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.

The stromal vascular fraction (SVF) has been widely explored in a number of therapeutic applications in several specialties. Its therapeutic potential is being increasingly demonstrated, although its mechanism of action is still unclear. To evaluate the quality of studies reporting on clinical applications of SVF. This is a systematic literature review that followed the PRISMA guidelines with the search of the studies from December 1, 2012, to December 1, 2022, in the following databases: MEDLINE, LILACS and EMBASE. The level of evidence of the studies was assessed using the GRADE system, and the rigor used in the publication of the results was assessed in relation to adherence to the guidelines indicated by the EQUATOR Network Group. The CLINIC – STRA-SVF reporting guideline was developed after the completion of this systematic review. A total of 538 articles were found, and 77 articles were selected after reading the titles and abstracts and removing duplicates. Then, 15 studies were removed for not meeting the inclusion criteria, leaving 62 studies. The CLINIC – STRA-SVF was developed and consists of 33 items and two tables. There is scientific evidence, although mostly with a low level of evidence, that the use of SVF in clinical applications is safe and effective. The information published in these studies should be standardized, and the CLINIC – STRA-SVF reporting guideline proposed in this study may assist in the design, conduct, recording and reporting of clinical trials and others clinical studies involving the SVF.