PMID- 19887013
OWN - NLM
STAT- MEDLINE
DCOM- 20100430
LR  - 20220409
IS  - 1466-609X (Electronic)
IS  - 1364-8535 (Print)
IS  - 1364-8535 (Linking)
VI  - 13
IP  - 6
DP  - 2009
TI  - Early release of high mobility group box nuclear protein 1 after severe trauma in 
      humans: role of injury severity and tissue hypoperfusion.
PG  - R174
LID - 10.1186/cc8152 [doi]
AB  - INTRODUCTION: High mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear 
      binding protein that has recently been shown to be an early trigger of sterile 
      inflammation in animal models of trauma-hemorrhage via the activation of the 
      Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation 
      endproducts (RAGE). However, whether HMGB1 is released early after trauma 
      hemorrhage in humans and is associated with the development of an inflammatory 
      response and coagulopathy is not known and therefore constitutes the aim of the 
      present study. METHODS: One hundred sixty eight patients were studied as part of 
      a prospective cohort study of severe trauma patients admitted to a single Level 1 
      Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room 
      before the administration of any fluid resuscitation. HMGB1, tumor necrosis 
      factor (TNF)-alpha, interleukin (IL)-6, von Willebrand Factor (vWF), 
      angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), 
      soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 
      (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using 
      standard techniques. Base deficit was used as a measure of tissue hypoperfusion. 
      Measurements were compared to outcome measures obtained from the electronic 
      medical record and trauma registry. RESULTS: Plasma levels of HMGB1 were 
      increased within 30 minutes after severe trauma in humans and correlated with the 
      severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and 
      hyperfibrinolysis as well with a systemic inflammatory response and activation of 
      complement. Non-survivors had significantly higher plasma levels of HMGB1 than 
      survivors. Finally, patients who later developed organ injury, (acute lung injury 
      and acute renal failure) had also significantly higher plasma levels of HMGB1 
      early after trauma. CONCLUSIONS: The results of this study demonstrate for the 
      first time that HMGB1 is released into the bloodstream early after severe trauma 
      in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, 
      and is associated with posttraumatic coagulation abnormalities, activation of 
      complement and severe systemic inflammatory response.
FAU - Cohen, Mitchell J
AU  - Cohen MJ
AD  - The Department of Surgery, San Francisco General Hospital, University of 
      California San Francisco, San Francisco, CA 94110, USA. mcohen@sfghsurg.ucsf.edu
FAU - Brohi, Karim
AU  - Brohi K
FAU - Calfee, Carolyn S
AU  - Calfee CS
FAU - Rahn, Pamela
AU  - Rahn P
FAU - Chesebro, Brian B
AU  - Chesebro BB
FAU - Christiaans, Sarah C
AU  - Christiaans SC
FAU - Carles, Michel
AU  - Carles M
FAU - Howard, Marybeth
AU  - Howard M
FAU - Pittet, Jean-Francois
AU  - Pittet JF
LA  - eng
GR  - K23 HL090833/HL/NHLBI NIH HHS/United States
GR  - R01 GM-62188/GM/NIGMS NIH HHS/United States
GR  - K08 GM-085689/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091104
PL  - England
TA  - Crit Care
JT  - Critical care (London, England)
JID - 9801902
RN  - 0 (Blood Proteins)
RN  - 0 (HMGB1 Protein)
SB  - IM
CIN - Crit Care. 2009;13(6):1004. PMID: 19930620
MH  - Adult
MH  - Blood Pressure
MH  - Blood Proteins/analysis
MH  - Cohort Studies
MH  - Craniocerebral Trauma/blood/complications
MH  - Female
MH  - HMGB1 Protein/*blood/metabolism
MH  - Heart Rate
MH  - Humans
MH  - Inflammation/blood
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Prothrombin Time
MH  - Respiration, Artificial
MH  - Resuscitation/methods
MH  - Survivors
MH  - Trauma Centers
MH  - Wounds and Injuries/*blood/*complications/mortality/therapy
MH  - Wounds, Penetrating/blood/complications
PMC - PMC2811903
EDAT- 2009/11/06 06:00
MHDA- 2010/05/01 06:00
PMCR- 2009/11/04
CRDT- 2009/11/06 06:00
PHST- 2009/01/22 00:00 [received]
PHST- 2009/06/05 00:00 [revised]
PHST- 2009/11/04 00:00 [accepted]
PHST- 2009/11/06 06:00 [entrez]
PHST- 2009/11/06 06:00 [pubmed]
PHST- 2010/05/01 06:00 [medline]
PHST- 2009/11/04 00:00 [pmc-release]
AID - cc8152 [pii]
AID - 10.1186/cc8152 [doi]
PST - ppublish
SO  - Crit Care. 2009;13(6):R174. doi: 10.1186/cc8152. Epub 2009 Nov 4.