The safety and efficacy of intra-arterial low-dose tirofiban administration during endovascular therapy in patients with large ischemic core volume

Abstract This study aimed to evaluate the safety and efficacy of intra-arterial (IA) administration of low- dose tirofiban during endovascular therapy in patients with large ischemic core volumes on initial brain CT. Patients were divided into two groups based on the use of IA tirofiban. We identified 87 patients (16 and 71 patients in the tirofiban and no-tirofiban groups, respectively) with acute ischemic stroke due to intracranial artery occlusion who underwent endovascular therapy with a low Alberta Stroke Program Early CT scores (2–5). Multivariate logistic regression analysis revealed no association between IA tirofiban administration and serious postprocedural hemorrhagic complications (adjusted odds ratio (aOR), 0.720; 95% confidence interval (CI) 0.099–5.219; p = 0.960), any radiologic hemorrhage (aOR 0.076; 95% CI 0.003–2.323; p = 0.139), or 3-month mortality (aOR, 0.087; 95% CI 0.005–1.501; p = 0.093). However, IA tirofiban was associated with a lower 90-day mRS score (aOR, 0.197; 95% CI 0.015–1.306; p = 0.017) and change of NIHSS compared with baseline (aOR, 0.698; 95% CI 0.531–0.917; p = 0.010). IA tirofiban administration during endovascular therapy in patients with large ischemic core volumes may be effective and safe

Robust Copper Metal–Organic Framework-Embedded Polysiloxanes for Biomedical Applications: Its Antibacterial Effects on MRSA and In Vitro Cytotoxicity

Polysiloxanes (PSs) have been widely utilized in the industry as lubricants, varnishes, paints, release agents, adhesives, and insulators. In addition, their applications have been expanded to include the development of new biomedical materials. To modify PS for application in therapeutic purposes, a flexible antibacterial Cu-MOF (metal–organic framework) consisting of glutarate and 1,2-bis(4-pyridyl)ethane ligands was embedded in PS via a hydrosilylation reaction of vinyl-terminated and H-terminated PSs at 25 °C. The bactericidal activities of the resulting Cu-MOF-embedded PS (PS@Cu-MOF) and the control polymer (PS) were tested against Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. PS@Cu-MOF exhibited more than 80% bactericidal activity toward the tested bacteria at a concentration of 100 μg⋅mL−1 and exhibited a negligible cytotoxicity toward mouse embryonic fibroblasts at the same concentration. Release tests of the Cu(II) ion showed PS@Cu-MOF to be particularly stable in a phosphate-buffered saline solution. Furthermore, its physical and thermal properties, including the phase transition, rheological measurements, swelling ratio, and thermogravimetric profile loss, were similar to those of the control polymer. Moreover, the low cytotoxicity and bactericidal activities of PS@Cu-MOF render it a promising candidate for use in medicinal applications, such as in implants, skin-disease treatment, wound healing, and drug delivery

Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer (BLOSSOM)

PURPOSELeptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs.MATERIALS AND METHODSIn this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6.RESULTSA total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set-T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2.CONCLUSIONThe study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status. 80 mg osimertinib achieved a median OS of 15.0 months in T790M (-) EGFR-mutated NSCLC with LM, after 1st/2nd G TKIN

Long-Term Clinical Outcomes and Its Predictors Between the 1-and 2-Stent Strategy in Coronary Bifurcation Lesions ? A Baseline Clinical and Lesion Characteristic-Matched Analysis ?

Background: Differences in the impact of the 1-or 2-stent strategy in similar coronary bifurcation lesion conditions are not well understood. This study investigated the clinical outcomes and its predictors between 1 or 2 stents in propensity score-matched (PSM) complex bifurcation lesions. Methods and Results: We analyzed the data of patients with bifurcation lesions, obtained from a multicenter registry of 2,648 patients (median follow up, 53 months). The patients were treated by second generation drug-eluting stents (DESs). The primary outcome was target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TVMI), and ischemia-driven target lesion revascularization (TLR). PSM was performed to balance baseline clinical and angiographic discrepancies between 1 and 2 stents. After PSM (N=333 from each group), the 2-stent group had more TLRs (hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.42-6.97, P=0.005) and fewer hard endpoints (composite of cardiac death and TVMI; HR 0.44, 95% CI 0.19-1.01, P=0.054), which resulted in a similar TLF rate (HR 1.40, 95% CI 0.83-2.37, P=0.209) compared to the 1-stent group. Compared with 1-stent, the 2-stent technique was more frequently associated with less TLF in the presence of main vessel (p(interaction)=0.008) and side branch calcification (p(interaction)=0.010). Conclusions: The 2-stent strategy should be considered to reduce hard clinical endpoints in complex bifurcation lesions, particularly those with calcifications.N