Detection of Alteration in Carotid Artery Volumetry Using Standard-of-care Computed Tomography Surveillance Scans Following Unilateral Radiation Therapy for Early-stage Tonsillar Squamous Cell Carcinoma Survivors: A Cross-Sectional Internally-Matched Carotid Isodose Analysis.

Purpose: Radiation induced carotid artery disease (RICAD) is a major cause of morbidity and mortality among survivors of oropharyngeal cancer. This study leveraged standard-of-care CT scans to detect volumetric changes in the carotid arteries of patients receiving unilateral radiotherapy (RT) for early tonsillar cancer, and to determine dose-response relationship between RT and carotid volume changes, which could serve as an early imaging marker of RICAD. Methods and Materials: Disease-free cancer survivors (>3 months since therapy and age >18 years) treated with intensity modulated RT for early (T1-2, N0-2b) tonsillar cancer with pre- and post-therapy contrast-enhanced CT scans available were included. Patients treated with definitive surgery, bilateral RT, or additional RT before the post-RT CT scan were excluded. Pre- and post-treatment CTs were registered to the planning CT and dose grid. Isodose lines from treatment plans were projected onto both scans, facilitating the delineation of carotid artery subvolumes in 5 Gy increments (i.e. received 50-55 Gy, 55-60 Gy, etc.). The percent-change in sub-volumes across each dose range was statistically examined using the Wilcoxon rank-sum test. Results: Among 46 patients analyzed, 72% received RT alone, 24% induction chemotherapy followed by RT, and 4% concurrent chemoradiation. The median interval from RT completion to the latest, post-RT CT scan was 43 months (IQR 32-57). A decrease in the volume of the irradiated carotid artery was observed in 78% of patients, while there was a statistically significant difference in mean %-change (±SD) between the total irradiated and spared carotid volumes (7.0±9.0 vs. +3.5±7.2, respectively, p<.0001). However, no significant dose-response trend was observed in the carotid artery volume change withing 5 Gy ranges (mean %-changes (±SD) for the 50-55, 55-60, 60-65, and 65-70+ Gy ranges [irradiated minus spared]: -13.1±14.7, -9.8±14.9, -6.9±16.2, -11.7±11.1, respectively). Notably, two patients (4%) had a cerebrovascular accident (CVA), both occurring in patients with a greater decrease in carotid artery volume in the irradiated vs the spared side. Conclusions: Our data show that standard-of-care oncologic surveillance CT scans can effectively detect reductions in carotid volume following RT for oropharyngeal cancer. Changes were equivalent between studied dose ranges, denoting no further dose-response effect beyond 50 Gy. The clinical utility of carotid volume changes for risk stratification and CVA prediction warrants further evaluation.

Contrast Neurotoxicity and its Association with Symptomatic Intracranial Hemorrhage After Mechanical Thrombectomy.

PURPOSE: Despite improved techniques and sophisticated postinterventional care, symptomatic intracranial hemorrhage (sICH) remains the most feared complication of mechanical thrombectomy (MT). Based on peri-interventional parameters, we aimed to discover which patients have a higher risk of sICH. METHODS: From March 2017 until March 2020 consecutive patients with acute ischemic stroke (AIS) and confirmed large-vessel occlusion who underwent MT were analyzed retrospectively. Demographic, clinical, and radiological variables and parameters specific to thrombectomy were reviewed. A univariate analysis was performed and statistically significant variables were included in a logistic regression model to identify independent factors predictive of sICH. RESULTS: A total of 236 patients with confirmed large-vessel occlusion were included and 22 (9.3%) had sICH. Univariate predictors of sICH included diabetes mellitus, glucose > 11.1 mmol/L, creatinine clearance (CrCl) ≤ 30 ml/min/1.73, ASPECTS indicating pretreatment infarct size, acute internal carotid artery (ICA) occlusion, stent implantation, tirofiban use, time from symptom onset to groin puncture > 4.5 h and high contrast medium consumption. In the adjusted analysis, ASPECTS < 6 (OR 3.673, p = 0.041), and amount of contrast injected ≥ 140 ml (OR 5.412, p = 0.003) were independent predictors of sICH, but not any more baseline glucose > 11.1 mmol/L (OR 1.467, p = 0.584), CrCl ≤ 30 ml/min/1.73 (OR 4.177, p = 0.069), acute ICA occlusion (OR 2.079, p = 0.181), stent implantation (OR 0.465, p = 0.512), tirofiban use (OR 5.164, p = 0.167), and time from onset-to-groin puncture (OR 1.453, p = 0.514). CONCLUSION: The amount of contrast medium used is a modifiable factor associated with sICH. This association is novel and may be related to the neurotoxicity of the contrast medium disrupting the blood-brain barrier.

Pre-activated blood platelets and a pro-thrombotic phenotype in APP23 mice modeling Alzheimer's disease.

Platelet activation and thrombus formation play a critical role in primary hemostasis but also represent a pathophysiological mechanism leading to acute thrombotic vascular occlusions. Besides, platelets modulate cellular processes including inflammation, angiogenesis and neurodegeneration. On the other hand, platelet activation and thrombus formation are altered in different diseases leading to either bleeding complications or pathological thrombus formation. For many years platelets have been considered to play a role in neuroinflammatory diseases such as Alzheimer's disease (AD). AD is characterized by deposits of amyloid-ß (Aß) and strongly related to vascular diseases with platelets playing a critical role in the progression of AD because exposure of platelets to Aß induces platelet activation, platelet Aß release, and enhanced platelet adhesion to collagen in vitro and at the injured carotid artery in vivo. However, the molecular mechanisms and the relation between vascular pathology and amyloid-ß plaque formation in the pathogenesis of AD are not fully understood. Compelling evidence is suggestive for altered platelet activity in AD patients. Thus we analyzed platelet activation and thrombus formation in aged AD transgenic mice (APP23) known to develop amyloid-ß deposits in the brain parenchyma and cerebral vessels. As a result, platelets are in a pre-activated state in blood of APP23 mice and showed strongly enhanced integrin activation, degranulation and spreading kinetics on fibrinogen surfaces upon stimulation. This enhanced platelet signaling translated into almost unlimited thrombus formation on collagen under flow conditions in vitro and accelerated vessel occlusion in vivo suggesting that these mice are at high risk of arterial thrombosis leading to cerebrovascular and unexpectedly to cardiovascular complications that might be also relevant in AD patients.