Citations

Targeting a kinase common to both the EGFR and TNFα signaling pathways may prevent drug resistance in glioblastoma.

Abstract Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age‐related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and AD.” The scientific sessions of the workshop focused on age‐related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory‐motor deficits in AD may enhance patient function as AD progresses.

AbstractBackgroundRegulatory qualification of a biomarker for a defined context of use provides scientifically robust assurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development.MethodsThe Coalition Against Major Diseases submitted a dossier to the Scientific Advice Working Party of the European Medicines Agency requesting a qualification opinion on the use of hippocampal volume as a biomarker for enriching clinical trials in subjects with mild cognitive impairment, incorporating a scientific rationale, a literature review and a de novo analysis of Alzheimer's Disease Neuroimaging Initiative data.ResultsThe literature review and de novo analysis were consistent with the proposed context of use, and the Committee for Medicinal Products for Human Use released an opinion in November 2011.ConclusionsWe summarize the scientific rationale and the data that supported the first qualification of an imaging biomarker by the European Medicines Agency.

AbstractBoth traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood‐level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One‐year follow‐up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at‐risk veterans as subjects, and provides the basis for a larger, more comprehensive study of dementia risk factors in veterans.

Background Shoulder arthroscopy is not common in the pediatric and adolescent population, but the frequency may be on the rise. The purpose of the study was to determine the incidence of acute complications of arthroscopic shoulder surgery in children and adolescents. Methods A retrospective, cross-sectional review was performed identifying patients aged 18 years or less who underwent an arthroscopic shoulder procedure from 1997 to 2009 at Institution 1 and 2007 to 2010 at Institution 2. Exclusion criteria included open procedures and missing records. Demographic and surgical data were collected, including intra-operative and post-operative complications during the first 6 months. The complications were divided into minor (no secondary treatment) and major (secondary treatment rendered). Results Two hundred children, mean age 15.9 years, met criteria and 73 % were boys. All procedures were performed under general anesthesia, but 51 % included inter-scalene regional anesthesia. There were 16 (8.0 %) total complications recorded. Major complications occurred in five (2.5 %) patients, including two tendinitis/bursitis requiring injections, one broken pain pump catheter requiring an accessory incision to retrieve, one pain control readmission, and one laceration of the cephalic vein requiring ligation. Minor complications occurred in 11 (5.5 %) patients, including allergic reactions, transient dysesthesias, headaches, bronchitis, syncope, transient hypotension, and uvula swelling. Conclusion Although we found no seriously deleterious outcomes, it is important to recognize that an additional service was rendered for 2.5 % of children undergoing shoulder arthroscopy. The events that did occur may be preventable and this study should serve as a baseline to improve quality and safety of shoulder arthroscopy in the pediatric population.

A patient presented with neuromuscular, respiratory and cardiac symptoms and was initially diagnosed with amyotrophic lateral sclerosis (ALS), myocardial ischaemia and pneumonia. He developed unexplained progressive kidney failure over the ensuing week, and his kidney biopsy showed thrombotic microangiopathy that led to the correct diagnosis of normotensive scleroderma renal crisis. His clinical presentation and course were consistent with systemic sclerosis and normotensive scleroderma renal crisis. He was treated with an ACE inhibitor (ACEi) and haemodialysis with significant functional improvement over the next 3 months to his prior baseline with the exception of kidney failure. This case highlights a diagnostic challenge requiring astute history and physical examination skills, and the value of a kidney biopsy in providing the final diagnosis.

Key Points Methylation analysis at ZAP-70 CpG+223 in CLL provides superior prognostic information vs IGHV status or CD38 or ZAP-70 expression. A pyrosequencing method for the feasible assessment of CpG+223 methylation in CLL samples is provided.