Optimizing Acute Ischemic Stroke Outcomes: The Role of Tenecteplase Before Mechanical Thrombectomy.

PURPOSE: Acute ischemic stroke (AIS) is a life-threatening condition demanding prompt reperfusion to salvage brain tissue. Thrombolytic drugs, like tenecteplase (TNK), offer clot dissolution, but time constraints and contraindications limit their use. Mechanical thrombectomy (MT) revolutionized AIS treatment, especially for large vessel occlusions (LVO). Recent evidence suggests that administering TNK before MT improves recanalization and outcomes, challenging the dominance of alteplase. METHODS: Relevant articles focusing on TNK before MT were retrieved from PubMed, Scopus, and Web of Science, looking for randomized controlled trials (RCT), clinical trials, and meta-analyses in humans until 2024. FINDINGS: TNK, a genetically engineered thrombolytic, exhibits superior fibrin specificity and a longer half-life than alteplase. Clinical trials comparing TNK and alteplase before MT showcase enhanced recanalization, functional outcomes, and safety with TNK. Advanced neuroimaging aids patient selection, though its cost-effectiveness warrants consideration. Dosing studies favor a 0.25 mg/kg dose for efficacy and reduced complications. Clinical guidelines from various associations acknowledge TNK's potential as an alteplase alternative for AIS treatment, particularly for LVOs eligible for thrombectomy. IMPLICATIONS: In conclusion, TNK emerges as a promising option for bridging therapy in AIS, displaying efficacy and safety benefits, especially when administered before MT. Its fibrin specificity, longer half-life, and potential for improved outcomes position TNK as a viable alternative to alteplase, potentially transforming the landscape of AIS treatment strategies. While limitations like small sample sizes and variations in protocols exist, future research should focus on large-scale RCT, subgroup analyses, and cost-effectiveness evaluations to further elucidate TNK's role in optimizing AIS management.

Sodium Phenylbutyrate and Tauroursodeoxycholic Acid: A Story of Hope Turned to Disappointment in Amyotrophic Lateral Sclerosis Treatment.

The absence of a definitive cure for amyotrophic lateral sclerosis (ALS) emphasizes the crucial need to explore new and improved treatment approaches for this fatal, progressive, and disabling neurodegenerative disorder. As at the end of 2023, five treatments - riluzole, edaravone, dextromethorphan hydrobromide + quinidine sulfate (DHQ), tofersen, and sodium phenylbutyrate-tauroursodeoxycholic acid (PB-TUDCA) - were FDA approved for the treatment of patients with ALS. Among them PB-TUDCA has been shown to impact DNA processing impairments, mitochondria dysfunction, endoplasmic reticulum stress, oxidative stress, and pathologic folded protein agglomeration defects, which have been associated with ALS pathophysiology. The Phase 2 CENTAUR trial demonstrated significant impact of PB-TUDCA on the ALS Functional Rating Scale-Revised (ALSFRS-R) risk of death, hospitalization, and the need for tracheostomy or permanent assisted ventilation in patients with ALS based on post hoc analyses. More recently, contrasting with the CENTAUR trial results, results from the Phase 3 PHOENIX trial (NCT05021536) showed no change in ALSFRS-R total score at 48 weeks. Consequently, the sponsor company initiated the process with the US FDA and Health Canada to voluntarily withdraw the marketing authorizations for PB-TUDCA. In the present article, we review ALS pathophysiology, with a focus on PB-TUDCA's proposed mechanisms of action and recent clinical trial results and discuss the implications of conflicting trial data for ALS and other neurological disorders.

WITHDRAWN: Comparison of the Efficacy of Oral Magnesium with Oral Ketorolac for Postoperative Pain Management in Anorectal Surgery: A Double-blinded Randomized Clinical Trial

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