the timely and effective treatment of these tragic occurrences during liver transplantation.
Topics: Humans; Tissue Plasminogen Activator; Liver Transplantation; Thrombosis; Pulmonary Embolism; Heart Diseases
PubMed: 37156300
DOI: 10.1016/j.ajt.2023.04.029 -
Prehospital Emergency Care Dec 2023The concept of early administration of P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI)...
BACKGROUND
The concept of early administration of P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) is widely accepted, but whether prehospital administration results in greater coronary reperfusion remains unclear. Our study aims to analyze the benefit and safety of prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor administration.
METHOD
Three databases (PubMed, EMBASE, and Cochrane Library) were searched from database inception to June 2023. We included all types of studies except for conference publications, abstract presentations, reviews, and case reports. The primary outcomes were pre-PCI TIMI flow grade 2-3 (TIMI = Thrombolysis in Myocardial Infarction) and major bleeding. The secondary outcomes included post-PCI TIMI flow grade 2-3, major adverse cardiac events (MACE), recurrent myocardial infarction (MI), and short-term (30-day) mortality.
RESULT
Eight individual studies with a total of 10823 patients were included in our meta-analysis. Compared with in-hospital P2Y12 inhibitor, prehospital P2Y12 inhibitor were associated with significantly higher rates of pre-PCI TIMI flow grade 2-3 (OR 1.32, 95% CI: 1.09-1.61, = 0.005) and post-PCI TIMI flow grade 2-3 (OR 1.43, 95% CI: 1.04-1.97, = 0.03), and a significantly lower risk of recurrent MI (OR 0.69, 95% CI: 0.49-0.96, = 0.03). There were no significant difference in the risk of major bleeding (OR 1.00, 95% CI: 0.75-1.32, = 0.98), MACE (OR 0.94, 95% CI: 0.70-1.25, = 0.65), or short-term mortality (OR 0.87, 95% CI: 0.50-1.51, = 0.61).
CONCLUSION
Prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor is associated with a significantly higher rate of pre-PCI and post-PCI TIMI flow grade 2-3, a reduced risk of recurrent MI, and no increase in major bleeding in STEMI patients undergoing primary PCI.
PubMed: 38019694
DOI: 10.1080/10903127.2023.2284819