Spurious Hyperphosphatemia in Two Children With End-Stage Renal Disease: A Case Report.

Spurious hyperphosphatemia, also known as pseudo-hyperphosphatemia, refers to artifactually elevated serum phosphate values that do not correspond to their actual systemic levels. Vascular access poses a significant challenge for individuals undergoing hemodialysis (HD) due to chronic kidney disease, primarily attributed to the elevated incidence of complications, such as infections or thrombosis associated with catheter use. To mitigate clotting risk during the inter-dialysis intervals, in recent years, a strategy involving the application of concentrated heparin (recombinant tissue plasminogen activator (rt-PA) e.g. alteplase) has been used. These infusions have a very high content of phosphorus, and if it is not removed sufficiently before collecting blood samples through the central venous catheter, it can cause erroneously high phosphate levels. Here we report two cases of pseudo-hyperphosphatemia caused by contaminated blood samples obtained from an HD catheter from the pediatric nephrology department. Absurd values found in routine samples led us to investigate the reason for these results. Further investigations carried out by the laboratory biochemistry department showed that all the analytical checks and proficiency testing performance were within acceptable limits. We hypothesized that there was a pre-analytical error such as possible contamination with the high phosphate content of heparin and alteplase solution in the catheter, contributing to the increased phosphate levels in these samples.

Early REperfusion Therapy with Intravenous Alteplase for Recovery of VISION in Acute Central Retinal Artery Occlusion (REVISION): Study Protocol of a Phase III Trial.

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data is lacking to address this question. AIMS: REVISION investigates intravenous alteplase within 4.5 hours of monocular vision loss due to acute CRAO. METHODS: Randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best corrected visual acuity of the Logarithm of the Minimum An-gle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy out-comes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomogra-phy/angiography, ultrasound and MRI biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 hours of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may trans-late to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

Thrombolysis for Wake-Up Stroke Versus Non-Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis.

BACKGROUND: Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups. METHODS: Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis. RESULTS: Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect (P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively (P=0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively (P=0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control. CONCLUSIONS: There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903.

Predictors of the unfavorable outcomes in acute ischemic stroke patients treated with alteplase, a multi-center randomized trial.

Worldwide, stroke is a leading cause of long-term disability in adults. Alteplase is the only approved treatment for acute ischemic stroke (AIS) and results in an improvement in a third of treated patients. We evaluated the post-stroke unfavourable outcome predictors in alteplase-treated patients from Egypt and Saudi Arabia. We assessed the effect of different risk factors on AIS outcomes after alteplase in Egypt and Saudi Arabia. Our study included 592 AIS alteplase-treated patients. The relationship between risk factors, clinical presentation, and imaging features was evaluated to predict factors associated with poor outcomes. An mRS score of three or more was used to define poor outcomes. Poor outcome was seen in 136 patients (23%), and Patients with unfavourable effects had significantly higher admission hyperglycaemia, a higher percentage of diabetes mellitus, cardioembolic stroke, and a lower percentage of small vessel stroke. Patients with higher baseline NIHSS score (OR 1.39; 95% CI 1.12-1.71; P = 0.003), admission hyperglycaemia (OR 13.12; 95% CI 3.37-51.1; P < 0.001), and post-alteplase intracerebral haemorrhage (OR 7.41; 95% CI 1.69-32.43; P = 0.008) independently predicted unfavourable outcomes at three months. In AIS patients treated with alteplase, similar to reports from other regions, in patients from Egypt and Saudi Arabia also reveal that higher NIHSS, higher serum blood sugar, and post-alteplase intracerebral haemorrhage were the predictors of unfavourable outcomes three months after ischemic stroke.Trial registration: (clinicaltrials.gov NCT06058884), retrospectively registered on 28/09/2023.

Effect of concomitant usage of alteplase and mechanical thrombectomy for M1 middle cerebral artery occlusion on clinical outcome: a retrospective analysis of 457 patients from two centers.

Introduction: Endovascular thrombectomy (EVT) and concomitant usage of intravenous alteplase (alteplase) in large vessel occlusion stroke may produce unwanted excess intracerebral hemorrhage (ICH). Whether this applies specifically to isolated occlusion of the M1 segment of the middle cerebral artery (MCA) is unknown. Methods: A retrospective study from two tertiary thrombectomy centers. ICH was determined according to Heidelberg Bleeding Classification (HBC). Factors associated with the occurrence of ICH in EVT alone vs. EVT with alteplase were evaluated using logistic regression analysis. Factors related to the clinical outcome as determined with a modified Rankin scale (mRS) were investigated with univariate and adjusted multivariate logistic regression analysis. The interaction between clinical variables and the usage of alteplase on the occurrence of ICH was evaluated. Results: Any ICH occurred in 156/457 (34.1%) patients Class 1a bleeding in 37 (8.1%), type 2 in 45 (9.8%) Class 1c in 22 (4.8%), Class 2 in 25 (5.5%), and Class 3 (extraparenchymal) in 27 (5.9%). ICH occurred in similar frequency between alteplase-treated patients vs. EVT alone (85/262 [32%] vs. 71/195 [36%]; OR 1.19 (95% CI 0.81-1.76). After adjustment, odds for clinical outcome were lower in ICH patients (OR 0.44 [95% CI 0.25-0.74]), p = 0.002). Higher ICH rate was associated with more EVT steps (p for interaction -0.005), and usage of only stent-retriever (p for interaction =0.005). Conclusion: Utilization of alteplase alongside EVT for MCA M1 occlusion did not result in excessive ICH occurrences or clinical deterioration.

Tenecteplase versus Alteplase before thrombectomy: A comprehensive evaluation of clinical and angiographic impact: Insights from the ETIS registry.

INTRODUCTION: Data on prior use of Tenecteplase versus Alteplase in acute stroke management by mechanical thrombectomy are controversial. Our primary objective was to make a comprehensive comparative assessment of clinical and angiographic efficacy and safety outcomes in a large prospective observational study. METHODS: We included stroke patients who were eligible for intravenous thrombolysis and endovascular thrombectomy between 2019 and 2021, from an ongoing registry in twenty comprehensive stroke centers in France. We divided patients into two groups based on the thrombolytic agent used (Alteplase vs Tenecteplase). We then compared their treatment times, and their angiographic (TICI scale), clinical (mRS at three months and sICH) and safety outcomes after controlling for potential confounders using propensity score methods. RESULTS: We evaluated 1131 patients having undergone thrombectomy for the final analysis, 250 received Tenecteplase and 881 Alteplase. Both groups were of the same median age (75 vs 74 respectively), and had the same baseline NIHSS score (16) and ASPECTS (8). There was no significant difference for First Pass Effect (OR 0.93, 95 % CI 0.76-1.14, p = 0.75), time required for reperfusion (OR 0.03, 95 % CI 0.09-0.16, p = 0.49), or for final reperfusion status. Clinically, functional independence at 90 days was similar in both groups (OR 0.82, 95 % CI 0.61-1.10, p = 0.18) with the same risk of sICH (OR 1.36, 95 % CI 0.77-2.41, p = 0.28). However, Tenecteplase patients had shorter imaging-to-groin puncture times (99 vs 142 min, p < 0.05). CONCLUSIONS: Tenecteplase showed no better clinical or angiographic impact on thrombectomy compared to Alteplase. Nevertheless, it appeared associated with a shorter thrombolysis-to-groin puncture time.

[Comparative characteristics of the efficacy and safety of the original alteplase and its complete biosimilar in the treatment of ischemic stroke in real clinical practice]. / Sravnitel'naya kharakteristika effektivnosti i bezopasnosti original'noi alteplazy i ee bioanaloga pri lechenii ishemicheskogo insul'ta v real'noi klinicheskoi praktike.

OBJECTIVE: To conduct a comparative analysis between the original alteplase and its biosimilar in terms of efficacy and safety in real clinical practice in the Republic of Belarus. MATERIAL AND METHODS: The cohort study included 420 patients. All included patients underwent thrombolytic therapy with alteplase within 4.5 hours of the onset of stroke symptoms according to the approved tactics of the Republic of Belarus and international recommendations. The patients were divided into 2 groups: 215 received the drug Revelisa, 205 - Actilyse. RESULTS: The patients were comparable in gender, age, ASPECTS assessment, but had statistically significant difference in NIHSS was found, due to the large number of patients with NIHSS=16-25 in the Actilyse group. The assessment of premorbid disability also showed a statistically significant difference: there were more patients in the Revelisa group who had functional limitations of varying degrees before the disease, 83 (38.6%) versus 62 (28.3%) patients in the comparison group. Clinical outcomes were comparable, the proportion of patients achieving mRS=0-1 at discharge was 41.5% in group A and 42.8% in group P. The Revelisa demonstrated a statistically significant lower number of deaths in 15 (7.0%) and 29 (14.1%) in the comparison group. The development of a greater number of clinically insignificant petechial hemorrhages was noted after the use of Actilyse. CONCLUSION: The analysis demonstrated a high level of safety in the use of alteplase preparations in routine practice. The compared fibrinolytics had comparable effectiveness in achieving functional independence after ischemic stroke, despite the more premorbid disability of patients who received a biosimilar.

[Cerebrolysin as an early add-on to reperfusion therapy: heterogeneous treatment effect analysis in ischemic stroke patients with varying risk of hemorrhagic transformation]. / Effektivnost' rannego primeneniya Tserebrolizina pri reperfuzionnoi terapii: analiz geterogennykh effektov vozdeistviya u bol'nykh s ishemicheskim insul'tom pri razlichnom riske gemorragicheskoi transformatsii.

OBJECTIVE: The study goal was the assessment of heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy in stroke patients with varying risk of hemorrhagic transformation (HT). MATERIAL AND METHODS: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n=238) were stratified by HT risk with the HTI score. The study outcomes were symptomatic and any HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable outcome was defined as an mRS score of ≤2. Heterogeneous treatment effect analysis was performed using techniques of meta-analysis and the matching-smoothing method. RESULTS: Heterogeneity of Cerebrolysin treatment effects was moderate (I2=36.98-69.3%, H2=1.59-3.26) and mild (I2=18.33-32.39%, H2=1.22-1.48) for symptomatic and any HT, respectively. A positive impact of the Cerebrolysin treatment on HT and functional outcome was observed in patients with moderate (HTI=1) and high (HTI≥2) HT risk. However, the effect was neutral in those with low risk (HTI=0). In high HT risk patients, there was a steady decline in the rate of symptomatic (HTI=0 vs. HTI≥2: by 3.8%, p=0.120 vs. 14.3%, p<0.001) and any HT (HTI=0 vs. HTI≥2: by 0.6%, p=0.864 vs. 19.5%, p<0.001). Likewise, Cerebrolysin treatment resulted in an overall decrease in the mRS scores (HTI=0 vs. HTI≥2: by 2.1%, p=0.893 vs. 63%, p<0.001) with a reciprocal increase of the fraction with favorable outcome (HTI=0 vs. HTI≥2: by 2% p=0.634 vs. 19.2%, p<0.001). CONCLUSION: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The Cerebrolysin positive impact was significant in those whose estimated on-admission HT risk was either moderate or high.

Tenecteplase versus alteplase for the treatment of acute ischemic stroke: a meta-analysis of randomized controlled trials.

OBJECTIVES: Tenecteplase, a modified variant of alteplase with greater fibrin specificity and longer plasma half-life, may have better efficacy and safety than alteplase in patients with acute ischemic stroke (AIS). We aimed to compare the benefits and risks of tenecteplase versus alteplase in the treatment of AIS. METHODS: Electronic databases were searched up to 10 February 2023 for randomized controlled trials evaluating the effect of tenecteplase versus alteplase in the treatment of AIS. The primary outcome was functional outcome at 90 days, and secondary outcomes including the symptomatic intracranial haemorrhage (SICH), and major neurological improvement. Subgroup analysis was performed based on the different dosage of tenecteplase. RESULTS: Ten studies with a total of 5123 patients were analysed in this meta-analysis. Overall, no significant difference between tenecteplase and alteplase was observed for functional outcome at 90 days (excellent: OR 1.08, 95%CI 0.93-1.26, I2 = 26%; good: OR 1.04, 95%CI 0.83-1.30, I2 = 56%; poor: OR 0.95, 95%CI 0.75-1.21, I2 = 31%), SICH (OR 1.12, 95%CI 0.79-1.59, I2 = 0%), and early major neurological improvement (OR 1.26, 95%CI 0.80-1.96, I2 = 65%). The subgroup analysis suggested that the 0.25 mg/kg dose of tenecteplase had potentially greater efficacy and lower symptomatic intracerebral haemorrhage risk compared with 0.25 mg/kg dose tenecteplase. CONCLUSIONS: Among AIS patients, there was no significant difference on clinical outcomes between tenecteplase and alteplase. Subgroup analysis demonstrated that 0.25 mg/kg doses of tenecteplase were more beneficial than 0.4 mg/kg doses of tenecteplase. Further studies are required to identify the optimal dosage of tenecteplase.

Randomized controlled trials exploring comparative efficacy and safety of tenecteplase and alteplase have been yielding inconsistent results on various outcomes and merit the conduction of a meta-analysis to adequately answer these questions.Analysis of evidence from randomized studies suggests that tenecteplase is as safe as alteplase for the treatment of acute ischemic stroke and tenecteplase is potentially associated with more favourable outcomes.Tenecteplase at 0.25 mg/kg dose is more efficacious and at least as safe as alteplase for stroke thrombolysis.

INTRAPLEURAL FIBRINOLYSIS WITH UROKINASE VERSUS ALTEPLASE IN COMPLICATED PLEURAL EFFUSIONS AND EMPYEMA: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL.

Introduction: Intrapleural fibrinolytic therapy is being used as an effective agent since 1949 in managing complicated pleural effusion and empyema. Several agents like streptokinase (STK), urokinase (UK), and recombinant tissue plasminogen activator (rt-PA) are found to effective with variable effectiveness. However, head-to-head controlled trial to compare the efficacy of the most frequently used i.e., UK and rt-PA (alteplase) in managing complicated pleural effusion has rarely been reported. Methodology: 50 patients were randomized in two intervention groups i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac unit. UK was given thrice daily for two days, followed by clamping to allow the drugs to retain in the pleural space for 2 hrs. rt-PA was instilled in the pleural space twice daily for two days, and the intercostal drainage was clamped for 1 hour. Results: A total of 50 patients were enrolled for the study out of which84% (n=42) were males and 16 % (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The of mean changes in the pleural opacity in the UK group was -33.0 % (SD +/- 9.9) and -41.0 % (SD +/- 14.9) in the alteplase group (P-value-0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and 40% (n=8) in the alteplase group (P-value 0.24) while fever was the second most common side effect. Patient who reported early (within 6 weeks of onset of symptoms) have shown greater response than who reported late for intervention. Conclusion: IPFT is a safe and effective option in managing complicated pleural effusion or empyema, and newer agents like alteplase have greater efficacy and similar adverse effects effect profile when compared with conventional agents like UK.

Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke.

Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single bolus administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits. The toxicities of rtPA and TNK were evaluated in endothelial cells, astrocytes, and neuronal cells. In addition, their in vivo efficacy was independently assessed at two research centers using an ischemic thromboembolic mouse model. Both therapies were tested via early (20 and 30 min) and late administration (4 and 4.5 h) after stroke. rtPA, but not TNK, caused cell death only in neuronal cultures. Mice were less sensitive to thrombolytic therapies than humans, requiring doses 10-fold higher than the established clinical dose. A single bolus dose of 2.5 mg/kg TNK led to an infarct reduction similar to perfusion with 10 mg/kg of rtPA. Early administration of TNK decreased the hemorrhagic transformations compared to that by the early administration of rtPA; however, this result was not obtained following late administration. These two independent preclinical studies support the use of TNK as a promising reperfusion alternative to rtPA.

Tenecteplase versus alteplase for acute ischemic stroke: a systematic review and meta-analysis of randomized and non-randomized studies.

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.

Efficacy of urokinase and alteplase intravenous thrombolysis in the treatment of acute phase cerebral infarction and impact on serum S-100ß and nerve growth factor levels.

OBJECTIVE: To compare the efficacy of urokinase and alteplase intravenous thrombolysis in the treatment of acute phase cerebral infarction and investigate their impact on serum S-100ß and nerve growth factor (NGF) levels. METHODS: Parameters assessed included NIHSS score reduction, vascular recanalization rates, mRS, Barthel Index, and adverse reactions. Post-treatment blood samples were also collected for further analysis. RESULTS: The clinical treatment effectiveness and Vascular recanalization rate in Group A was higher than in Group B, with p < 0.05. After treatment, the NIHSS score in Group A was lower than in Group B (p < 0.05), and the mRS score was slightly lower, but the difference was not significant (p > 0.05). After treatment, the levels of IL-6, TNF-α, and CRP in Group A were lower than in the control group (p < 0.05). The S-100ß level in Group A was lower than in Group B, and NGF level was higher than in Group B (p < 0.05). Group A had better prognosis. CONCLUSION: The efficacy and safety of both urokinase and alteplase intravenous thrombolysis for acute phase cerebral infarction have been demonstrated, yet disparities exist in neurological function recovery and regulation of biochemical indicators. Alteplase intravenous thrombolysis emerges as the superior option, displaying greater effectiveness and safety, alongside improved regulation of serum S-100ß and NGF levels. Tailoring treatment plans to individual patient characteristics and drug mechanisms is essential. Given these findings, the promotion of alteplase intravenous thrombolysis in the management of acute phase cerebral infarction is justified.

Endovascular thrombectomy without versus with different pre-intravenous thrombolysis in acute ischemic stroke: a network meta-analysis of randomized controlled trials.

Background: The current guideline recommended the use of intravenous thrombolysis (IVT) before Endovascular thrombectomy (EVT), but the effectiveness and safety of tenecteplase compare to alteplase in patients before EVT remain uncertain. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library to identify eligible articles from inception until September 16, 2023. The primary outcome was functional independence (mRS 0-2) at 90 days. Secondary outcomes included excellent outcome (mRS 0-1) at 90 days, all-cause mortality at follow-up, successful reperfusion (TICI 2b-3) after the end of EVT, symptomatic intracranial hemorrhage (sICH) or any intracranial hemorrhage (aICH). The PROSPERO registration number is CRD42023470419. Results: Eight randomized controlled trials (RCTs) were included involving 2,836 acute ischemic stroke (AIS) patients. Compared to EVT alone, tenecteplase (0.25 mg/kg and 0.4 mg/kg) + EVT and 0.9 mg/kg alteplase + EVT were significant difference associated with higher successful reperfusion (TICI 2b-3) after the end of EVT (RR = 2.31; 95% CI 1.15-4.63; RR = 2.31; 95% CI 1.00-5.33; RR = 1.05; 95% CI 1.01-1.09). And compared to 0.25 mg/kg tenecteplase + EVT, alteplase (0.6 mg/kg and 0.9 mg/kg) + EVT were significant difference associated with lower successful reperfusion (TICI 2b-3) after the end of EVT (RR = 0.45; 95% CI 0.22-0.90; RR = 0.45; 95% CI 0.23-0.91). The risk of aICH (RR = 1.50; 95% CI 1.07-2.09) was significantly higher for 0.6 mg/kg alteplase + EVT than EVT alone. There was no significant difference in functional independence (mRS 0-2), excellent outcome (mRS 0-1), all-cause mortality or sICH among the different IVT strategies (0.25 mg/kg or 0.4 mg/kg tenecteplase and 0.6 mg/kg or 0.9 mg/kg alteplase) before EVT. Conclusion: The use of alteplase before EVT may potentially improve the successful reperfusion after EVT compared to tenecteplase. Due to the insufficient sample size, more high-quality RCTs are needed to confirm effectiveness and safety of tenecteplase compare to alteplase in patients before EVT. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023470419.

Efficacy and safety outcomes of Tenecteplase versus Alteplase for thrombolysis of acute ischemic stroke: A meta-analysis of 9 randomized controlled trials.

BACKGROUND: In recent years, Tenecteplase (TNK), a genetically modified variant of alteplase, has been verified as a potential substitute for alteplase in the reperfusion therapy of acute ischemic stroke (AIS). Given the emergence of new randomized controlled trials (RCTs) of this subject, a meta-analysis was conducted to evaluate the present comparative evidence regarding the efficacy and safety outcomes of TNK and alteplase in thrombolysis for AIS. METHODS: Following predefined inclusion criteria, we searched the databases of PubMed, Web of Science, and Cochrane Library. RCTs satisfying our inclusion criteria were selected for meta-analysis. Outcome indicators were categorized into efficacy outcomes (early vessel recanalization, excellent recovery, good recovery and early neurological improvement) and safety outcomes (poor recovery, symptomatic intracerebral hemorrhage, parenchymal hemorrhage type 2(PH2) post thrombolysis, and mortality). We extracted data on efficacy outcomes and safety outcomes for patients with AIS in the TNK group at a dose of 0.25 mg/kg and the alteplase group at a dose of 0.9 mg/kg, and expressed the relative risks between the 2 groups as odds ratios (ORs) and 95% confidence intervals (CIs) using the Mantel-Haenszel method. For further insight, we performed a network meta-analysis using a Bayesian framework to compare different doses of TNK (0.1, 0.25, 0.32, and 0.4 mg/kg) with alteplase (0.9 mg/kg). RESULTS: A total of 2994 patients in 9 RCTs comparing efficacy and safety outcomes in patients with AIS treated with TNK and alteplase were included. In a pairwise analysis of TNK 0.25 mg/kg and alteplase 0.9 mg/kg, regarding efficacy outcomes, the aggregated results show that TNK 0.25 mg/kg statistically significant increased early vessel recanalization (N = 368, TNK vs. alteplase, OR: 2.07,95%CI: [1.19,3.59], I2 = 0%) and excellent recovery (N = 3548, TNK vs. alteplase, OR: 1.15,95%CI: [1.01,1.32], I2 = 0%). There was no significant difference in good recovery (N = 3486, TNK vs. alteplase, OR: 1.38,95%CI: [0.89,2.15], I2 = 84%) or early neurological improvement (N = 1686, TNK vs. alteplase, OR: 1.06,95%CI: [0.87,1.28], I2 = 24%) between the TNK 0.25 mg/kg group and the alteplase 0.9 mg/kg group. In the safety outcomes, pooled results showed no significant difference in poor recovery (N = 3548, TNK vs. alteplase, OR: 0.94,95%CI: [0.81,1.10], I2 = 0%) and symptomatic intracerebral hemorrhage (N = 3567, TNK vs. alteplase, OR: 1.06,95%CI: [0.70,1.60], I2 = 0%) and PH2(N = 3103, TNK vs. alteplase, OR: 1.26,95%CI:[0.39,4.07], I2 = 56%)and mortality (N = 3447, TNK vs. alteplase, OR: 0.99,95%CI: [0.80,1.23], I2 = 33%) between the TNK group and the alteplase group. In a network meta-analysis, competing treatments were not significantly different from one another (TNK 0.1 mg/kg, TNK 0.25 mg/kg, TNK 0.32 mg/kg, TNK 0.4 mg/kg, alteplase 0.9 mg/kg) in either efficacy outcomes or safety outcomes. CONCLUSION: In this analysis of 9 RCTs in patients with AIS, TNK 0.25 mg/kg was comparable to alteplase 0.9 mg/kg from the perspective of efficacy outcomes and safety outcomes after thrombolysis within 4.5 h of AIS occurrence.

European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke.

A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.

A bibliometric analysis of tenecteplase research utilizing a commonly used citation index.

BACKGROUND AND PURPOSE: Tenecteplase is increasingly being used as a first-line treatment for acute ischemic stroke after several randomized studies demonstrated its safety and efficacy, resulting in a massive increase in the number of published studies on this topic. Our aim was to investigate the most impactful authors and relevant journals that have been instrumental in validating this treatment, in hopes of identifying objective research trends that may assist scientists, health organizations, and funding agencies to collaborate and plan future avenues of research. METHODS: Using the search terms "Tenecteplase" and "Tenecteplase" AND "Stroke," 2683 and 1150 references were queried, respectively, using the abstract and citation database, Scopus. Scopus Citation Analysis was used to categorize the countries and authors who produced the most research. Metadata was retrieved and transferred to bibliographic visualization software, VOSviewer, for co-authorship and co-occurrence analyses to identify trends in tenecteplase research. RESULTS: Data visualization software identified three tenecteplase research clusters - myocardial infarction, pulmonary embolism, and acute ischemic stroke. Our bibliographic analysis graphically identified that ischemic stroke currently leads both myocardial infarction and pulmonary embolism in annual publications pertaining to tenecteplase therapy, and further pinpointed perfusion imaging and wake-up strokes as the most relevant areas of study. The United States led all countries in tenecteplase publications, including exclusively stroke studies. The European Heart Journal led all journals in overall publications, while Stroke led all journals in stroke-related studies. CONCLUSIONS: Through the use of bibliographic analysis and data visualization, we identified major articles and journals that reflected and shaped the current landscape of tenecteplase; recognized authors who engaged in tenecteplase research as it progressed from cardiopulmonary disease to stroke; and postulated future avenues of research.

Prehospital Fibrinolysis Therapy in Acute Myocardial Infarction: A Narrative Review.

Acute myocardial infarction is a fatal condition. Acute myocardial infarction requires appropriate timely reperfusion therapy to improve the outcomes. Fibrinolysis and percutaneous coronary intervention are the cornerstone strategies for managing such cases. In this review, our objective is to summarize the available evidence concerning the administration of prehospital fibrinolysis and its impact on patient outcomes in patients with acute myocardial infarction. We conducted a comprehensive literature search across PubMed, Cochrane Library, Scopus, and Web of Science databases. Our search strategy included the following terms: "Prehospital," "EMS," "Emergency Medical Services," "ambulance," "Fibrinolytic Therapy," "alteplase," "streptokinase," "reteplase," "tenecteplase," "Acute Myocardial Infarction," and "patient outcomes." We found prehospital administration of fibrinolysis may improve the outcomes and decrease the mortality rate. We found that some recommendations were to use prehospital fibrinolysis only if the percutaneous coronary intervention was not accessible within two hours. Additionally, we discussed recommendations to use newer prehospital fibrinolysis as they have better efficacy and safety outcomes. In conclusion, prehospital fibrinolysis decreases the total ischemic time and improves outcomes in acute myocardial infarction patients when timely percutaneous coronary intervention is not available. The guidelines strongly recommend it when the anticipated time for percutaneous coronary intervention exceeds two hours. Ongoing research optimizes patient selection, treatment tools, and prehospital systems of care.

[Endovascular treatment of deep vein thrombosis of the upper extremities]. / Endovaskulyarnoe lechenie trombozov glubokikh ven verkhnikh konechnostei.

OBJECTIVE: To improve the results of treatment of deep vein thrombosis of the upper extremities sing endovascular technologies. MATERIAL AND METHODS: We analyzed safety and effectiveness of treatment in 24 patients with deep vein thrombosis of the upper extremities. All ones were divided into 2 homogeneous groups by 12 people each. In the first group, conventional anticoagulation was performed. In the second group, we used additional regional catheter thrombolysis with alteplase and, if necessary, venous stenting or balloon angioplasty for residual stenosis. Patients received apixaban at baseline and throughout 6 postoperative months. After 12 months, we performed ultrasound and clinical examination to identify deep vein patency and venous outflow disorders. Vein recanalization was evaluated as follows: <50% - minimal, 50-99% - partial, 100% - complete. The quality of life of patients was studied using the SF-36 questionnaire. RESULTS: In the first group, we observed complete vein recanalization in 25% of cases, partial - in 33%, minimal - in 41% of cases; in the second group - 83.3% and 16.7% of patients, respectively. In the first group, clinical manifestations of venous outflow disorders were absent in 25% of patients, mild disorders - 25%, moderate - 8.3%, severe - 41.7% of patients. In the second group, venous outflow was not impaired in 83.7% of patients, mild violations occurred in 16.7% of patients. In the first group, physical health was equal to 44.2±1.7 scores, psychological health - 49.3±2.3 scores; in the second group - 69.3±5.7 and 71.3±5.4 scores, respectively. CONCLUSION: Endovascular treatment improved postoperative outcomes.

Comparison of pharmacokinetic properties of alteplase and tenecteplase. The future of thrombolysis in acute ischemic stroke.

INTRODUCTION: The drug most frequently used for thrombolysis in cases of acute ischemic stroke (AIS) is alteplase. However, there is moderate-to-high-quality evidence that tenecteplase has similar or higher efficacy and safety. With improved pharmacokinetic properties over alteplase, tenecteplase could be a significant advantage in treating AIS. AREAS COVERED: After conducting an extensive search on Scopus and PubMed, this manuscript reviews and compares the pharmacokinetic properties of alteplase and tenecteplase. Additionally, it provides information on pharmacodynamics, clinical efficacy, safety, tolerability, and drug-drug interactions. EXPERT OPINION: The pharmacokinetic profile of alteplase and tenecteplase is derived from studies in patients with acute myocardial infarction. Thanks to its pharmacokinetic properties, tenecteplase is the drug closest to being the ideal fibrinolytic for AIS. Its longer half-life enables a single-bolus administration, which is particularly useful in emergencies. Tenecteplase has proven to have a good efficacy and safety profile in randomized clinical trials. Although we are awaiting the results of the ongoing phase 3 randomized clinical trials, we believe that tenecteplase has the potential to revolutionize the treatment of AIS through thrombolysis.