Predictors of mortality and rehabilitation location in adults with prolonged coma following traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and disability, often resulting in prolonged coma and disordered consciousness. There are currently gaps in understanding the factors affecting rehabilitation location and outcome after TBI. OBJECTIVE: To identify the impact of demographics, comorbidities, and complications on discharge disposition in adults with prolonged coma following TBI. DESIGN: Retrospective cohort study. SETTING: Tertiary care hospitals and trauma centers in the United States. PARTICIPANTS: Patients 18 years of age or older with TBI and prolonged coma during the years 2008 to 2015. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Demographics, clinical injury data, comorbidities, and complications were collected, and odds ratios (ORs) and descriptive analysis were calculated for mortality, long-term rehabilitation, and home discharge without services. RESULTS: A total of 6929 patients with TBI and prolonged coma were included in the final analysis; 3318 (47.9%) were discharged to rehabilitation facilities, 1859 (26.8%) died, and 1752 (25.3%) were discharged home. Older patients and those with higher injury severity scores had significantly higher ORs for mortality and rehab discharge. A total of 58.3% of patients presented with at least one comorbidity. Non-White ethnicities and self-pay/uninsured patients were significantly less likely to be discharged to a rehab facility. Furthermore, comorbidities including congestive heart failure (CHF) and diabetes were associated with a significantly increased OR for mortality and rehab discharge compared to home discharge without services. CONCLUSIONS: Comorbidities, age, and injury severity were the most significant risk factors for increased mortality and acute rehab discharge. Maximizing the treatment of comorbidities including CHF and diabetes has the potential to decrease mortality and adverse outcomes following TBI with prolonged coma.

Lung Cancer Clinical Trials in Latin America in the Era of Cooperative Groups: A 20-Year Analysis.

PURPOSE: The aim of this study is to characterize lung cancer treatment clinical trials in Latin America before (January 2001-December 2011) and after (January 2012-December 2021) the organization of major Latin American oncology cooperative groups. MATERIALS AND METHODS: Interventional clinical trials were identified in ClinicalTrials.gov using the search terms "lung cancer," country filters for 20 Latin American countries, and study start dates January 1, 2001-December 31, 2011, and January 1, 2012-December 31, 2021. Clinical trials were categorized as either originating in Latin America (LA) or outside Latin America (non-LA) with participation of Latin American countries. Descriptive statistics, two-sided Z-scores, and chi-square analyses with 95% CIs were calculated. RESULTS: Overall, 273 clinical trials involving Latin American countries between 2001 and 2021 were identified. Comparing 2001-2011 with 2012-2021, there was an increase in total clinical trials (100 v 173; P < .001). Only 9% (26 of 273) of all trials were LA trials. There was a marked decrease in the proportion of LA trials (14% v 7%, P = .058) and estimated enrollment to LA trials (3,245 v 1,190 patients; P < .001). Recruiting of patients with EGFR (29% v 7%; P < .01) and KRAS (18% v 2%; P < .01) driver mutations also decreased. Trial participation was highest in Brazil, Mexico, Argentina, Chile, and Peru and increased over time: Brazil (61 v 108; 77% increase), Mexico (40 v 88; 120% increase), Argentina (50 v 78; 56% increase), Chile (25 v 57; 128% increase), and Peru (14 v 37; 164% increase). CONCLUSION: There was a significant increase in clinical trial participation by Latin American countries, from 2001-2011 to 2012-2021. However, there were few clinical trials which originated in Latin America or focused on patients with driver mutations.

Novel influenza inhibitors designed to target PB1 interactions with host importin RanBP5.

In search of novel targets for influenza inhibitors, a site on PB1 was selected for its high conservation and probable interaction with a host protein, RanBP5, that is key to nuclear import of PB1, where it complexes with PB2, PA, and NP to transcribe viral RNA. Docking with libraries of drug-like compounds led to a selection of five candidates that bound tightly and with a pose likely to inhibit protein binding. These were purchased and tested in vitro, found to be active, and then one was synthetically expanded to explore the structure-activity relationship. The top candidates had a carboxylic acid converted to an ester and electron-withdrawing substituents added to a phenyl group in the original structure. Resistance was slow to develop, but cytotoxicity was moderately high. Nuclear localization of PB1 and in vitro polymerase activity were both strongly inhibited.