Systemic inflammation and remote organ damage following bilateral femur fracture requires Toll-like receptor 4

Levy, Ryan M.; Prince, José M.; Yang, Runkuan; Mollen, Kevin P.; Liao, Hong; Watson, Gregory A.; Fink, Mitchell P.; Vodovotz, Yoram; Billiar, Timothy R.

doi:10.1152/ajpregu.00793.2005

Cited by 91 publications

(88 citation statements)

References 66 publications

(74 reference statements)

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“…Avoiding undesirable manipulation forces, while obtaining an acceptable alignment, is important to prevent additional injury to soft tissues. [14] In this study, we describe the design and preliminary clinical evaluation of an automated system developed to provide detailed information about the three-dimensional forces and moments applied by a surgeon during the Figure 6. Changes in the traction force measured over the entire fracture reduction procedure.…”

Section: Discussion and Future Workmentioning

confidence: 99%

Force–torque intraoperative measurements for femoral shaft fracture reduction

Zhu

Liang

Wang

et al. 2016

Computer Assisted Surgery

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Background: The minimally invasive technique of closed intramedullary (IM) nailing fixation is currently considered the standard of treatment for the operative management of displaced traumatic fractures of the femur, with fracture reduction and repositioning being the first and most important step of the procedure. Skeletal-muscle traction and alignment of the fracture fragments are always performed as individual components of the reduction and repositioning phase of the procedure. Methods: As use of high traction force and repositioning forces and torques can cause additional soft tissue injury, we developed a sensor-based system to monitor these forces and torques during the treatment of diaphyseal fractures of the femur, including the monitoring of traction forces during the entire procedure, from reduction to IM nail implantation and fixation. Results: Based on a local coordinate system localized at the center of the fracture, maximum forces of 203 N along the medial-lateral (X) axis, 517 N along the anterior-posterior (Y) axis and 505 N along the shaft of the femur (Z-axis) were identified, with maximum torques of 16.4 Nm calculated around Y-axis and 38.3 Nm around X-axis. The pressure between the counteraction post and the perineum was also recorded, with magnitudes as high as 523 N being recorded. Excessive forces were identified and the difference in force-torque magnitudes during different stages of the reduction and fixation procedure were calculated. Conclusion: The measurement system provides surgeons with real-time information which can assist them in performing effective repositioning of fracture fragments within safe margins of applied forces and torques.

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Section: Discussion and Future Workmentioning

confidence: 99%

Force–torque intraoperative measurements for femoral shaft fracture reduction

Zhu

Liang

Wang

et al. 2016

Computer Assisted Surgery

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“…We measured NF-jB activity using electrophoretic mobility shift assays with nuclear extracts prepared from the tissue. Electrophoretic mobility shift assays were performed as described previously [21].…”

Section: Methodsmentioning

confidence: 99%

“…Studies of cytokine pattern and the evolution of remote organ dysfunction after bilateral femur fractures in mice [13,18,21] demonstrate such trauma initiates a complex systemic inflammatory response in which the pro-and antiinflammatory cytokines, such as IL-6 and IL-10, play a pivotal role in systemic inflammation [18,21]. Kobbe et al [19] demonstrated fracture-associated soft tissue injury is a major contributor to the systemic inflammation found after long-bone fractures.…”

Section: Introductionmentioning

confidence: 99%

Cumulative Effects of Bone and Soft Tissue Injury on Systemic Inflammation: A Pilot Study

Pfeifer

Darwiche

Kohut

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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Background In multiply injured patients, bilateral femur fractures invoke a substantial systemic inflammatory impact and remote organ dysfunction. However, it is unclear whether isolated bone or soft tissue injury contributes to the systemic inflammatory response and organ injury after fracture. Questions/purposes We therefore asked whether the systemic inflammatory response and remote organ dysfunction are attributable to the bone fragment injection, adjacent soft tissue injury, or both. Methods Male C57/BL6 mice (8-10 weeks old, 20-30 g) were assigned to four groups: bone fragment injection (BF, n = 9) group; soft tissue injury (STI, n = 9) group; BF + STI (n = 9) group, in which both insults were applied; and control group, in which neither insult was applied. Animals were sacrificed at 6 hours. As surrogates for systemic inflammation, we measured serum IL-6, IL-10, osteopontin, and alanine aminotransferase (ALT) and nuclear factor (NF)-jB and myeloperoxidase (MPO) in the lung. Results The systemic inflammatory response (mean IL-6 level) was similar in the BF (61.8 pg/mL) and STI (67.9 pg/mL) groups. The combination (BF + STI) of both traumatic insults induced an increase in mean levels of inflammatory parameters

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“…The precise mechanics of the activation pathway therefore remain unclear. A variety of receptor interactions have been identified in vitro 33,36,45,76 . In animal trauma models, a Toll-like receptor (TLR) 4 mechanism has been convincingly established for HMGB1 37 .…”

Section: Alarmins Released Passively By Damageinduced (Non-programmedmentioning

confidence: 99%

Trauma alarmins as activators of damage-induced inflammation

Manson

Thiemermann

Brohi

2011

British Journal of Surgery

150

132

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Background: A systemic inflammatory response syndrome (SIRS) is frequently observed after traumatic injury. The response is sterile and the activating stimulus is tissue damage. Endogenous molecules, called alarmins, are reputed to be released by injured tissues but the precise identity of these mediators is unclear. This review summarizes current preclinical and clinical evidence for trauma alarmins and their role in innate immune activation.Methods: A comprehensive literature review of putative alarmins in tissue damage after traumatic injury was conducted.Results: The presence of SIRS at admission is an independent predictor of mortality after trauma. The primary initiators of the human immune response are unclear. Several endogenous substances display alarmin characteristics in vitro. Preclinical studies demonstrate that blockade of certain endogenous substances can reduce adverse clinical sequelae after traumatic injury. Human evidence for trauma alarmins is extremely limited. Conclusion:The magnitude of acute inflammation is predictive of outcome after trauma, suggesting that an early opportunity for immune modulation may exist. An understanding of the mechanisms of innate immune activation following trauma may lead to new therapeutic agents and improved patient survival.

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Systemic inflammation and remote organ damage following bilateral femur fracture requires Toll-like receptor 4

Cited by 91 publications

References 66 publications

Force–torque intraoperative measurements for femoral shaft fracture reduction

Force–torque intraoperative measurements for femoral shaft fracture reduction

Cumulative Effects of Bone and Soft Tissue Injury on Systemic Inflammation: A Pilot Study

Trauma alarmins as activators of damage-induced inflammation

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