Risultati per: Scoperta una nuova molecola anti-cancro

Comunicato del 09/02/2022 n°5

Stroke, Volume 53, Issue Suppl_1, Page AWMP1-AWMP1, February 1, 2022. Approved thrombolytic agents are limited in their use for the treatment of acute ischemic stroke (AIS) due to their benefit-risk profile beyond 4.5 h since last known normal (LKN). TMS-007 is a small molecule, SMTP family member with a novel mode of action: promotion of plasminogen-fibrin binding to enhance physiological thrombolysis while inhibiting inflammation at the site of thrombosis. TMS-007 may extend the treatment time window based on nonclinical pharmacological evidence. We evaluated TMS-007 in a randomized, placebo-controlled, double-blind, dose-escalation phase 2a study. TMS-007 or placebo was administered as a single intravenous infusion at a dose of 1, 3, or 6 mg/kg to AIS patients who were ineligible for t-PA or thrombectomy within 12 h of LKN. The number of patients allocated to placebo and TMS-007 at doses 1, 3, and 6 mg/kg were 38, 6, 18, and 28, respectively. The combined TMS-007 dosing group (Group T; n = 52) was compared with placebo group (Group P; n = 38). The average age was ~72 years old and time since LKN to treatment was ~9 h in both groups (not significantly different). The incidence of symptomatic intracranial hemorrhage (ICH) with worsening NIHSS score of

Stroke, Volume 53, Issue Suppl_1, Page ATP167-ATP167, February 1, 2022. Antiplatelet agents are administered before and after neuroendovascular surgery to minimize implant-associated thromboembolic events. Dual antiplatelet therapy (DAPT) uses aspirin plus P2Y12 receptor inhibitors: clopidogrel, ticagrelor, or prasugrel. Effects are quantified in P2Y12 reactivity units (PRU) and aspirin reactivity units (ARU) by the point-of-care assay, Accumetrics VerifyNow. We hypothesized that intraoperative events such as anesthesia may affect platelet inhibition, increasing the risk of unanticipated ischemic events in the early postoperative period.This retrospective study was approved by the institutional review board. 50 patients who underwent Verify Now testing preoperatively and within 12 hours postoperatively after placement of cervical or intracranial stents at a single institution (January 1, 2018 – May 25, 2021) were included. PRU values > 194 and ARU values > 550 were considered subtherapeutic. Anesthetic agents, heparin dosage, clopidogrel responsiveness, platelet count, liver function, procedure type and length, NIH stroke scale scores, and demographics were compared to perioperative platelet inhibition values.Our results indicate that P2Y12 inhibition is likely affected by intraoperative events. Approximately 25% of patients exhibited marginal (170-193) or subtherapeutic ( > 194) PRU values during the first 8 hours following neuroendovascular procedures. The greatest variation occurred in the ticagrelor group (PRU median change 84) and was more likely to occur with reduced doses of both ticagrelor and clopidogrel. A single prasugrel patient (clopidogrel non-responder) exhibited the greatest absolute change (PRU 156 – > 316). ARU variations were less pronounced suggesting that perioperative aspirin platelet inhibition is more resilient.In conclusion, patients undergoing elective neuroendovascular procedures may be at risk for thromboembolic ischemic complications during the first 8 hours postoperatively due to shifts in P2Y12 mediated platelet inhibition. ARU values were less effected, supporting the use of DAPT as an ongoing clinical standard of care.