Assessing frailty in elderly patients with hip fractures: A retrospective review comparing geriatrician and orthopedic trainee assessments.

To assess the correlation of orthopedic surgery residents compared with expert geriatricians in the assessment of frailty stage using the Clinical Frailty Scale (CFS) in patients with hip fractures. A retrospective chart review was performed from January 1, 2015 to December 31, 2019. Patients admitted with a diagnosis of hip fracture were identified. Those patients with a CFS score completed by orthopedic residents with subsequent CFS score completed by a geriatrician during their admission were extracted. Six hundred and forty-eight patients over age 60 (mean 80.5 years, 73.5% female) were admitted during the study period. Orthopaedic residents completed 286 assessments in 44% of admissions. Geriatric medicine consultation was available for 215 patients such that 93 patients were assessed by both teams. Paired CFS data were extracted from the charts and tested for agreement between the 2 groups of raters. CFS assessments by orthopedic residents and geriatrician experts were significantly different at P < .05; orthopedic residents typically assessed patients to be one CFS grade less frail than geriatricians. Despite this, the CFS assessments showed good agreement between residents and geriatricians. Orthopaedic surgery residents are reliable assessors of frailty but tend to underestimate frailty level compared with specialist geriatricians. Given the evidence to support models such as orthogeriatrics to improve outcomes for frail patients, our findings suggest that orthopedic residents may be well positioned to identify patients who could benefit from such early interventions. Our findings also support recent evidence that frailty assessments by orthopedic surgeons may have predictive validity. Low rates of initial frailty assessment by orthopedic residents suggests that further work is required to integrate more global comprehensive care.

OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation.

Glioblastoma contains a rare population of self-renewing brain tumor stem cells (BTSCs) which are endowed with properties to proliferate, spur the growth of new tumors, and at the same time, evade ionizing radiation (IR) and chemotherapy. However, the drivers of BTSC resistance to therapy remain unknown. The cytokine receptor for oncostatin M (OSMR) regulates BTSC proliferation and glioblastoma tumorigenesis. Here, we report our discovery of a mitochondrial OSMR that confers resistance to IR via regulation of oxidative phosphorylation, independent of its role in cell proliferation. Mechanistically, OSMR is targeted to the mitochondrial matrix via the presequence translocase-associated motor complex components, mtHSP70 and TIM44. OSMR interacts with NADH ubiquinone oxidoreductase 1/2 (NDUFS1/2) of complex I and promotes mitochondrial respiration. Deletion of OSMR impairs spare respiratory capacity, increases reactive oxygen species, and sensitizes BTSCs to IR-induced cell death. Importantly, suppression of OSMR improves glioblastoma response to IR and prolongs lifespan.

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons.

Cerebellar granule neurons (CGNs) are a commonly used neuronal model, forming an abundant homogeneous population in the cerebellum. In light of their post-natal development, abundance, and accessibility, CGNs are an ideal model to study neuronal processes, including neuronal development, neuronal migration, and physiological neuronal activity stimulation. In addition, CGN cultures provide an excellent model for studying different modes of cell death including excitotoxicity and apoptosis. Within a week in culture, CGNs express N-methyl-D-aspartate (NMDA) receptors, a specific ionotropic glutamate receptor with many critical functions in neuronal health and disease. The addition of low concentrations of NMDA in conjunction with membrane depolarization to rodent primary CGN cultures has been used to model physiological neuronal activity stimulation while the addition of high concentrations of NMDA can be employed to model excitotoxic neuronal injury. Here, a method of isolation and culturing of CGNs from 6 day old pups as well as genetic manipulation of CGNs by adenoviruses and lentiviruses are described. We also present optimized protocols on how to stimulate NMDA-induced excitotoxicity, low-potassium-induced apoptosis, oxidative stress and DNA damage following transduction of these neurons.