Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma

Vanzant, Erin; López, Carmen; Ozrazgat‐Baslanti, Tezcan; Ungaro, Ricardo; Davis, Ruth; Cuenca, Alex G.; Gentile, Lori F.; Nacionales, Dina C.; Cuenca, Angela L.; Bïhorac, Azra; Leeuwenburgh, Christiaan; Lanz, Jennifer; Baker, Henry V.; McKinley, Bruce A.; Moldawer, Lyle L.; Moore, Frederick A.; Efron, Philip A.

doi:10.1097/ta.0b013e3182ab1ab5

Cited by 154 publications

(124 citation statements)

References 23 publications

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“…This time point was chosen after analysis of the data from the Phase 2a study of AB103 [5] and on the definition of persistent inflammation and immunosuppression syndrome (PICS), defining patients with long duration (>14 d) ICU stays as the ones with complicated clinical outcomes as a result of persistent immune dysfunction and inflammation [13,14]. Resolution of mSOFA was stratified on the basis of the d 14 mSOFA score.…”

Section: Discussionmentioning

confidence: 99%

Impact and Progression of Organ Dysfunction in Patients with Necrotizing Soft Tissue Infections: A Multicenter Study

Bulger

May

Bernard

et al. 2015

Surgical Infections

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Section: Discussionmentioning

confidence: 99%

Impact and Progression of Organ Dysfunction in Patients with Necrotizing Soft Tissue Infections: A Multicenter Study

Bulger

May

Bernard

et al. 2015

Surgical Infections

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“…Trauma is no different; severe traumatic injury is responsible for a major percentage of deaths worldwide [9]. Although advances in critical care have substantially improved the initial mortality associated with sepsis and trauma, many patients who survive the initial injury succumb from complications [10][11][12][13][14]. To date, immune modulation therapy and pharmacotherapeutic agents have proven disappointing in regards to modifying any human outcome, despite promising results from preclinical studies [15] Much of this preclinical work was done in rodent models [15].…”

Section: Introductionmentioning

confidence: 99%

The future of murine sepsis and trauma research models

Efron

Mohr

Moore

et al. 2015

Journal of Leukocyte Biology

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Recent comparisons of the murine and human transcriptome in health and disease have called into question the appropriateness of the use of murine models for human sepsis and trauma research. More specifically, researchers have debated the suitability of mouse models of severe inflammation that is intended for eventual translation to human patients. This mini-review outlines this recent research, as well as specifically defines the arguments for and against murine models of sepsis and trauma research based on these transcriptional studies. In addition, we review newer advancements in murine models of infection and injury and define what we envision as an evolving but viable future for murine studies of sepsis and trauma. J. Leukoc. Biol. 98: 945-952;

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“…First, in the absence of a universally agreed definition of PRMODS, our definitions are selected somewhat arbitrarily. Previous authors suggest that a ''complicated'' course of MODS may encompass a critical care stay of 7 to 10 days (6, 10) or a ''time to recovery'' of greater than 14 days (6,7,11). We elected to use an MODS duration of greater than 7 days to represent our PRMODS group as it appeared to capture patients at risk of particularly poor outcomes in terms of infection and mortality.…”

Section: Discussionmentioning

confidence: 99%

“…The second pattern describes patients whose MODS fails to recover, instead developing a prolonged or ''persistent'' course associated with long critical care unit stays, high rates of infection, and greater mortality (3,5). This form is described variably in the recent literature as ''persistant immunosuppression and protein catabolism syndrome (PICS)'' (5), ''cumulative'' MODS (3), or ''complicated'' MODS (6,7), although they all share prolonged critical care stays as a common feature. It remains unclear whether these two forms of MODS, here referred to as early resolving MODS (ERMODS) and prolonged MODS (PRMODS), are different clinical entities or are simply manifestations of different severity of physical and physiological insults.…”

Section: Introductionmentioning

confidence: 99%

Contemporary Patterns of Multiple Organ Dysfunction in Trauma

2017

Shock

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ABSTRACT-Background: Multiple organ dysfunction syndrome (MODS) is associated with poor outcomes for trauma patients. Different forms of MODS may exist and have different consequences. The ability to distinguish them clinically may have implications for prognosis and treatment. We wished to study whether prolonged MODS (PRMODS) could be observed as a distinct clinical entity to early resolving MODS (ERMODS) in critically injured patients. Methods: Adult major trauma patients recruited to a prospective observational study at a single major trauma center were eligible for inclusion. MODS was defined as Sequential Organ Failure Assessment (SOFA) score >5; and PRMODS as lasting >7 days. Time to recovery (TTR) was calculated as the number of days before the SOFA fell below the MODS threshold ( 5). Results: Five hundred ninety-five patients were enrolled of whom 285 developed ERMODS (48%) and 184 (31%) PRMODS. Organ dysfunction was more severe and protracted in PRMODS, especially in patients without brain injury (mean SOFA 11 vs. 6, Day 2, P < 0.001; TTR 17 vs. 3 days, P < 0.001). PRMODS exhibited higher rates of hepatic and renal dysfunction (84% vs. 56%; and 78% vs. 47%, P 0.001). Patterns of recovery were distinct in hepatic, renal, and neurological systems (TTR 15 vs. 4; 20 vs. 3; and 28 vs. 7 days, P < 0.01). PRMODS was associated with higher infection and mortality rates (91% vs. 41%; and 22% vs. 7%, P < 0.001). Conclusion: PRMODS appears common, a distinct clinical entity, and associated with worse patient outcomes. PRMODS may represent an important endpoint for studies evaluating outcomes following trauma.

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Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma

Cited by 154 publications

References 23 publications

Impact and Progression of Organ Dysfunction in Patients with Necrotizing Soft Tissue Infections: A Multicenter Study

Impact and Progression of Organ Dysfunction in Patients with Necrotizing Soft Tissue Infections: A Multicenter Study

The future of murine sepsis and trauma research models

Contemporary Patterns of Multiple Organ Dysfunction in Trauma

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