BACKGROUND: A minority of patients with stroke qualify for intravenous thrombolysis (IVT) within 4.5-hour window. The safety and efficacy of IVT beyond this period have not been well studied. METHODS: We systematically searched MEDLINE, Embase, Cochrane, and ClinicalTrials.gov for relevant randomized clinical trials. Randomized clinical trials comparing IVT versus standard medical care in patients with ischemic stroke beyond 4.5 hours of symptom onset or last known well without mechanical thrombectomy (MT) were included. Primary outcomes were excellent (modified Rankin Scale score of 0–1) and good (modified Rankin Scale score of 0–2) functional outcomes at 90 days, symptomatic intracerebral hemorrhage (sICH), and death at 90 days. Pooled odds ratios (ORs) with 95% CIs were calculated using a random-effects model. Heterogeneity was assessed by Q test and quantified by I ² values. RESULTS: Eight randomized clinical trials (1742 patients; mean age, 69.8±9 years, 63.5% men) were included. Compared with standard medical care, IVT achieved higher rates of excellent (OR, 1.43 [95% CI, 1.17–1.75]; Q =2.30; P =0.94; I ² =0%) and good functional outcomes (OR, 1.36 [95% CI, 1.12–1.66]; Q =2.07; P =0.96; I ² =0%) at 90 days but also increased sICH rates (OR, 4.25 [95% CI, 1.67–10.84], Q =0.48; P =0.99; I ² =0%). Mortality at 90 days did not significantly differ between treatment groups (OR, 1.28 [95% CI, 0.87–1.89]; Q =4.63; P =0.59; I ² =0%). Subanalyses yielded numerically higher odds of excellent functional outcomes when patients were selected with perfusion imaging (3 studies, OR, 1.45 [95% CI, 1.08–1.94]) compared with diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch (3 studies, OR, 1.34 [95% CI, 0.94–1.91]) and when treated with tenecteplase (3 studies, OR, 1.47 [95% CI, 1.06–2.04]) compared with alteplase (5 studies, OR, 1.38 [95% CI, 1.08–1.78]). CONCLUSIONS: IVT for ischemic stroke beyond 4.5 hours, without MT, led to increased odds of excellent and good functional outcomes compared with standard medical care, despite higher odds of sICH, and a nonsignificant numerical increase in mortality.

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2−) early-stage breast cancer (esBC) is still to be confirmed. Methods: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant. Results: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829). Conclusions: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2− esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits.

Introduction: The simultaneous occurrence of intracranial aneurysms (IA) and primary brain tumors (BT) is frequently reported, with an estimated incidence of 0.5–7.4%. Among the tumor types associated with IA, pituitary adenomas (PA) are the most prevalent. Methods: The authors selected articles, published from 1960 to December 2023, on the Medline, Embase, Scopus, Cochrane Library, and Web of Science databases. The extraction form contains information specific to the aneurysm and tumor, rupture of the aneurysm, treatment proposal for both and order of treatment and outcome. Results: The study evaluated 118 patients from 25 articles. The most frequent types of tumors were non-functioning hormone (NFA) producers, present in 45.8% ( n =54) of the cases, and growth hormone (GH) secretors, which represent 23.0% ( n =27) of the cases. The main treatment used was surgery, with subtotal resection (STR) performed in 4.2% ( n =5) of cases, gross total resection (GTR) in 3.4% ( n =4), and transsphenoidal resection (TSR) in 7.6% ( n =9). 16.0% ( n =19) of patients had two or more aneurysms concomitant with the adenoma. IA treatment was performed before PA surgery in 25 patients (21.2%) and 15 patients received simultaneous treatment to IA and PA (12.7%). Conclusion: Patients with PAs have a considerable prevalence of IAs. Hormonal imbalances and mechanical changes induced by tumor growth, particularly influenced by GH and IGF-1, contribute to this coexistence. Surgical intervention is common, requiring meticulous precautions to avoid complications. More longitudinal studies including close follow-up with a description of outcomes are necessary to guide treatment protocols for this condition.