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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, allcause 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. [ABSTRACT FROM AUTHOR]

Angeles Lakers. A total of 189 U.S. fans of LeBron James were recruited for the study. Results indicate that James's image became worse (in terms of mean scores) for every out-group condition, while being slightly improved if opting to remain in the in-group; however, images were significantly different from other out-groups in the scenario in which LeBron James opted to join the Golden State Warriors--the Cavaliers most immediate rival at the time. [ABSTRACT FROM AUTHOR]

Background: The study aimed to report a boy with familial exudative vitreoretinopathy and amblyopia harboring a new mutation of the LRP5 and OPA1 gene abnormality. Case presentation: A 9-year-old boy presented with a 2-year history of deteriorating visual acuity in the right eye. His best-corrected visual acuity was -7.00/-1.75 × 100 = 0.3 in the right eye and -2.50/-1.50 × 170 = 0.8 in the left eye. Two autosomal dominant gene mutation sites were identified in the patient: LRP5 (c.2551C > T, p.His851Tyr) from his father and OPA1 (c.565G > A, p.Glu189Lys) from his mother. Interestingly, his fraternal twin brother harbored no abnormal gene mutations, and his eye tests were normal. Conclusion: This case expands the spectrum of LRP5 gene mutations among Chinese patients with familial exudative vitreoretinopathy, and it is the first time to report a patient harboring both LRP5 and OPA1 gene mutations having anisometropic amblyopia and strabismus as the primary manifestations. These four family members exhibited individual heterogeneity of phenotypes and genotypes associated with hereditary ophthalmopathy. A comprehensive analysis of clinical phenotypes and genotypes provides clinical clues for improving the level of clinical and genetic diagnoses and a deeper understanding of the disease. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab and cemiplimab have been approved as treatment for advanced non-small-cell lung cancer (NSCLC) with high programmed death ligand-1 (PD-L1) expression. This study aimed to evaluate the cost-effectiveness of pembrolizumab compared with that of cemiplimab in the treatment of advanced NSCLC with high PD-L1 expression from a societal perspective in the United States. Materials and methods: Cost-effectiveness analysis integration of the network meta-analysis framework was performed using data from the EMPOWER-Lung 1, KEYNOTE 024, and KEYNOTE 042 phase 3 randomized clinical trials. A network meta-analysis including 2289 patients was constructed, and the Markov and partitioned survival (PS) models were used to assess the costeffectiveness of pembrolizumab compared with that of cemiplimab for the treatment of high PD-L1 expression (=50% of tumor cells). The time horizon was 10 years. The main outcomes were overall costs, incremental costeffectiveness ratios (ICERs), quality-adjusted life-years (QALYs), life-years, incremental net health benefits (INHB), and incremental net monetary benefits (INMB). The robustness of the model was verified using one-way and probabilistic sensitivity analyses, and subgroup analyses were conducted. Results: Treatment of advanced NSCLC with high PD-L1 expression with pembrolizumab achieved 0.093 QALYs and was associated with an incremental cost of $10,657 compared with cemiplimab, yielding an ICER of $114,246/QALY. The ICER in the PS model was similar to that in the Markov model, with a difference of $3,093/QALY. At a willingness-to-pay (WTP) threshold of $100,000/QALY, INHB, and INMB of pembrolizumab were -0.013 QALYs and -$1,329, respectively, and the probability of cemiplimab was 51% when compared with pembrolizumab. When the WTP threshold increased to $150,000/QALY, the INHB and INMB of pembrolizumab were 0.022 QALYs and $3,335, respectively, and the probability of pembrolizumab was 51.85%. Oneway sensitivity analysis indicated that the models were sensitive to pembrolizumab and cemiplimab costs. Subgroup analysis revealed that treatment with pembrolizumab was related to a higher INHB in several subgroups, including patients with brain metastases at baseline. Conclusion: Our findings suggest that the WTP threshold should be considered when choosing between cemiplimab and pembrolizumab to treat advanced NSCLC with high PD-L1 expression. Reducing the cost of pembrolizumab may lead to valuable outcomes. [ABSTRACT FROM AUTHOR]

Objective: Nivolumab improves overall survival (OS) and is associated with fewer adverse events than sorafenib for the treatment of advanced hepatocellular carcinoma (aHCC). However, the cost-effectiveness of nivolumab compared with sorafenib treatment for aHCC remains unclear. This study evaluated the cost-effectiveness of nivolumab and sorafenib in the treatment of aHCC. Materials and methods: A partitioned survival model that included three mutually exclusive health states was used to evaluate the cost-effectiveness of nivolumab and sorafenib for treating aHCC. The clinical characteristics and outcomes of the patients in the model were obtained from the CheckMate 459. We performed deterministic one-way sensitivity and probabilistic sensitivity analyses to evaluate the robustness of the model. Subgroup analyses were also performed. Costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were measured. Results: The base case analysis showed that compared with sorafenib, treatment with nivolumab was associated with an increment of 0.50 (2.45 vs. 1.95) life-years and an increment of 0.32 (1.59 vs. 1.27) QALYs, as well as a $69,762 increase in cost per patient. The ICER was $220,864/QALY. The INHB and INMB were -0.15 QALYs and -$22,362 at a willingness-to-pay (WTP) threshold of $150,000/QALY, respectively. The probabilistic sensitivity analysis demonstrated that the probability of nivolumab being cost-effective was only 10.38% at a WTP threshold of $150,000/QALY. The model was most sensitive to the costs of sorafenib and nivolumab according to the one-way sensitivity analysis. When the price of sorafenib exceeded $0.93/mg or nivolumab was less than $24.23/mg, nivolumab was more cost-effective. The subgroup analysis illustrated that the probability of costeffectiveness was >50% in the Barcelona Clinic Liver Cancer Stage B subgroups for nivolumab at a WTP threshold of $150,000/QALY. This study also showed that the probability of cost-effectiveness was <50% in most subgroups. Conclusion: Nivolumab was not cost-effective, although it was associated with better clinical benefit and a favorable safety profile for the treatment of aHCC compared with sorafenib from the third-party payer perspective in the United States. If the price of nivolumab is substantially reduced, favorable cost-effectiveness can be achieved among patients with aHCC. [ABSTRACT FROM AUTHOR]