Cody C. Wyles

Utility of Synovial Fluid Aspirations in Failed Metal-On-Metal Total Hip Arthroplasty

White blood cell (WBC) count and neutrophil percentage from preoperative synovial fluid aspirations are used to help determine the presence or absence of periprosthetic joint infection (PJI) in failed total hip arthroplasty (THA). The clinical levels indicative of infection have not been delineated in metal-on-metal (MoM) bearings. We identified 39 patients who received a preoperative synovial fluid aspiration prior to MoM revision. Thirty-five of 39 cases were culture negative and 4 of 39 were culture positive. WBC count >3000 cells/μL was 100% sensitive and 57.1% specific. Neutrophil percentage >80% was 100% sensitive and 97.1% specific. Both CRP and ESR >8.0mg/L and >22 mm/h, respectively were 75.0% sensitive and 67.6% specific. Our data suggest that synovial WBC count and serum ESR and CRP have poor predictive value in diagnosing PJI for failed MoM THA, whereas synovial neutrophil percentage is a highly accurate marker for diagnosing infection in this patient population.

Mesenchymal stem cell therapy for osteoarthritis: current perspectives

Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.

The John Charnley Award: Redefining the Natural History of Osteoarthritis in Patients With Hip Dysplasia and Impingement.

BackgroundStructural hip deformities including developmental dysplasia of the hip (DDH) and femoroacetabular impingement (FAI) are thought to predispose patients to degenerative joint changes. However, the natural history of these malformations is not clearly delineated.Questions/purposes(1) Among patients undergoing unilateral THA who have a contralateral hip without any radiographic evidence of hip disease, what is the natural history and progression of osteoarthritis in the native hip based on morphological characteristics? (2) Among patients undergoing unilateral THA who have a contralateral hip without any radiographic evidence of hip disease, what are the radiographic parameters that predict differential rates of degenerative change?MethodsWe identified every patient 55 years of age or younger at our institution who received unilateral primary THA from 1980 to 1989 (n = 722 patients). Preoperative radiographs were reviewed on the contralateral hip and only hips with Tönnis Grade 0 degenerative change that had minimum 10-year radiographic followup were included. A total of 172 patients met all eligibility criteria with the following structural diagnoses: 48 DDH, 74 FAI, and 40 normal morphology, and an additional 6% (10 of the 172 patients) met all eligibility criteria but were lost to followup before the 10-year minimum. Mean age at the time of study inclusion was 47 years (range, 18–55 years), and 56% (91 of 162) of the patients in this study were female. Mean followup was 20 years (range, 10–35 years). Radiographic metrics, in conjunction with the review of two experienced arthroplasty surgeons, determined the structural hip diagnosis as DDH, FAI, or normal morphology. Every available followup AP radiograph was reviewed to determine progression from Tönnis Grade 0 to 3 until the time of last followup or operative intervention with THA. Survivorship was analyzed by Kaplan-Meier methodology, hazard ratios, and multistate modeling. Thirty-five patients eventually underwent THA: 16 (33%) DDH, 13 (18%) FAI, and six (15%) normal morphology.ResultsDegenerative change was most rapid in patients with DDH followed by FAI and normal morphology. Among patients who recently developed Tönnis 1 degenerative change, the probability of undergoing THA in 10 years based on hip morphology was approximately one in three for DDH and one in five for both FAI and normal morphology hips, whereas the approximate probability at 20 years was two in three for DDH and one in two for both FAI and normal morphology hips. The likelihood of radiographic degeneration was increased in patients with the following findings: femoral head lateralization > 8 mm, femoral head extrusion index > 0.20, acetabular depth-to-width index < 0.30, lateral center-edge angle < 25°, and Tönnis angle > 8°.ConclusionsDegenerative change occurred earliest in patients with DDH, whereas the natural history of patients with FAI was quite similar to structurally normal hips. However, patients with cam deformities and concomitant acetabular dysplasia developed osteoarthritis more rapidly. Although the results of this study cannot be directly correlated to highly active patients with FAI, these findings suggest that correction of FAI to a normal morphology may only minimally impact the natural history, especially if intervention takes place beyond Tönnis 0. Analysis of radiographic parameters showed that incremental changes toward dysplastic morphology increase the risk of degenerative change.Level of EvidenceLevel III, prognostic study.

There Are No Differences in Short- to Mid-term Survivorship Among Total Hip-bearing Surface Options: A Network Meta-analysis

BackgroundTotal hip arthroplasty (THA) is increasingly being performed in patients with long life expectancies and active lifestyles. Newer implant bearing surfaces, with superior wear characteristics, often are used in this cohort with the goal of improving longevity of the prosthesis, but comparisons across the numerous available bearing surfaces are limited, so the surgeon and patient may have difficulty deciding which implants to use.Questions/purposesThe purpose of this study was to answer the following question: Is there a short- to mid-term survivorship difference between common THA bearings used in patients younger than age 65 years?MethodsWe conducted a systematic review to identify randomized clinical trials (RCTs) published after 2000 that reported survivorship of ceramic-on-ceramic (CoC), ceramic-on-highly crosslinked polyethylene (CoPxl), or metal-on-highly crosslinked polyethylene (MoPxl) bearings. To qualify for our review, RCTs had to have a minimum 2-year followup and study patients were required to have an average age younger than 65 years. Direct-comparison meta-analysis and network meta-analysis were performed to combine direct and indirect evidence.ResultsDirect-comparison meta-analysis found no differences among the bearing surfaces in terms of the risk of revision; this approach demonstrated a risk ratio for revision of 0.65 (95% confidence interval [CI], 0.19–2.23; p = 0.50) between CoC and CoPxl and a risk ratio for revision of 0.40 (95% CI, 0.06–2.63; p = 0.34) between CoC and MoPxl. Network meta-analysis (with post hoc modification) likewise found no differences in survivorship across the three implant types, demonstrating the following probabilities of most effective implant with 95% credible intervals (CrI): CoC = 64.6% (0%–100%); CoPxl = 24.9% (0%–100%); and MoPxl = 9.9% (0%–100%). The CrIs ranged from 0% to 100% for all three bearing surfaces. Direct-comparison meta-analysis allowed for pooling of five RCTs, including 779 THAs, whereas network meta-analysis (before post hoc analysis) enabled pooling of 18 RCTs, including 2599 THAs.ConclusionsCurrent published evidence does not support survivorship differences among commonly used bearing surfaces in patients younger than age 65 years undergoing THA at short- to mid-term followup. Long-term RCT data will be needed to determine if a survivorship benefit is realized in younger, more active patients over time.Level of Evidence Level I, therapeutic study.

Is Local Infiltration Analgesia Superior to Peripheral Nerve Blockade for Pain Management After THA: A Network Meta-analysis.

BackgroundLocal infiltration analgesia and peripheral nerve blocks are common methods for pain management in patients after THA but direct head-to-head, randomized controlled trials (RCTs) have not been performed. A network meta-analysis allows indirect comparison of individual treatments relative to a common comparator; in this case placebo (or no intervention), epidural analgesia, and intrathecal morphine, yielding an estimate of comparative efficacy.Questions/purposesWe asked, when compared with a placebo, (1) does use of local infiltration analgesia reduce patient pain scores and opioid consumption, (2) does use of peripheral nerve blocks reduce patient pain scores and opioid consumption, and (3) is local infiltration analgesia favored over peripheral nerve blocks for postoperative pain management after THA?MethodsWe searched six databases, from inception through June 30, 2014, to identify RCTs comparing local infiltration analgesia or peripheral nerve block use in patients after THA. A total of 35 RCTs at low risk of bias based on the recommended Cochrane Collaboration risk assessment tool were included in the network meta-analysis (2296 patients). Primary outcomes for this review were patient pain scores at rest and cumulative opioid consumption, both assessed at 24 hours after THA. Because of substantial heterogeneity (variation of outcomes between studies) across included trials, a random effect model for meta-analysis was used to estimate the weighted mean difference (WMD) and 95% CI. The gray literature was searched with the same inclusion criteria as published trials. Only one unpublished trial (published abstract) fulfilled our criteria and was included in this review. All other studies included in this systematic review were full published articles. Bayesian network meta-analysis included all RCTs that compared local infiltration analgesia or peripheral nerve blocks with placebo (or no intervention), epidural analgesia, and intrathecal morphine.ResultsCompared with placebo, local infiltration analgesia reduced patient pain scores (WMD, −0.61; 95% CI, −0.97 to −0.24; p = 0.001) and opioid consumption (WMD, −7.16 mg; 95% CI, −11.98 to −2.35; p = 0.004). Peripheral nerve blocks did not result in lower pain scores or reduced opioid consumption compared with placebo (WMD, −0.43; 95% CI, −0.99 to 0.12; p = 0.12 and WMD, −3.14 mg, 95% CI, −11.30 to 5.02; p = 0.45). However, network meta-analysis comparing local infiltration analgesia with peripheral nerve blocks through common comparators showed no differences between postoperative pain scores (WMD, −0.36; 95% CI, −1.06 to 0.31) and opioid consumption (WMD, −4.59 mg; 95% CI, −9.35 to 0.17), although rank-order analysis found local infiltration analgesia to be ranked first in more simulations than peripheral nerve blocks, suggesting that it may be more effective.ConclusionsUsing the novel statistical network meta-analysis approach, we found no differences between local infiltration analgesia and peripheral nerve blocks in terms of analgesia or opioid consumption 24 hours after THA; there was a suggestion of a slight advantage to peripheral nerve blocks based on rank-order analysis, but the effect size in question is likely not large. Given the slight difference between interventions, clinicians may choose to focus on other factors such as cost and intervention-related complications when debating which analgesic treatment to use after THA.Level of EvidenceLevel I, therapeutic study.

Stem cell treatment for avascular necrosis of the femoral head: current perspectives

Avascular necrosis (AVN) of the femoral head is a progressive disease that predominantly affects younger patients. Although the exact pathophysiology of AVN has yet to be elucidated, the disease is characterized by a vascular insult to the blood supply of the femoral head, which can lead to collapse of the femoral head and subsequent degenerative changes. If AVN is diagnosed in the early stages of the disease, it may be possible to attempt surgical procedures which preserve the hip joint, including decompression of the femoral head augmented with concentrated bone marrow. The use of autologous stem cells has shown promise in halting the progression of AVN of the femoral head, and subsequently preventing young patients from undergoing total hip arthroplasty. The purpose of this study was to review the current use of stem cells for the treatment of AVN of the femoral head.

Antibacterial and Biocompatible Titanium-Copper Oxide Coating May Be a Potential Strategy to Reduce Periprosthetic Infection: An In Vitro Study

BackgroundPeriprosthetic infections are devastating for patients and more efficacious preventive strategies are needed. Surface-modified implants using antibacterial coatings represent an option to cope with this problem; however, manufacturing limitations and cytotoxicity have curbed clinical translation. Among metals with antibacterial properties, copper has shown superior in vitro antibacterial performance while maintaining an acceptable cytotoxicity profile. A thin film containing copper could prevent early biofilm formation to limit periprosthetic infections. This pilot study presents the in vitro antibacterial effect, cytotoxicity, and copper ion elution pattern of a thin film of titanium-copper oxide (TiCuO).Questions/purposes(1) Do titanium alloy (Ti6Al4V) discs coated with a thin film of TiCuO reduce Staphylococcus epidermidis biofilm and planktonic cell density compared with uncoated discs? (2) Do Ti6Al4V discs coated with a thin film of TiCuO affect normal human osteoblast viability compared with untreated cells? (3) Is copper ion concentration generated by coated discs lower than previously published copper ion concentrations that cause 50% toxicity in similar human cell lines in vitro (TC50)?MethodsNinety Ti6Al4V discs (12.5 mm diameter; 1.25 mm thick) were used in this study. Seventy-two Ti6Al4V discs were coated with a thin film of either titanium oxide (TiO) or TiCuO containing 20%, 40%, or 80% copper using high-power impulse magnetron sputtering (HiPIMS). Eighteen Ti6Al4V discs remained uncoated for control purposes. We tested antibacterial properties of S epidermidis grown on discs in wells containing growth medium. After 24 hours, planktonic bacteria as well as biofilms removed by sonication were quantitatively cultured. Annexin/Pi staining was used to quantify in vitro normal human osteoblast cell viability at 24 hours and Day 7, respectively. Copper elution was measured at Days 1, 2, 3, 7, 14, and 28 using an inductively coupled plasma mass spectrometer to analyze aliquots of culture medium. Copper ion concentration achieved at 24 hours was compared with previously published TC50 for gingival fibroblast, a phenotypically similar cell line with available data regarding copper ion exposure.ResultsDiscs coated with TiCuO 80% copper showed greater biofilm and planktonic cell density reduction when compared with other tested compositions (analysis of variance [ANOVA]; p < 0.001). Discs coated with TiCuO 80% copper showed mean biofilm and planktonic cell density of 4.0 log10 (SD = 0.4) and 5.7 log10 (SD = 0.2). Discs coated with TiCuO 80% showed a mean difference in biofilm and planktonic cell density of 2.5 log10 (95% confidence interval [CI], 1.9–3.1 log10; p < 0.001) and 1.2 (95% CI, 0.6–1.8; p < 0.001), respectively, when compared with uncoated discs. Normal human osteoblast viability did not differ among all groups at 24 hours (ANOVA; p = 0.2) and Day 7 (ANOVA; p = 0.7). Discs coated with TiCuO 80% copper showed a mean difference (95% CI) in relative cell viability (%) at 24 hours and Day 7 of 31.1 (95% CI, −19.4 to 81.7; p = 0.4) and −5.0 (95% CI, −7.8 to 17.9; p = 0.9), respectively, when compared with untreated cells. For all TiCuO-coated discs, copper ion elution peaked at 24 hours and slowly decreased in a curvilinear fashion to nearly undetectable levels by Day 28. Discs coated with TiCuO 80% copper showed mean copper ion concentration at 24 hours of 269.4 µmol/L (SD = 25.2 µmol/L) and this concentration was lower than previously published TC50 for similar human cell lines at 24 hours (344 µmol/L, SEM = 44 µmol/L).ConclusionsThis pilot study demonstrates a proof of concept that a thin-film implant coating with TiCuO can provide a potent local antibacterial environment while remaining relatively nontoxic to a human osteoblast cell line. Further research in an animal model will be necessary to establish efficacy and safety of this technique and whether it might be useful in the design of implants.Clinical RelevanceA thin film coating with TiCuO demonstrates high antibacterial activity and low cellular cytotoxicity to human osteoblasts in vitro. Taken together, these properties represent a potential strategy for preventing periprosthetic infection if further work in animal models can confirm these results in vivo.

Decreased Osteogenic Activity of Mesenchymal Stem Cells in Patients With Corticosteroid-Induced Osteonecrosis of the Femoral Head

BACKGROUND Osteonecrosis (ON) of the femoral head occurs when cells of trabecular bone spontaneously die. Mesenchymal stem cells (MSCs) have been introduced into the femoral head in an attempt to halt progression of the disease. The purpose of this study was to functionally compare MSCs in patients with ON of the femoral head with patients without. METHODS Mesenchymal stem cells were isolated from 20 patients with corticosteroid-induced ON and 10 controls without. Colony-forming unit and proliferation assays were used to assess MSC proliferation. Mesenchymal stem cells were differentiated into bone, fat, and cartilage. Functional assays were used to quantify the differentiation capacity. RESULTS Control MSCs demonstrated greater cellular growth potential and improved ability to differentiate into bone. CONCLUSION The decreased ability to differentiate into bone may be a reason why patients treated with autologous MSC infusion fail regenerative treatment strategies and progress to collapse.

Cam Deformities and Limited Hip Range of Motion Are Associated With Early Osteoarthritic Changes in Adolescent Athletes: A Prospective Matched Cohort Study

Background: The natural history of femoroacetabular impingement (FAI) remains incompletely understood. In particular, there is limited documentation of joint damage in adolescent patients with limited range of motion (LROM) of the hip, which is commonly associated with FAI. Purpose: To evaluate changes in magnetic resonance imaging (MRI), radiographs, and clinical examinations over 5 years in a group of athletes from a wide variety of sports with asymptomatic LROM of the hip compared with matched controls. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: The authors screened 226 male and female athletes aged 12 to 18 years presenting for preparticipation sports physical examinations. Using a goniometer, we identified 13 participants with at least one hip having internal rotation <10° with the hip flexed to 90°. Overall, 21 of 26 hips (81%) had internal rotation <10°. These participants were age- and sex-matched to 13 controls with internal rotation >10°. At the time of enrollment, all participants were asymptomatic and underwent a complete hip examination and radiographic imaging with radiographs (anteroposterior [AP] and von Rosen views) and non-arthrogram MRI. Participants returned at 5-year follow-up and underwent repeat hip examinations, imaging (AP and lateral radiographs and non-arthrogram MRI), and hip function questionnaires. MRI scans were classified as “normal” versus “abnormal” based on the presence of any of 13 scored chondral, labral, or osseous abnormalities. Comparisons between the LROM group and control group were performed using generalized linear models (either linear, logistic, or log-binomial regression as appropriate for the outcome) with generalized estimating equations to account for the within-participant correlation due to patients having both hips included. Relative risk (RR) estimates are reported with 95% CIs. Results: At the time of study enrollment, 16 of 26 hips (62%) in the LROM group had abnormal MRI findings within the acetabular labrum or cartilage compared with 8 of 26 hips (31%) in the control group (RR, 2.0; 95% CI, 0.95-4.2; P = .067). The mean alpha angle measured from radial MRI sequences was 58° in the LROM group versus 44° in the control group (P < .0001). In the LROM group, 13 of 26 hips (50%) had a positive anterior impingement sign, whereas 0 of 26 hips (0%) had a positive anterior impingement sign in the control group. At 5-year follow-up, 18 of 19 hips (95%) in the LROM group had abnormal MRI findings compared with 14 of 26 hips (54%) in the control group (RR, 1.7; 95% CI, 1.1-2.7; P = .014). New or progressive findings were documented on MRI in 15 of 20 hips in the LROM group compared with 8 of 26 hips in the control group (RR, 2.4; 95% CI, 1.2-4.8; P = .011). Six of 22 hips (27%) in the LROM group progressed from Tönnis grade 0 to Tönnis grade 1 in degenerative changes, whereas all 26 hips in the control group remained at Tönnis grade 0 on hip radiographs. In the LROM group, 11 of 22 hips (50%) had a positive anterior impingement sign, whereas 1 of 26 hips (4%) had a positive anterior impingement sign in the control group. A cam deformity (alpha angle >55° on lateral radiographs) was present in 20 of 22 hips (91%) in the LROM group and 12 of 26 hips (46%) in the control group (P = .0165). The following variables at baseline were associated with an increased risk of degenerative changes at 5-year follow-up for the entire cohort: decreased hip internal rotation, positive anterior impingement sign, decreased hip flexion, increased alpha angle, and presence of a cam lesion. Conclusion: At 5 years, young athletes with LROM of the hip showed increased progressive degenerative changes on MRI and radiographs compared with matched controls. Although the majority of these participants remained asymptomatic, those with features of FAI had radiographic findings consistent with early osteoarthritis. These outcomes suggest that more aggressive screening and counseling of young active patients may be helpful to prevent hip osteoarthritis in those with FAI.

Collagen and Fractionated Platelet-rich Plasma Scaffold for Dermal Regeneration

Background: Current options for in vivo regeneration of dermal tissue remain limited. The purpose of this study was to engineer a unique scaffold capable of recruiting dermal stem cells from adjacent tissue, thus circumventing the need to seed the scaffolds with stem cells before implantation, leading to skin regeneration. Methods: A hydrogel scaffold was created through combination of type I collagen along with fractionated platelet-rich plasma. This was compared to a control hydrogel consisting of type I collagen and fetal bovine serum. Hydrogels were cultured with fresh human skin tissue and incubated with supplemental media. Gels were digested weekly for cellular content as examined by flow cytometry at the 4- and 8-week time points. The fractionated platelet-rich plasma and collagen gels were then implanted onto full-thickness skin defects on the backs of rats and compared to wounds healing by secondary intention. Wound area was evaluated for epithelialization and neovascularization. Results: Platelet-rich plasma fractionation increased platelet-derived growth factors. In contrast to collagen scaffolds, fractionated platelet-rich plasma–supplemented scaffolds recruited more dermal-derived stem cells from fresh skin tissue compared with collagen hydrogels at the 4- and 8-week time points. Furthermore, fractionated platelet-rich plasma–supplemented hydrogels accelerated wound healing, angiogenesis, and hair and sweat gland formation, ultimately regenerating a dermis-like tissue. Conclusions: Generation of hydrogels with fractionated platelet-rich plasma was able to improve cellular recruitment and growth and differentiation of dermal-derived stem cells, leading to hair growth and sweat gland formation. This provides a novel approach to regenerate skin for treating large defects.