Reina, Nicolas

ABSTRACTArthrofibrosis is a common complication following total knee arthroplasty caused by pathologic fibroblast activation and excessive collagen deposition around a synovial joint leading to debilitating loss of motion. Treatment options are limited because the pathologic mechanisms remain to be characterized. Dysregulation of the inflammatory cascade may lead to communication between myofibroblasts and immune cells triggering tissue metaplasia, and excessive collagen deposition described clinically as arthrofibrosis. We explored the novel use of celecoxib (selective cyclooxygenase‐2 [COX‐2] inhibitor) to disrupt the downstream effects of the post‐traumatic inflammatory cascade and inhibit scar tissue formation in a validated rabbit model of arthrofibrosis combined with new parameters for quantifying the stiffness of the posterior capsule. Biomechanical and molecular analyses, of contracted rabbit knee posterior capsule tissue after COX‐2 inhibition revealed increased maximal passive extension and down‐regulation of collagen messenger RNA compared with controls. Histopathologic examination suggested a trend of decreased quantities of dense fibrous connective tissue with COX‐2 inhibition. These data may suggest that inhibiting the inflammatory cascade could potentially reduce pathologic myofibroblast activation, thereby reducing scar tissue formation and increasing the range of motion in arthrofibrotic joints. Implementing a multi‐modal pharmacologic approach may simultaneously target numerous cellular components contributing to the complex process of arthrofibrogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2609–2620, 2019

Aims Concurrent hip and spine pathologies can alter the biomechanics of spinopelvic mobility in primary total hip arthroplasty (THA). This study examines how differences in pelvic orientation of patients with spine fusions can increase the risk of dislocation risk after THA. Patients and Methods We identified 84 patients (97 THAs) between 1998 and 2015 who had undergone spinal fusion prior to primary THA. Patients were stratified into three groups depending on the length of lumbar fusion and whether or not the sacrum was involved. Mean age was 71 years (40 to 87) and 54 patients (56%) were female. The mean body mass index (BMI) was 30 kg/m2 (19 to 45). Mean follow-up was six years (2 to 17). Patients were 1:2 matched to patients with primary THAs without spine fusion. Hazard ratios (HR) were calculated. Results Dislocation in the fusion group was 5.2% at one year versus 1.7% in controls but this did not reach statistical significance (HR 1.9; p = 0.33). Compared with controls, there was no significant difference in rate of dislocation in patients without a sacral fusion. When the sacrum was involved, the rate of dislocation was significantly higher than in controls (HR 4.5; p = 0.03), with a trend to more dislocations in longer lumbosacral fusions. Patient demographics and surgical characteristics of THA (i.e. surgical approach and femoral head diameter) did not significantly impact risk of dislocation (p > 0.05). Significant radiological differences were measured in mean anterior pelvic tilt between the one-level lumbar fusion group (22°), the multiple-level fusion group (27°), and the sacral fusion group (32°; p < 0.01). Ten-year survival was 93% in the fusion group and 95% in controls (HR 1.2; p = 0.8). Conclusion Lumbosacral spinal fusions prior to THA increase the risk of dislocation within the first six months. Fusions involving the sacrum with multiple levels of lumbar involvement notably increased the risk of postoperative dislocation compared with a control group and other lumbar fusions. Surgeons should take care with component positioning and may consider higher stability implants in this high-risk cohort.

ABSTRACTTrauma, surgery, and other inflammatory conditions can lead to debilitating joint contractures. Adjunct pharmacologic modalities may permit clinical prevention and treatment of recalcitrant joint contractures. We investigated the therapeutic potential of rosiglitazone by intra‐articular delivery via oligo[poly(ethylene glycol)fumarate] (OPF) hydrogels in an established rabbit model of arthrofibrosis. OPF hydrogels loaded with rosiglitazone were characterized for drug elution properties upon soaking in minimum essential media (MEM) with 10% fetal bovine serum and measurements of drug concentrations via High Performance Liquid Chromatography (HPLC). Drug‐loaded scaffolds were surgically implanted into 24 skeletally mature female New Zealand White rabbits that were divided into equal groups receiving OPF hydrogels loaded with rosiglitazone (1.67 mg), or vehicle control (10 µl DMSO). After 8 weeks of joint immobilization, rabbits were allowed unrestricted cage activity for 16 weeks. Contracture angles of rabbit limbs treated with rosiglitazone showed statistically significant improvements in flexion compared to control animals (mean angles, respectively, 64.4° vs. 53.3°, p < 0.03). At time of sacrifice (week 24), animals in the rosiglitazone group continued to exhibit less joint contracture than controls (119.0° vs. 99.5°, p = 0.014). The intra‐articular delivery of rosiglitazone using implanted OPF hydrogels decreases flexion contractures in a rabbit model of arthrofibrosis without causing adverse effects (e.g., gross inflammation or arthritis). Statement of Clinical Significance: Post‐traumatic joint contractures are common and debilitating, with limited available treatment options. Pharmacologic interventions can potentially prevent and treat such contractures. This study is translational in that a commercially approved medication has been repurposed through a novel delivery device. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2949–2955, 2018.

ABSTRACTThe current method of measuring arthrofibrosis in live rabbits is critically limited. Specifically, this method involves radioactive fluoroscopy, error‐prone goniometric measurements, and static joint angle outcomes that fail to approximate the compliance of tissues surrounding the joint. This study aims to validate a novel method of capturing the compliance of contracted tissues surrounding the joint without the use of fluoroscopy or animal sacrifice. Surgically induced contractures of one‐hundred and eight rabbits were measured using the current standard of contracture measurement (a pulley system) as well as a newly designed dynamic load cell (DLC) device. The DLC device was highly reliable when compared to the pulley system (r = 0.907, p < 0.001). Finally, the DLC device produced joint stiffness hysteresis curves capable of approximating the compliance of stiff joint tissues, ultimately calculating a mean joint stiffness of 1.57 ± 1.31 N · m · rad−1 (range, 0.33–6.37 N · m · rad−1). In conclusion, the DLC device represents a valid method for measuring joint contractures. Further, the DLC device notably improves current techniques by introducing the capacity to approximate the compliance of contracted tissues in living rabbits. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2186–2192, 2018.

Aims The pathogenesis of intraneural ganglion cysts is controversial. Recent reports in the literature described medial plantar intraneural ganglion cysts (mIGC) with articular branches to subtalar joints. The aim of the current study was to provide further support for the principles underlying the articular theory, and to explain the successes and failures of treatment of mICGs. Patients and Methods Between 2006 and 2017, five patients with five mICGs were retrospectively reviewed. There were five men with a mean age of 50.2 years (33 to 68) and a mean follow-up of 3.8 years (0.8 to 6). Case history, physical examination, imaging, and intraoperative findings were reviewed. The outcomes of interest were ultrasound and/or MRI features of mICG, as well as the clinical outcomes. Results The five intraneural cysts followed the principles of the unifying articular theory. Connection to the posterior subtalar joint (pSTJ) was identified or suspected in four patients. Re-evaluation of preoperative MRI demonstrated a degenerative pSTJ and denervation changes in the abductor hallucis in all patients. Cyst excision with resection of the articular branch (four), cyst incision and drainage (one), and percutaneous aspiration/steroid injection (two) were performed. Removing the connection to the pSTJ prevented recurrence of mIGC, whereas medial plantar nerves remained cystic and symptomatic when resection of the communicating articular branch was not performed. Conclusion Our findings support a standardized treatment algorithm for mIGC in the presence of degenerative disease at the pSTJ. By understanding the pathoanatomic mechanism for every cyst, we can improve treatment that must address the articular branch to avoid the recurrence of intraneural ganglion cysts, as well as the degenerative pSTJ to avoid extraneural cyst formation or recurrence. Cite this article: Bone Joint J 2018;100-B:183–9.

AimsThe primary aim of this study was to define the standard minimum follow-up required to produce a reliable estimate of the rate of re-operation after radial head arthroplasty (RHA). The secondary objective was to define the leading reasons for re-operation.Materials and MethodsFour electronic databases, between January 2000 and March 2017 were searched. Articles reporting reasons for re-operation (Group I) and results (Group II) after RHA were included. In Group I, a meta-analysis was performed to obtain the standard minimum follow-up, the mean time to re-operation and the reason for failure. In Group II, the minimum follow-up for each study was compared with the standard minimum follow-up.ResultsA total of 40 studies were analysed: three were Group I and included 80 implants and 37 were Group II and included 1192 implants. In Group I, the mean time to re-operation was 1.37 years (0 to 11.25), the standard minimum follow-up was 3.25 years; painful loosening was the main indication for re-operation. In Group II, 33 Group II articles (89.2%) reported a minimum follow-up of < 3.25 years.ConclusionThe literature does not provide a reliable estimate of the rate of re-operation after RHA. The reproducibility of results would be improved by using a minimum follow-up of three years combined with a consensus of the definition of the reasons for failure after RHA. Cite this article: Bone Joint J 2017;99-B:1561–70.

AbstractSubstance P (SP), a neurotransmitter released after injury, has been linked to deregulated tissue repair and fibrosis in musculoskeletal tissues and other organs. Although SP inhibition is an effective treatment for nausea, it has not been previously considered as an anti‐fibrotic therapy. Although there are extensive medical records of individuals who have used SP antagonists, our analysis of human registry data revealed that patients receiving these antagonists and arthroplasty are exceedingly rare, thus precluding a clinical evaluation of their potential effects in the context of arthrofibrosis. Therefore, we pursued in vivo studies to assess the effect of SP inhibition early after injury on pro‐fibrotic gene expression and contractures in an animal model of post‐traumatic joint stiffening. Skeletally mature rabbits (n = 24) underwent surgically induced severe joint contracture, while injected with either fosaprepitant (a selective SP antagonist) or saline (control) early after surgery (3, 6, 12, and 24 h). Biomechanical testing revealed that differences in mean contracture angles between the groups were not statistically significant (P = 0.27), suggesting that the drug neither mitigates nor exacerbates joint contracture. However, microarray gene expression analysis revealed that mRNA levels for proteins related to cell signaling, pro‐angiogenic, pro‐inflammatory, and collagen matrix production were significantly different between control and fosaprepitant treated rabbits (P < 0.05). Hence, our study demonstrates that inhibition of SP alters expression of pro‐fibrotic genes in vivo. This finding will motivate future studies to optimize interventions that target SP to reduce the formation of post‐traumatic joint contractures.

AbstractIt is widely hypothesized that mechanical loading, specifically repetitive low‐intensity tasks, influences the inner structure of cancellous bone. As such, there is likely a relationship between handedness and bone morphology. The aim of this study is to determine patterns in trabecular bone between dominant and non‐dominant hands in modern humans. Seventeen healthy patients between 22 and 32 years old were included in the study. Radial carpal bones (lunate, capitate, scaphoid, trapezium, trapezoid, 1st, 2nd and 3rd metacarpals) were analyzed with high‐resolution micro‐computed tomography. Additionally, crush and pinch grip were recorded. Factorial analysis indicated that bone volume ratio, trabeculae number (Tb.N), bone surface to volume ratio (BS.BV), body weight, stature and crush grip were all positively correlated with principal components 1 and 2 explaining 78.7% of the variance. Volumetric and trabecular endostructural parameters (BV/TV, BS/BV or Tb.Th, Tb.N) explain the observed inter‐individual variability better than anthropometric or clinical parameters. Factors analysis regressions showed correlations between these parameters and the dominant side for crush strength for the lunate (r2 = 0.640, P < 0.0001), trapezium (r2 = 0.836, P < 0.0001) and third metacarpal (r2 = 0.763). However, despite a significant lateralization in grip strength for all patients, the endostructural variability between dominant and non‐dominant sides was limited in perspective to inter‐individual differences. In conclusion, handedness is unlikely to generate trabecular patterns of asymmetry. It appears, however, that crush strength can be considered for endostructural analysis in the modern human wrist.