Measurement of preoperative acute phase reactants may provide an objective means to predict a patient's risk of postoperative dysregulation of the APR and complications.
BackgroundPeri-articular injury may result in functional deficits and pain. In particular, post-traumatic elbow stiffness is a debilitating condition, precluding patients from performing activities of daily living. As such, clinicians and basic scientists alike, aim to develop novel therapeutic interventions to prevent and treat elbow stiffness; thereby reducing patient morbidity. Yet, there is a paucity of pre-clinical models of peri-articular stiffness, especially of the upper extremity, necessary to develop and test the efficacy of therapeutics. We set out to develop a pre-clinical murine model of elbow stiffness, resulting from soft tissue injury, with features characteristic of pathology observed in these patients.MethodsA soft tissue peri-elbow injury was inflicted in mice using cardiotoxin. Pathologic tissue repair was induced by creating an investigator-imposed deficiency of plasminogen, a protease essential for musculoskeletal tissue repair. Functional testing was conducted through analysis of grip strength and gait. Radiography, microcomputed tomography, and histological analyses were employed to quantify development of heterotopic ossification.ResultsAnimals with peri-elbow soft tissues injury in conjunction with an investigator-imposed plasminogen deficiency, developed a significant loss of elbow function measured by grip strength (2.387 ± 0.136 N vs 1.921 ± 0.157 N, ****, p < 0.0001) and gait analysis (35.05 ± 2.775 mm vs 29.87 ± 2.075 mm, ***, p < 0.0002). Additionally, plasminogen deficient animals developed capsule thickening, delayed skeletal muscle repair, fibrosis, chronic inflammation, and heterotopic ossification; all features characteristic of pathology observed in patients with trauma-induced elbow stiffness.ConclusionA soft tissue injury to the peri-elbow soft tissue with a concomitant deficiency in plasminogen, instigates elbow stiffness and pathologic features similar to those observed in humans. This pre-clinical model is valuable for translational studies designed to investigate the contributions of pathologic features to elbow stiffness or as a high-throughput model for testing therapeutic strategies designed to prevent and treat trauma-induced elbow stiffness.Electronic supplementary materialThe online version of this article (10.1186/s40634-018-0155-3) contains supplementary material, which is available to authorized users.
Purpose
Complications following total knee arthroplasty (TKA) lead to patient morbidity and cost. While acute phase reactants, such as c-reactive protein (CRP) and fibrinogen, have been used to predict complications following TKA, the extent and duration of changes in albumin levels following TKA are unknown. It is hypothesized that like CRP and fibrinogen, albumin, and the fibrinogen/albumin ratio (FAR) represent useful measures of the acute phase response (APR) following TKA. The purpose of this study was to describe the longitudinal course of albumin and FAR in healthy patients following TKA, relative to established biomarkers, and examine if the variance in albumin or FAR correlates with patient comorbidities.
Methods
This retrospective cohort study of patients undergoing TKA at a tertiary medical center. CRP, fibrinogen, and albumin values were collected pre- and post-operatively. An age-adjusted Charlson comorbidity index (CCI) was utilized as a measure of patient comorbidity status.
Results
The median preoperative albumin value was 4.3 g/dL, which dropped to 3.6 g/dL on postoperative day 1 following TKA. The albumin value returned to 93% of the baseline by postoperative week 2. The course of albumin inversely mirrored the course of CRP (r = -0.41). Median preoperative FAR was 0.087 g/L, which rose to 0.130 g/L by postoperative week 2 and returned to baseline by postoperative week 6. While preoperative FAR strongly correlated with postoperative week 2 values (r = 0.74), there was a weak positive correlation between age-adjusted CCI and pre-operative FAR (r = 0.24) in patients undergoing primary TKA.
Conclusion
Albumin levels follow a predictable postoperative decline that inversely correlates with CRP in healthy patients following TKA. Given the low cost and abundance of laboratories offering albumin levels, direct albumin levels and/or albumin ratios such as FAR may be underutilized biomarkers for monitoring the APR following TKA.
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