Hydrogel-Embedded Precision-Cut Lung Slices Model Lung Cancer Premalignancy Ex Vivo.

Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best prevention, 50% of lung cancer diagnoses occur in people who have quit smoking. Research into treatment options for high-risk patients is constrained to rodent models, which are time-consuming, expensive, and require large cohorts. Embedding precision-cut lung slices (PCLS) within an engineered hydrogel and exposing this tissue to vinyl carbamate, a carcinogen from cigarette smoke, creates an in vitro model of lung cancer premalignancy. Hydrogel formulations are selected to promote early lung cancer cellular phenotypes and extend PCLS viability to six weeks. Hydrogel-embedded PCLS are exposed to vinyl carbamate, which induces adenocarcinoma in mice. Analysis of proliferation, gene expression, histology, tissue stiffness, and cellular content after six weeks reveals that vinyl carbamate induces premalignant lesions with a mixed adenoma/squamous phenotype. Putative chemoprevention agents diffuse through the hydrogel and induce tissue-level changes. The design parameters selected using murine tissue are validated with hydrogel-embedded human PCLS and results show increased proliferation and premalignant lesion gene expression patterns. This tissue-engineered model of human lung cancer premalignancy is the foundation for more sophisticated ex vivo models that enable the study of carcinogenesis and chemoprevention strategies.

Tissue-engineered models of lung cancer premalignancy.

Lung cancer is the leading global cause of cancer-related deaths. Although smoking cessation is the best preventive action, nearly 50% of all lung cancer diagnoses occur in people who have already quit smoking. Research into treatment options for these high-risk patients has been constrained to rodent models of chemical carcinogenesis, which are time-consuming, expensive, and require large numbers of animals. Here we show that embedding precision-cut lung slices within an engineered hydrogel and exposing this tissue to a carcinogen from cigarette smoke creates an in vitro model of lung cancer premalignancy. Hydrogel formulations were selected to promote early lung cancer cellular phenotypes and extend PCLS viability up to six weeks. In this study, hydrogel-embedded lung slices were exposed to the cigarette smoke derived carcinogen vinyl carbamate, which induces adenocarcinoma in mice. At six weeks, analysis of proliferation, gene expression, histology, tissue stiffness, and cellular content revealed that vinyl carbamate induced the formation of premalignant lesions with a mixed adenoma/squamous phenotype. Two putative chemoprevention agents were able to freely diffuse through the hydrogel and induce tissue-level changes. The design parameters selected using murine tissue were validated with hydrogel-embedded human PCLS and results showed increased proliferation and premalignant lesion gene expression patterns. This tissue-engineered model of human lung cancer premalignancy is the starting point for more sophisticated ex vivo models and a foundation for the study of carcinogenesis and chemoprevention strategies.

Quality improvement initiative to improve inpatient outcomes for Neonatal Abstinence Syndrome.

OBJECTIVES: To improve Neonatal Abstinence Syndrome (NAS) inpatient outcomes through a comprehensive quality improvement (QI) program. DESIGN: Inclusion criteria were opioid-exposed infants ≥36 weeks. QI methodology including stakeholder interviews and plan-do-study-act (PDSA) cycles were utilized. We compared pre- and post-intervention NAS outcomes after a QI initiative that included: A non-pharmacologic care bundle, function-based assessments consisting of symptom prioritization and then the "Eat, Sleep, Console" (ESC) Tool; and a switch to methadone for pharmacologic treatment. RESULTS: Pharmacologic treatment decreased from 87.1 to 40.0%; adjunctive agent use from 33.6 to 2.4%; hospitalization length from a mean 17.4 to 11.3 days, and opioid treatment days from 16.2 to 12.7 (p < 0.001 for all). Total hospital charges decreased from $31,825 to $20,668 per infant. Parental presence increased from 55.6 to 75.8% (p < 0.0001). No adverse events were noted. CONCLUSIONS: A comprehensive QI program focused on non-pharmacologic care, function-based assessments, and methadone resulted in significant sustained improvements in NAS outcomes. These findings have important implications for establishing potentially better practices for opioid-exposed newborns.