Patients undergoing transurethral resection of the prostate (TURP) surgery can develop TURP syndrome and post-TURP bleeding. Post-TURP bleeding can be surgical, from arteries or venous sinuses, or non-surgical, due to coagulopathy preventing clot formation. Non-surgical post-TURP bleeding may be due to high concentrations of urokinase and tissue plasminogen activator (tPA) in the urine that cause fibrinolytic changes and increase bleeding risk. Urine urokinase and tPA may have both local and systemic fibrinolytic effects that may prevent blood clot formation locally at the site of surgery, and cause fibrinolytic changes systemically through leaking into the blood stream. Another post-TURP complication that may happen is TURP syndrome, due to absorption of hypotonic glycine fluid through the prostatic venous plexus. TURP syndrome may present with hyponatremia, bradycardia, and hypotension, which may be preceded by hypertension. In this case report, we had a patient with benign prostatic hyperplasia (BPH) who developed both TURP syndrome and non-surgical post-TURP bleeding. These complications were transient for one day after surgery. The local effect of urine urokinase and tPA explains the non-surgical bleeding after TURP by preventing clot formation and inducing bleeding. Coagulation studies showed fibrinolytic changes that may be explained by urokinase and tPA leakage into the blood stream. In conclusion, non-surgical bleeding after TURP can be explained by the presence of fibrinolytic agents in the urine, including urokinase and tPA. There is a deficiency in existing studies explaining the pathophysiology of the fibrinolytic changes and risk of bleeding after TURP. Herein, we discuss the possible pathophysiology of developing fibrinolytic changes after TURP. More research effort should be directed to explore this area to investigate the appropriate medications to treat and prevent post-TURP bleeding. We suggest monitoring patients\' coagulation profiles and electrolytes after TURP because of the risk of developing severe acute hyponatremia, TURP syndrome, fibrinolytic changes, and non-surgical bleeding. In our review of the literature, we discuss current clinical trials testing the use of an antifibrinolytic agent, Tranexamic acid, locally in the irrigation fluid or systemically to prevent post-TURP bleeding by antagonizing the fibrinolytic activity of urine urokinase and tPA.

OBJECTIVE: To review relevant literature regarding the role of metformin in angiogenesis among diabetic patients.
METHODS: The systematic review and meta-analysis conducted from May to September 2022, and comprised search on Medline, ScienceDirect, ProQuest, Web of Science, EBSCOhost and Cochrane Library databases. The studies included were published in the English language and were human studies having angiogenesis endothelial markers as the outcomes of interest among patients of type 2 diabetes mellitus undergoing metformin therapy. Endothelial markers, including vascular endothelial growth factor, von-Willebrand-factor, plasminogen activator inhibitor-1, soluble vascular adhesion molecule- 1, intercellular adhesion molecule-1, soluble endothelialselectin, tissue plasminogen activator, urinary albumin excretion, platelet endothelial cell adhesion molecule-1 and thrombin-activatable fibrinolysis inhibitor, were assessed as angiogenesis outcomes. Data was statistically analysed using Review Manager 5.4.
RESULTS: Of the 413 studies identified, 8(1.9%) were included; 5(62.5%) randomised control trials, 2(25.0%) cross-sectional, and 1(12.5%) cohort studies, with overall 1199 patients. Among the outcomes, von-Willebrandfactor (p=0.01), soluble vascular adhesion molecule-1 (p<0.00001), intercellular adhesion molecule-1 (p=0.0003), soluble endothelial-selectin (p=0.007), and tissue plasminogen activator (p<0.00001) showed significantly lower levels after metformin treatment using the random effect methods.
CONCLUSIONS: Metformin was found to have an additional effect of endothelial function improvement.

OBJECTIVE: 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 × 10-13, 95% CrI = 3.4 × 10-40-0.07).
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.

OBJECTIVE: To determine the effectiveness of extraventricular drainage (EVD) combined with fibrinolytics in reducing morbidity and mortality rates associated with intraventricular cerebral hemorrhage (IVH).
METHODS: A literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration number: CRD42022332152). Articles were selected from various sources, including PubMed, Trip Database, LILACS, Cochrane Library, and ScienceDirect. Clinical trials focusing on IVH treatment using EVD and/or fibrinolytics were considered. The Risk of Bias in Non-randomized Studies of Interventions (ROB 2) tool was employed for bias assessment. A fixed-effects regression model was used following heterogeneity analysis. Treatment effectiveness was evaluated based on mortality outcomes.
RESULTS: A total of 531 patients from four studies were included. The use of fibrinolytics significantly decreased IVH mortality compared with a placebo. The odds ratio (OR) for recombinant tissue plasminogen activator (rtPA) or alteplase was 0.54 [0.36; 0.82]. For urokinase (UK), the OR was 0.21 [0.03; 1.54], rendering it statistically non-significant. The overall OR was 0.52 [0.35; 0.78], and the heterogeneity I2 was 0% (indicating low heterogeneity).
CONCLUSIONS: While EVD alone is a common approach for managing hydrocephalus, its effectiveness is limited by potential blockages and infections. Combining EVD with UK or rtPA demonstrated improved patient outcomes. rtPA stands out as a reliable and effective option, while limited data are available regarding UK\'s effectiveness in reducing IVH mortality.

The efficacy and safety of dual antiplatelet therapy (DAPT) relative to intravenous (IV) alteplase in patients with acute minor ischemic stroke are insufficiently established. Therefore, we aimed to perform a meta-analysis to compare DAPT with IV alteplase in patients with acute minor stroke. MEDLINE, Embase, and Cochrane were searched for studies comparing DAPT with IV alteplase in patients with minor stroke. Functional and safety outcomes in 90 days were analyzed. Statistical analysis was performed using Rstudio 4.3.1. Subanalyses were performed restricted to non-disabling minor strokes and NIHSS score ≤ 3. PROSPERO (CRD42023440986). We included five studies with a total of 6,340 patients, of whom 4,050 (63.9%) received DAPT. The follow-up period for all included studies was 90 days. There was no significant difference for individual outcomes of mRS 0-1 (OR 1.26; 95% CI 0.85-1.89; p = 0.25), mRS 0-2 (OR 0.99; 95% CI 0.69-1.43; p = 0.97), or all-cause mortality (OR 0.80; 95% CI 0.20-3.13; p = 0.75) between groups. Symptomatic intracranial hemorrhage (sICH) was significantly lower (OR 0.11; 95% CI 0.003-0.36; p < 0.001) in patients treated with DAPT compared with IV alteplase. In terms of mRS 0-1 and mRS 0-2, we found no significant difference in both subgroup analyses. We found no statistically significant difference between DAPT and IV alteplase regarding functional outcome (mRS scores of 0-1 and 0-2) or all-cause mortality at 90 days in patients with minor ischemic stroke. Additionally, DAPT was associated with a significantly lower rate of sICH.

Although intravenous thrombolysis with alteplase remains the primary treatment for acute ischemic stroke, tenecteplase has shown potential advantages over alteplase. Animal studies have demonstrated the favorable pharmacokinetics and pharmacodynamics of tenecteplase. Moreover, it is easier to administer. Clinical trials have demonstrated that tenecteplase is not inferior to alteplase and may even be superior in cases of acute ischemic stroke with large vessel occlusion. Current evidence supports the time and cost benefits of tenecteplase, suggesting that it could potentially replace alteplase as the main option for thrombolytic therapy, especially in patients with large vessel occlusion.

OBJECTIVE: To compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS).
METHODS: Following Cochrane and PRISMA guidelines, we analyzed observational studies and clinical trials comparing DAPT and IV t-PA in patients with minor AIS. Databases included PubMed, Scopus, and Web of Science. Data extraction included study characteristics, patient demographics, and analyzed outcomes. RevMan 5.3 and OpenMetaAnalyst 2021 were used to analyze the data and assess heterogeneity, respectively. The risk of bias was determined using RoB 2.0 and the Newcastle-Ottawa scale.
RESULTS: This meta-analysis included five studies with 3,978 DAPT-treated patients and 2,224 IV t-PA-treated patients. We found no significant differences in achieving modified Rankin scale (mRS) scores of 0-1 (OR 1.11, 95 % CI: 0.79, 1.55, p = 0.56) and 0-2 (OR 0.90, 95 % CI: 0.61, 1.31, p = 0.57), as well as combined mRS scores (OR 1.05, 95 % CI: 0.82, 1.34, p = 0.72). Similarly, there were no significant disparities between the two treatment groups in NIHSS score change from baseline (MD 0.32, 95 % CI: -0.35, 0.98, p = 0.35) and in mortality rates (OR 0.87, 95 % CI: 0.26, 2.93, p = 0.83). Notably, in comparison to the IV t-PA group, the DAPT group exhibited a significantly lower incidence of bleeding (OR 0.31, 95 % CI: 0.14, 0.69, p = 0.004) and symptomatic intracranial hemorrhage (sICH) (OR 0.10, 95 % CI: 0.04, 0.26, p < 0.00001).
CONCLUSIONS: Our meta-analysis found no significant differences in efficacy between DAPT and IV t-PA. However, DAPT demonstrated a significantly lower risk of sICH and bleeding compared with IV t-PA.

To systematically review the risk prediction model of Hemorrhages Transformation (HT) after intravenous thrombolysis in patients with Acute Ischemic Stroke (AIS).
Web of Science, The Cochrane Library, PubMed, Embase, CINAHL, CNKI, CBM, WanFang, and VIP were searched from inception to February 25, 2023 for literature related to the risk prediction model for HT after thrombolysis in AIS.
A total of 17 included studies contained 26 prediction models, and the AUC of all models at the time of modeling ranged from 0.662 to 0.9854, 16 models had AUC>0.8, indicating that the models had good predictive performance. However, most of the included studies were at risk of bias. the results of the Meta-analysis showed that atrial fibrillation (OR=2.72, 95% CI:1.98-3.73), NIHSS score (OR=1.09, 95% CI:1.07-1.11), glucose (OR=1.12, 95% CI:1.06-1.18), moderate to severe leukoaraiosis (OR=3.47, 95% CI:1.61-7.52), hyperdense middle cerebral artery sign (OR=2.35, 95% CI:1.10-4.98), large cerebral infarction (OR=7.57, 95% CI:2.09-27.43), and early signs of infarction (OR=4.80, 95% CI:1.74-13.25) were effective predictors of HT after intravenous thrombolysis in patients with AIS.
The performance of the models for HT after thrombolysis in patients with AIS in the Chinese population is good, but there is some risk of bias. Future post-intravenous HT conversion prediction models for AIS patients in the Chinese population should focus on predictors such as atrial fibrillation, NIHSS score, glucose, moderate to severe leukoaraiosis, hyperdense middle cerebral artery sign, massive cerebral infarction, and early signs of infarction.

UNASSIGNED: The efficacy of thrombolysis (IVT) in minor stroke (National Institutes of Health Stroke Scale score, 0-5) remains inconclusive. The aim of this study is to compare the effectiveness and safety of IVT with best medical therapy (BMT) by means of a systematic review and meta-analysis of randomized controlled trials and observational studies.
UNASSIGNED: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to IVT in minor stroke from inception until August 10, 2023. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days. The associations were calculated for the overall and preformulated subgroups by using the odds ratios (ORs). This study was registered with PROSPERO (CRD42023445856).
UNASSIGNED: A total of 20 high-quality studies, comprised of 13 397 patients with acute minor ischemic stroke, were included. There were no significant differences observed in the modified Rankin Scale scores of 0 to 1 (OR, 1.10 [95% CI, 0.89-1.37]) and 0 to 2 (OR, 1.16 [95% CI, 0.95-1.43]), mortality rates (OR, 0.67 [95% CI, 0.39-1.15]), recurrent stroke (OR, 0.89 [95% CI, 0.57-1.38]), and recurrent ischemic stroke (OR, 1.09 [95% CI, 0.68-1.73]) between the IVT and BMT group. There were differences between the IVT group and the BMT group in terms of early neurological deterioration (OR, 1.81 [95% CI, 1.17-2.80]), symptomatic intracranial hemorrhage (OR, 7.48 [95% CI, 3.55-15.76]), and hemorrhagic transformation (OR, 4.73 [95% CI, 2.40-9.34]). Comparison of modified Rankin Scale score of 0 to 1 remained unchanged in subgroup patients with nondisabling deficits or compared with those using antiplatelets.
UNASSIGNED: These findings indicate that IVT does not yield significant improvement in the functional prognosis of patients with acute minor ischemic stroke. Additionally, it is associated with an increased risk of symptomatic intracranial hemorrhage when compared with the BMT. Moreover, IVT may not have superiority over BMT in patients with nondisabling deficits or those using antiplatelets.

OBJECTIVE: Alteplase is the current standard of care for acute ischemic stroke. Tenecteplase is a newer fibrinolytic agent with preferable administration and lower costs; however, its comparative effectiveness to alteplase remains uncertain. We set out to perform a systematic review and meta-analysis to establish the benefits and harms of tenecteplase versus alteplase for acute ischemic stroke.
METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to April 2023 for randomized and non-randomized studies that compared tenecteplase versus alteplase for acute ischemic stroke. Paired reviewers independently assessed risk of bias and extracted data. We performed both conventional meta-analyses and Bayesian network meta-analyses (NMA) with random-effects models and used the GRADE approach to evaluate the certainty of evidence. Our primary efficacy outcome was excellent functional outcome at 3 months, defined as a score of 0-1 on the modified Rankin Scale. Our primary safety outcomes were symptomatic intracranial hemorrhage and all-cause mortality.
RESULTS: Thirty-six studies were eligible for review, including 12 randomized (n = 5533) and 24 non-randomized studies (n = 44,956). Moderate certainty evidence showed that there was no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months (odds ratio [OR], 1.10; 95% CI 0.98-1.23; risk difference [RD] 2.4%, 95% CI - 0.5 to 5.2), while moderate certainty evidence from NMA suggested that 0.25 mg/kg tenecteplase significantly improved excellent functional outcome at 3 months (OR, 1.16; 95% credible interval 1.02-1.32). Moderate certainty evidence showed that, compared to alteplase, tenecteplase may make little to no difference in the prevalence of symptomatic intracranial hemorrhage (OR, 1.12; 95% CI 0.79-1.59; RD 0.3%, 95% CI - 0.5 to 1.4), and probably reduces all-cause mortality (adjusted odds ratio [aOR], 0.44; 95% CI 0.30-0.64; RD - 4.6%; 95% CI - 5.8 to - 2.9).
CONCLUSIONS: Moderate certainty evidence suggested that there was little to no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months and the risk of symptomatic intracranial hemorrhage, while compared to alteplase, tenecteplase probably reduce all-cause mortality. Administration of 0.25 mg/kg tenecteplase after acute ischemic stroke is suggestive of increasing the proportion of patients that achieve excellent functional outcome at 3 months.