RESUMEN
BACKGROUND: Retained hemothorax (rHTX) requiring intervention occurs in up to 20% of patients who undergo chest tube (TT) placement for a hemothorax (HTX). Thoracic irrigation at the time of TT placement decreases the need for secondary intervention in this patient group but those findings are limited because of the single center design. A multi-center study was conducted to evaluate the effectiveness of thoracic irrigation. METHODS: A multi-center, prospective, observational study was conducted between June 2018 and July 2023. Eleven sites contributed patients. Patients were included if they had a TT placed for a HTX and were excluded if: age < 18 years, TT for pneumothorax, thoracotomy or VATS performed within 6 hours of TT, TT >24 hours after injury, TT removed <24 hours, or death within 48 hours. Thoracic irrigation was performed at the discretion of the attending. Each hemithorax was considered separately if bilateral HTX. The primary outcome was secondary intervention for HTX-related complications (rHTX, effusion, or empyema). Secondary intervention was defined as: TT placement, instillation of thrombolytics, VATS, or thoracotomy. Irrigated and non-irrigated hemithoraces were compared using a propensity weighted analysis with age, sex, mechanism of injury, Abbreviated Injury Scale (AIS) chest and TT size as predictors. RESULTS: 493 patients with 462 treated hemothoraces were included, 123 (25%) had thoracic irrigation at TT placement. There were no significant demographic differences between the cohorts. Fifty-seven secondary interventions were performed, 10 (8%) and 47 (13%) in the irrigated and non-irrigated groups, respectively (p = 0.015). Propensity weighted analysis demonstrated a reduction in secondary interventions in the irrigated cohort (Odds Ratio 0.56 (0.34-0.85); p = 0.005). CONCLUSION: This Western Trauma Association multi-center study demonstrates a benefit of thoracic irrigation at the time of TT placement for a HTX. Thoracic irrigation reduces the odds of a secondary intervention for rHTX-related complications by 44%. LEVEL OF EVIDENCE: Therapeutic Study, Level II.
RESUMEN
Tyrosine kinase inhibitors were found to be clinically effective for treatment of patients with certain subsets of cancers carrying somatic mutations in receptor tyrosine kinases. However, the duration of clinical response is often limited, and patients ultimately develop drug resistance. Here, we use single-cell RNA sequencing to demonstrate the existence of multiple cancer cell subpopulations within cell lines, xenograft tumors and patient tumors. These subpopulations exhibit epigenetic changes and differential therapeutic sensitivity. Recurrently overrepresented ontologies in genes that are differentially expressed between drug tolerant cell populations and drug sensitive cells include epithelial-to-mesenchymal transition, epithelium development, vesicle mediated transport, drug metabolism and cholesterol homeostasis. We show analysis of identified markers using the LINCS database to predict and functionally validate small molecules that target selected drug tolerant cell populations. In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones. In this study, we describe the spectrum of changes associated with drug tolerance and inhibition of specific tolerant cell subpopulations with combination agents.