Vasquez, M. M., Zhou, M., Hu, C., Martinez, F. D., & Guerra, S. (2018). Reply to Bush: Low Lung Function in Young Adult Life Is Associated with Early Mortality. American journal of respiratory and critical care medicine, 197(4), 539.
Hsu, C., Taylor, J. M., & Hu, C. (2015). Analysis of accelerated failure time data with dependent censoring using auxiliary variables via nonparametric multiple imputation. Statistics in medicine, 34(19), 2768-80.
We consider the situation of estimating the marginal survival distribution from censored data subject to dependent censoring using auxiliary variables. We had previously developed a nonparametric multiple imputation approach. The method used two working proportional hazards (PH) models, one for the event times and the other for the censoring times, to define a nearest neighbor imputing risk set. This risk set was then used to impute failure times for censored observations. Here, we adapt the method to the situation where the event and censoring times follow accelerated failure time models and propose to use the Buckley-James estimator as the two working models. Besides studying the performances of the proposed method, we also compare the proposed method with two popular methods for handling dependent censoring through the use of auxiliary variables, inverse probability of censoring weighted and parametric multiple imputation methods, to shed light on the use of them. In a simulation study with time-independent auxiliary variables, we show that all approaches can reduce bias due to dependent censoring. The proposed method is robust to misspecification of either one of the two working models and their link function. This indicates that a working proportional hazards model is preferred because it is more cumbersome to fit an accelerated failure time model. In contrast, the inverse probability of censoring weighted method is not robust to misspecification of the link function of the censoring time model. The parametric imputation methods rely on the specification of the event time model. The approaches are applied to a prostate cancer dataset.
Spaite, D. W., Hu, C., Bobrow, B. J., Chikani, V., Sherrill, D., Barnhart, B., Gaither, J. B., Denninghoff, K. R., Viscusi, C., Mullins, T., & Adelson, P. D. (2017). Mortality and Prehospital Blood Pressure in Patients With Major Traumatic Brain Injury Implications for the Hypotension Threshold. JAMA SURGERY, 152(4), 360-368.
Fukushima, H., Panczyk, M., Hu, C., Dameff, C., Chikani, V., Vadeboncoeur, T., Spaite, D. W., & Bobrow, B. J. (2017). Description of Abnormal Breathing Is Associated With Improved Outcomes and Delayed Telephone Cardiopulmonary Resuscitation Instructions. Journal of the American Heart Association, 6(9).
Emergency 9-1-1 callers use a wide range of terms to describe abnormal breathing in persons with out-of-hospital cardiac arrest (OHCA). These breathing descriptors can obstruct the telephone cardiopulmonary resuscitation (CPR) process.
Spivak-Kroizman, T. R., Hostetter, G., Posner, R., Aziz, M., Hu, C., Demeure, M. J., Von Hoff, D., Hingorani, S. R., Palculict, T. B., Izzo, J., Kiriakova, G. M., Abdelmelek, M., Bartholomeusz, G., James, B. P., & Powis, G. (2013). Hypoxia triggers hedgehog-mediated tumor-stromal interactions in pancreatic cancer. Cancer research, 73(11).
Pancreatic cancer is characterized by a desmoplastic reaction that creates a dense fibroinflammatory microenvironment, promoting hypoxia and limiting cancer drug delivery due to decreased blood perfusion. Here, we describe a novel tumor-stroma interaction that may help explain the prevalence of desmoplasia in this cancer. Specifically, we found that activation of hypoxia-inducible factor-1α (HIF-1α) by tumor hypoxia strongly activates secretion of the sonic hedgehog (SHH) ligand by cancer cells, which in turn causes stromal fibroblasts to increase fibrous tissue deposition. In support of this finding, elevated levels of HIF-1α and SHH in pancreatic tumors were determined to be markers of decreased patient survival. Repeated cycles of hypoxia and desmoplasia amplified each other in a feed forward loop that made tumors more aggressive and resistant to therapy. This loop could be blocked by HIF-1α inhibition, which was sufficient to block SHH production and hedgehog signaling. Taken together, our findings suggest that increased HIF-1α produced by hypoxic tumors triggers the desmoplasic reaction in pancreatic cancer, which is then amplified by a feed forward loop involving cycles of decreased blood flow and increased hypoxia. Our findings strengthen the rationale for testing HIF inhibitors and may therefore represent a novel therapeutic option for pancreatic cancer.
