Oral Prednisone Use Following Primary Total Knee Arthroplasty Does Not Increase Infections, But Can be Associated with Higher Risk for Medical and Surgical Complications.

INTRODUCTION: Postoperative use of oral prednisone to augment the effect of multimodal pain regimens after total knee arthroplasty (TKA) has increased in popularity. However, data on the risks of its utilization, especially as it relates to infection, has been lacking. We tested the null hypothesis that perioperative prednisone use is not associated with the incidence of surgical and medical complications after TKA. METHODS: Using a national administrative claims database, we identified 949,555 patients undergoing primary TKA. We excluded patients who filled oral prednisone prescriptions within 90 days prior to surgery or between 90 and 364 days after surgery. Patients who had acute prednisone use were defined as those who filled prednisone prescriptions only within 30 days after surgery. Outcomes consisted of surgical and medical complications after TKA. Multivariable logistic regression models were used to evaluate the association between acute prednisone use and complications, adjusting for age, sex, region, insurance plan, and Elixhauser comorbidities. RESULTS: Patients in the acute prednisone cohort had greater adjusted odds of subsequent manipulation under anesthesia (adjusted OR [odds ratio] = 1.23 [95% CI (confidence interval): 1.09 to 1.38]; P < 0.001) and lysis of adhesions (adjusted OR = 1.58 [95% CI: 1.02 to 2.33]; P = 0.03) compared to patients who did not have acute prednisone use. Patients who had acute prednisone use also had greater adjusted odds of acute kidney injury (adjusted OR = 1.47 [95% CI: 1.25 to 1.71]; P < 0.001) and pneumonia (adjusted OR = 4.04 [95% CI: 3.53 to 4.59]; P < 0.001). There was no increased incidence of infection. CONCLUSION: Prednisone use shortly following TKA may be associated with a higher incidence of certain surgical and medical complications, but without increased risk for infection. However, given these risks, the optimal patient profile for postoperative prednisone use remains to be defined.

Acute Total Hip Arthroplasty Following Acetabular Fracture is Associated with a High Risk of Revision, Dislocation, and Periprosthetic Fracture.

BACKGROUND: The aim of this study was to compare outcomes between acute, subacute, and delayed arthroplasty for acetabular fractures occurring within one week, from one week to six months, or longer than six months before the index total hip arthroplasty (THA), versus THA without a history of acetabular fracture as a control. METHODS: We analyzed the records of patients undergoing primary THA who were enrolled in a national database for at least two years before and after the index procedure. Patients who had an initial diagnostic code for acetabular fracture occurring less than one week, from one week to six months, or at least more than six months before the THA were classified as acute THA (aTHA), subacute (saTHA), or delayed (dTHA), respectively. The control group was patients undergoing THA who did not have a history of acetabular fracture. There were 430,349 control primary THAs, 462 aTHAs, 675 saTHAs, and 1,162 dTHAs. RESULTS: After adjusting for age, sex, region, and comorbidities, patients who had an aTHA and saTHA experienced statistically significant increased odds of revision, dislocation, and periprosthetic fracture compared to primary THA without a history of acetabular fracture. Similarly, dTHA was associated with increased odds of revision, dislocation, and periprosthetic fractures compared to primary THA. In the multivariate analysis, aTHA had statistically significant higher rates of dislocation when compared to dTHA. CONCLUSION: Patients who had a history of acetabular fractures undergoing aTHA, saTHA, or dTHA have significantly increased rates of revision, periprosthetic fracture, and dislocation compared to primary THA in those who did not have a history of acetabular fractures.

Medicaid Insurance is Associated With Decreased MRI Use for Ankle Sprains Compared With Private Insurance: A Retrospective Database Analysis.

BACKGROUND: Advanced imaging modalities are expensive, and access to advanced imaging services may vary by socioeconomic factors, creating the potential for unwarranted variations in care. Ankle sprains are a common injury for which variations in MRI use can occur, both via underuse of indicated MRIs (appropriate use) and overuse of nonindicated MRIs (inappropriate use). High-value, equitable healthcare would decrease inappropriate use and increase appropriate use of MRI for this common injury. It is unknown whether socioeconomic factors are associated with underuse of indicated MRIs and overuse of nonindicated MRIs for ankle sprains. QUESTIONS/PURPOSES: Using ankle sprains as a paradigm injury, given their high population incidence, we asked: (1) Does MRI use for ankle sprains vary by insurance type? (2) After controlling for relevant confounding variables, did patients who received an MRI have higher odds of undergoing ankle surgery? METHODS: Between 2011 and 2019, a total of 6,710,223 patients were entered into the PearlDiver Mariner Patient Records Database with a diagnosis of ankle sprain. We considered patients with continuous enrollment in the database for at least 1 year before and 2 years after the diagnosis as potentially eligible. Based on that, 68% (4,567,106) were eligible; a further 20% (1,372,478) were excluded because of age younger than 18 years, age at least 65 years with Medicaid insurance, or age < 65 years with Medicare insurance. Another 0.1% (9169) had incomplete data, leaving 47% (3,185,459) for analysis here. Patients with Medicaid insurance differed from patients with Medicare Advantage or private insurance with respect to age, gender, region, and comorbidity burden. The primary outcome was ankle MRI occurring within 12 months after diagnosis. The use of ankle surgery after MRI in each cohort was measured as a secondary outcome. We used multivariable logistic regression models to evaluate the association between insurance type and MRI use while adjusting for age, gender, region, and comorbidity burden. Separate multivariable regression models were created to evaluate the association between receiving an MRI and subsequent ankle surgery for each insurance type, adjusting for age, gender, region, and comorbidity burden. Within 12 months of an ankle sprain diagnosis, 1% (3522 of 339,457) of patients with Medicaid, 2% (44,793 of 2,627,288) of patients with private insurance, and 1% (1660 of 218,714) of patients with Medicare Advantage received an MRI. RESULTS: After controlling for age, gender, region, and comorbidity burden, patients with Medicaid had lower odds of receiving an MRI within 12 months after ankle sprain diagnosis than patients with private insurance (odds ratio 0.60 [95% confidence interval 0.57 to 0.62]; p < 0.001). Patients with Medicaid who received an MRI had higher adjusted odds of undergoing subsequent ankle surgery (OR 23 [95% CI 21 to 26]; p < 0.001) than patients with private insurance (OR 12.7 [95% CI 12 to 13]; p < 0.001). CONCLUSION: Although absolute MRI use was generally low, there was substantial relative variation by insurance type. Given the high incidence of ankle sprains in the general population, these relative differences can translate to tens of thousands of MRIs. Further studies are needed to evaluate the reasons for decreased appropriate MRI use in patients with Medicaid and overuse of MRI in patients with private insurance. The establishment of clinical practice guidelines by orthopaedic professional societies and more stringent gatekeeping for MRI use by health insurers could reduce unwarranted variations in MRI use. LEVEL OF EVIDENCE: Level III, prognostic study.

Tension-activated nanofiber patches delivering an anti-inflammatory drug improve repair in a goat intervertebral disc herniation model.

Conventional microdiscectomy treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus, resulting in a high incidence of recurrent herniation and persistent dysfunction. The lack of repair and the acute inflammation that arise after injury can further compromise the disc and result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annulus fibrosus repair and local delivery of the anti-inflammatory factor anakinra (a recombinant interleukin-1 receptor antagonist). TARPs transmit physiologic strain to mechanically activated microcapsules embedded within the patch, which release encapsulated bioactive molecules in direct response to spinal loading. Mechanically activated microcapsules carrying anakinra were loaded into TARPs, and the effects of TARP-mediated annular repair and anakinra delivery were evaluated in a goat model of annular injury in the cervical spine. TARPs integrated with native tissue and provided structural reinforcement at the injury site that prevented aberrant disc-wide remodeling resulting from detensioning of the annular fibrosus. The delivery of anakinra by TARP implantation increased matrix deposition and retention at the injury site and improved maintenance of disc extracellular matrix. Anakinra delivery additionally attenuated the inflammatory response associated with TARP implantation, decreasing osteolysis in adjacent vertebrae and preserving disc cellularity and matrix organization throughout the annulus fibrosus. These results demonstrate the therapeutic potential of TARPs for the treatment of intervertebral disc herniation.

In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis.

Autologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). However, the clinical outcomes after PRP administration are often variable, and there is limited information about the specific characteristics of PRP that impact bioactivity and clinical responses. In this study, we aimed to develop an integrative workflow to evaluate responses to PRP in vitro, and to assess if the in vitro responses to PRP are associated with the PRP composition and clinical outcomes in patients with knee OA. To do this, we used a coculture system of macrophages and fibroblasts paired with transcriptomic analyses to comprehensively characterize the modulation of inflammatory responses by PRP in vitro. Relying on patient-reported outcomes and achievement of minimal clinically important differences in OA patients receiving PRP injections, we identified responders and non-responders to the treatment. Comparisons of PRP from these patient groups allowed us to identify differences in the composition and in vitro activity of PRP. We believe that our integrative workflow may enable the development of targeted approaches that rely on PRP and other orthobiologics to treat musculoskeletal pathologies.

Biological and Mechanical Predictors of Meniscus Function: Basic Science to Clinical Translation.

Progressive knee joint degeneration occurs following removal of a torn meniscus. However, there is significant variability in the rate of development of post-meniscectomy osteoarthritis (OA). While there is no current consensus on the risk factors for development of knee OA in patients with meniscus tears, it is likely that both biological and biomechanical factors play critical roles. In this perspective paper, we review the mechanical and the biological predictors of the response of the knee to partial meniscectomy. We review the role of patient-based studies, in vivo animal models, cadaveric models, bioreactor systems, and statistically augmented computational models for the study of meniscus function and post-meniscectomy OA, providing insight into the important interplay between biomechanical and biologic factors. We then discuss the clinical translation of these concepts for "biologic augmentation" of meniscus healing and meniscus replacement. Ultimately, collaborative studies between engineers, biologists, and clinicians is the optimal way to improve our understanding of meniscus pathology and response to injury and/or disease, and to facilitate effective translation of laboratory findings to improved treatments for our patients. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:937-945, 2020.

Cell Therapy-a Basic Science Primer for the Sports Medicine Clinician.

PURPOSE OF REVIEW: The emergence of cell-based therapies has brought much excitement to the field of orthopedic sports medicine. However, the significant inconsistency of reporting has led to the poor understanding, misinformation, and false expectations for patients and clinicians alike. In this paper, we aim to clarify the available cell-therapy treatments and summarize some of the latest research. RECENT FINDINGS: Although this technology is in early development, our understanding of cell biology has grown significantly over the last decade. Furthermore, it is becoming evident that tissue specificity may play a significant role in determining the effectiveness and overall clinical benefit attributed to cell therapy. Cell therapy is an emerging field with tremendous potential for clinically significant benefit. However, in its current state, clinical application of these treatments is limited by federal regulations, variability in formulation, and limited understanding of the biologic activity of various cell formulations.

Engineering a highly elastic human protein-based sealant for surgical applications.

Surgical sealants have been used for sealing or reconnecting ruptured tissues but often have low adhesion, inappropriate mechanical strength, cytotoxicity concerns, and poor performance in biological environments. To address these challenges, we engineered a biocompatible and highly elastic hydrogel sealant with tunable adhesion properties by photocrosslinking the recombinant human protein tropoelastin. The subcutaneous implantation of the methacryloyl-substituted tropoelastin (MeTro) sealant in rodents demonstrated low toxicity and controlled degradation. All animals survived surgical procedures with adequate blood circulation by using MeTro in an incisional model of artery sealing in rats, and animals showed normal breathing and lung function in a model of surgically induced rat lung leakage. In vivo experiments in a porcine model demonstrated complete sealing of severely leaking lung tissue in the absence of sutures or staples, with no clinical or sonographic signs of pneumothorax during 14 days of follow-up. The engineered MeTro sealant has high potential for clinical applications because of superior adhesion and mechanical properties compared to commercially available sealants, as well as opportunity for further optimization of the degradation rate to fit desired surgical applications on different tissues.