Sarcopenia defined by a computed tomography estimate of the psoas muscle area does not predict frailty in geriatric trauma patients.

INTRODUCTION: The aim of our study was to assess the correlation between frailty & sarcopenia and impact of each condition on outcomes in geriatric trauma patients. METHODS: We performed a four-year (2013-2016) secondary analysis of our prospectively maintained frailty database and included all trauma patients age ≥65 y who had CT-abdomen. Trauma-Specific-Frailty-Index (TSFI) was used to calculate frailty. Patients were classified as non-frail or frail. Sarcopenia was defined as the lowest sex-specific-quartile of total-psoas-index (TPI). Outcome measures included in-hospital complications, mortality and adverse disposition. RESULTS: 325 patients were included in the study, 36% (n = 117) were frail and 24.9% (n = 81) had sarcopenia. There was a weak correlation between frailty and sarcopenia (R2 = 0.04). The overall rate of complications and mortality was 19.4% and 7.7% respectively. On regression analysis, after controlling for possible confounding variables and frailty status, sarcopenia was associated with adverse disposition (OR:1.41,p = 0.01). However, it was not associated with in-hospital complications (OR:1.21,p = 0.54) or in-hospital mortality (OR:1.12,p = 0.73). CONCLUSION: Sarcopenia as an individual marker might not be an effective screening tool for risk assessment in geriatric-trauma patients. Frailty assessment should be a part of risk assessment and prognostication.

A pharmacophore derived phenytoin analogue with increased affinity for slow inactivated sodium channels exhibits a desired anticonvulsant profile.

Phenytoin (DPH) is a clinically useful sodium (Na) channel blocker with efficacy against partial and generalized seizures. We have developed a novel hydantoin compound (HA) using comparative molecular field analysis (CoMFA) and evaluated its effects on hNa(v)1.2 channels. Both DPH and HA demonstrated affinity for resting (K(r)=13.9microM for HA, K(r)=464microM for DPH) and slow inactivated channels (K(I)=975nM for HA, K(I)=20.6microM for DPH). However, HA also exhibited an affinity for fast inactivated channels (K(I)=2.5microM) and shifted the V(1/2) for activation in the depolarizing direction. Furthermore, HA exhibited profound use dependent block at both 5 and 10Hz stimulation frequencies. In the 6Hz seizure model (32mA) HA had an ED(50) of 47.1mg/kg and a TD(50) of 131mg/kg (protective index (PI)=2.8). In comparison, the ED(50) for DPH was approximately 27.5mg/kg with a TD(50) of 35.6mg/kg (PI approximately 1.3). These findings provide evidence for the utility of CoMFA in the design of novel anticonvulsants and support the hypothesis that states selectivity plays an important role in achieving optimal protection with minimal side effects.