Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .).

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For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.

Background It is uncertain if endovascular stroke therapy leads to improved clinical outcomes due to a paucity of data from randomized placebo-controlled trials. The aim of this study was to determine if MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion. Methods Consecutive patients, scheduled to undergo endovascular therapy within 12 hours of stroke onset, were enrolled in a multi-center prospective cohort study. Aided by an automated image analysis software program, investigators interpreted the baseline MRI. They determined, prior to endovascular treatment, if the patient had an MRI profile (Target Mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI and defined as a >50% reduction in the volume of the baseline perfusion lesion. A favorable clinical response was defined as a ≥8 point improvement on the NIH Stroke Scale (NIHSS) between baseline and day 30 or an NIHSS score of 0–1 at 30 days. Findings Following endovascular therapy reperfusion occurred in 46 of 78 (59%) Target Mismatch patients and in 12 of 21 (57%) No Target Mismatch patients. The adjusted odds ratio for favorable clinical response associated with reperfusion was 8·5 (95% CI 2·6 – 28) in the Target Mismatch group and 0·2 (95% CI 0·0 – 1·6) in the No Target Mismatch group (p=0·003 for difference between odds ratios). Reperfusion was associated with an increased odds of good functional outcome at 90 days (OR is 5.2, 95% CI 1.4–19) and attenuation of infarct growth at 5 days (30 ml of median growth with reperfusion vs. 73 ml without reperfusion, p=0·01) in the Target Mismatch group but not in patients without Target Mismatch. Interpretation Target Mismatch patients who achieved early reperfusion following endovascular stroke therapy had more favorable clinical outcomes and less infarct growth. No association between reperfusion and favorable outcomes was present in patients without Target Mismatch. These data support a randomized controlled trial of endovascular treatment in patients with the Target Mismatch profile.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.