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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 -
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 -
International Journal of Stroke :... Jan 2024The no-reflow phenomenon refers to the absence of microvascular reperfusion despite macrovascular reperfusion. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The no-reflow phenomenon refers to the absence of microvascular reperfusion despite macrovascular reperfusion.
AIM
The aim of this analysis was to summarize the available clinical evidence on no-reflow in patients with acute ischemic stroke.
METHODS
A systematic literature review and a meta-analysis of clinical data on definition, rates, and impact of the no-reflow phenomenon after reperfusion therapy was carried out. A predefined research strategy was formulated according to the Population, Intervention, Comparison, and Outcome (PICO) model and was used to screen for articles in PubMed, MEDLINE, and Embase up to 8 September 2022. Whenever possible, quantitative data were summarized using a random-effects model.
RESULTS
Thirteen studies with a total of 719 patients were included in the final analysis. Most studies (n = 10/13) used variations of the Thrombolysis in Cerebral Infarction scale to evaluate macrovascular reperfusion, whereas microvascular reperfusion and no-reflow were mostly assessed on perfusion maps (n = 9/13). In one-third of stroke patients with successful macrovascular reperfusion (29%, 95% confidence interval (CI), 21-37%), the no-reflow phenomenon was observed. Pooled analysis showed that no-reflow was consistently associated with reduced rates of functional independence (odds ratio (OR), 0.21, 95% CI, 0.15-0.31).
CONCLUSION
The definition of no-reflow varied substantially across studies, but it appears to be a common phenomenon. Some of the no-reflow cases may simply represent remaining vessel occlusions, and it remains unclear whether no-reflow is an epiphenomenon of the infarcted parenchyma or causes infarction. Future studies should focus on standardizing the definition of no-reflow with more consistent definitions of successful macrovascular reperfusion and experimental set-ups that could detect the causality of the observed findings.
Topics: Humans; No-Reflow Phenomenon; Myocardial Infarction; Stroke; Ischemic Stroke; Reperfusion
PubMed: 37231702
DOI: 10.1177/17474930231180434 -
Frontiers in Cardiovascular Medicine 2023Preventing ischemia-reperfusion injury is the main direction of myocardial infarction treatment in the convalescent stage. Some studies have suggested that saponins in... (Review)
Review
Effect and possible mechanisms of saponins in Chinese herbal medicine exerts for the treatment of myocardial ischemia-reperfusion injury in experimental animal: a systematic review and meta-analysis.
INTRODUCTION
Preventing ischemia-reperfusion injury is the main direction of myocardial infarction treatment in the convalescent stage. Some studies have suggested that saponins in Traditional Chinese medicine (TCM) preparations can protect the myocardium by various mechanisms. Our meta-analysis aims to evaluate the efficacy of TCM saponins in treating myocardial ischemia-reperfusion injury (MIRI) and to summarize the potential molecular mechanisms further.
METHODS
We conducted a literature search in six electronic databases [Web of Science, PubMed, Embase, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI)] until October 2022.
RESULTS
Seventeen eligible studies included 386 animals (254 received saponins and 132 received vehicles). The random effect model is used to calculate the combined effect. The effect size is expressed as the weighted average difference (WMD) and 95% confidence interval (CI). Compared with placebo, saponins preconditioning reduced infarct size after MIRI significantly (WMD: -3.60,95% CI: -4.45 to -2.74, < 0.01, : 84.7%, < 0.001), and significantly increased EF (WMD: 3.119, 95% CI: 2.165 to 4.082, < 0.01, : 82.9%, < 0.0 L) and FS (WMD: 3.157, 95% CI: 2.218 to 4.097, < 0.001, : 81.3%, < 0.001).
DISCUSSION
The results show that the pre-administration of saponins from TCM has a significant protective effect on MIRI in preclinical studies, which provides an application prospect for developing anti-MIRI drugs with high efficiency and low toxicity.
PubMed: 37564906
DOI: 10.3389/fcvm.2023.1147740 -
Microsurgery Feb 2024Ischemia and ischemia-reperfusion injury contribute to partial or complete flap necrosis. Traditionally, skin histology has been used to evaluate morphological and... (Review)
Review
Systematic review of pathologic markers in skin ischemia with and without reperfusion injury in microsurgical reconstruction: Biomarker alterations precede histological structure changes.
BACKGROUND
Ischemia and ischemia-reperfusion injury contribute to partial or complete flap necrosis. Traditionally, skin histology has been used to evaluate morphological and structural changes, however histology does not detect early changes. We hypothesize that morphological and structural skin changes in response to ischemia and IRI occur late, and modification of gene and protein expression are the earliest changes in ischemia and IRI.
METHODS
A systematic review was performed in accordance with PRISMA guidelines. Studies reporting skin histology or gene/protein expression changes following ischemia with or without reperfusion injury published between 2002 and 2022 were included. The primary outcomes were descriptive and semi-quantitative histological structural changes, leukocyte infiltration, edema, vessel density; secondary outcomes were quantitative gene and protein expression intensity (PCR and western blot). Model type, experimental intervention, ischemia method and duration, reperfusion duration, biopsy location and time point were collected.
RESULTS
One hundred and one articles were included. Hematoxylin and eosin (H&E) showed inflammatory infiltration in early responses (12-24 h), with structural modifications (3-14 days) and neovascularization (5-14 days) as delayed responses. Immunohistochemistry (IHC) identified angiogenesis (CD31, CD34), apoptosis (TUNEL, caspase-3, Bax/Bcl-2), and protein localization (NF-κB). Gene (PCR) and protein expression (western blot) detected inflammation and apoptosis; endoplasmic reticulum stress/oxidative stress and hypoxia; and neovascularization. The most common markers were TNF-α, IL-6 and IL-1β (inflammation), caspase-3 (apoptosis), VEGF (neovascularization), and HIF-1α (hypoxia).
CONCLUSION
There is no consensus or standard for reporting skin injury during ischemia and IRI. H&E histology is most frequently performed but is primarily descriptive and lacks sensitivity for early skin injury. Immunohistochemistry and gene/protein expression reveal immediate and quantitative cellular responses to skin ischemia and IRI. Future research is needed towards a universally-accepted skin injury scoring system.
Topics: Humans; Caspase 3; Reperfusion Injury; Ischemia; Biomarkers; Inflammation; Hypoxia; Apoptosis
PubMed: 38361264
DOI: 10.1002/micr.31141 -
Journal of Cerebral Blood Flow and... Jan 2024The reported incidence of persistent hypoperfusion despite complete recanalization as surrogate for impaired microvascular reperfusion (IMR) has varied widely among... (Review)
Review
Incidence, severity and impact on functional outcome of persistent hypoperfusion despite large-vessel recanalization, a potential marker of impaired microvascular reperfusion: Systematic review of the clinical literature.
The reported incidence of persistent hypoperfusion despite complete recanalization as surrogate for impaired microvascular reperfusion (IMR) has varied widely among clinical studies, possibly due to differences in i) definition of complete recanalization, with only recent Thrombolysis in Cerebral Infarction (TICI) grading schemes allowing distinction between complete (TICI3) and partial recanalization with distal occlusions (TICI2c); ii) operational definition of IMR; and iii) consideration of potential alternative causes for hypoperfusion, notably carotid stenosis, re-occlusion and post-thrombectomy hemorrhage. We performed a systematic review to identify clinical studies that carried out brain perfusion imaging within 72 hrs post-thrombectomy for anterior circulation stroke and reported hypoperfusion rates separately for TICI3 and TICI2c grades. Authors were contacted if this data was missing. We identified eight eligible articles, altogether reporting 636 patients. The incidence of IMR after complete recanalization (i.e., TICI3) tended to decrease with the number of considered alternative causes of hypoperfusion: range 12.5-42.9%, 0-31.6% and 0-9.1% in articles that considered none, two or all three causes, respectively. No study reported the impact of IMR on functional outcome separately for TICI-3 patients. Based on this systematic review, IMR in true complete recanalization appears relatively rare, and reported incidence highly depends on definition used and consideration of confounding factors.
Topics: Humans; Incidence; Treatment Outcome; Retrospective Studies; Stroke; Cerebral Infarction; Thrombectomy; Reperfusion; Brain Ischemia
PubMed: 37871624
DOI: 10.1177/0271678X231209069 -
Journal of Neurointerventional Surgery Dec 2023There is limited evidence on the indication and role of mechanical thrombectomy (MT) in patients with distal medium-vessel occlusions (DMVOs). The aim of this systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is limited evidence on the indication and role of mechanical thrombectomy (MT) in patients with distal medium-vessel occlusions (DMVOs). The aim of this systematic review and meta-analysis was to evaluate all the evidence available on the efficacy and safety of MT techniques (stent retriever, aspiration) in primary and secondary DMVOs.
METHODS
Five databases were searched from inception to January 2023 for studies of MT in primary and secondary DMVOs. Outcomes of interest included favorable functional outcome (90-day modified Rankin scale (mRS) 0-2), successful reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2b-3), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. Prespecified subgroup meta-analyses according to the specific MT technique and to the vascular territory (distal M2-M5, A2-A5, P2-P5) were also performed.
RESULTS
A total of 29 studies with 1262 patients were included. For primary DMVOs (n=971 patients), pooled rates of successful reperfusion, favorable outcome, 90-day mortality and sICH were 84% (95% confidence interval (CI) 76 to 90%), 64% (95% CI 54 to 72%), 12% (95% CI 8 to 18%), and 6% (95% CI 4 to 10%), respectively. For secondary DMVOs (n=291 patients), pooled rates of successful reperfusion, favorable outcome, 90-day mortality and sICH were 82% (95% CI 73 to 88%), 54% (95% CI 39 to 69%), 11% (95% CI 5 to 20%), and 3% (95% CI 1 to 9%), respectively. Subgroup analyses by MT technique and by vascular territory showed no differences in primary and secondary DMVOs.
CONCLUSION
Our findings suggest that MT using aspiration or stent retriever techniques appears to be effective and safe in primary and secondary DMVOs. However, given the level of evidence of our results, further confirmation in well-designed randomized controlled trials is needed.
Topics: Humans; Stroke; Brain Ischemia; Thrombectomy; Treatment Outcome; Cerebral Hemorrhage; Ischemic Stroke; Stents
PubMed: 36797050
DOI: 10.1136/jnis-2022-019975 -
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 -
Journal of Vascular and Interventional... Apr 2024To perform a qualitative systematic review of endovascular management of renal artery aneurysms (RAAs). (Review)
Review
PURPOSE
To perform a qualitative systematic review of endovascular management of renal artery aneurysms (RAAs).
MATERIALS AND METHODS
A comprehensive electronic search of PubMed, MEDLINE, Embase, Google Scholar, and Cochrane databases from 2000 to 2022 was performed using the search terms "renal artery," "aneurysm," and "endovascular." Means of outcome measures were calculated with a primary end point focused on RAA-related mortality and rupture. Secondary end points included reintervention rate and renal infarction.
RESULTS
Twenty-six, single-center, retrospective, observational studies were included. There were 454 RAAs treated in 427 patients using endovascular techniques. Mean age was 53.8 years, with a female predominance (62%). A variety of endovascular treatments of RAA were used with excellent technical success (96%), renal parenchymal preservation, and a low rate of moderate/severe adverse events (AEs). Primary coil embolization was the most commonly used technique (44.7%). There was an overall AE rate of 22.9%, of which 6.7% were moderate/severe and there was 0% periprocedural mortality. The most common AE was renal infarction (49 patients, 11.5%); however, renal function was preserved in 84% of patients. Nephrectomy rate was 0.4%. Computed tomography (CT) angiography was the most common imaging follow-up modality used in 72% of studies. Only 9 studies (34%) reported anticoagulant use. Although the risk of delayed aneurysm reperfusion warrants clinical and imaging surveillance, relatively few patients (3%) required reintervention in this cohort.
CONCLUSIONS
Endovascular management of RAA is a technically feasible treatment option with low rates of AEs and reintervention. The present study highlights the techniques available for interventional radiologists, a need for standardization of AE reporting, anticoagulation therapy, and follow-up imaging.
PubMed: 38626869
DOI: 10.1016/j.jvir.2024.04.004 -
Journal of Stroke and Cerebrovascular... Jul 2024Endovascular therapy (EVT) is recommended for patients with acute large-vessel occlusion (LVO) However, its efficacy and safety compared to medical management (MM) in... (Meta-Analysis)
Meta-Analysis
A comparison of endovascular therapy and medical management in patients with large vessel occlusion mild stroke treated between 2015 and 2023: a systematic review and meta-analysis.
OBJECTIVE
Endovascular therapy (EVT) is recommended for patients with acute large-vessel occlusion (LVO) However, its efficacy and safety compared to medical management (MM) in patients with a National Institutes of Health Stroke Scale (NIHSS) score of ≤6 remains unclear. This meta-analysis compared EVT with medical MM in patients with large vessel occlusion mild stroke treated between 2015 and 2023, following the publication of the first randomized controlled trial.
MATERIALS AND METHODS
Biomedical database searches (inception to March 21, 2023) retrieved articles reporting favorable functional outcome(modified Rankin Scale [mRS] 0-1) and functional independence (mRS 0-2), 90-day mortality and symptomatic intracranial hemorrhage (sICH). We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) to maintain methodological rigor and transparency in our meta-analysis.
RESULTS
We conducted a meta-analysis of 22 studies (4,985 patients) to reveal no significant differences in favorable functional outcomes and independence across all groups. However, in patients treated between 2015 and 2023, EVT exhibited a higher risk of 90-day mortality (Odds Ratio [OR] = 1.84, 95% Confidence Interval [CI] [1.10, 3.07], p = 0.02) and sICH (OR = 3.36, 95% CI [1.96, 6.66], p < 0.01). EVT correlated with elevated sICH in the anterior circulation (OR=2.94, 95%CI [1.82, 4.74], p<0.01) regardless of the proximal (OR=2.20, 95%CI [1.04, 4.69], p=0.04) or distal (OR=3.44, 95%CI [1.43, 8.32], p<0.01) location of the occlusion. EVT correlated with elevated sICH rates in patients treated within 6 hours of symptom onset or those with NHISS≤5.
CONCLUSION
In patients treated between 2015 and 2023, EVT and MM did not differ in efficacy in acute LVO mild stroke; MM associated with better safety outcomes. Rigorous randomized controlled trials are warranted.
Topics: Humans; Endovascular Procedures; Treatment Outcome; Recovery of Function; Time Factors; Risk Factors; Functional Status; Aged; Female; Male; Disability Evaluation; Middle Aged; Severity of Illness Index; Risk Assessment; Intracranial Hemorrhages; Aged, 80 and over; Ischemic Stroke; Stroke
PubMed: 38616013
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107721