BackgroundRecent advances toward an effective therapy for prion diseases employ RNA interference to suppress PrPC expression and subsequent prion neuropathology, exploiting the phenomenon that disease severity and progression correlate with host PrPC expression levels. However, delivery of lentivirus encoding PrP shRNA has demonstrated only modest efficacy in vivo.Methodology/Principal FindingsHere we describe a new siRNA delivery system incorporating a small peptide that binds siRNA and acetylcholine receptors (AchRs), acting as a molecular messenger for delivery to neurons, and cationic liposomes that protect siRNA-peptide complexes from serum degradation.Conclusions/SignificanceLiposome-siRNA-peptide complexes (LSPCs) delivered PrP siRNA specifically to AchR-expressing cells, suppressed PrPC expression and eliminated PrPRES formation in vitro. LSPCs injected intravenously into mice resisted serum degradation and delivered PrP siRNA throughout the brain to AchR and PrPC-expressing neurons. These data promote LSPCs as effective vehicles for delivery of PrP and other siRNAs specifically to neurons to treat prion and other neuropathological diseases.

Trauma patients have a high risk for venous thromboembolism (VTE) such that an increased enoxaparin dose is necessary to reduce related complications. Given that most trauma patients require an enoxaparin dose of at least 40 mg every 12 hours for VTE prophylaxis, we sought to identify which patients require enoxaparin 30 mg every 12 hours and hypothesized that both weight and low creatinine clearance (CrCl) would more likely determine enoxaparin dosing than age, body mass index (BMI), or body surface area (BSA). Single institution data were collected on trauma patients between August 2014 and February 2018 to compare trauma patients who required enoxaparin 30 mg to those who required ≥40 mg every 12 hours. Of the 245 patients included, 86 (35.1%) required enoxaparin at 30 mg to achieve the goal anti-factor Xa trough level. Factors associated with low dose enoxaparin were older age (59.6 vs. 46.2 years, P ≤ .01) and lower CrCl (81.5 mL/min vs. 93.7 mL/min, P ≤ .01). Weight, BSA, and BMI did not alter the dose of enoxaparin. A regression model determined that only CrCl predicted the need for low dose enoxaparin (adjusted odds ratio .982, 95% CI: .975-.990, P < .01). Although an initial dose of enoxaparin 40 mg is appropriate for most trauma patients, patients with low CrCl should receive 30 mg. Increased age and low weight were not associated with the need for a lower enoxaparin dose.

Introduction Enoxaparin dosed by an anti-Xa trough level is effective at reducing venous thromboembolism (VTE) in trauma patients. We identified the patient characteristics associated with higher enoxaparin dosing based on anti-Xa trough levels. Methods A retrospective review was conducted on trauma patients admitted between August 2014 and February 2018 who received enoxaparin dosed by the anti-Xa trough level. Patients who received enoxaparin < 50 mg every 12 hours were compared to those who required ≥ 50 mg every 12 hours. Results Of the 246 patients included, 32 (13.0%) required enoxaparin ≥ 50 mg every 12 hours to achieve the prophylactic trough level. Factors associated with a higher dose of enoxaparin were male (96.8% vs. 3.2%, P < .01), younger age (39.5 vs. 52.7 years, P < .01), higher creatinine clearance (CrCl) (125.9 vs. 93.7 mL/min, P < .01), higher body surface area (2 m2 vs. 1.8 m2, P < .01), and higher injury severity score (18.4 vs. 10.8, P < .01). Height, weight, and body mass index were not significant factors. On regression analysis, CrCl was the only independent predictor for higher enoxaparin dose. There was an increased deep venous thrombosis rate in the higher dose cohort (12.5% vs. 0, P < .01) but no significant differences in transfusion rates. Conclusion Trauma patients who require higher enoxaparin doses to achieve prophylactic anti-Xa trough levels have a higher CrCl. Patients with high CrCl may benefit from an initial higher dose of enoxaparin to achieve a target anti-Xa level in a shorter time interval to decrease VTE risk.

BACKGROUND:Severe pain and pulmonary complications commonly follow rib fractures, both of which may be improved by surgical stabilization of rib fractures (SSRFs). However, significant postoperative pain still persists which may negatively impact in-hospital outcomes.Combining intercostal nerve cryoablation (INCA) with SSRF may improve those outcomes by further decreasing postoperative pain, opioid consumption, and pulmonary complications. The hypothesis is that INCA plus SSRF reduces opioids consumption compared with SSRF alone. METHODS:The retrospective analysis included trauma patients 18 years or older who underwent SSRF, with or without INCA, in a Level I trauma center between 2015 and 2021. Patients received INCA at the surgeons' discretion based on familiarity with the procedure and absence of contraindications. Patients without INCA were the historical control group. Reported data include demographics, mechanism and severity of injury, number of ribs stabilized, cryoablated nerves, intubation rates and duration of mechanical ventilation. The primary outcome was total morphine milligrams equivalent consumption. Secondary outcomes were intensive care unit length of stay, hospital length of stay, incidence of pneumonia, and tracheostomy rates, and discharge disposition. Longterm outcomes were examined up to 6 months for adverse events. RESULTS:Sixty-eight patients were included, with 44 receiving INCA. There were no differences in rates of pneumonia ( p = 0.106) or duration of mechanical ventilation ( p = 0.687), and hospital length of stay was similar between groups ( p = 0.059). However, the INCA group demonstrated lower total morphine milligrams equivalent ( p = 0.002), shorter intensive care unit length of stay ( p = 0.021), higher likelihood of home discharge ( p = 0.044), and lower rate of intubation ( p = 0.002) and tracheostomy ( p = 0.032). CONCLUSION:Combining INCA with SSRF may further improve in-hospital outcomes for patients with traumatic rib fractures.

Introduction: Physical stressors are common predisposing factors for takotsubo cardiomyopathy (TTC). However, the role of traumatic injuries in TTC has not been well defined. This study describes the characteristics of TTC in the broad spectrum of traumatic injuries using the information available in the National Trauma Data Bank (NTDB).Materials and methods: This retrospective study analyzed trauma patients ≥ 18 years old in the NTDB, from 2007 to 2018, with a diagnosis of TTC.Results: A total of 95 TTC diagnoses were found. The median age was 68 years old (interquartile range: 55-80). Patients were predominantly female (67.4%), white (88.4%), and sustained blunt mechanisms of injury (90.5%). Penetrating trauma was most common in males (16%). Most diagnoses were related to extremity trauma (53.7%), followed by head injury (26.3%). The most common severity scores were Glasgow Coma Scale (GCS) > 13 or < 8, and Injury Severity Score (ISS) < 15 or > 25. Males more commonly presented with GCS < 8 (68%), ISS > 25 (33%), high intensive care unit (ICU) admission rate (77.4%), and mechanical ventilation (51.6%). The median duration of the mechanical ventilation was eight days for both sexes. The ICU length of stay (LOS) was six days with a hospital LOS of nine days and a trend toward a longer LOS in males. The in-hospital mortality rate was 11.7% for both sexes.Conclusions: TTC in traumatic injuries is common at both ends of the severity spectrum and has different sex distribution. TTC patients are predominantly females and have more commonly extremity trauma than head injury. Males are more severely injured and under mechanical ventilation.