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Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES), in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT) is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma.Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012.Results. We identified 14 patients with a total of 27 lesions from osteosarcoma(n=19)or ES(n=8). The median total curative/definitive SBRT dose delivered was 40 Gy in 5 fractions (range, 30–60 Gy in 3–10 fractions). The median total palliative SBRT dose delivered was 40 Gy in 5 fractions (range, 16–50 Gy in 1–10 fractions). Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation.Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity.

AbstractIntroductionAlzheimer's disease (AD) is characterized by the accumulation of β‐amyloid (Aβ) associated with brain atrophy and cognitive decline. The functional form to model the association between Aβ and regional brain atrophy has not been well defined. To determine the relationship between Aβ and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Aβ to identify subjects as Aβ+ and Aβ− with a trilinear spline model of CSF Aβ.MethodsOne hundred and eighty‐three subjects with mild cognitive impairment and 108 cognitively normal controls with baseline CSF Aβ and up to 4 years of longitudinal magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed using mixed‐effects regression. Piecewise‐linear splines were used to evaluate the nonlinear nature of the association between CSF Aβ and regional atrophy and to identify points of acceleration of atrophy with respect to Aβ. Several parameterizations of CSF Aβ were compared using likelihood ratio tests and the Akaike information criterion. Periods of acceleration of atrophy in which subjects transition from CSF Aβ negativity to CSF Aβ positivity were estimated from the spline models and tested for significance.ResultsSpline models resulted in better fits for many temporal and parietal regions compared with the dichotomous models. The trilinear model showed that periods of acceleration of atrophy varied greatly by region with early changes seen in the insula, amygdala, precuneus, hippocampus, and other temporal regions, occurring before the clinical threshold for CSF Aβ positivity.DiscussionThe use of piecewise‐linear splines provides an improved model of the nonlinear association between CSF Aβ and regional atrophy in regions implicated in the progression of AD. The important biological finding of this work is that some brain regions show periods of accelerated volume loss well before the CSF Aβ42 threshold. This implies that signs of brain atrophy develop before the current conventional definition of “preclinical AD”.

Background: Telemedicine has created access to emergency stroke care for patients in all communities, regardless of geography. We hypothesized that there is no difference in speed of assessment between vascular neurologist (VN) robotic telepresence and standard VN-supervised stroke alert patients in a metropolitan primary stroke center. Materials and Methods: A retrospective stroke alert database was used to identify all robotic telepresence and standardly supervised stroke alert patient assessments at a primary stroke center emergency department from 2009 to 2012. The primary outcome measure was the duration of assessment from stroke alert activation to treatment or downgrade. Results: The sample size was 196 subjects. The mean duration of time from stroke alert activation to initiation of intravenous (IV) thrombolytic treatment or downgrade was 8.6 min longer in the robotic group than in the standard group ( p =0.03). Among the subgroup of acute ischemic stroke patients treated with IV thrombolysis, the mean duration of time from activation to treatment was 18 min longer in the robotic group than in the standard group ( p =0.01). Safety outcomes including thrombolysis protocol violations (0% versus 1%), post-thrombolysis symptomatic intracranial hemorrhagic complications (3% versus 1%), and death during hospitalization (8% versus 6%) were low in the robotic group and not significantly different from that in the standard group. Conclusions: Standard VN-supervised acute stroke team assessments were swifter than those supervised by robotic telepresence. Safety outcomes of robotic telepresence-supervised stroke alerts were excellent, and this modality may be preferred in circumstances when a VN is not immediately available on-site.

Blood eosinophilia (≥0.5 × 109/l) may be an early sign of hematological malignancy. We investigated associations between levels of blood eosinophils and risks of hematological malignancies and mortality in order to provide clinically derived cut‐offs for referral to specialist hematology care. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count encompassing the eosinophil count during 2000–2007 and matched these laboratory data with Danish nationwide health registers. We used multivariable logistic regression to calculate odds ratios (ORs) for the 4‐year incidences of hematological malignancies and mortality between the eosinophil counts and a reference count of 0.16 × 109/l which was the median eosinophil count in our data. Risks of hematological malignancies and mortality increased above the median eosinophil count. At the 99th percentile, corresponding to an eosinophil count of 0.75 × 109/l, risks of hematological malignancies were increased more than twofold with OR (95% C.I.) of 2.39 (1.91–2.99). Interestingly, risks reached a plateau around an eosinophil count of 1.0 × 109/l. Risks also increased when the eosinophil count approached zero. Here, counts associated relatively more with acute myeloid leukemia and myelodysplastic syndromes whereas counts above 0.16 × 109/l associated more with myeloproliferative neoplasms. Eosinophil counts associate with hematological malignancies and mortality even below the definition of eosinophilia. The observed plateau of risks around 1.0 × 109/l is important for physicians encountering patients with eosinophilia since even mild‐to‐moderate eosinophilia according to traditional definitions confers maximally increased risks of subsequent/subclinical hematological malignancy. Am. J. Hematol. 90:225–229, 2015. © 2014 Wiley Periodicals, Inc.

Patients are increasingly being prescribed antiplatelet agents (APAs) for a growing number of medical and surgical conditions. These agents are associated with an increased risk of hemorrhage, including intracranial hemorrhage (ICH). In the setting of warfarin use and ICH, strategies to reverse the drug effects have improved outcomes. No such strategy exists for APAs, and these patients continue to have poor posthemorrhage outcomes. One strategy is the use of platelet transfusions to provide functional, circulating platelets. Studies have shown mixed results regarding the benefit of this practice. Other strategies include the use of desmopressin and recombinant factor VIIa. More studies are necessary to delineate the effectiveness of the various strategies.

Objective To better characterize the genomics of patients with biochemical recurrence ( BCR ) who have metastatic disease progression in order to improve treatment decisions for prostate cancer. Methods The expression profiles of three clinical outcome groups after radical prostatectomy ( RP ) were compared: those with no evidence of disease ( NED ; n = 108); those with BCR (rise in prostate‐specific antigen [ PSA ] level without metastasis; n = 163); and those with metastasis ( n = 192). The patients were profiled using Human Exon 1.0 ST microarrays, and outcomes were supported by a median 18 years of follow‐up. A metastasis signature was defined and verified in an independent RP cohort to ensure the robustness of the signature. Furthermore, bioinformatics characterization of the signature was conducted to decipher its biology. Results Minimal gene expression differences were observed between adjuvant treatment‐naïve patients in the NED group and patients without metastasis in the BCR group. More than 95% of the differentially expressed genes (metastasis signature) were found in comparisons between primary tumours of metastasis patients and the two other outcome groups. The metastasis signature was validated in an independent cohort and was significantly associated with cell cycle genes, ubiquitin‐mediated proteolysis, DNA repair, androgen, G‐protein coupled and NOTCH signal transduction pathways. Conclusion This study shows that metastasis development after BCR is associated with a distinct transcriptional programme that can be detected in the primary tumour. Patients with NED and BCR have highly similar transcriptional profiles, suggesting that measurement of PSA on its own is a poor surrogate for lethal disease. Use of genomic testing in patients undergoing RP with an initial rise in PSA level may be useful to improve secondary therapy decision‐making.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with increased cardiovascular morbidity and all‐cause mortality. Our aim was to determine the impact of preexisting AF on patients undergoing liver transplantation (LT). A retrospective case‐control study was performed. Records from patients who underwent LT between January 2005 and December 2008 at Mayo Clinic Florida were reviewed. Patients with preexisting AF were identified and matched to patients who did not have a diagnosis of AF. Thirty‐two of 717 LT recipients (4.5%) had AF before LT. These patients were compared to a control group of 63 LT recipients. Pre‐LT left ventricular hypertrophy (P = 0.03), a history of congestive heart failure (P = 0.04), and a history of stroke or transient ischemic attack (P = 0.03) were significantly more prevalent in patients with AF versus controls. Intraoperative adverse cardiac events (P = 0.02) and AF‐related adverse postoperative events (P < 0.001) were more common in the recipients with known AF. Six patients with paroxysmal AF (19%) developed chronic/persistent AF postoperatively. Graft survival and patient survival were similar in the groups. Although patients with AF had a higher incidence of intraoperative cardiac events, a higher cardiovascular morbidity rate, and a complicated postoperative course, this did not affect overall graft and patient survival. Liver Transpl 21:314–320, 2015. © 2014 AASLD.