Matt Harmon

72 Chapter three to reconcile an adaptive response in rodents to an evidently increased mortality noted in observational studies in patients. 1 A remark on the interpretation of findings in experimental models is that regulation of body temperature in rodents is profoundly different than in humans due to differences in the ratio of body content to body surface. 5 Therefore, experimental results need to be validated in clinical studies. We look forward to the results of an interventional study in which spontaneous hypothermia is allowed or prevented within the hypothermic subset of patients with sepsis. We would like to participate in this effort and we suggest that this trial includes analyses on the host response, including markers of immune suppression and endothelial dysfunction, to provide further insight into the etiology of hypothermia in sepsis pathogenesis. References 1 Wiewel, M. A. et al. Risk factors, host response and outcome of hypothermic sepsis. Critical care 20, 328, doi:10.1186/s13054-016-1510-3 (2016). 2 Fonseca, M. T. et al. Spontaneous hypothermia in human sepsis is a transient, self-limiting and non- terminal response. Journal of applied physiolog y , jap 00004 02016, doi:10.1152/japplphysiol.00004.2016 (2016). 3 Drewry, A. M., Fuller, B. M., Skrupky, L. P. & Hotchkiss, R. S. The Presence of Hypothermia Within 24 Hours of Sepsis Diagnosis Predicts Persistent Lymphopenia. Crit Care Med , doi:10.1097/ CCM.0000000000000940 (2015). 4 Corrigan, J. J., Fonseca, M. T., Flatow, E. A., Lewis, K. & Steiner, A. A. Hypometabolism and hypothermia in the rat model of endotoxic shock: independence of circulatory hypoxia. J Physiol 592, 3901-3916, doi:10.1113/jphysiol.2014.277277 (2014). 5 Wagner, F., Asfar, P., Calzia, E., Radermacher, P. & Szabo, C. Bench-to-bedside review: Hydrogen sulfide--the third gaseous transmitter: applications for critical care. Critical care 13, 213, doi:10.1186/ cc7700 (2009).