Citations

Abstract Introduction Quantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B–based and florbetapir‐based amyloid imaging in the same participants from two independent cohorts using a crossover design. Methods Pittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter‐individual variability of the two tracers were compared using multivariate linear models both cross‐sectionally and longitudinally. Results Global amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers. Discussion Although the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.

AbstractBackgroundWe reviewed the disease control and complications of the treatment of sacrococcygeal chordoma from four tertiary cancer centers with emphasis on the effects of radiotherapy in surgically treated patients.MethodsA total of 193 patients with primary sacrococcygeal chordoma from 1990 to 2015 were reviewed. There were 124 males, with a mean age of 59 ± 15 years and a mean follow‐up of 7 ± 4 years. Eighty‐nine patients received radiotherapy with a mean total dose of 61.8 ± 10.9 Gy.ResultsThe 10‐year disease‐free and disease‐specific survival was 58% and 72%, respectively. Radiation was not associated with local recurrence (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.59‐2.17; P = 0.71), metastases (HR, 0.93; 95% CI, 0.45‐1.91; P = 0.85) or disease‐specific survival (HR, 0.96; 95% CI, 0.46‐2.00; P = 0.91). Higher doses (≥70 Gy; HR, 0.52; 95% CI, 0.20‐1.32; P = 0.17) may be associated with reduced local recurrence. Radiotherapy was associated with wound complications (HR, 2.76; 95% CI, 1.64‐4.82;, P < 0.001) and sacral stress fractures (HR, 4.73; 95% CI, 1.88‐14.38; P < 0.001).ConclusionsIn this multicenter review, radiotherapy was not associated with tumor outcome but associated with complications. The routine use of radiotherapy with en‐bloc resection of sacrococcygeal chordomas should be reconsidered in favor of a selective, individualized approach with a radiation dose of ≥70 Gy.

Abstract Genetic forms of frontotemporal dementia are most commonly due to mutations in three genes, C9orf72, GRN or MAPT, with presymptomatic carriers from families representing those at risk. While cerebral blood flow shows differences between frontotemporal dementia and other forms of dementia, there is limited evidence of its utility in presymptomatic stages of frontotemporal dementia. This study aimed to delineate the cerebral blood flow signature of presymptomatic, genetic frontotemporal dementia using a voxel-based approach. In the multicentre GENetic Frontotemporal dementia Initiative (GENFI) study, we investigated cross-sectional differences in arterial spin labelling MRI-based cerebral blood flow between presymptomatic C9orf72, GRN or MAPT mutation carriers (n = 107) and non-carriers (n = 113), using general linear mixed-effects models and voxel-based analyses. Cerebral blood flow within regions of interest derived from this model was then explored to identify differences between individual gene carrier groups and to estimate a timeframe for the expression of these differences. The voxel-based analysis revealed a significant inverse association between cerebral blood flow and the expected age of symptom onset in carriers, but not non-carriers. Regions included the bilateral insulae/orbitofrontal cortices, anterior cingulate/paracingulate gyri, and inferior parietal cortices, as well as the left middle temporal gyrus. For all bilateral regions, associations were greater on the right side. After correction for partial volume effects in a region of interest analysis, the results were found to be largely driven by the C9orf72 genetic subgroup. These cerebral blood flow differences first appeared approximately 12.5 years before the expected symptom onset determined on an individual basis. Cerebral blood flow was lower in presymptomatic mutation carriers closer to and beyond their expected age of symptom onset in key frontotemporal dementia signature regions. These results suggest that arterial spin labelling MRI may be a promising non-invasive imaging biomarker for the presymptomatic stages of genetic frontotemporal dementia.

Objective: The overall risk of ischemic stroke from a chronically occluded internal carotid artery (COICA) is around 5%-7% per year despite receiving the best medical therapy. We propose a radiographic classification of COICA that can be used as a guide to determine the technical success and safety of endovascular recanalization for symptomatic COICA. Methods: The radiographic images of 100 consecutive subjects with COICA were analyzed. A new classification of COICA was proposed based on the morphology, location of occlusion, and presence or absence of reconstitution of the distal ICA. The classification was used to predict successful revascularization in 32 symptomatic COICAs in 31 patients. Patients were included in the study if they had a COICA with ischemic symptoms refractory to medical therapy. Results: Four types (A-D) of radiographic COICA were identified. Types A and B were more amenable to safe revascularization than types C and D. Recanalization was successful at a rate of 68.75% (22/32 COICAs; type A: 8/8; type B: 8/8; type C: 4/8; type D: 2/8). The perioperative complication rate was 18.75% (6/32; type A: 0/8 [0%]; type B: 1/8 [12.50%]; type C: 3/8 [37.50%], type D: 2/8 [25.00%]). None of these complications led to permanent morbidity or death. Twenty (64.52%) of 31 subjects had improvement in their symptoms at the 2-6 months' follow-up. A statistically significant decrease in systolic blood pressure (SBP) was noted in 17/21 (80.95%) patients who had successful revascularization, which persisted on follow-up (p = 0.0001). The remaining 10 subjects in whom revascularization failed had no significant changes in SBP (p = 0.73). Conclusions: The pilot study suggested that our proposed classification of COICA may be useful as an adjunctive guide to determine the technical feasibility and safety of revascularization for symptomatic COICA using endovascular techniques. Additionally, successful revascularization may lead to a significant decrease in SBP postprocedure. A Phase 2b trial in larger cohorts to assess the efficacy of endovascular revascularization using our COICA classification is warranted.

Purpose of review Cardiovascular disease (CVD) is a common cause of mortality after liver transplantation. The transplant community is focused on improving long-term survival. Understanding the prevalence of CVD in liver transplant recipients, precipitating factors as well as prevention and management strategies is essential to achieving this goal. Recent findings CVD is the leading cause of death within the first year after transplant. Arrhythmia and heart failure are the most often cardiovascular morbidities in the first year after transplant which could be related to pretransplant diastolic dysfunction. Pretransplant diastolic dysfunction is reflective of presence of cirrhotic cardiomyopathy which is not as harmless as it was thought. Multiple cardiovascular risk prediction models have become available to aid management in liver transplant recipients. Summary A comprehensive prevention and treatment strategy is critical to minimize cardiovascular morbidity and mortality after liver transplant. Weight management and metabolic syndrome control are cornerstones to any prevention and management strategy. Bariatric surgery is an underutilized tool in liver transplant recipients. Awareness of ‘metabolic-friendly’ immunosuppressive regimens should be sought. Strict adherence to the cardiology and endocrine society guidelines with regard to managing metabolic derangements post liver transplantation is instrumental for CVD prevention until transplant specific recommendations can be made.

Background Optimism and pessimism are related to several mental health and brain disorders, are significant predictors of physical and psychological health outcomes, and implicated as psychosocial determinants of the pain experience. Despite this promising evidence, limited information is available on optimism and pessimism in headache disorders. Objective To evaluate the influence of optimism and pessimism in meeting criteria for migraine and related disability in a population‐based sample. Methods This is an observational, cross‐sectional study. The sample population was selected through a stratified, multi‐stage area probability sample of households, as used by the last Brazilian Census. A validated questionnaire eliciting data on demographics, headache features, migraine‐related disability, depression (PHQ‐9), anxiety (GAD‐7), optimism, and pessimism (life orientation test – revised) was administered to people with migraine and headache‐free control participants from the general population in São Paulo, Brazil via trained interviewers. Six hundred individuals were contacted. The odds for having migraine/no headache diagnosis were calculated by binary logistic regression, and ordinal regression was performed to check associations between migraine‐related disability and optimism. Results A total of 302 individuals (mean ± SD age: 39.7 ± 12.7; BMI: 26.5 ± 5.9) met inclusion criteria and were included, 140 controls (with no history of headache disorders) and 162 people meeting criteria for migraine (29 with chronic migraine, that is, 15 or more headache days/month). People with migraine were less optimistic and more pessimistic than controls, and endorsed higher levels of anxious and depressive symptoms. Pessimism (OR 95% CI = 1.16 [1.05–1.28], P = .005) and anxiety (OR 95% CI = 1.19 [1.10–1.29], P < .001) were predictors of meeting criteria for migraine, while optimism (β 95% CI = −0.915 [−1.643, −0.188], P = .01) was inversely associated with migraine‐related disability. Conclusions Optimism and pessimism are associated with migraine and migraine‐related disability. These concepts should be further explored in people with migraine with regard to their potential influences on clinical research outcomes and treatments.

Abstract Osteosarcomas are bone tumors that frequently metastasize to the lung. Aberrant expression of the transcription factor, runt‐related transcription factor 2 (RUNX2), is a key pathological feature in osteosarcoma and associated with loss of p53 and miR‐34 expression. Elevated RUNX2 may transcriptionally activate genes mediating tumor progression and metastasis, including the RUNX2 target gene osteopontin ( OPN/SPP1 ). This gene encodes a secreted matricellular protein produced by osteoblasts to regulate bone matrix remodeling and tissue calcification. Here we investigated whether and how the RUNX2/OPN axis regulates lung metastasis of osteosarcoma. Importantly, RUNX2 depletion attenuates lung metastasis of osteosarcoma cells in vivo. Using next‐generation RNA‐sequencing, protein‐based assays, as well as the loss‐ and gain‐of‐function approaches in selected osteosarcoma cell lines, we show that osteopontin messenger RNA levels closely correlate with RUNX2 expression and that RUNX2 controls the levels of secreted osteopontin. Elevated osteopontin levels promote heterotypic cell–cell adhesion of osteosarcoma cells to human pulmonary microvascular endothelial cells, but not in the presence of neutralizing antibodies. Collectively, these findings indicate that the RUNX2/OPN axis regulates the ability of osteosarcoma cells to attach to pulmonary endothelial cells as a key step in metastasis of osteosarcoma cells to the lung.

Purpose To describe the clinical history of a series of primary, lateral patellar dislocations and determine long‐term predictors of recurrent instability while accounting for patients undergoing early operative management. Methods A large geographic database of more than 500,000 patients was used to identify patients who sustained a first‐time lateral patellar dislocation between 1990 and 2010. Charts were individually reviewed to document demographics, radiographic measures including tibial tubercle to trochlear groove distance (TT‐TG) and patellar length (PL), recurrent episodes of instability, and patellar stabilization surgery. A risk score that accounted for early surgical management was calculated using Fine and Gray competing risk regression, and its ability to stratify patients was examined using cumulative incidence curves. Results Eighty‐one patients (mean age 19.9 ± 9.4 years, 38 male, 43 female) were identified and followed for a mean of 10.1 years (range 4.1‐20.2). Thirty‐eight patients (46.9%) experienced an episode of recurrent instability and 30 (37.0%) underwent patellar stabilization surgery, including 7 who did so before recurrent dislocation. A multivariate, statistically derived scoring system, the Recurrent Instability of the Patella Score (RIP Score), that employed age, skeletal maturity, trochlear dysplasia, and TT‐TG/PL ratio to predict recurrent instability while accounting for patients managed surgically, was generated. The resulting RIP score stratified patients into low‐, intermediate‐, and high‐risk categories, with 0.0%, 30.6%, and 79.2% 10‐year recurrent instability rates, respectively ( P = .000004), and an area under the curve of 0.875 ( P = .00002). Conclusions Patients who sustain a first‐time, lateral patellar dislocation can be readily classified into low‐, intermediate‐, and high‐risk categories employing the RIP score based on age, skeletal maturity, trochlear dysplasia, and TT‐TG/PL ratio. This long‐term risk stratification holds significant potential clinical utility for determination of patients who are at high risk for recurrent instability after primary patellar dislocation. Level of Evidence Level III, retrospective comparative study.