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Damage- and pathogen-associated molecular patterns play differential roles in late mortality after critical illness.

ABSTRACT: Multiple organ failure (MOF) is the leading cause of late mortality and morbidity in patients who are admitted to intensive care units (ICUs). However, there is an epidemiologic discrepancy in the mechanism of underlying immunologic derangement dependent on etiology between sepsis and trauma patients in MOF. We hypothesized that damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), while both involved in the development of MOF, contribute differently to the systemic innate immune derangement and coagulopathic changes. We found that DAMPs not only produce weaker innate immune activation than counterpart PAMPs, but also induce less TLR signal desensitization, contribute to less innate immune cell death, and propagate more robust systemic coagulopathic effects than PAMPs. This differential contribution to MOF provides further insight into the contributing factors to late mortality in critically ill trauma and sepsis patients. These findings will help to better prognosticate patients at risk of MOF and may provide future therapeutic molecular targets in this disease process.

SUBMITTER: Eppensteiner J

PROVIDER: S-EPMC6777836 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Damage- and pathogen-associated molecular patterns play differential roles in late mortality after critical illness.

Eppensteiner John J Kwun Jean J Scheuermann Uwe U Barbas Andrew A Limkakeng Alexander T AT Kuchibhatla Maggie M Elster Eric A EA Kirk Allan D AD Lee Jaewoo J

JCI insight 20190822 16

Multiple organ failure (MOF) is the leading cause of late mortality and morbidity in patients who are admitted to intensive care units (ICUs). However, there is an epidemiologic discrepancy in the mechanism of underlying immunologic derangement dependent on etiology between sepsis and trauma patients in MOF. We hypothesized that damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), while both involved in the development of MOF, contribute differently to ...[more]

PMID: 31434802

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Project description:Preventing rehospitalizations for patients with serious chronic illnesses is a focus of national quality initiatives. Although 8 million people are admitted yearly to an ICU, the frequency of rehospitalizations (readmissions to the hospital after discharge) is unknown. We sought to determine the frequency of rehospitalization after an ICU stay, outcomes for rehospitalized patients, and factors associated with rehospitalization.Retrospective cohort study using the New York Statewide Planning and Research Cooperative System, an administrative database of all hospital discharges in New York State.ICUs in New York State.ICU patients who survived to hospital discharge in 2008-2010.None.Primary outcome was the cumulative incidence of first early rehospitalization (within 30 days of discharge), and secondary outcome was the cumulative incidence of late rehospitalization (between 31 and 180 d). Factors associated with rehospitalization within both time periods were identified using competing risk regression models. Of 492,653 ICU patients, 79,960 had a first early rehospitalization (cumulative incidence, 16.2%) and an additional 73,250 late rehospitalizations (cumulative incidence, 18.9%). Over one quarter of all rehospitalizations (28.6% for early; 26.7% for late) involved ICU admission. Overall hospital mortality for rehospitalized patients was 7.6% for early and 4.6% for late rehospitalizations. Longer index hospitalization (adjusted hazard ratio, 1.61; 95% CI, 1.57-1.66 for 7-13 d vs < 3 d), discharge to a skilled nursing facility versus home (adjusted hazard ratio, 1.54; 95% CI, 1.51-1.58), and having metastatic cancer (adjusted hazard ratio, 1.46; 95% CI, 1.41-1.51) were associated with the greatest hazard of early rehospitalization.Approximately 16% of ICU survivors were rehospitalized within 30 days of hospital discharge; rehospitalized patients had high rates of ICU admission and hospital mortality. Few characteristics were strongly associated with rehospitalization, suggesting that identifying high-risk individuals for intervention may require additional predictors beyond what is available in administrative databases.

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Damage- and pathogen-associated molecular patterns play differential roles in late mortality after critical illness.

Publications

Damage- and pathogen-associated molecular patterns play differential roles in late mortality after critical illness.

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