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Journal of Stroke and Cerebrovascular... Jun 2024Tenecteplase (TNK) is a promising alternative to alteplase (ALT) as the thrombolytic agent for acute ischemic stroke (AIS). However, its clinical outcomes in certain...
OBJECTIVES
Tenecteplase (TNK) is a promising alternative to alteplase (ALT) as the thrombolytic agent for acute ischemic stroke (AIS). However, its clinical outcomes in certain populations remain unclear. This study aimed to compare the efficacy and safety among different doses of TNK in AIS patients.
METHODS
We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Embase for studies comparing at least one dose of TNK to another dose of TNK or ALT 0.90 mg/kg. We conducted Bayesian network meta-analyses to estimate the relative risks (RRs) and 95% credible intervals (CrIs) for all outcomes using ALT 0.90 mg/kg as the reference. The treatments were ranked according to their surface under the cumulative ranking (SUCRA) values.
RESULTS
We included 11 trials from 16 publications comprising 5423 participants. There were no significant differences between any doses of TNK and ALT for reperfusion, 3-month modified Rankin Score (mRS) 0-1 (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.68), mRS 0-2 (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.86), mortality (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.82), intracranial hemorrhage (ICH) (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.88), symptomatic ICH (sICH) (rank 1st: TNK 0.10 mg/kg; SUCRA = 0.70), and parenchymal hematoma (rank 1st: TNK 0.10 mg/kg; SUCRA = 0.68). TNK 0.40 mg/kg had a significantly higher sICH rate compared to TNK 0.25 mg/kg (RR = 2.39, 95% CrI = 1.00-7.92). Among elderly patients, TNK 0.25 mg/kg had a significantly lower rate of sICH than ALT 0.9 mg/kg (RR = 3.0 × 10, 95% CrI = 3.4 × 10-0.07).
CONCLUSIONS
TNK has efficacy and safety outcomes comparable to those of ALT. TNK 0.25 mg/kg may be the optimal dose of TNK for patients with AIS.
PubMed: 38897370
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107822 -
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 -
Mitochondrion Jun 2024Mitochondrial dysfunction contributes to pathological conditions like ischemia-reperfusion (IR) injury. To address the lack of effective therapeutic interventions for IR... (Review)
Review
Mitochondrial dysfunction contributes to pathological conditions like ischemia-reperfusion (IR) injury. To address the lack of effective therapeutic interventions for IR injury and potential knowledge gaps in the current literature, we systematically reviewed 3800 experimental studies across 5 databases and identified 20 mitochondrial genes impacting IR injury in various organs. Notably, CyPD, Nrf2, and GPX4 are well-studied genes consistently influencing IR injury outcomes. Emerging genes like ALDH2, BNIP3, and OPA1 are supported by human genetic evidence, thereby warranting further investigation. Findings of this review can inform future research directions and inspire therapeutic advancements.
PubMed: 38848983
DOI: 10.1016/j.mito.2024.101908 -
Stroke and Vascular Neurology May 2024Recently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the...
BACKGROUND
Recently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the clinical implications of its haemodynamic features, which were systematically reviewed in this study.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements, we searched PubMed and Embase up to March 2024 and screened for articles reporting clinical implications of haemodynamic parameters in sICAS derived from CFD models.
RESULTS
19 articles met the inclusion criteria, all studies recruiting patients from China. Most studies used CT angiography (CTA) as the source image for vessel segmentation, and generic boundary conditions, rigid vessel wall and Newtonian fluid assumptions for CFD modelling, in patients with 50%-99% sICAS. Pressure and wall shear stress (WSS) were quantified in almost all studies, and the translesional changes in pressure and WSS were usually quantified with a poststenotic to prestenotic pressure ratio (PR) and stenotic-throat to prestenotic WSS ratio (WSSR). Lower PR was associated with more severe stenosis, better leptomeningeal collaterals, prolonged perfusion time and internal borderzone infarcts. Higher WSSR and other WSS measures were associated with positive vessel wall remodelling, regression of luminal stenosis and artery-to-artery embolism. Lower PR and higher WSSR were both associated with the presence and severity of cerebral small vessel disease. Moreover, translesional PR and WSSR were promising predictors for stroke recurrence in medically treated patients with sICAS and outcomes after acute reperfusion therapy, which also provided indicators to assess the effects of stenting treatment on focal haemodynamics.
CONCLUSIONS
CFD is a promising tool in investigating the pathophysiology of ICAS and in risk stratification of patients with sICAS. Future studies are warranted for standardisation of the modelling methods and validation of the simulation results in sICAS, for its wider applications in clinical research and practice.
PubMed: 38806205
DOI: 10.1136/svn-2024-003202 -
Critical Care Explorations Jun 2024Measurement of blood pressure taken from different anatomical sites, are often perceived as interchangeable, despite them representing different parts of the systemic... (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVES
Measurement of blood pressure taken from different anatomical sites, are often perceived as interchangeable, despite them representing different parts of the systemic circulation. We aimed to perform a systematic review and meta-analysis on blood pressure differences between central and peripheral arterial cannulation in critically ill patients.
DATA SOURCES
We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase from inception to December 26, 2023, using Medical Subject Headings (MeSH) terms and keywords.
STUDY SELECTION
Observation study of adult patients in ICUs and operating rooms who underwent simultaneous central (femoral, axillary, or subclavian artery) and peripheral (radial, brachial, or dorsalis pedis artery) arterial catheter placement in ICUs and operating rooms.
DATA EXTRACTION
We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool.
DATA SYNTHESIS
Twenty-four studies that enrolled 1598 patients in total were included. Central pressures (mean arterial pressure [MAP] and systolic blood pressure [SBP]) were found to be significantly higher than their peripheral counterparts, with mean gradients of 3.5 and 8.0 mm Hg, respectively. However, there was no statistically significant difference in central or peripheral diastolic blood pressure (DBP). Subgroup analysis further highlighted a higher MAP gradient during the on-cardiopulmonary bypass stage of cardiac surgery, reperfusion stage of liver transplant, and in nonsurgical critically ill patients. SBP or DBP gradient did not demonstrate any subgroup specific changes.
CONCLUSIONS
SBP and MAP obtained by central arterial cannulation were higher than peripheral arterial cannulation; however, clinical implication of a difference of 8.0 mm Hg in SBP and 3.5 mm Hg in MAP remains unclear. Our current clinical practices preferring peripheral arterial lines need not change.
Topics: Humans; Critical Illness; Arterial Pressure; Catheterization, Peripheral; Blood Pressure Determination; Blood Pressure; Intensive Care Units
PubMed: 38787296
DOI: 10.1097/CCE.0000000000001096 -
Translational Gastroenterology and... 2024Local ischemic preconditioning (LIPC) has been proven to be a protective strategy against hepatic ischemia-reperfusion injury (HIRI) during hepatectomy. Growing evidence...
Comparing the protective effects of local and remote ischemic preconditioning against ischemia-reperfusion injury in hepatectomy: a systematic review and network meta-analysis.
BACKGROUND
Local ischemic preconditioning (LIPC) has been proven to be a protective strategy against hepatic ischemia-reperfusion injury (HIRI) during hepatectomy. Growing evidence suggests remote ischemic preconditioning (RIPC) has the potential to reduce liver injury in hepatectomy. Few studies have directly compared the protective effects of these two mechanical preconditioning strategies. Therefore, we performed a network meta-analysis to compare the efficacy of LIPC and RIPC for hepatic injury during liver resection.
METHODS
We searched Cochrane, PubMed, Embase, and China National Knowledge Infrastructure (CNKI) from the database inception to January 2023. We included studies directly comparing the effectiveness of LIPC and RIPC and those comparing LIPC or RIPC with no-preconditioning in liver resection. Postoperative liver function and surgical events were analyzed. Data were expressed as standardized mean differences (SMDs) or odds ratios (ORs) and analyzed using network meta-analysis with random effects model.
RESULTS
Following the screening of 268 citations, we identified 26 eligible randomized clinical trials (RCTs) involving 1,476 participants (LIPC arm: 789, RIPC arm: 859, no-preconditioning arm: 1,072). LIPC and RIPC were superior to no-preconditioning in reducing postoperative serum transaminase levels [aspartate aminotransferase (AST): SMD RIPC versus no-preconditioning: -2.05, 95% confidence interval (CI): -3.39, -0.71; SMD LIPC versus no-preconditioning: -1.10, 95% CI: -2.07, -0.12; alanine aminotransferase (ALT): SMD RIPC versus no-preconditioning: -2.24, 95% CI: -4.15, -0.32; SMD LIPC versus no-preconditioning: -1.32, 95% CI: -2.63, -0.01]. No significant difference was observed between RIPC and LIPC in postoperative liver function and surgical outcomes (AST: SMD RIPC versus LIPC: -0.95, 95% CI: -2.52, 0.62; ALT: SMD RIPC versus LIPC: -0.91, 95% CI: -3.11, 1.28). In addition, the subgroup analysis revealed the potential benefits of RIPC in improving liver function, especially in patients who diagnosed with cirrhosis or underwent major resection.
CONCLUSIONS
RIPC and LIPC could serve as effective strategies in relieving HIRI during hepatectomy. No significant differences were observed between LIPC and RIPC, however, RIPC may be an easily applicable strategy to relieve liver injury in hepatectomy.
PubMed: 38716220
DOI: 10.21037/tgh-23-95 -
BMC Cardiovascular Disorders May 2024Cerebral malperfusion (CM) is a common comorbidity in acute type A aortic dissection (ATAAD), which is associated with high mortality and poor neurological prognosis.... (Meta-Analysis)
Meta-Analysis
Two surgical strategies (early carotid reperfusion vs. Central aortic repair-first) of acute type a aortic dissection complicated with cerebral malperfusion syndrome: a meta-analysis and systematic review.
OBJECTIVE
Cerebral malperfusion (CM) is a common comorbidity in acute type A aortic dissection (ATAAD), which is associated with high mortality and poor neurological prognosis. This meta-analysis investigated the surgical strategy of ATAAD patients with CM, aiming to compare the difference in therapeutic effectiveness between the central repair-first and the early reperfusion-first according to clinical outcomes.
METHODS
The meta-analysis and systematic review was conducted based on studies sourced from the PubMed, Embase, and Cochrane literature database, in which cases of ATAAD with CM underwent surgical repair were included. Data for baseline characteristics, mortality, survival were extracted, and risk ratio (RR) values and the pooled mortality were calculated.
RESULTS
A total of 17 retrospective studies were analyzed, including 1010 cases of ATAAD with CM underwent surgical repair. The pooled early mortality in early reperfusion group was lower (8.1%; CI, 0.02 to 0.168) than that in the central repair group (16.2%; CI, 0.115 to 0.216). The pooled long-term mortality was 7.9% in the early reperfusion cohort and 17.4% the central repair-first cohort, without a statistically significant heterogeneity (I [2] = 51.271%; p = 0.056). The mean time of symptom-onset-to-the-operation-room in all the reports was 8.87 ± 12.3 h.
CONCLUSION
This meta-analysis suggested that early reperfusion-first may achieved better outcomes compared to central repair-first in ATAAD patients complicated with CM to some extent. Early operation and early restoration of cerebral perfusion may reduce the occurrence of some neurological complications.
TRIAL REGISTRATION
The meta-analysis was registered in the International Prospective Register of Systematic Reviews database (No. CRD CRD42023475629) on Nov. 8th, 2023.
Topics: Humans; Aortic Dissection; Treatment Outcome; Cerebrovascular Circulation; Risk Factors; Time Factors; Aortic Aneurysm; Female; Male; Middle Aged; Aged; Acute Disease; Cerebrovascular Disorders; Adult; Blood Vessel Prosthesis Implantation; Risk Assessment; Reperfusion; Time-to-Treatment
PubMed: 38714966
DOI: 10.1186/s12872-024-03910-2 -
BMC Anesthesiology May 2024Remote ischemic conditioning (RIC) has the potential to benefit graft function following kidney transplantation by reducing ischemia-reperfusion injury; however, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Remote ischemic conditioning (RIC) has the potential to benefit graft function following kidney transplantation by reducing ischemia-reperfusion injury; however, the current clinical evidence is inconclusive. This meta-analysis with trial sequential analysis (TSA) aimed to determine whether RIC improves graft function after kidney transplantation.
METHODS
A comprehensive search was conducted on PubMed, Cochrane Library, and EMBASE databases until June 20, 2023, to identify all randomized controlled trials that examined the impact of RIC on graft function after kidney transplantation. The primary outcome was the incidence of delayed graft function (DGF) post-kidney transplantation. The secondary outcomes included the incidence of acute rejection, graft loss, 3- and 12-month estimated glomerular filtration rates (eGFR), and the length of hospital stay. Subgroup analyses were conducted based on RIC procedures (preconditioning, perconditioning, or postconditioning), implementation sites (upper or lower extremity), and graft source (living or deceased donor).
RESULTS
Our meta-analysis included eight trials involving 1038 patients. Compared with the control, RIC did not significantly reduce the incidence of DGF (8.8% vs. 15.3%; risk ratio = 0.76, 95% confidence interval [CI], 0.48-1.21, P = 0.25, I = 16%), and TSA results showed that the required information size was not reached. However, the RIC group had a significantly increased eGFR at 3 months after transplantation (mean difference = 2.74 ml/min/1.73 m, 95% CI: 1.44-4.05 ml/min/1.73 m, P < 0.0001, I = 0%), with a sufficient evidence suggested by TSA. The secondary outcomes were comparable between the other secondary outcomes. The treatment effect of RIC did not differ between the subgroup analyses.
CONCLUSION
In this meta-analysis with trial sequential analysis, RIC did not lead to a significant reduction in the incidence of DGF after kidney transplantation. Nonetheless, RIC demonstrated a positive correlation with 3-month eGFR. Given the limited number of patients included in this study, well-designed clinical trials with large sample sizes are required to validate the renoprotective benefits of RIC.
TRIAL REGISTRATION
This systematic review and meta-analysis was registered at the International Prospective Register of Systematic Reviews (Number CRD42023464447).
Topics: Humans; Kidney Transplantation; Ischemic Preconditioning; Delayed Graft Function; Randomized Controlled Trials as Topic; Graft Rejection
PubMed: 38702625
DOI: 10.1186/s12871-024-02549-y -
Future Healthcare Journal Mar 2024With health and surgery increasingly aided by digital technologies, there exists a growing impetus to understand how such tools must integrate into existing clinical...
With health and surgery increasingly aided by digital technologies, there exists a growing impetus to understand how such tools must integrate into existing clinical pathways to ensure a positive impact on patient and organisational outcomes. Consequently, this study sought to collate evidence on the use of digital technology in cardiac reperfusion surgeries. We systematically searched three scientific databases for relevant articles. In total, 1,092 articles were retrieved, with 126 screened using inclusion/exclusion criteria, and 21 selected for analysis. Articles reported on the use of virtual reality, mHealth and telehealth in cardiovascular reperfusion procedures, ranging from surgical training regimens to postoperative rehabilitation. Here, despite clinical advantages, limitations were highlighted, including cost, ineffective interfaces and extensive training needed to operate novel digital tools. Nevertheless with further development and input from patient stakeholders, many limitations look set to dematerialise and provide tangible improvements to the benefit of patients and hard-pressed health institutions.
PubMed: 38689702
DOI: 10.7861/fhj.2023-0033 -
Systematic Reviews Apr 2024Intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is the standard treatment for patients with acute ischemic stroke caused by large vessel occlusion... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is the standard treatment for patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). However, the efficacy and safety of IVT before EVT in AIS-LVO patients with atrial fibrillation (AF) remains controversial. Thus, this study aims to assess the benefit of IVT plus EVT and direct EVT alone in AIS-LVO patients with AF.
METHOD
Relevant studies that evaluated the outcomes of IVT plus EVT versus direct EVT alone in AIS-LVO patients with AF were systematically searched in PubMed, Embase, and Cochrane Library from inception to August 10, 2023. The outcomes included successful reperfusion (score of 2b to 3 for thrombolysis in cerebral infarction), symptomatic intracerebral hemorrhage (sICH), good clinical outcome (modified Rankin scale score ≤ 2) at 3 months, and 3-month mortality.
RESULT
Eight eligible observational studies involving 6998 (3827 in the IVT plus EVT group and 3171 in the direct EVT group) patients with AIS-LVO complicated by AF were included. Compared with direct EVT, IVT plus EVT resulted in better 3-month clinical outcomes (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.05-1.54) and lower 3-month mortality (OR 0.78, 95% CI 0.68-0.88). However, the incidence of sICH (OR 1.26, 95% CI 0.91-1.75) and the rate of successful reperfusion (OR 0.98, 95% CI 0.83-1.17) were not significantly different between treatment modalities.
CONCLUSION
IVT plus EVT leads to better functional outcomes and lower mortality in AIS-LVO patients with AF. Withholding IVT plus EVT from patients with AF alone may not be justified.
Topics: Humans; Atrial Fibrillation; Ischemic Stroke; Thrombolytic Therapy; Thrombectomy; Treatment Outcome; Fibrinolytic Agents; Administration, Intravenous; Endovascular Procedures; Combined Modality Therapy
PubMed: 38689365
DOI: 10.1186/s13643-024-02532-1