OBJECTIVE:The objective of this study was to determine whether baseline computed tomography (CT) markers of cerebral small vessel disease (cSVD), as a surrogate of brain frailty, explain the association between age and functional outcome, potentially accounting for the reduced apparent benefit of mechanical thrombectomy (MT) in elderly patients in the RESILIENT trial. METHODS:RESILIENT was a multicenter, prospective, randomized, open-label trial with blinded outcome assessment conducted in Brazil. Patients with anterior circulation large-vessel occlusion stroke were randomized to MT plus guideline-based care or guideline-based care alone, including intravenous alteplase when eligible. A vascular neurologist blinded to clinical data evaluated baseline CT scans for cSVD markers (leukoaraiosis, lacunes, and atrophy) to derive a composite cSVD score. Multivariable logistic regression identified independent predictors of good functional outcome (modified Rankin Scale [mRS] = 0-2 at 90 days). Treatment effects were assessed across subgroups defined by age (<70 or ≥70 years) and cSVD score (0-1 vs 2-3). Mediation analysis quantified the indirect effect of age on outcome through cSVD. RESULTS:Patients with good outcomes were younger, had lower National Institutes of Health Stroke Scale (NIHSS) scores, better collaterals, lower glucose levels, lower cSVD burden, and were more frequently treated with MT. Independent predictors of good outcome included lower NIHSS, MT, lower cSVD score, and lower glucose levels. MT benefit was restricted to patients <70 years with low cSVD burden (odds ratio [OR] = 4.16, 95% confidence interval [CI] = 1.6-10.4, p < 0.01). No benefit was observed in older patients or in those with cSVD > 1. Mediation analysis showed that cSVD significantly mediated the association between age and outcome (average causal mediation effect [ACME] = -0.003, 95% CI = -0.005 to 0.00, p = 0.010). INTERPRETATION:Baseline CT markers of cSVD were independently associated with poorer outcomes and mediated the association between age and functional outcome in the RESILIENT trial, potentially explaining the lack of MT efficacy in older patients. ANN NEUROL 2026;100:361-369.
AimsShrinking lung syndrome (SLS) is a rare pulmonary manifestation of systemic lupus erythematosus (SLE) and affects approximately 0.5-1% of patients. This systematic review aimed to summarize the clinical features, imaging findings, therapeutic strategies, and outcomes of SLS in patients with SLE.MethodsThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies published between 2015 and 2025 were identified using the terms "shrinking lung syndrome" AND "systemic lupus erythematosus." Clinical characteristics, imaging findings, pulmonary function tests, treatments, and outcomes were analyzed.ResultsA total of 52 cases were included, comprising 44 cases from the literature and 8 from a single-center case series. The mean age was 31.5 ± 7.5 years in our cohort and 38.6 years in the literature, with a marked female predominance. All patients had a prior diagnosis of SLE. Dyspnea was present in all the patients, followed by pleuritic chest pain and dry cough. The most common imaging finding was reduced lung volume with elevated diaphragmatic domes, which was observed in all the patients in our cohort and in 77.2% of the reported cases, followed by basal atelectasis. Diaphragmatic ultrasonography, performed in half of our patients, demonstrated reduced diaphragmatic excursion. Pulmonary function tests consistently revealed a restrictive ventilatory pattern with reduced diffusing capacity for carbon monoxide (DLCO). Immunosuppressive therapy as a corticosteroid-sparing strategy was used in all patients from our cohort and was the most frequently reported treatment in the literature, with rituximab being the most commonly used agent. Improvement in pulmonary function occurred in 62.5% of our patients and 50% of the reported patients, whereas stabilization was observed in approximately one-quarter of the patients. Two cases of clinical worsening, including one death, were reported.ConclusionSLS represents a potentially severe and underrecognized pulmonary complication of SLE. Despite the lack of standardized therapy, early diagnosis and timely initiation of immunosuppressive treatment beyond corticosteroids are critical for improving clinical outcomes, as evidenced by improvement in pulmonary function tests in approximately 52% of patients and the availability of effective steroid-sparing options. Prospective studies are needed to establish standardized treatment strategies.
BACKGROUND AND OBJECTIVES:Time to endovascular thrombectomy (EVT) is a critical determinant of outcomes for large vessel occlusion (LVO) strokes presenting within 6 hours of onset. Its impact in the extended (6-24-hour) window remains uncertain. We aimed to evaluate the association between treatment times and outcomes in this window. METHODS:Individual patient-level data from 6 randomized trials enrolling patients in the extended window were pooled. The primary outcome was degree of disability at 90 days (modified Rankin Scale [mRS] 0-6). Secondary outcomes included functional independence (mRS 0-2), mortality, and symptomatic intracranial hemorrhage. RESULTS:Among 505 participants (median age 70 years; baseline NIH Stroke Scale 16; 51.3% female; advanced imaging selection 86.5%), 266 (52.7%) received EVT and 239 (47.3%) medical therapy alone. In EVT-treated patients, longer onset-to-randomization times were not associated with differences in disability (adjusted odds ratio [aOR] per 60 minutes 1.02; 95% CI 0.96-1.08; p = 0.53) or functional independence (aOR 1.06; 95% CI 0.95-1.17; p = 0.28). Conversely, control patients exhibited worse outcomes with increasing onset-to-randomization times (aOR for disability 0.93; 95% CI 0.87-1.00; p = 0.041; functional independence 0.84; 95% CI 0.73-0.97; p = 0.019), resulting in greater treatment benefit at later times (p-interaction = 0.033 and 0.003, respectively). No association was observed between onset-to-puncture or onset-to-reperfusion and outcomes in EVT patients. However, longer randomization-to-reperfusion times correlated with worse disability (aOR 0.58; 95% CI 0.37-0.91; p = 0.018) and lower functional independence (aOR 0.51; 95% CI 0.28-0.96; p = 0.038). DISCUSSION:This study demonstrates that the benefit of EVT is consistently preserved across the extended (6-24-hour) time window when patients are selected using advanced imaging criteria. In this highly selected population, enriched with slow progressors, the apparent increase in treatment effect with longer onset-to-presentation times reflects the validity of physiologic selection rather than true time insensitivity. However, this observation should not diminish the critical importance of time: imaging-based selection effectively resets the treatment clock, masking the harmful impact of prehospital delays. Notably, longer in-hospital delays were strongly associated with worse outcomes, reinforcing that "time is brain," even in extended-window cohorts.
Breast-conserving surgery (BCS) followed by adjuvant radiotherapy is the standard of care for early-stage breast cancer. However, reoperations after BCS may compromise aesthetic outcomes, increase surgical complications, and cause psychological distress. This study aimed to determine the reoperation rate after BCS in a multi-institutional cohort from Brazil and to identify predictive factors associated with reoperation. This retrospective multicenter cohort study included female breast cancer patients (AJCC clinical stage 0–III) who underwent BCS followed by adjuvant radiotherapy at six treatment centers in Brazil between January 2016 and December 2022. Logistic regression was used to assess the association between potential risk factors and reoperation. The overall reoperation rate was 5.2
Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers and lacks expression of estrogen receptor, progesterone receptor, and HER2, limiting targeted options. Recent neoadjuvant therapy (NAT) advances include immune checkpoint inhibitors (ICIs) and PARP inhibitors, improving pathologic complete response (pCR) and survival but raising concerns about severe toxicity. Despite broader adoption of these regimens, a systematic analysis of Grade ≥3 adverse events (AEs) from contemporary phase III trials is lacking. We conducted a PRISMA-guided systematic review and meta-analysis (PROSPERO: CRD42024562785). MEDLINE, Embase, and Cochrane were searched for phase III randomized trials (Jan 2010-Jun 2025) evaluating NAT in non-metastatic TNBC and reporting Grade ≥3 AEs (CTCAE). One phase II trial (WSG-ADAPT-TN; n=336) with robust comparative design and AE reporting was also included. Pooled prevalence and risk ratios (RR) with 95% CI were calculated using DerSimonian-Laird random-effects models. Subgroup analyses included: Group A (PARP inhibitors), B (immunotherapy), and C (platinum-based regimens). Heterogeneity was assessed via I2. Six trials with 3,316 TNBC patients were included (BrighTNess, IMpassion031, KEYNOTE-522, NeoTRIP, PARTNER, WSG-ADAPT-TN). Neutropenia was the most common Grade ≥3 AE, highest with immunotherapy (33.5%), followed by PARP inhibitors (23.7%) and platinum regimens (16.0%) (Q=71.8, p<0.0001). PARP inhibitors significantly increased neutropenia risk (RR=1.84), while immunotherapy showed no increase (RR=1.00, p=0.94). Grade ≥3 anemia was higher with PARP inhibitors (20.6%) vs. immunotherapy (9.9%), with doubled risk vs. placebo (RR=2.08, p=0.02). Thrombocytopenia was most prevalent with immunotherapy (7.9%), but PARP inhibitors showed the highest risk (RR=3.56, p=0.0001). Febrile neutropenia was more common with ICIs (14.9%) than PARP inhibitors (3.0%). ALT elevation was more frequent in platinum regimens (6.4%), without significant differences across groups. Fatal AEs were <1% in all trials. Modern NAT regimens improve outcomes in TNBC but confer significant Grade ≥3 toxicity. PARP inhibitors pose the highest hematologic risk, while ICIs increase febrile neutropenia. Platinum regimens showed the most favorable toxicity profile. Findings highlight the need for biomarker-driven, individualized treatment and vigilant AE monitoring in early TNBC. M. Antonini, A. Mattar, F. P. Cavalcante, F. P. Zerwes, E. C. Millen, F. P. Brenelli, A. L. Frasson, M. D. Teixeira, M. Madeira, G. Facina, H. L. Couto, G. T. Tosello, R. Arakelian, A. D. Lima, G. N. Garcia, F. Bagnoli, A. G. Amorim, M. F. de Figueiredo, L. R. Soares, R. Freitas Júnior, L. H. Gebrim. Adverse Events in Neoadjuvant Therapy for Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis of Phase III Trials [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-03.
