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Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture.

ABSTRACT: An estimated 12% of patients seeking surgical intervention for symptomatic arthritis have an etiology of post-traumatic arthritis (PTA). The onset of PTA is rapid in the setting of articular fracture (AF). The investigation began with development of a murine model of a closed AF that develops PTA. In the process of characterizing this model a technique was developed for assessing quantitative synovial fluid biomarker concentrations. The work began with observations of the natural history of PTA development in the C57BL/6 strain of mice. A species of mice (MRL/MpJ) was found that is protected from PTA after AF. Further work identified key differences between mouse strains that did and did not develop PTA. This knowledge led to an intervention based on anti-cytokine (interleukin 1 receptor antagonist, (IL-1Ra) delivery in the C57BL/6 strain of mice that successfully prevented PTA following AF. This success in preventing PTA in the murine model has elucidated several important clinical implications: 1) Pro-inflammatory cytokines play an important role in the development of PTA after joint injury, 2) Pharmacologic intervention can lessen the severity of PTA after an AF, and 3) The murine AF model of joint injury provides a novel means of studying mechanisms of PTA development.

SUBMITTER: Olson SA

PROVIDER: S-EPMC4529755 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture.

Olson Steven A SA Furman Bridgette D BD Kraus Virginia B VB Huebner Janet L JL Guilak Farshid F

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20150607 9

An estimated 12% of patients seeking surgical intervention for symptomatic arthritis have an etiology of post-traumatic arthritis (PTA). The onset of PTA is rapid in the setting of articular fracture (AF). The investigation began with development of a murine model of a closed AF that develops PTA. In the process of characterizing this model a technique was developed for assessing quantitative synovial fluid biomarker concentrations. The work began with observations of the natural history of PTA ...[more]

PMID: 25939531

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Project description:ObjectivesTo quantify fracture severity for a series of displaced intra-articular calcaneal fractures (DIACFs) and to correlate it with Sanders classification, post-traumatic osteoarthritis (PTOA), and patient outcomes.DesignRetrospective review and fracture severity analysis.SettingLevel 1 trauma center affiliated with the University of Iowa in Iowa City, IA.Patients/participantsThirty-six patients with 48 DIACFs were selected from 153 patients previously treated. All patients 18 years of age and older who had available electronic preop and postop computed tomography (CT) scans, good-quality postop and follow-up radiographs, and a follow-up ≥18 months were selected for study.InterventionFractures were treated with percutaneous reduction, using multiple small stab incisions and fluoroscopy to guide manipulation of articular fragments using cork screws or Steinmann pins, with subsequent fixation using 3.5- and 4.0-mm screws.Main outcome measurementsPreop CT scans were used to grade fractures according to the Sanders classification and to quantify fracture severity. Fracture severity was objectively quantified using a CT-based measure of fracture energy. PTOA was assessed on follow-up radiographs using the Kellgren-Lawrence scale. Patient outcomes were assessed using the Short Form 36 (SF-36) questionnaire and a visual analog scale pain score.ResultsFracture energies for the 48 DIACFs ranged from 14.1 to 26.2 J (19.3 ± 3.1 J) and correlated with Sanders classification (rho = 0.53, P = 0.0001); type I (16.3 ± 0.9 J); type II (18.0 ± 2.7 J); type III (20.8 ± 2.8 J); and type IV (22.0 ± 0.7 J). Fracture energy was higher for fractures in which the subtalar joint developed PTOA (19.5 ± 2.7 J) than for those that did not (18.9 ± 3.3 J), but the difference did not reach statistical significance. The Sanders classification predicted PTOA risk [odds ratio (OR) = 4.04, 95% confidence interval = 1.43-11.39, P = 0.0084]. No relationship was observed between fracture energy and visual analog scale pain scores. Higher fracture energy correlated with lower SF-36 scores.ConclusionsFracture energy positively correlates with Sanders classification for DIACFs, which can be used to identify more severe fractures at greater risk of progressing to PTOA.Level of evidencePrognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Project description:OBJECTIVE Minimal aortic injuries (MAIs) are being recognized more frequently due to the increasing use of high-resolution diagnostic techniques. The objective of this case series review was to report the clinical and radiological characteristics and outcomes of a series of patients with MAI. METHODS From January 2000 to December 2011, 54 major blunt trauma patients were admitted to our institution with traumatic aortic injuries. Nine of them presented with MAI, whereas the remaining 45 patients suffered a significant aortic injury (SAI). RESULTS MAIs accounted for 17% of the overall traumatic aortic injuries in our series. Major trauma patients with MAI and SAI were similar regarding the presence of severe associated non-aortic injuries and the expected mortality calculated by injury severity score, revised trauma score and trauma injury severity score. There were no statistically significant differences in in-hospital mortality between MAI (22.2%) and SAI (30.2%). No death in the MAI group was aortic related, whereas five deaths in the SAI group were caused by an aortic complication. The survival of MAI patients was 77.8% at 1 and 5 years. There was no late mortality among MAI patients. The survival of SAI patients was 69.7% at 1 year and 63.6% at 5 and 10 years. None of the seven surviving patients with MAI presented a progression of the aortic injury. In six patients, the intimal tear completely healed in imaging controls, whereas one patient developed a small saccular pseudoaneurysm. CONCLUSIONS Blunt traumas presenting MAI are as severe as traumas that associate SAI and present similar in-hospital mortality. In contrast to SAI traumas, in-hospital mortality due to MAI is not usually related to the aortic injury, so these injuries are more amenable to a conservative management. It is mandatory to perform a close imaging surveillance to detect early any potential adverse evolution of an MAI. Nevertheless, a balance must be struck between a close serial imaging surveillance and the potentially detrimental effects of obtaining high-resolution additional images.

Dataset Information

Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture.

Publications

Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture.

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