Obesity as a Predictor of Prolonged Mechanical Ventilation.

OBJECTIVE: To examine the effect of including obesity with parameters of the I-TRACH scale in predicting the need for prolonged mechanical ventilation. STUDY DESIGN: A retrospective cohort study. SETTING: Tertiary care academic medical center. SUBJECTS AND METHODS: Consecutive patients were identified retrospectively over a 45-month period based on need for mechanical ventilation in the medical intensive care unit. Chart review was performed to collect demographic information as well as clinical data, including duration of mechanical ventilation, body mass index (BMI), and I-TRACH parameters (heart rate >110, serum urea nitrogen >25, serum pH <7.25, serum creatinine >2, serum bicarbonate <20). Statistical analysis was performed to identify any predictors of prolonged mechanical ventilation, defined as ≥14 days and as ≥10 days. RESULTS: In total, 455 patients were identified, with an average duration of mechanical ventilation of 10.4 days (range, 0-248 days). On univariate and multivariate regression analysis, only BMI >30 reached statistical significance with respect to prolonged mechanical ventilation (P < .05). The I-TRACH parameters-either alone or in combination-were not significantly predictive. CONCLUSION: This study challenges previous findings regarding the I-TRACH scale and the relation of its parameters to prolonged mechanical ventilation. Furthermore, BMI >30 alone was predictive of prolonged intubation. Inclusion of BMI in predictive models could assist current decision making in determining the likelihood of prolonged mechanical ventilation in medical intensive care unit patients going forward, and obesity should be considered a predictor of prolonged mechanical ventilation.

Cancer-Associated Fibroblasts Drive Glycolysis in a Targetable Signaling Loop Implicated in Head and Neck Squamous Cell Carcinoma Progression.

Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late-stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted HGF facilitates HNSCC progression; however, very little is known about the role of CAFs in HNSCC metabolism. Here, we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis. CAF-secreted HGF induced basic FGF (bFGF) secretion from HNSCC. CAFs were more efficient than HNSCC in using lactate as a carbon source. HNSCC-secreted bFGF increased mitochondrial oxidative phosphorylation and HGF secretion from CAFs. Combined inhibition of c-Met and FGFR significantly inhibited CAF-induced HNSCC growth in vitro and in vivo (P < 0.001). Our cumulative findings underscore reciprocal signaling between CAF and HNSCC involving bFGF and HGF. This contributes to metabolic symbiosis and a targetable therapeutic axis involving c-Met and FGFR.Significance: HNSCC cancer cells and CAFs have a metabolic relationship where CAFs secrete HGF to induce a glycolytic switch in HNSCC cells and HNSCC cells secrete bFGF to promote lactate consumption by CAFs. Cancer Res; 78(14); 3769-82. ©2018 AACR.

Radiation-induced fibrosis: mechanisms and implications for therapy.

PURPOSE: Radiation-induced fibrosis (RIF) is a long-term side effect of external beam radiation therapy for the treatment of cancer. It results in a multitude of symptoms that significantly impact quality of life. Understanding the mechanisms of RIF-induced changes is essential to developing effective strategies to prevent long-term disability and discomfort following radiation therapy. In this review, we describe the current understanding of the etiology, clinical presentation, pathogenesis, treatment, and directions of future therapy for this condition. METHODS: A literature review of publications describing mechanisms or treatments of RIF was performed. Specific databases utilized included PubMed and clinicaltrials.gov, using keywords "Radiation-Induced Fibrosis," "Radiotherapy Complications," "Fibrosis Therapy," and other closely related terms. RESULTS: RIF is the result of a misguided wound healing response. In addition to causing direct DNA damage, ionizing radiation generates reactive oxygen and nitrogen species that lead to localized inflammation. This inflammatory process ultimately evolves into a fibrotic one characterized by increased collagen deposition, poor vascularity, and scarring. Tumor growth factor beta serves as the primary mediator in this response along with a host of other cytokines and growth factors. Current therapies have largely been directed toward these molecular targets and their associated signaling pathways. CONCLUSION: Although RIF is widely prevalent among patients undergoing radiation therapy and significantly impacts quality of life, there is still much to learn about its pathogenesis and mechanisms. Current treatments have stemmed from this understanding, and it is anticipated that further elucidation will be essential for the development of more effective therapies.