Anemia as an independent predictor of adverse outcomes after carotid revascularization.

BACKGROUND: Anemia has been identified as a risk factor for postoperative morbidity and mortality after major vascular procedures. Carotid revascularization carries less cardiac morbidity and physiologic stress compared with other vascular interventions. This study evaluated the association between preoperative anemia and major adverse events after carotid revascularization. METHODS: Patients undergoing carotid endarterectomy (CEA) and carotid artery stenting (CAS) between January 2012 and June 2018 in the Vascular Quality Initiative database were identified. Anemia was defined as a preoperative hemoglobin level of <12 g/dL in women and <13 g/dL in men. Multivariable logistic analysis and 1:1 coarsened exact matching were used to study the association between preoperative anemia and in-hospital major adverse cardiac events (MACEs), defined as a composite of stroke, death, and myocardial infarction, and between anemia and 30-day mortality after CEA and CAS. RESULTS: Of 102,719 patients included in the analysis, 34.8% were anemic (CEA, 34.1%; CAS, 37.8%; P < .001). Anemic patients were older and had more medical comorbidities compared with nonanemic patients. In-hospital MACEs (2.8% vs 1.9%; P < .001) and 30-day mortality (0.9% vs 0.4%; P < .001) were higher among anemic patients. On multivariable analysis, anemia was associated with 18% higher odds of in-hospital MACEs (odds ratio, 1.18; 95% confidence interval, 1.07-1.31, P = .001) and 74% higher odds of 30-day mortality (odds ratio, 1.74; 95% confidence interval, 1.40-2.17, P < .001). Coarsened exact matching showed similar results. The association between preoperative anemia and adverse outcomes was similar in both CAS and CEA and in symptomatic and asymptomatic patients (P interaction > .05). CONCLUSIONS: Anemia is associated with increased odds of adverse events after CEA and CAS. It should be factored into the preoperative risk assessment of patients undergoing carotid revascularization. Prospective studies are needed to study the effectiveness of correcting low preoperative hemoglobin levels in these patients and the association between anemia and long-term outcomes after CEA and CAS.

Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3.

Emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) may be due to cell-to-cell transmission of misfolded preformed fibrils (PFF) of α-synuclein (α-syn). The mechanism by which α-syn PFF spreads from neuron to neuron is not known. Here, we show that LAG3 (lymphocyte-activation gene 3) binds α-syn PFF with high affinity (dissociation constant = 77 nanomolar), whereas the α-syn monomer exhibited minimal binding. α-Syn-biotin PFF binding to LAG3 initiated α-syn PFF endocytosis, transmission, and toxicity. Lack of LAG3 substantially delayed α-syn PFF-induced loss of dopamine neurons, as well as biochemical and behavioral deficits in vivo. The identification of LAG3 as a receptor that binds α-syn PFF provides a target for developing therapeutics designed to slow the progression of PD and related α-synucleinopathies.