The authors reply
Such a statement fails to recognize that studying “the immunologic response associated with sepsis” over the past 3 decades has led to a better understanding of early and late multiple organ failure pathogenesis and has advanced care that has reduced in-hospital mortality. Further progress in sepsis is in desperate need of testable hypotheses if interventions other than supportive therapy are ever to improve the outcomes of this cohort. As stated in our review (2), PICS is a hypothesis, and testing our PICS hypothesis will advance our understanding of sepsis regardless of whether the hypothesis is or is not correct. The authors’ statement that “We simply do not understand the pathophysiology of prolonged critical illness and a premature focus on the immune system is not helpful” is contrary to the scientific method, and PICS provides the framework to explain the long-term disabilities associated with chronic critical illness. Host protective immunity represents one of the most fundamental responses to infection and sepsis, even when focusing on individual organ injury, as proposed by the authors. There is ample experimental evidence on which to base our proposed paradigm, and emerging data suggest that we may be correct (4, 5). PICS is intended to provide a hypothesis that can be experimentally tested, and if correct, can then be the basis for novel interventions and biomarkers.
We appreciate the authors’ concern about the proliferation of acronyms in sepsis and chronic critical illness. But acronyms serve a valuable purpose. Rather than attempting to explain sepsis pathophysiology in its entirety, the acronym, PICS, apportions sepsis into a collection of testable hypotheses and provides a framework for future investigation into the long-term consequences of sepsis-associated chronic critical illness. Testable hypotheses focusing on other features of sepsis pathophysiology are needed, and if another acronym assisted in the understanding of the underlying biology, it too would be welcome.