RESUMO
OBJECTIVE: Treatment goals of prophylactic endovascular aortic repair of complex aneurysms involving the renal-mesenteric arteries (complex endovascular aortic repair [cEVAR]) include achieving both technical success and long-term survival benefit. Mortality within the first year after cEVAR likely indicates treatment failure owing to associated costs and procedural complexity. Notably, no validated clinical decision aid tools exist that reliably predict mortality after cEVAR. The purpose of this study was to derive and validate a preoperative prediction model of 1-year mortality after elective cEVAR. METHODS: All elective cEVARs including fenestrated, branched, and/or chimney procedures for aortic disease extent confined proximally to Ishimaru landing zones 6 to 9 in the Society for Vascular Surgery Vascular Quality Initiative were identified (January 2012 to August 2023). Patients (n = 4053) were randomly divided into training (n = 3039) and validation (n = 1014) datasets. A logistic regression model for 1-year mortality was created and internally validated by bootstrapping the AUC and calibration intercept and slope, and by using the model to predict 1-year mortality in the validation dataset. Independent predictors were assigned an integer score, based on model beta-coefficients, to generate a simplified scoring system to categorize patient risk. RESULTS: The overall crude 1-year mortality rate after elective cEVAR was 11.3% (n = 456/4053). Independent preoperative predictors of 1-year mortality included chronic obstructive pulmonary disease, chronic renal insufficiency (creatinine >1.8 mg/dL or dialysis dependence), hemoglobin <12 g/dL, decreasing body mass index, congestive heart failure, increasing age, American Society of Anesthesiologists class ≥IV, current tobacco use, history of peripheral vascular intervention, and increasing extent of aortic disease. The 1-year mortality rate varied from 4% among the 23% of patients classified as low risk to 23% for the 24% classified as high risk. Performance of the model in validation was comparable with performance in the training data. The internally validated scoring system classified patients roughly into quartiles of risk (low, low/medium, medium/high and high), with 52% of patients categorized as medium/high to high risk, which had corresponding 1-year mortality rates of 11% and 23%, respectively. Aneurysm diameter was below Society for Vascular Surgery recommended treatment thresholds (<5.0 cm in females, <5.5 cm in males) in 17% of patients (n = 679/3961), 41% of whom were categorized as medium/high or high risk. This subgroup had significantly increased in-hospital complication rates (18% vs 12%; P = .02) and 1-year mortality (13% vs 5%; P < .0001) compared with patients in the low- or low/medium-risk groups with guideline-compliant aneurysm diameters (≥5.0 cm in females, ≥5.5 cm in males). CONCLUSIONS: This validated preoperative prediction model for 1-year mortality after cEVAR incorporates physiological, functional, and anatomical variables. This novel and simplified scoring system can effectively discriminate mortality risk and, when applied prospectively, may facilitate improved preoperative decision-making, complex aneurysm care delivery, and resource allocation.
Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Masculino , Feminino , Humanos , Medição de Risco , Aneurisma da Aorta Abdominal/cirurgia , Resultado do Tratamento , Fatores de Risco , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologiaRESUMO
DNA methylation has been identified as a powerful and activity-dependent regulator of changes in the brain that may underlie neuroadaptations in response to various types of stimuli, including exposure to drugs of abuse. Indeed, the medial prefrontal cortex (mPFC) projections to the nucleus accumbens (NAc) are critically important for reinstated cocaine-seeking in a rodent model of cocaine relapse. This circuitry undergoes several epigenetic modifications following cocaine exposure, including changes in DNA methylation that are associated with drug-seeking behavior. We have previously shown that methyl supplementation via L-Methionine (MET) administration attenuates cocaine-seeking behavior and reverses expression and methylation patterns of the immediate early gene c-fos, suggesting that MET may act by altering the excitability of this circuitry during cocaine reinstatement. In the current study, male rats were microinjected with an adeno-associated virus overexpressing halorhodopsin in the mPFC, optical fibers were surgically implanted into the NAc, and the rats were given injections of MET daily. Rats underwent acquisition of cocaine self-administration (0.75 mg/kg/infusion, 2-h sessions) followed by extinction training in the absence of drug-paired cues. Two reinstatement tests were conducted: cue-induced reinstatement without optogenetic manipulations and cocaine-primed reinstatement with optogenetic inhibition of mPFC-to-NAc projections. There were no group differences before the cocaine-primed reinstatement session, and all groups showed robust cue-induced reinstatement. Both rats treated with MET and rats that received mPFC-to-NAc inhibition showed an abolishment of cocaine-primed reinstatement, suggesting that systemic methyl supplementation may act through this critical circuity.