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Cureus Aug 2023Myocardial infarction (MI) is a significant cause of morbidity and mortality in low- and middle-income countries. Fibrinolytic agents and percutaneous coronary... (Review)
Review
Myocardial infarction (MI) is a significant cause of morbidity and mortality in low- and middle-income countries. Fibrinolytic agents and percutaneous coronary intervention (PCI) are the main approaches for the recanalization and reperfusion of the myocardium following MI. Many studies have shown that PCI is superior to thrombolytics due to better outcomes and decreased mortality. Nevertheless, PCI's mortality gain over thrombolysis decreases as the time between presentation and PCI procedure increases. Furthermore, PCI is not widely available in most developing countries; thus, it cannot be delivered promptly. Most patients in developing countries cannot afford the cost of PCI. Thus, thrombolytic therapy remains essential to managing MI in developing countries and should not be disregarded. Tenecteplase (TNK) and streptokinase (SK) are the two most widely used fibrinolytics in managing MI in underdeveloped nations. Despite their widespread availability, comparative studies on them have been inconclusive. This study aims to review the available literature on the effectiveness and safety of TNK versus SK in managing MI in resource-poor nations. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) extension and analyzed according to Cochrane guidelines on synthesis without meta-analysis. A comprehensive literature search for studies comparing TNK and STK was conducted on EMBASE, Cochrane Library, Web of Science, CINAHL, Scopus, Google Scholar, and Ovid version of MEDLINE databases. A reference list of the eligible articles and systematic reviews was also screened. A narrative synthesis of the available data was done by representing the data on the effect direction plot, followed by vote counting. Of the 2284 references retrieved from the databases, only 17 studies met the inclusion criteria and were selected for final analysis. The study suggested that TNK is more effective in complete ST-segment resolution (80% vs 10% on the effect direction plot) and symptom relief (80% vs 20%) than SK. SK and TNK were comparable in achieving successful fibrinolysis (50% vs 50%). For the safety parameters, TNK is associated with a lesser risk of major bleeding than SK (88.9% vs 11.1%) and minor bleeding (25% vs 75%). SK was linked with a higher risk of hypotension/shock (77.8% vs 11.1%) and anaphylaxis/allergy (100% vs 0%). Long-term mortality was higher in the SK arm (100% vs 0%). In-hospital mortality is comparable between the two agents (37.5% vs 37.5%). There is conflicting evidence regarding other safety and efficacy endpoints. Compared to SK, TNK results in better complete ST-segment resolution and symptom relief. A higher risk of long-term mortality, increased risk of major and minor bleeding, hypotension, and allergy/anaphylaxis was observed in patients who received SK. Both agents were comparable in terms of in-hospital mortality and successful fibrinolysis. Controversy exists regarding which agent is linked with increased risk of 30-35-day mortality benefit and stroke. Randomized controlled trials (RCTs) with large sample sizes are needed to establish TNK vs SK superiority in efficacy and safety. The long-term duration of follow-up of the mortality rate of the two agents is also essential, as most patients in these regions cannot afford the recommended PCI post-fibrinolysis.
PubMed: 37750155
DOI: 10.7759/cureus.44125 -
Frontiers in Neurology 2023Computed tomography perfusion (CTP) has successfully extended the time window for reperfusion therapies in ischemic stroke. However, the published perfusion parameters...
BACKGROUND AND PURPOSE
Computed tomography perfusion (CTP) has successfully extended the time window for reperfusion therapies in ischemic stroke. However, the published perfusion parameters and thresholds vary between studies. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines, we conducted a systematic review to investigate the accuracy of parameters and thresholds for identifying core and penumbra in adult stroke patients.
METHODS
We searched Medline, Embase, the Cochrane Library, and reference lists of manuscripts up to April 2022 using the following terms "computed tomography perfusion," "stroke," "infarct," and "penumbra." Studies were included if they reported perfusion thresholds and undertook co-registration of CTP to reference standards. The quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and Standards for Reporting of Diagnostic Accuracy (STARD) guidelines.
RESULTS
A total of 24 studies were included. A meta-analysis could not be performed due to insufficient data and significant heterogeneity in the study design. When reported, the mean age was 70.2 years (SD+/-3.69), and the median NIHSS on admission was 15 (IQR 13-17). The perfusion parameter identified for the core was relative cerebral blood flow (rCBF), with a median threshold of <30% (IQR 30, 40%). However, later studies reported lower thresholds in the early time window with rapid reperfusion (median 25%, IQR 20, 30%). A total of 15 studies defined a single threshold for all brain regions irrespective of collaterals and the gray and white matter.
CONCLUSION
A single threshold and parameter may not always accurately differentiate penumbra from core and oligemia. Further refinement of parameters is needed in the current era of reperfusion therapy.
PubMed: 37885475
DOI: 10.3389/fneur.2023.1255526 -
International Urology and Nephrology Oct 2023There is currently no FDA-approved medical therapy for delayed graft function (DGF). Dexmedetomidine (DEX) has multiple reno-protective effects preventing ischemic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
There is currently no FDA-approved medical therapy for delayed graft function (DGF). Dexmedetomidine (DEX) has multiple reno-protective effects preventing ischemic reperfusion injury, DGF, and acute kidney injury. Therefore, we aimed to evaluate the reno-protective effects of perioperative DEX during renal transplantation.
METHODS
A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, PubMed, and CENTRAL until June 8th, 2022. We used the risk ratio (RR) for dichotomous outcomes and the mean difference for continuous outcomes; both presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022338898.
RESULTS
We included four RCTs with 339 patients. Pooled risk ratio found no difference between DEX and placebo in reducing DGF (RR: 0.58 with 95% CI [0.34, 1.01], p = 0.05) and acute rejection (RR: 0.88 with 95% CI [0.52, 1.49], p = 0.63). However, DEX improved short-term creatinine on day 1 (MD: - 0.76 with 95% CI [- 1.23, - 0.3], p = 0.001) and day 2 (MD: - 0.28 with 95% CI [- 0.5, - 0.07], p = 0.01); and blood urea nitrogen on day 2 (MD: - 10.16 with 95% CI [- 17.21, - 3.10], p = 0.005) and day 3 (MD: - 6.72 with 95% CI [- 12.85, - 0.58], p = 0.03).
CONCLUSION
Although there is no difference between DEX and placebo regarding reducing DGF and acute rejection after kidney transplantation, there may be some evidence that it has reno-protective benefits because we found statistically significant improvement in the short-term serum creatinine and blood urea nitrogen levels. More trials are required to investigate the long-term reno-protective effects of DEX.
Topics: Humans; Kidney Transplantation; Dexmedetomidine; Randomized Controlled Trials as Topic; Kidney
PubMed: 36997837
DOI: 10.1007/s11255-023-03568-3 -
Biomedicines Oct 2023Cerebral microbleeds (CMBs), a notable neuroimaging finding often associated with cerebral microangiopathy, demonstrate a heightened prevalence in patients diagnosed...
Prevalence and Impact of Cerebral Microbleeds on Clinical and Safety Outcomes in Acute Ischaemic Stroke Patients Receiving Reperfusion Therapy: A Systematic Review and Meta-Analysis.
BACKGROUND
Cerebral microbleeds (CMBs), a notable neuroimaging finding often associated with cerebral microangiopathy, demonstrate a heightened prevalence in patients diagnosed with acute ischemic stroke (AIS), which is in turn linked to less favourable clinical prognoses. Nevertheless, the exact prevalence of CMBs and their influence on post-reperfusion therapy outcomes remain inadequately elucidated.
MATERIALS AND METHODS
Through systematic searches of PubMed, Embase and Cochrane databases, studies were identified adhering to specific inclusion criteria: (a) AIS patients, (b) age ≥ 18 years, (c) CMBs at baseline, (d) availability of comparative data between CMB-positive and CMB-negative groups, along with relevant post-reperfusion therapy outcomes. The data extracted were analysed using forest plots of odds ratios, and random-effects modelling was applied to investigate the association between CMBs and symptomatic intracerebral haemorrhage (sICH), haemorrhagic transformation (HT), 90-day functional outcomes, and 90-day mortality post-reperfusion therapy.
RESULTS
In a total cohort of 9776 AIS patients who underwent reperfusion therapy, 1709 had CMBs, with a pooled prevalence of 19% (ES 0.19; 95% CI: 0.16, 0.23, < 0.001). CMBs significantly increased the odds of sICH (OR 2.57; 95% CI: 1.72; 3.83; < 0.0001), HT (OR 1.53; 95% CI: 1.25; 1.88; < 0.0001), as well as poor functional outcomes at 90 days (OR 1.59; 95% CI: 1.34; 1.89; < 0.0001) and 90-day mortality (OR 1.65; 95% CI: 1.27; 2.16; < 0.0001), relative to those without CMBs, in AIS patients undergoing reperfusion therapy (encompassing intravenous thrombolysis [IVT], endovascular thrombectomy [EVT], either IVT or EVT, and bridging therapy). Variations in the level of association can be observed among different subgroups of reperfusion therapy.
CONCLUSIONS
This meta-analysis underscores a significant association between CMBs and adverse postprocedural safety outcomes encompassing sICH, HT, poor functional outcome, and increased mortality in AIS patients undergoing reperfusion therapy. The notable prevalence of CMBs in both the overall AIS population and those undergoing reperfusion therapy emphasizes their importance in post-stroke prognostication.
PubMed: 37893237
DOI: 10.3390/biomedicines11102865 -
EXCLI Journal 2024Ischemic heart disease (IHD) is the leading cause of mortality worldwide and can be complicated by myocardial infarction (MI), leading to cardiac failure. Inorganic... (Review)
Review
Ischemic heart disease (IHD) is the leading cause of mortality worldwide and can be complicated by myocardial infarction (MI), leading to cardiac failure. Inorganic nitrite and nitrate, which release nitric oxide (NO), can protect the heart against myocardial injury. This animal systematic review and meta-analysis aims to assess whether the administration of nitrite/nitrate decreases myocardial infarct size. We systematically searched PubMed, Scopus, and Web of Science databases until October 2023; 15 eligible animal studies (35 study arms for in-vivo and 10 for in-vitro studies) published between 1989 and 2023 were included. studies were conducted on rats, mice, cats, and dogs, and studies on rats and mice with an overall exposure of 0.03 to 12713 mg/kg to nitrate/nitrite administrated before, after, or during ischemia mainly by intravenous single bolus or by oral over 270 days. All studies used nitrite/nitrate before ischemia, with the concentration ranging between 0.34 to 201 μM. MI was induced by occlusion of the left anterior diagonal or left circumflex arteries in studies and by isoproterenol in studies. Infarct size was measured by direct staining of the sliced heart sections. In studies, nitrite (overall effect size (ES)=-17.0 %, 95 % confidence interval (CI)=-21.3, -12.8, P<0.001) and nitrate (overall ES= -9.6 %, 95 % CI=-15.7, -3.4, P=0.002) reduced myocardial infarct size. In studies, nitrite (overall ES=-15.8 %, 95 % CI=-25.5, -6.2, P=0.001) reduced the infarct size. Sensitivity analysis showed that the overall effect of nitrite on myocardial infarct size was unaffected by doses or health conditions in and studies. In conclusion, our meta-analysis showed that nitrite/nitrate administration can effectively reduce myocardial infarct size. However, these results should be approached with caution because of the limitations of animal studies and the existing high heterogeneity.
PubMed: 38357094
DOI: 10.17179/excli2023-6740 -
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 -
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 -
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 -
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 -
Interventional Neuroradiology : Journal... Jun 2024Transradial access (TRA) is becoming more popular in neurointerventional radiology procedures and has been associated with reduced mortality, morbidity and access site... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Transradial access (TRA) is becoming more popular in neurointerventional radiology procedures and has been associated with reduced mortality, morbidity and access site complications. Guidelines state that TRA is a feasible option for posterior circulation thrombectomy however the evidence base is limited and no systematic literature review has yet been undertaken to evaluate its safety and efficacy.
METHODS
The Cochrane Library, PubMed, Web of Science, Scopus, TRIP and Embase databases were searched. Outcomes collected included TICI scores, puncture to recanalisation time, mRS scores at 90 days and access site complications.
RESULTS
291 records were identified and 31 full text articles were assessed for eligibility. Eight studies met the inclusion criteria and were meta-analysed. The rate of TICI 2b-3 was 94.7% (89.7-99.8% at 95% CI), TICI 3 was 67.9% (42.2-93.6% at 95% CI) and mRS 0-2 at 90 days was 49.8% (31.5-68.1% at 95% CI). Median puncture to reperfusion times were extracted from three studies as 24 (IQR 18-40), 24 (IQR 17.5-56.5) and 27 (IQR 24-33.5) minutes. No access site complications were reported. TICI 2b-3, TICI 3 and mRS scores were comparable to data for transfemoral access (TFA) from a large systematic review. Puncture to recanalisation times appeared lower than the TFA data but statistical comparison of this outcome was not possible.
CONCLUSIONS
The use of TRA in posterior circulation thrombectomy is safe and effective with comparable results to TFA. Further research with a larger sample size is required to fully investigate the potential for shortened puncture to recanalisation times.
Topics: Humans; Thrombectomy; Radial Artery; Stroke
PubMed: 35673707
DOI: 10.1177/15910199221107259