The role of NIGMS P50 sponsored team science in our understanding of multiple organ failure

Abstract

The history of the National Institute of General Medical Sciences (NIGMS) Research Centers in Peri-operative Sciences (RCIPS) is the history of clinical, translational, and basic science research into the etiology and treatment of posttraumatic multiple organ failure (MOF). Born out of the activism of trauma and burn surgeons after the Viet Nam War, the P50 trauma research centers have been a nidus of research advances in the field and the training of future academic physician-scientists in the fields of trauma, burns, sepsis, and critical illness. For over 40 years, research conducted under the aegis of this funding program has led to numerous contributions at both the bedside and at the bench. In fact, it has been this requirement for team science with a clinician-scientist working closely with basic scientists from multiple disciplines that has led the RCIPS to its unrivaled success in the field. This review will briefly highlight some of the major accomplishments of the RCIPS program since its inception, how they have both led and evolved as the field moved steadily forward, and how they are responsible for much of our current understanding of the etiology and pathology of MOF. This review is not intended to be all encompassing nor a historical reference. Rather, it serves as recognition to the foresight and support of many past and present individuals at the NIGMS and at academic institutions who have understood the cost of critical illness and MOF to the individual and to society.

Figure 1

Depicts the P50 NIGMS RCIPS grants by first year of funding, general focus, program director(s) and host institution. Many were funding through multiple cycles and therefore had multiple program directors.

Figure 2

Depicts timeline of evolving epidemiology of multiple organ failure (MOF). ICU, intensive care unit; PACs, pulmonary artery catheters; TPN, total parenteral nutrition;VO₂, oxygen consumption; ATLS, advanced trauma life support; PMN, neutrophil; SIRS, systemic inflammatory response syndrome; CARS, compensatory anti-inflammatory response syndrome; DAMP; damage associated molecular patterns; PAMPs, pathogen associated molecular patterns; IEDs, immune enhancing diets SOPs, standard operating procedures; PICS, persistent, inflammation, immunosuppression, catabolism syndrome. (Reprinted with permission of Wolters Kluwer Health, Inc, from Gentile LF, Cuenca AG, Efron PA, Ang D, Bihorac A, McKinley BA, Moldawer LL, Moore FA. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg. 2012; volume 72, issue 6:1491–501).

Figure 3

The gut is the starter and the liver is the motor of MOF. Complement factors C3a and C5a; PGE₂, prostaglandin E₂; IL-1, interleukin-1; O₂⁻, superoxide radical; ATN, acute tubular necrosis; ARDS, acute respiratory distress syndrome. (Reprinted with permission of Wolters Kluwer Health, Inc, from Moore FA, Moore EE, Jones TN, McCroskey BL, Peterson VM. TEN versus TPN Following Major Abdominal Trauma – Reduced Septic Morbidity. J Trauma.1989; volume 29, issue 7:916–23).

Figure 4

Depicts the “two hit” model of multiple organ failure (MOF). (Reprinted with permission of Elsevier from Moore FA. Presidential Address: Imagination Trumps Knowledge. Am J Surg. 2010, volume 200, issue 6:671–77).

Figure 5

Depicts the SIRS/CARS paradigm for bimodal multiple organ failure (MOF). SIRS, systemic inflammatory response syndrome; CARS, compensatory anti-inflammatory response syndrome. (Reprinted with permission of Wolters Kluwer Health, Inc, from Moore FA, Sauaia A, Moore EE, Haenel JB, Burch JM, Lezotte DC. Postinjury multiple organ failure: a bimodal phenomenon. J Trauma. 1996, volume 40, issue 4, pp 501–12).

Figure 6

Depicts the role of the gut in multiple organ failure (MOF). SIRS, systemic inflammatory response syndrome; CARS, compensatory anti-inflammatory response syndrome. (Reprinted with permission of Elsevier from Moore FA. The Role of the Gastrointestinal Tract in Postinjury Multiple Organ Failure. Am J Surg. 1999, volume 78, issue 6:449–53).

Figure 7

Depicts the persistent, inflammation, immunosuppression, catabolism syndrome (PICS). SIRS, systemic inflammatory response syndrome; CARS, compensatory anti-inflammatory response syndrome; CCI, chronic critical illness. (Reprinted with permission of Wolters Kluwer Health, Inc, from Gentile LF, Cuenca AG, Efron PA, Ang D, Bihorac A, McKinley BA, Moldawer LL, Moore FA. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg. 2012; volume 72, issue 6:1491–501).