RESUMO
Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD = 69, non-AD = 54) from the Boston University Alzheimer's disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195-205, 212-221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC = 89.8), p-tau231 (AUC = 83.4), and p-tau205 (AUC = 81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR < 1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217 = 15.29, ORp-tau205 = 5.05 and ORp-tau231 = 3.86) and Braak staging (ORp-tau217 = 14.29, ORp-tau205 = 5.27 and ORp-tau231 = 4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease.
Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Proteínas tau , Autopsia , BiomarcadoresRESUMO
INTRODUCTION: Sequential compression devices (SCDs) are the mainstay of mechanical prophylaxis for venous thromboembolism in perioperative neurosurgical patients and are especially crucial when chemical prophylaxis is contraindicated. OBJECTIVES: This study aimed to characterise and improve SCD compliance in neurosurgery stepdown patients. METHODS: SCD compliance in a neurosurgical stepdown unit was tracked across 13 months (August 2022-August 2023). When not properly functioning, the missing element was documented. Compliance was calculated daily in all patients with SCD orders, and then averaged monthly. Most common barriers to compliance were identified. With nursing, we implemented a best practice alert to facilitate nursing education at month 3 and tracked compliance over 9 months, with two breaks in surveillance. At month 12, we implemented a patient-engagement measure through creating and distributing a patient-directed infographic and tracked compliance over 2 months. RESULTS: Compliance averaged 19.7% (n=95) during August and 38.4% (n=131) in September. After implementing the best practice alert and supply chain upgrades, compliance improved to 48.8% (n=150) in October, 41.2% (n=104) in March and 45.9% (n=76) in April. The infographic improved compliance to 51.4% (n=70) in July and 55.1% (n=34) in August. Compliance was significantly increased from baseline in August to October (z=4.5838, p<0.00001), sustained through March (z=3.2774, p=0.00104) and further improved by August (z=3.9025, p=0.0001). CONCLUSION: Beyond an initial Hawthorne effect, implementation of the best practice nursing alert facilitated sustained improvement in SCD compliance despite breaks in surveillance. SCD compliance nonetheless remained below 50% until implementation of patient-engagement measures which were dependent on physician involvement.
Assuntos
Fidelidade a Diretrizes , Procedimentos Neurocirúrgicos , Humanos , Fidelidade a Diretrizes/estatística & dados numéricos , Fidelidade a Diretrizes/normas , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/normas , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Tromboembolia Venosa/prevenção & controle , Melhoria de Qualidade , Feminino , MasculinoRESUMO
BACKGROUND: Advances in the use of flow diversion (FD) now extend to bifurcation aneurysms; herein, we compare thromboembolic events in patients with internal carotid artery (ICA) aneurysms treated with and without exclusion of the anterior cerebral artery (ACA). METHODS: Retrospective analysis of aneurysms in the terminal ICA treated with FD from 2013 to 2023 at a single-center study. Procedures were classified according to the coverage at the origin of the ACA and compared through bivariate-analysis. A review was also carried on PubMed, Web of Science, and EMBASE until April 2024, adhering to the PRISMA reporting guidelines. RESULTS: Ninety-five patients harboring 113 aneurysms treated in 102 procedures were evaluated. Fifty-eight were treated covering the ACA origin. Dual antiplatelet regimens included aspirin-clopidogrel (50%), aspirin-ticagrelor (44.1%), and aspirin-prasugrel (4.9%). Thromboembolic events occurred in 6 patients (5.9%), all of which presented with large vessel occlusion of the ICA, but without reaching statistical difference in the 2 treated cohorts (P = 0.46). At a median clinical follow-up of 5.95 months, there were no differences in the functional outcomes in the 2 groups (P = 0.22). Contralateral angiographic runs post-treatment after covering the ACA origin demonstrated increase in the A1 (median: 0.45 mm; IQR = 0.4-1.2) and ICA diameter (median: 0.55 mm; IQR = 0.1-1.2). After pooling data from literature and our cohort, complete side branch occlusion after the coverage of ACA was seen in 25% of branches (95%CI = 0.16-0.36), and thromboembolic events were observed after 3% (95%CI = 0.01-0.04) of procedures. CONCLUSIONS: Thromboembolic events can occur in distal ICA aneurysms treated with FD, but no significant association was seen with covering the ACA origin.
Assuntos
Artéria Cerebral Anterior , Aneurisma Intracraniano , Tromboembolia , Humanos , Aneurisma Intracraniano/cirurgia , Artéria Cerebral Anterior/cirurgia , Artéria Cerebral Anterior/diagnóstico por imagem , Tromboembolia/prevenção & controle , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Masculino , Procedimentos Endovasculares/métodos , Idoso , Artéria Carótida Interna/cirurgia , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias/epidemiologiaRESUMO
OBJECTIVE: Concern about thromboembolic events after flow diversion (FD) warrants dual antiplatelet therapy for 3 to 6 months. Platelet function tests are routinely performed prior to the procedure to detect clopidogrel responsiveness, as resistance is associated with CYP2C19 gene polymorphisms. This study aimed to identify optimal cutoff values in light transmission aggregometry (LTA) for clopidogrel and aspirin as predictive indicators of thromboembolic complications. METHODS: The authors conducted a retrospective analysis of aneurysms treated with FD between 2013 and 2023 at a single academic institution. Patients with LTA data for adenosine diphosphate (ADP) and arachidonic acid (ARA) were included, excluding those with aborted procedures. Receiver operating characteristic curves were plotted for ADP and ARA assays to determine optimal cutoff values. RESULTS: A total of 442 patients harboring 552 aneurysms treated in 485 procedures were selected for this analysis. Complete and near-complete aneurysm occlusion on the last radiological follow-up was achieved in 81.8% of aneurysms in a median last imaging follow-up of 13.9 months. A good functional outcome (modified Rankin Scale score ≤ 2) was achieved in 96.3% of patients on the last follow-up. Thromboembolic complications occurred in 4.9% of procedures, and intracranial hemorrhagic complications in 1.9%. For the ADP assay, a value ≥ 40% reached a sensitivity of 82.1% and a specificity of 42.9% with a positive likelihood ratio (LR) of 1.50. For the ARA assay, a value ≥ 13.5% reached a sensitivity of 82.1% and a specificity of 45.6% with a positive LR of 1.51. CONCLUSIONS: This study analyzed the largest FD-treated cohort in which optimal LTA platelet function thresholds for clopidogrel were evaluated and is the first to assess LTA values for aspirin. The authors found that values ≥ 40% for clopidogrel and ≥ 13.5% for aspirin were optimal for predicting thromboembolic complications after FD in treating aneurysms.
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BACKGROUND: Flow diversion for bifurcation aneurysms requires excluding one of the branches from the parent artery, raising concern for ischemic events. We evaluated thromboembolic events and their relationship with covering the origin of the posterior cerebral artery (PCA). METHODS: This retrospective analysis included patients with confirmed basilar and proximal PCA aneurysms treated with flow diversion between 2013 and 2023. Procedures were classified according to the coverage of the origin of the PCA. Thromboembolic events associated with the excluded PCA were evaluated. RESULTS: Of the total 28 aneurysms included, 7 were at the basilar tip, 16 in the basilar trunk, and 5 in the first segment of the PCA; 15 were treated by excluding one of the PCAs. Dual antiplatelet therapy included aspirin and ticagrelor (57.1%), aspirin and clopidogrel (35.7%), or aspirin and prasugrel (3.57%). Complete and near-complete aneurysm occlusion was achieved in 80.8% of the aneurysms treated at a median follow-up of 12.31 months. Thromboembolic complications occurred in 3 patients (2 with basilar perforator stroke and 1 with basilar in-stent thrombosis). However, the difference in these events was not statistically significant between patients with PCA coverage and those without (P = 0.46). Diminished flow and a lack of flow was seen in 8 and 7 of the covered vessels, respectively. A modified Rankin scale score of ≤2 was reported for 89.3% of patients at a median clinical follow-up of 5.5 months. CONCLUSIONS: The incidence of thromboembolic events is high in distal basilar and proximal PCA aneurysms; however, PCA coverage was not associated with their occurrence. There was no difference in postprocedural disability between patients whose aneurysms were treated by excluding one of the PCAs and those who were not.
Assuntos
Aneurisma Intracraniano , Artéria Cerebral Posterior , Tromboembolia , Humanos , Feminino , Masculino , Aneurisma Intracraniano/cirurgia , Pessoa de Meia-Idade , Artéria Cerebral Posterior/cirurgia , Estudos Retrospectivos , Idoso , Tromboembolia/etiologia , Tromboembolia/epidemiologia , Adulto , Procedimentos Endovasculares/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , StentsRESUMO
BACKGROUND AND OBJECTIVES: The pipeline embolization device (PED) Flex with Shield technology is a third-generation flow diverter used for intracranial aneurysm treatment designed to decrease thrombogenicity through a phosphorylcholine coating. Herein, we aim to compare the rate of thromboembolic events in PED with Shield technology and PED without it through propensity score matching. METHODS: We conducted a retrospective analysis of aneurysms treated with PED first-generation/PED Flex and PED with Shield between 2013 and 2023 at a single academic institution. Patients were matched through propensity score by controlling for confounding factors including age, smoking history, diabetes, previous subarachnoid hemorrhage, modified Rankin Scale pretreatment, location, aneurysm size, previous treatment, and clopidogrel or aspirin resistance. After matching, we evaluated for periprocedural and postoperative thromboembolic events. Data analysis was performed using Stata 14. RESULTS: A total of 543 patients with 707 aneurysms treated in 605 procedures were included in the analysis. From these, 156 aneurysms were treated with PED with Shield (22.07%) and 551 (77.93%) without Shield technology. Propensity score matching resulted in 84 matched pairs. The rate of thromboembolic events was 3.57% for PED Shield and 10.71% for PED first-generation/PED Flex ( P = .07), while retreatment rates were 2.38% for PED Shield and 8.32% for PED Flex ( P = .09). Complete occlusion at first ( P = .41) and last imaging follow-up ( P = .71), in-stent stenosis ( P = .95), hemorrhagic complications ( P = .31), and functional outcomes ( P = .66) were comparable for both groups. CONCLUSION: This is the first study in the literature performing a propensity scored-matched analysis comparing PED with PED with Shield technology. Our study suggests a trend toward lower thromboembolic events for PED Shield, even after controlling for aspirin and clopidogrel resistance, and a trend toward lower aneurysm retreatment rates with PED Shield, without reaching statistical significance.
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Embolização Terapêutica , Aneurisma Intracraniano , Pontuação de Propensão , Tromboembolia , Humanos , Masculino , Embolização Terapêutica/instrumentação , Embolização Terapêutica/métodos , Embolização Terapêutica/efeitos adversos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/terapia , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Idoso , Adulto , Resultado do TratamentoRESUMO
BACKGROUND: Factors impacting the rate of aneurysm occlusion after FD have been well described in the literature. In this paper, we sought to evaluate those variables to develop and validate a scoring system predicting aneurysm incomplete occlusion after FD. METHODS: Retrospective review of patients with intracranial aneurysms treated with FD at a single institution between March 2013 and March 2023. Multivariable logistic regression model was developed using factors associated with aneurysm incomplete occlusion. The ABC scoring system consisted of: Age (< 60 years old: 0, 60-69 years: 1, 70-79: 2, and ≥80: 3), Branch coming out of the aneurysm dome/neck (yes: 2, no:0), and Cigarette smoking history (never-smoker:1, current or past smoker: 0). The scoring system performance was evaluated with receiver operating characteristic curve and calculating the area under the curve (AUC). RESULTS: A total of 449 patients with 563 aneurysms treated in 482 procedures were evaluated. Most cases were females (81.7%) with a median age of 59 years-old. At a median follow-up of 13.2 months, 84.0% of aneurysms were completely or near-complete occluded. The scoring system had an AUC of 0.71. A value ≥2, reached a sensitivity of 74.4%, specificity of 60.9%, an LR+ of 1.90, and proved to be reliable in predicting the risk of incomplete occlusion (OR=4.53; 95% confidence interval, 2.73-7.54; P < 0.001). CONCLUSION: The proposed ABC scoring system can be used to evaluate the risk of aneurysm incomplete occlusion after treatment with FD, identifying patients who would benefit from adjunctive coiling or alternate treatment modalities.