N -acetylcysteine is associated with reduction of postconcussive symptoms in elderly patients: A pilot study.

INTRODUCTION: N -acetylcysteine (NAC) may be neuroprotective by minimizing postconcussion symptoms after mild traumatic brain injury (TBI), but limited data exist. This study evaluated the effects of NAC on postconcussion symptoms in elderly patients diagnosed with mild TBI. METHODS: This prospective, quasirandomized, controlled trial enrolled patients 60 years or older who suffered mild TBI. Patients were excluded if cognitive function could not be assessed within 3-hours postinjury. Patients were allocated to receive NAC plus standard care, or standard care alone, based on the trauma center where they presented. The primary study outcome was the severity of concussive symptoms measured using the Rivermeade Postconcussion Symptoms Questionnaire (RPQ). Symptoms were evaluated on days 0, 7, and 30. The RPQ scores were compared both within and between treatment groups. RESULTS: There were 65 patients analyzed (NAC, n = 34; control, n = 31) with an average age of 76 ± 10 years. Baseline demographics and clinical variables were similar. No group differences in head Abbreviated Injury Scale score or Glasgow Coma Scale score were observed. Baseline RPQ scores (6 [0-20] vs. 11 [4-20], p = 0.300) were indistinguishable. The RPQ scores on day 7 (2 [0-8] vs. 10 [3-18], p = 0.004) and 30 (0 [0-4] vs. 4 [0-13], p = 0.021) were significantly lower in the NAC group. Within-group differences were significantly lower in the NAC ( p < 0.001) but not control group ( p = 0.319). CONCLUSION: N -acetylcysteine was associated with significant improvements in concussion symptoms in elderly patients with mild TBI. These results justify further research into using NAC to treat TBI. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Cyst(e)inase-Rapamycin Combination Induces Ferroptosis in Both In Vitro and In Vivo Models of Hereditary Leiomyomatosis and Renal Cell Cancer.

Renal cell carcinomas associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) are notoriously aggressive and represent the leading cause of death among patients with HLRCC. To date, a safe and effective standardized therapy for this tumor type is lacking. Here we show that the engineered synthetic therapeutic enzyme, Cyst(e)inase, when combined with rapamycin, can effectively induce ferroptosis in HLRCC cells in vivo. The drug combination promotes lipid peroxidation to a greater degree than cysteine deprivation or Cyst(e)inase treatment alone, while rapamycin treatment alone does not induce ferroptosis. Mechanistically, Cyst(e)inase induces ferroptosis by depleting the exogenous cysteine/cystine supply, while rapamycin reduces cellular ferritin level by promoting ferritins' destruction via ferritinophagy. Since both Cyst(e)inase and rapamycin are well tolerated clinically, the combination represents an opportunity to exploit ferroptosis induction as a cancer management strategy. Accordingly, using a xenograft mouse model, we showed that the combination treatment resulted in tumor growth suppression without any notable side effects. In contrast, both Cyst(e)inase only and rapamycin only treatment groups failed to induce a significant change when compared with the vehicle control group. Our results demonstrated the effectiveness of Cyst(e)inase-rapamycin combination in inducing ferroptotic cell death in vivo, supporting the potential translation of the combination therapy into clinical HLRCC management.

In-Home Delivery of Constraint-Induced Movement Therapy via Virtual Reality Gaming.

PURPOSE: People with chronic hemiparesis are frequently dissatisfied with the recovery of their hand and arm, yet many lack access to effective treatments. Constraint-induced movement therapy (CI therapy) effectively increases arm function and spontaneous use in persons with chronic hemiparesis. The purpose of this study was to determine the feasibility and measure safety and outcomes of an in-home model of delivering CI therapy using a custom, avatar-based virtual reality game. METHODS: Seventeen individuals with chronic hemiparesis participated in this pretest/posttest quasi-experimental design study. The 10-day intervention had three components: 1) high-repetition motor practice using virtual reality gaming; 2) constraint of the stronger arm via a padded restraint mitt; and 3) a transfer package to reinforce arm use. Feasibility of the intervention was evaluated through comparison to traditional CI therapy and through participants' subjective responses. The primary outcome measures were the Wolf Motor Function Test (WMFT) and the Motor Activity Log quality of movement scale (MAL-QOM). RESULTS: On average, participants completed 17.2 ± 8 hours and 19,436 repetitions of motor practice. No adverse events were reported. Of 7 feasibility criteria, 4 were met. WMFT rate and MAL-QOM increased, with effect size (Cohen's d) of 1.5 and 1.1, respectively. CONCLUSIONS: This model of delivering CI therapy using a custom, avatar-based virtual reality game was feasible, well received, and showed preliminary evidence of being a safe intervention to use in the home for persons with chronic hemiparesis.