Citations

LBA2000 Background: Formalin-fixed, paraffin embedded GBM tumor tissue, adequate for conventional MGMT methylation analyses, was required for entry onto the RTOG 0525 clinical trial. Methods: Four prognostic biomarkers were evaluated on a training set of 220 retrospectively obtained GBM samples, consisting of IDH1 mutation, the glioma-CpG island methylator phenotype (G-CIMP), a microarray-based mRNA panel and a novel MGMT promoter methylation assay. For each biomarker, 2 (IDH1 and mRNA) or 3 subgroups (G-CIMP and MGMT) were defined based on associations with overall survival. All combinations (36 possible) of each of the 4 biomarker-derived subgroups were then defined and compared with survival data and then consolidated into 4 risk groups. Once created in the training set, this model was applied to the RTOG 0525 samples (n=763) for external validation. Results: Application of the molecular risk classification to RTOG 0525 samples (left table) showed a highly significant survival association (p<0.001). When compared to the recursive partitioning analysis (RPA, table on right), this composite molecular classifier better identified patients with long term survival and appears to improve resolution by revealing an additional distinct risk group. The molecular classifier was prognostic in each of the treatment arms individually. Conclusions: Four distinct biomarkers or biomarker panels were tested in GBM. These biomarkers were compared with clinical outcome in a training set to optimize a method to combine them into a classifier. This classifier was then validated on a large sample set from a large phase III clinical trial. This composite panel may represent an improvement over the existing RPA with respect to risk stratification of patients for GBM. Additionally, it has the potential to impact future clinical trial designs and provide enhanced opportunities for personalization of therapy for GBM. Support: NCI U10 CA2121661, U10 CA37422, P50 CA127001. [Table: see text]

Background: Therapy programs to treat thumb carpometacarpal (CMC) arthritis may engage selective activation and reeducation of thenar muscles, particularly the first dorsal interosseous (FDI) and opponens pollicis (OP) to reduce subluxation of the joint. We describe the effect of simulated selective activation of the FDI and OP muscles upon radiographic subluxation of the thumb CMC joint. Methods: In a cadaver model of CMC subluxation, loads were applied to the FDI, the OP, and then concomitantly at 0%, 25%, 50%, 75%, and 100% maximal loads and radial subluxation of the joint and reduction in subluxation was measured. Results: Selective activation of the OP, alone, improved the subluxation ratio (SR) in a dose-dependent manner. Selective activation of FDI, alone, demonstrated minimal effects on SR. Concomitant activation of OP and FDI improved the SR across all loading states, and activation of 75% and greater, when compared with FDI activation alone, resulted in a statistically significant improvement in SR to within 10% of the presubluxed joint. Conclusions: Concomitant activation of the FDI and OP acts to reduce subluxation of the thumb CMC joint in a dose-dependent fashion. The OP is likely the predominant reducing force. Hand therapy programs that focus on selective strengthening programs likely function in part to encourage patients to activate the easily palpable and easily understood FDI. Concomitant coactivation of the OP may be the major reducing force to elicit clinical and radiographic reduction of subluxation, improved thumb positioning, and reduction of pain and arthritic symptoms.

Abstract Introduction Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods We conducted a transethnic genome‐wide association study (GWAS) for late‐onset AD in Stage 1 sample including whites of European Ancestry, African‐Americans, Japanese, and Israeli‐Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results Genome‐wide significant (GWS) associations in single‐nucleotide polymorphism (SNP)–based tests ( P < 5 × 10 −8 ) were identified for SNPs in PFDN1/HBEGF , USP6NL/ECHDC3 , and BZRAP1‐AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence ( P < 2.7 × 10 −6 ) for gene‐based association in the total sample with a novel locus, TPBG ( P = 1.8 × 10 −6 ). Discussion Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

SummaryTwo patients who shared similar presenting clinical features of anterograde and retrograde autobiographical amnesia typical of transient epileptic amnesia (TEA) underwent prolonged video electroencephalogram (VEEG) monitoring and were found to have sleep‐activated epileptiform activity and frequent subclinical bitemporal seizures predominantly during sleep. Case 1 is a 59‐year‐old woman whose presenting complaint was memory impairment. Over 18 months, she had three distinct 8‐h‐long episodes of confusion and disorientation with persistent anterograde and retrograde autobiographical amnesia. VEEG recorded frequent interictal bitemporal sharp waves confined to sleep, and 14 subclinical seizures, also mostly during sleep. Case 2 is a 50‐year‐old woman with known focal epilepsy also presented with memory complaints. Over the course of 1 year, she had two discrete 2‐h‐long episodes of amnesia, with ongoing anterograde and retrograde autobiographical amnesia. VEEG recorded independent bitemporal sharp waves, and 14 subclinical seizures during sleep and drowsiness. Memory impairment improved in both patients with successful treatment of their seizures. Although the etiology of accelerated long‐term forgetting (ALF) and remote memory impairment (RMI) in transient epileptic amnesia (TEA) is unknown, these cases suggest frequent sleep‐related seizures may contribute, and they highlight the importance of video‐EEG monitoring.

Objectives We aimed to determine the rates of readmission and reoperation for patients undergoing surgery for pelvic organ prolapse (POP). Methods The American College of Surgeons National Surgical Quality Improvement Program Participant User File was used to select all surgeries performed for POP from 2012 through 2014. The cohort was then reviewed for unplanned readmissions and unplanned reoperations within 30 days of POP surgery. Patient and procedural factors associated with readmission or reoperation were compared using χ2 analyses and Student t test. Multivariable logistic regression determined independent risk factors for both readmission and reoperation. Results A total of 23,419 patients underwent surgery for POP. Of these, there were 435 (1.9%) readmissions and 341 (1.5%) reoperations within 30 days. Median numbers of days from index procedure to readmission or reoperation were 9 and 8 days, respectively. Those who were readmitted had higher American Society of Anesthesia (ASA) scores, longer operative times, and longer lengths of stay than those who were not readmitted (all P < 0.001). Patients who underwent unplanned reoperation also had higher ASA scores, longer operative times, and longer lengths of stay than those who did not undergo reoperation (all P < 0.01). The most common reasons for readmission were surgical site infection (SSI) (19.3%) and non-SSI (15.9%). The most common reason for reoperation was urologic (27.6%) such as cystoscopy or stent placement. Conclusions Readmission and reoperation rates are relatively low for patients undergoing surgery for POP. Infection, both SSI and non-SSI, accounted for 35.2% of readmissions. Identification of ASA score of 3 or higher, longer total operating time, and increased length of stay is associated with unplanned readmission and reoperation.