A novel antibacterial compound decreases MRSA biofilm formation without the use of antibiotics in a murine model.

Despite significant advancements in material science, surgical site infection (SSI) rates remain high and prevention is key. This study aimed to demonstrate the in vivo safety and antibacterial efficacy of titanium implants treated with a novel broad-spectrum biocidal compound (DBG21) against methicillin-resistant Staphylococcus aureus (MRSA). Titanium (Ti) discs were covalently bound with DBG21. Untreated Ti discs were used as controls. All discs were implanted either untreated for 44 control mice or DBG21-treated for 44 treated mice. After implantation, 1 × 107 colony forming units (CFU) of MRSA were injected into the operating site. Mice were killed at 7 and 14 days to determine the number of adherent bacteria (biofilm) on implants and in the peri-implant surrounding tissues. Systemic and local toxicity were assessed. At both 7 and 14 days, DBG21-treated implants yielded a significant decrease in MRSA biofilm (3.6 median log10 CFU [99.97%] reduction [p < 0.001] and 1.9 median log10 CFU [98.7%] reduction [p = 0.037], respectively) and peri-implant surrounding tissues (2.7 median log10 CFU/g [99.8%] reduction [p < 0.001] and 5.6 median log10 CFU/g [99.9997%] reduction [p < 0.001], respectively). There were no significant differences between control and treated mice in terms of systemic and local toxicity. DBG-21 demonstrated a significant decrease in the number of biofilm bacteria without associated toxicity in a small animal implant model of SSI. Preventing biofilm formation has been recognized as a key element of preventing implant-related infections.

Friend or foe? Inflammation and the foreign body response to orthopedic biomaterials.

The use of biomaterials and implants for joint replacement, fracture fixation, spinal stabilization and other orthopedic indications has revolutionized patient care by reliably decreasing pain and improving function. These surgical procedures always invoke an acute inflammatory reaction initially, that in most cases, readily subsides. Occasionally, chronic inflammation around the implant develops and persists; this results in unremitting pain and compromises function. The etiology of chronic inflammation may be specific, such as with infection, or be unknown. The histological hallmarks of chronic inflammation include activated macrophages, fibroblasts, T cell subsets, and other cells of the innate immune system. The presence of cells of the adaptive immune system usually indicates allergic reactions to metallic haptens. A foreign body reaction is composed of activated macrophages, giant cells, fibroblasts, and other cells often distributed in a characteristic histological arrangement; this reaction is usually due to particulate debris and other byproducts from the biomaterials used in the implant. Both chronic inflammation and the foreign body response have adverse biological effects on the integration of the implant with the surrounding tissues. Strategies to mitigate chronic inflammation and the foreign body response will enhance the initial incorporation and longevity of the implant, and thereby, improve long-term pain relief and overall function for the patient. The seminal research performed in the laboratory of Dr. James Anderson and co-workers has provided an inspirational and driving force for our laboratory's work on the interactions and crosstalk among cells of the mesenchymal, immune, and vascular lineages, and orthopedic biomaterials. Dr. Anderson's delineation of the fundamental biologic processes and mechanisms underlying acute and chronic inflammation, the foreign body response, resolution, and eventual functional integration of implants in different organ systems has provided researchers with a strategic approach to the use of biomaterials to improve health in numerous clinical scenarios.

Cost-Effectiveness Analysis of Treatment of Radial Head Subluxation.

PURPOSE: Radial head subluxation (RHS), also called nursemaid's elbow, is a common injury in young children treated by various health care providers. The diagnosis typically does not require radiographs, but they are often ordered in the emergency room. This study aimed to determine if there was a difference in the efficacy, cost, and amount of radiographs taken in RHS treatment according to the provider, specifically between orthopedic surgeons and pediatricians. METHODS: We reviewed the charts of 207 patients presenting with RHS in the emergency department (mean age of presentation = 2.1 years, range: 0.3 to 6.5 years) to determine the provider treating the condition, the number of attempts at reduction, the number of radiographs taken, the post-reduction management, and total hospital cost incurred. RESULTS: One hundred forty-four patients were treated by orthopedic surgeons, 51 by pediatricians, and 13 by residents. The mean number of radiographs obtained was 0.1, 0.8, and 0.5 for groups treated by an orthopedic surgeon, a pediatrician, and a resident, respectively (p = 0.04). The mean cost for reduction of an RHS was $114, $648, and $267 for groups treated by an orthopedic surgeon, a pediatrician, and a resident, respectively (p = 0.04) Conclusion: Although all three groups were effective in treating RHS, there was a significantly reduced hospital cost and a reduced need for radiographs when the provider was an orthopedic surgeon.

John N. Insall Award: Randomized Clinical Trial of Cementless Versus Cemented Tibial Components: Durable and Reliable at a Mean 10-Years Follow-Up.

BACKGROUND: Cementless fixation is gaining popularity for primary total knee arthroplasties (TKAs). The prior 5-year results of our randomized clinical trial that included 3 different tibial designs found minimal differences. The purpose of the current study was to investigate the 10-year results in the same cohort. METHODS: Between 2003 and 2006, 389 primary TKAs were randomized: traditional modular cemented tibia (135); hybrid (cemented baseplate with uncemented pegs) monoblock tibia (128); and cementless monoblock tibia (126). Implant survivorships, radiographs, and clinical outcomes were analyzed. Mean age at TKA was 68 years (range, 41 to 85), 46% were male, and mean body mass index was 32 (range, 21 to 59). The mean follow-up was 10 years. RESULTS: The 10-year survivorship free of any revision was similar between the hybrid monoblock and cementless monoblock groups at 96%, but lower (89%) for the traditional modular cemented tibia (P = .05). The traditional modular cemented tibia group had significantly more revisions for aseptic tibial loosening than the other 2 groups (7 versus 0%) at 10 years (P = .003). The traditional modular cemented tibia group had significantly more nonprogressive radiolucent lines than the hybrid and cementless monoblock groups (24, 12, and 9%, respectively). Clinical outcomes were similar and excellent between all 3 groups. CONCLUSION: Cementless and hybrid monoblock tibial components have excellent implant survivorship (96%) with no cases of aseptic tibial loosening to date. The traditional cemented modular tibial group had a 7% cumulative incidence of aseptic loosening at 10 years. LEVEL OF EVIDENCE: Level I, Prospective Randomized Control Trial.

Doctor, what does my ceramic-on-ceramic hip arthroplasty weigh?

BACKGROUND: While total hip arthroplasty (THA) is generally very successful, certain patients remain dissatisfied. A common concern, especially in younger and more active patients, is the weight the implant will add to the hip. However, there is very little data available to help guide surgeons in addressing this concern. The goal of this study was therefore to compare the weight of the total hip arthroplasty implants to that of tissue removed. HYPOTHESIS: That the weight of the total hip arthroplasty implants would exceed that removed tissue. PATIENTS AND METHODS: A prospective study was conducted in 104 patients, without interfering with surgical plans. To account for different implant designs, especially relating to stem fixation, we included both cementless (n=51) and cemented (n=53) femoral stems. During the procedure, the removed bone and soft tissues, as well as the post-implantation cement were collected and weighed. The weight of the implants was provided by the manufacturer. RESULTS: Both cemented and cementless THA implants proved significantly heavier than the removed bone and soft tissues. The median weight gained was 145g [IQR: 123-168] with the cementless implant and 241g [221-364] with the cemented implant (p<0.001). Multivariable regression analysis of patient- or implant factors influencing weight gain after THA revealed that weight gain decreased with patient BMI (ß=-1.0, 95% CI: -2.0--0.1 (p=0.034)). In contrast, weight gain increased slightly with total implant weight (ß=0.7, 95% CI: 0.6-0.8 (p≤0.001)). Further, weight gain was greater for women (ß=19.0, 95% CI: 9.1-29.0 (p≤0.001) (men 150g [135-219], women 211g [157-250] (p=0.010)) and patients who received the cemented stem (ß=40.0, 95% CI, 19.4-46.5, p≤0.001). DISCUSSION: Current models cause a two- to three-fold gain of weight at the hip joint after THA. While it is not clear whether this weight increase has any clinical repercussions, this finding can be helpful when a patient raises questions on this topic during the preoperative counseling. More research is necessary to determine whether lighter implants may be beneficial for patients. LEVEL OF EVIDENCE: III, case control study.

Erratum to 'Fracture of the Neck of a Modern Cementless, Titanium Femoral Stem' [Arthroplasty Today 6 (2020) 176-179].

[This corrects the article DOI: 10.1016/j.artd.2020.04.004.].

Surgical Management of Tibial Bone Loss in Revision Total Knee Arthroplasty: Clinical Outcomes and Radiographic Analysis of Tantalum Cones, Titanium Cones and Titanium Sleeves.

Background: The use of metaphyseal cones and sleeves has improved the ability to manage tibial bone loss in revision total knee arthroplasty (TKA). The purpose of this study was to compare the outcomes of three systems used for tibial metaphyseal reconstruction in revision TKA. Methods: We performed a retrospective review of a consecutive series of 723 revision TKAs, including 145 (20%) knee revisions using tibial cones or sleeves. We compared porous tantalum (TM) cones, titanium (Ti) cones and titanium sleeves. The mean follow-up was 2.5 years. Results: The rate of revision for any reason was similar among all groups. Revision-free survival rates were similar among all systems studied at a mean follow-up of 2.5 years (TM cones 93%, Ti cones 94%, titanium sleeves 89%). Ti cones had a lower complication rate (6%) compared to TM cones (24%) and sleeves (29%). TM cones (15%) and titanium sleeves (13%) had higher reoperation rates (for any cause) than Ti cones (2%). Radiographic loosening was higher for sleeves (11%) than TM and Ti cones (2%). Conclusion: Metaphyseal reconstruction for tibial bone loss in revision TKA using tantalum cones, titanium cones and titanium sleeves showed successful and comparable early clinical outcomes at a mean follow-up of 2.5 years with higher rates of radiographic loosening for titanium sleeves. Level of Evidence: III.

Macrophage Polarization and the Osteoimmunology of Periprosthetic Osteolysis.

PURPOSE OF REVIEW: Joint replacement has revolutionized the treatment of end-stage arthritis. We highlight the key role of macrophages in the innate immune system in helping to ensure that the prosthesis-host interface remains biologically robust. RECENT FINDINGS: Osteoimmunology is of great interest to researchers investigating the fundamental biological and material aspects of joint replacement. Constant communication between cells of the monocyte/macrophage/osteoclast lineage and the mesenchymal stem cell-osteoblast lineage determines whether a durable prosthesis-implant interface is obtained, or whether implant loosening occurs. Tissue and circulating monocytes/macrophages provide local surveillance of stimuli such as the presence of byproducts of wear and can quickly polarize to pro- and anti-inflammatory phenotypes to re-establish tissue homeostasis. When these mechanisms fail, periprosthetic osteolysis results in progressive bone loss and painful failure of mechanical fixation. Immune modulation of the periprosthetic microenvironment is a potential intervention to facilitate long-term durability of prosthetic interfaces.

Massive Osteolysis in a Modern Total Knee Prosthesis.

CASE: An 82-year-old woman underwent right total knee replacement with a sequentially irradiated and annealed highly cross-linked polyethylene insert. At 9 years, she was found to have a massive femoral osteolysis with an impending fracture. CONCLUSION: This case demonstrates a rare occurrence of massive femoral osteolysis, requiring revision surgery, with a sequentially irradiated and annealed highly cross-linked polyethylene.

What Are the Rate and Risk Factors for Developing a Complication With the Pavlik Method for the Treatment of Hip Dysplasia?

BACKGROUND: The Pavlik method for the treatment of developmental dysplasia of the hip (DDH) has been proven successful for over 85 years. The high success rate and reproducibility have made it the mainstay of treatment. METHODS: We performed a retrospective cohort study of patients with DDH treated with the Pavlik method between September 2016 and August 2018 with at least 24 months of follow up in a single academic center. We excluded patients with neuromuscular conditions, teratologic dislocations, and arthrogryposis. We identified and included a total of 307 patients in the analysis. There were 66 patients with dysplasia, 97 with instability, and 144 with a dislocation. Data collected included age at initiation of the Pavlik method, diagnosis (isolated dysplasia, subluxation, or dislocation), duration of treatment, follow up duration and any complication. At final follow up, anteroposterior radiographs of the pelvis were used to determine the Severin classification. RESULTS: Major complications were proximal femoral growth disturbance (5.8%) and femoral nerve palsy (0.98%). Multivariate analysis showed that an initial diagnosis of a dislocated hip (odds ratio, 2.20; P<0.01), was significantly associated with developing a complication. At final follow up, we found Severin type I or II radiographic findings in 100% of patients with dysplasia, 95% of patients with instability and 54% of patients with dislocation (P=0.001). CONCLUSIONS: Complications are not entirely uncommon when the Pavlik method is used for the treatment of DDH. The overall rate of major complications was 7%. The Pavlik method is safe, and independent risk factors for complications were being over 5 months of age and having a dislocated hip at initial presentation. LEVEL OF EVIDENCE: Level IV-cohort study.

Has There Been a Change in the Age of Presentation of Patients With DDH After the Implementation of a Dedicated Ultrasound-screening Program?

BACKGROUND: We sought to determine if the age of patients presenting to a tertiary subspecialty hospital dedicated to pediatric orthopaedics has changed over the last 21 years and determine if a dedicated ultrasound-screening program implemented in 2006 made any difference. METHODS: We reviewed the hospital charts for 9299 patients diagnosed with developmental dysplasia of the hip (DDH) and determined the age at the time of presentation; this was a consecutive series of all patients presenting between 1998 and 2019. We determined the diagnosis and age from the chart, 8011 were female (86.15%), and 1288 were male (13.85%). The left hip was affected in 4588 cases (49.34%), the right hip in 1824 cases (19.62%), and there were 2887 bilateral cases (31.05%). RESULTS: Over the 21 years, the mean age of presentation was 2.36 years (range, 0.1 to 17 y). In 1998, the mean age was 2.49 years (range, 0.1 to 16 y). In 2006, a dedicated ultrasound-screening clinic was instituted. The mean age decreased to 1.70 years in 2019 (range, 0.1 to 14 y). The mean age at presentation decreased significantly from 2.65 years, between 1998 and 2005, to 2.19 between 2006 and 2019 (P=0.0067). CONCLUSIONS: The implementation of a dedicated ultrasound-screening protocol was significantly correlated with a decrease in the mean age of diagnosis of DDH. The results of treatment of DDH are known to be better the sooner the diagnosis is made. Given that the age of presentation remains a challenge, especially in developing countries, a dedicated ultrasound-screening program is one step to improve our ability to detect DDH in patients at a younger age. LEVEL OF EVIDENCE: Level IV-diagnostic.

Interleukin-4 repairs wear particle induced osteolysis by modulating macrophage polarization and bone turnover.

Periprosthetic osteolysis remains as a major complication of total joint replacement surgery. Modulation of macrophage polarization with interleukin-4 (IL-4) has emerged as an effective means to limit wear particle-induced osteolysis. The aim of this study was to evaluate the efficacy of local IL-4 delivery in treating preexisting particle-induced osteolysis. To this end, recently established 8 week modification of murine continuous femoral intramedullary particle infusion model was utilized. Subcutaneous infusion pumps were used to deliver polyethylene (PE) particles into mouse distal femur for 4 weeks to induce osteolysis. IL-4 was then added to the particle infusion for another 4 weeks. This delayed IL-4 treatment (IL-4 Del) was compared to IL-4 delivered continuously (IL-4 Cont) with PE particles from the beginning and to the infusion of particles alone for 8 weeks. Both IL-4 treatments were highly effective in preventing and repairing preexisting particle-induced bone loss as assessed by µCT. Immunofluorescence indicated a significant reduction in the number of F4/80 + iNOS + M1 macrophages and increase in the number of F4/80 + CD206 + M2 macrophages with both IL-4 treatments. Reduction in the number of tartrate resistant acid phosphatase + osteoclasts and increase in the amount of alkaline phosphatase (ALP) + osteoblasts was also observed with both IL-4 treatments likely explaining the regeneration of bone in these samples. Interesting, slightly more bone formation and ALP + osteoblasts were seen in the IL-4 Del group than in the IL-4 Cont group although these differences were not statistically significant. The study is a proof of principle that osteolytic lesions can be repaired via modulation of macrophage polarization.

A Learner-Centered Education Strategy: Optimizing an Interactive and Multimodal Learning Format in Orthopaedic Hip & Knee Arthroplasty.

OBJECTIVE: The Accreditation Council for Graduate Medical Education (ACGME) and The American Board of Orthopaedic Surgery proposed The Orthopaedic Surgery Milestone Project. Training residency and fellowship programs have evolved accordingly adjusting academic curriculums. A new comprehensive Learner-Centered Education Curriculum (LCEC) was designed based on critical reviews and interactive collaboration between faculty, residents, and fellows using structured interviews and iterative feedback. We aim to evaluate the results at 4 years after implementation of a new curriculum. DESIGN: The new adult arthroplasty LCEC was implemented in 2015; data collected between 2015 and 2019 was retrospectively reviewed and analyzed. Our primary goal was to evaluate educational, research, and quality successes using objective and quantitative academic quality metrics including annual Orthopedic In-Training Examination scores for the Hip & Knee domain to evaluate the medical knowledge competency. SETTING: This study was conducted at the Department of Orthopedic Surgery residency and fellowship program of Adult Arthroplasty and Joint Reconstruction Surgery, University of Florida (tertiary care center). PARTICIPANTS: Participants include 25 learners (PGY-1 to 5, Clinical fellows) and faculty of an ACGME-accredited orthopedic surgery residency and adult arthroplasty fellowship program. RESULTS: Significant improvements in academic, research and quality metrics were obtained since implementation of the LCEC: Orthopedic In-Training Examination scores for Hip & Knee domain increased from 50th to 87th percentile (P=0.042), annual learner peer-reviewed publications and research awards from none before intervention to 20 and 8 respectively (p < 0.05). Resident and fellows conference attendance improved from 81% to 99% (p = 0.0001). The ACGME resident Likert-evaluations also improved from 4.6 to 4.8. CONCLUSION: This LCEC, by enhancing an interactive and active academic learning experience, positively influenced fund of knowledge, conceptual thinking, and interest in the specialty and learner attitudes. Significant and consistent improvements in academic, research, and quality metrics were obtained, while maintaining the highest resident evaluation scores in the program.

Outpatient total knee arthroplasty: is it economically feasible in the hospital setting?

BACKGROUND: With the removal of total knee arthroplasty (TKA) from the Medicare inpatient-only list, outpatient TKA can now be offered, irrespective of payer, in multiple sites. We compared time- and cost-effectiveness of outpatient TKA performed in a hospital outpatient department (HOPD) to that at an inpatient academic medical center (AMC). METHODS: We reviewed all outpatient TKAs performed at our AMC and our HOPD from August 2018 to July 2019. Time efficiency by phase of care was determined, and cost data were obtained from the hospital financial department. Patient selection for outpatient surgery was identical for each site of care. RESULTS: We identified 21 knees that had surgery at the HOPD and 65 knees that had surgery at the AMC. Demographics were similar in both groups. The AMC group had significantly longer in-facility to operating room (Δ (difference) = 33.5 minute, P = .0003), postanesthesia care unit to discharge (Δ = 158.8 minute, P < .0001) and in-facility to discharge (Δ = 199.3 minute, P < .0001) time periods compared to the HOPD group. The HOPD was significantly more cost-effective for the preoperative period (Δ = $75.7, P < .0001), postoperative period (Δ = $315.1, P < .0001), and total cost (Δ = $241, P < .0001). CONCLUSIONS: Outpatient TKAs performed in an HOPD spend significantly less time within the facility than the ones performed in an AMC and cost significantly less. It is expected that approval of Medicare TKAs at ambulatory surgery centers will further improve cost and efficiency.

Fracture of the Neck of a Modern Cementless, Titanium Femoral Stem.

Intraprosthetic fracture of a femoral component is a rare but devastating complication after total hip arthroplasty (THA). We present the case of a 68-year-old man who presented with acute hip pain approximately 8 years after a left THA with a modern cementless, titanium femoral component. Radiographs revealed a fracture of the midportion of the neck of the stem, below the level of the trunnion. The patient underwent an isolated 1-component revision THA with a modular exchange. To our knowledge, this is the only reported case of a catastrophic failure fracture of this particular prosthesis.

Diagnosis and management of implant debris-associated inflammation.

Introduction: Total joint replacement is one of the most common, safe, and efficacious operations in all of surgery. However, one major long-standing and unresolved issue is the adverse biological reaction to byproducts of wear from the bearing surfaces and modular articulations. These inflammatory reactions are mediated by the innate and adaptive immune systems.Areas covered: We review the etiology and pathophysiology of implant debris-associated inflammation, the clinical presentation and detailed work-up of these cases, and the principles and outcomes of non-operative and operative management. Furthermore, we suggest future strategies for prevention and novel treatments of implant-related adverse biological reactions.Expert opinion: The generation of byproducts from joint replacements is inevitable, due to repetitive loading of the implants. A clear understanding of the relevant biological principles, clinical presentations, investigative measures and treatments for implant-associated inflammatory reactions and periprosthetic osteolysis will help identify and treat patients with this issue earlier and more effectively. Although progressive implant-associated osteolysis is currently a condition that is treated surgically, with further research, it is hoped that non-operative biological interventions could prolong the lifetime of joint replacements that are otherwise functional and still salvageable.

Mesenchymal stem cell-macrophage crosstalk and bone healing.

Recent research has brought about a clear understanding that successful fracture healing is based on carefully coordinated cross-talk between inflammatory and bone forming cells. In particular, the key role that macrophages play in the recruitment and regulation of the differentiation of mesenchymal stem cells (MSCs) during bone regeneration has been brought to focus. Indeed, animal studies have comprehensively demonstrated that fractures do not heal without the direct involvement of macrophages. Yet the exact mechanisms by which macrophages contribute to bone regeneration remain to be elucidated. Macrophage-derived paracrine signaling molecules such as Oncostatin M, Prostaglandin E2 (PGE2), and Bone Morphogenetic Protein-2 (BMP2) have been shown to play critical roles; however the relative importance of inflammatory (M1) and tissue regenerative (M2) macrophages in guiding MSC differentiation along the osteogenic pathway remains poorly understood. In this review, we summarize the current understanding of the interaction of macrophages and MSCs during bone regeneration, with the emphasis on the role of macrophages in regulating bone formation. The potential implications of aging to this cellular cross-talk are reviewed. Emerging treatment options to improve facture healing by utilizing or targeting MSC-macrophage crosstalk are also discussed.

Acetabular reinforcement rings associated with allograft for severe acetabular defects.

Acetabular revisions with severe bone defects can be challenging procedures. Several grading systems have been set into place to help the surgeon adequately gauge the degree of bone loss within the acetabulum. Internationally innovative research in orthopedics and bio-engineering has helped with progression of successful techniques and rings to re-establish the normal anatomy of the hip. The purpose of this review is to evaluate the outcomes of the different acetabular reinforcement rings in the setting of severe acetabular defects. A successive report of relevant data from the literature of multiple techniques will be provided. The procedures include the cup-cage, the Müller ring, the Ganz Ring, the Kerboull acetabular reinforcement device (KARD), the graft augmentation prosthesis (GAP) ring, and the Burch-Schneider ring. The main focus of this overview is rings only; other devices such as trabecular augments, custom-made cages, or oblong cups are not discussed. Furthermore, a special emphasis on the surgical technique of the KARD is also given. Procedures using these rings are usually associated with bone grafts either bulk or morselized. When considering the available data on these various rings used for reconstruction of the severely damaged acetabulum, the cup-cage, the KARD, and the Burch-Schneider ring appear to be reliable options for more successful long-term outcomes.

Inflammation, ageing, and bone regeneration.

SUMMARY: Bone healing involves complex biological pathways and interactions among various cell types and microenvironments. Among them, the monocyte-macrophage-osteoclast line-age and the mesenchymal stem cell-osteoblast lineage are critical, in addition to an initial inflammatory microenvironment. These cellular interactions induce the necessary inflammatory milieu and provide the cells for bone regeneration and immune modulation. Increasing age is accompanied with a rise in the basal state of inflammation, potentially impairing osteogenesis. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Translational research has shown multiple interactions between inflammation, ageing, and bone regeneration. This review presents recent, relevant considerations regarding the effects of inflammation and ageing on bone healing.