'Diagnostic anchoring' and a delayed diagnosis of reversible cerebral vasoconstriction syndrome.

We present a case of a woman in her 60s with acute left hemispheric ischaemic stroke syndrome due to tandem occlusions of the proximal left internal carotid artery and left middle cerebral artery. This was treated with emergent carotid artery stenting and endovascular clot retrieval. The patient made a complete recovery and was discharged home only to represent a few days later with focal neurological symptoms, profound headache and labile blood pressure. The diagnostic and management challenges of reversible cerebral vasoconstriction syndrome, including imaging assessment and the importance of avoiding 'diagnostic anchoring' are discussed.

Association of Endovascular Thrombectomy vs Medical Management With Functional and Safety Outcomes in Patients Treated Beyond 24 Hours of Last Known Well: The SELECT Late Study.

Importance: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well. Objective: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well. Design, Setting, and Participants: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well. Interventions: Endovascular thrombectomy or medical management (control). Main Outcomes and Measures: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts. Results: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P < .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02). Conclusions and Relevance: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation.

Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases.

In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1ß (IL-1ß) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1ß, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.