Radiation-induced brain injury (RIBI) is a debilitating sequela after radiotherapy to treat head and neck cancer, and 20 to 30% of patients with RIBI fail to respond to or have contraindications to the first-line treatments of bevacizumab and corticosteroids. Here, we reported a Simon’s minmax two-stage, single-arm, phase 2 clinical trial (NCT03208413) to assess the efficacy of thalidomide in patients with RIBI who were unresponsive to or had contraindications to bevacizumab and corticosteroid therapies. The trial met its primary endpoint, with 27 of 58 patients enrolled showing ≥25% reduction in the volume of cerebral edema on fluid-attenuated inversion recovery–magnetic resonance imaging (FLAIR-MRI) after treatment (overall response rate, 46.6%; 95% CI, 33.3 to 60.1%). Twenty-five (43.1%) patients demonstrated a clinical improvement based on the Late Effects Normal Tissues–Subjective, Objective, Management, Analytic (LENT/SOMA) scale, and 36 (62.1%) experienced cognitive improvement based on the Montreal Cognitive Assessment (MoCA) scores. In a mouse model of RIBI, thalidomide restored the blood-brain barrier and cerebral perfusion, which were attributed to the functional rescue of pericytes secondary to elevation of platelet-derived growth factor receptor β (PDGFRβ) expression by thalidomide. Our data thus demonstrate the therapeutic potential of thalidomide for the treatment of radiation-induced cerebral vasculature impairment.

Introduction: Successful reperfusion does not always lead to good neurological outcomes and impaired microcirculation can be one of the underlying causes. Intra-arterial alteplase after mechanical thrombectomy (MT) may improve microcirculation contributing to neurological recovery, but prospective randomised studies are still needed to validate its efficacy and safety. We aim to assess the efficacy and safety of intra-arterial alteplase after MT for acute ischaemic stroke (AIS) with large-vessel occlusion (LVO). Methods and analysis: The Intra-arterial Alteplase for Acute Ischaemic Stroke After Mechanical Thrombectomy (PEARL) study is a multicentre, prospective, open-label, blinded-endpoint, randomised controlled trial. We consecutively screen AIS patients with anterior circulation LVO and National Institute of Health Stroke Scale of 6–25, who reach stable expanded Thrombolysis in Cerebral Infarction scores of 2b50-3 on angiography after MT. Eligible participants are 1:1 randomly assigned to the experimental group and the control group. Participants in the experimental group will receive intra-arterial alteplase (0.225 mg/kg and a maximum dose of 20 mg) after MT and standard medical treatment, while those in the control group will receive standard medical treatment alone after the procedure. The primary outcome is the proportion of patients with a 90-day modified Rankin scale of 0–1. A total of 324 participants are required to test the superiority hypothesis with 80% power at a two-tailed significance level of 0.05. Ethics and dissemination: This study has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (SYSKY-2023-390-02) and will be conducted following the Declaration of Helsinki. Ethical approvals have been obtained separately for all centres participating in the study. Study results will be published in peer-reviewed academic journals. Trial registration number: NCT05856851 .

Migraine imposes a substantial global burden, with unmet patient-centered therapeutic needs. Rimegepant, a CGRP receptor antagonist, has trial-proven efficacy, but real-world evidence for its dual acute and preventive use in Chinese migraine populations is limited. This study evaluated its effectiveness in Chinese patients using patient-reported outcomes. A multicenter, single-arm, prospective, non-interventional observational study was conducted across five hospitals in the Guangdong-Hong Kong-Macao Greater Bay Area, China. A total of 120 adult migraine patients who were prescribed rimegepant for either acute (AT) or preventive treatment (PT) were enrolled. Patient-reported outcomes were assessed at baseline and after 4 weeks using Headache Impact Test (HIT-6), Treatment Satisfaction Questionnaire for Medication (TSQM), the European Five-Dimension Five-Level Health Scale (EQ-5D-5L) and the Work Productivity and Activity Impairment Questionnaire - General Health (WPAI-GH). We employed the Wilcoxon signed-rank test for within-group comparisons of pre- and post-treatment scale scores, with statistically significant defined as a two-tailed p-value < 0.05. A total of 120 migraine patients meeting all inclusion criteria were enrolled but 12 potential participants (10.0%) did not initiate rimegepant therapy. The study was completed by 108 patients (median age 37.0 (31.5,46.0) years; 83% female), including 89 in the AT group and 19 in the PT group. After 4 weeks, both groups showed significant improvements. In the AT group, the HIT-6 score decreased by 4.8 (95% CI: -6.1, -3.0), while TSQM scores increased in Effectiveness (20.6; 95% CI: 14.3, 26.8), Side Effects (12.6; 95% CI: 6.8, 18.5), and Global Satisfaction (16.2, 95% CI: -10.8, 21.5); for all comparisons to baseline, P < 0.0001. The PT group also showed an improvement in the HIT-6 (-5.8 [95% CI: -9.5, -2.2]) and improvements in TSQM (11.4 [95% CI: -0.8, 23.6] for Effectiveness, 13.2 [95% CI: -0.1, 26.4] for Side Effects,12.0 [95% CI: 0.2, 23.8] for Global Satisfaction). Both the AT and PT groups reported improvement in EQ-5D-5L VAS scores (3.6 [95% CI: 1.0, 6.2] and 7.6 [95% CI: 1.8, 13.5]) and improvement in WPAI-GH measures, including presenteeism (-10.6 and − 26.4) and overall work impairment (-11.3 and − 22.4); for all comparisons to baseline, P < 0.05). A clinically relevant improvement (≥ 6-point reduction in HIT-6 scores) was achieved by 52.6% of PT group and 34.1% of AT group. The PT group was relatively small, and due to the limited duration of follow-up, it may have demonstrated preliminary preventive effects. Rimegepant demonstrated improvements across multiple patient-centered outcomes, including headache-related impacts (HIT-6), treatment satisfaction (TSQM), quality of life (EQ-5D-5L), functional capacity and work productivity (WPAI). Therapeutic benefits were observed in both AT and PT, with the PT group showing preliminary evidence of preventive effects, further supporting rimegepant’s dual indications in migraine management. The study is registered on ClinicalTrials.gov (NCT06221267).

Key words: onabotulinumtoxinA [Supplementary Concept]; Randomized Controlled Trials as Topic; Meta-Analysis [Publication Type]; Review Literature as Topic

Malnutrition is related to worsened prognosis, but the association between nutritional risk status and overall survival in radiation-induced brain necrosis (RN) has never been studied. We included consecutive patients who had received radiotherapy for head and neck cancer (HNC) and subsequently developed RN from 8 January 2005 through to 19 January 2020. The primary outcome was overall survival. We utilized three commonly-used nutritional assessments: the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and the COntrolling NUTritional Status (CONUT) measure, to quantify the baseline nutritional risk. A total of 398 eligible patients were included. During a median follow-up of 2.3 years, 42 (10.6%) patients died of any cause. Malnutrition at admission was associated with an increased risk of future death, as assessed by the GNRI (per 1-point decreased, HR 1.05, 95%CI 1.02–1.09, p = 0.001), the PNI (per 1-point decreased, HR 1.07, 95%CI 1.03–1.12, p = 0.002), and the CONUT (per 1-point increased, HR 1.22, 95%CI 1.08–1.37, p = 0.001). There were no nonlinear correlations between all three indices and post-RN survival. Among HNC survivors with RN, the assessment of nutritional risk by composite indices upon admission could help identify patients who might be at high risk of future death and deliver better nutritional management.