Citations

Abstract Background Microbleeds have been associated with Alzheimer's disease (AD), although it is unclear whether they occur in atypical presentations of AD, such as the logopenic variant of primary progressive aphasia (lvPPA). We aimed to assess the presence and clinical correlates of microbleeds in lvPPA. Methods Thirteen lvPPA subjects underwent 3T T2*‐weighted and fluid‐attenuated inversion recovery magnetic resonance imaging and Pittsburgh compound B (PiB) positron emission tomography imaging. Microbleeds were identified on manual review and assigned a regional location. Total and regional white matter hyperintensity (WMH) burden was measured. Results Microbleeds were observed in four lvPPA subjects (31%), most commonly in the frontal lobe. Subjects with microbleeds were older, more likely female, and had a greater burden of WMH than those without microbleeds. The regional distribution of microbleeds did not match the regional distribution of WMH. All cases were PiB positive. Conclusions Microbleeds occur in approximately one third of subjects with lvPPA, with older women at the highest risk.

BackgroundThe purpose of this study was to report the treatment outcomes of patients with advanced oropharyngeal cancer treated with transoral laser microsurgery (TLM) followed by radiation therapy (RT) at Mayo Clinic in Arizona.MethodsA retrospective study of 80 patients treated from January 1, 2000 to November 7, 2011 was performed. All patients had stage III/IV oropharyngeal tumors and underwent TLM with neck dissection. Adjuvant RT was then given. Thirty‐seven patients received concurrent adjuvant chemotherapy. The primary outcome was locoregional control.ResultsMedian follow‐up was 47.3 months (range, 9.7–139.2 months). The 3‐year locoregional control, recurrence‐free survival, and overall survival rates were 98.6% (95% confidence interval [CI], 91% to 100%), 91.1% (95% CI, 81% to 96%), and 93.7% (95% CI, 84% to 98%), respectively. There were a total of 5 treatment failures, 1 regional and 4 distant. Twenty‐six patients underwent neck only RT with exclusion of the primary site.ConclusionTLM followed by RT for advanced oropharyngeal cancer results in excellent locoregional control rates. © 2013 Wiley Periodicals, Inc. Head Neck 36: 220–225, 2014

Abstract Purpose: This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination. Experimental Design: Patients received vorinostat (200 mg orally, three times a day, for 14 days) on a 21-day cycle, combined with 2 different alvocidib administration schedules: a 1-hour intravenous infusion, daily × 5; or a 30-minute loading infusion followed by a 4-hour maintenance infusion, weekly × 2. The alvocidib dose was escalated using a standard 3+3 design. Results: Twenty-eight patients were enrolled and treated. The alvocidib MTD was 20 mg/m2 (30-minute loading infusion) followed by 20 mg/m2 (4-hour maintenance infusion) on days one and eight, in combination with vorinostat. The most frequently encountered toxicities were cytopenias, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, and QT prolongation. Dose-limiting toxicities (DLT) were cardiac arrhythmia-atrial fibrillation and QT prolongation. No objective responses were achieved although 13 of 26 evaluable patients exhibited stable disease. Alvocidib seemed to alter vorinostat pharmacokinetics, whereas alvocidib pharmacokinetics were unaffected by vorinostat. Ex vivo exposure of leukemia cells to plasma obtained from patients after alvocidib treatment blocked vorinostat-mediated p21CIP1 induction and downregulated Mcl-1 and p-RNA Pol II for some specimens, although parallel in vivo bone marrow responses were infrequent. Conclusions: Alvocidib combined with vorinostat is well tolerated. Although disease stabilization occurred in some heavily pretreated patients, objective responses were not obtained with these schedules. Clin Cancer Res; 19(7); 1873–83. ©2013 AACR.

Abstract Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987–. ©2013 AACR.

Objective To describe the extent of use and in‐hospital outcomes of open and laparoscopic pyeloplasty for paediatric pelvi‐ureteric junction ( PUJ ) obstruction in the USA . Patients and Methods Using the 2004–2008 N ationwide I npatient S ample, we identified 4590 paediatric patients (≤18 years old) who underwent open or laparoscopic pyeloplasty for PUJ obstruction at 195 hospitals. Multivariable regression models were used to test the associations between hospital and patient covariates (age, gender, race, primary health insurance), type of admission (emergent vs elective), and hospital characteristics (teaching vs non‐teaching status; rural vs urban location) with complications, length of stay ( LOS ), and total hospitalization costs. Results During the 5‐year study interval, 4426 (96.4%) and 164 (3.6%) paediatric patients diagnosed with PUJ obstruction underwent open and laparoscopic pyeloplasty, respectively. The proportion of patients undergoing laparoscopic pyeloplasty gradually increased from 2.4% in 2004 to 4.4% in 2008, but this increase was not significant ( P = 0.22 for trend). On multivariable analysis, laparoscopic pyeloplasty was observed to have rates of postoperative complications (2.51 vs 5.00; P = 0.67), LOS (2.42 vs 2.75; P = 0.33) and total hospitalization cost ($9755 vs $8537; P = 0.24) similar to those of open pyeloplasty. Conclusions While laparoscopic pyeloplasty was generally an infrequent operation performed for paediatric PUJ obstruction during the period studied, this minimally invasive surgery provided similar outcomes in terms of in‐hospital complications, LOS and total hospitalization costs. The results of this study inform policymakers about the comparative effectiveness of laparoscopic and open pyeloplasty.

Abstract In shotgun proteomics, database search algorithms rely on fragmentation models to predict fragment ions that should be observed for a given peptide sequence. The most widely used strategy (Naive model) is oversimplified, cleaving all peptide bonds with equal probability to produce fragments of all charges below that of the precursor ion. More accurate models, based on fragmentation simulation, are too computationally intensive for on-the-fly use in database search algorithms. We have created an ordinal-regression-based model called Basophile that takes fragment size and basic residue distribution into account when determining the charge retention during CID/higher-energy collision induced dissociation (HCD) of charged peptides. This model improves the accuracy of predictions by reducing the number of unnecessary fragments that are routinely predicted for highly-charged precursors. Basophile increased the identification rates by 26% (on average) over the Naive model, when analyzing triply-charged precursors from ion trap data. Basophile achieves simplicity and speed by solving the prediction problem with an ordinal regression equation, which can be incorporated into any database search software for shotgun proteomic identification.