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    Indiana University School of Medicine Orthopaedic Surgery Annual Report 2022
    (Indiana University School of Medicine Department of Orthopaedic Surgery, 2022) Orthopaedic Surgery, Indiana University School of Medicine
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    Incidence and risk factors for non-union of the superior ramus osteotomy when hip dysplasia is treated with periacetabular osteotomy
    (Oxford University Press, 2023-04-12) Sivamurugan, Ganesh; Westermann, Robert W.; Glass, Natalie; Davison, John C.; Miller, Aspen; Henrichsen, Jacob; McKinley, Todd O.; Willey, Michael C.; Orthopaedic Surgery, School of Medicine
    Periacetabular osteotomy (PAO) is a well-established surgical treatment for hip dysplasia. Few studies report risk factors for the development of superior ramus osteotomy non-union. The purpose of this investigation was to document the incidence and risk factors for this complication. We identified 316 consecutive hips that underwent PAO for symptomatic acetabular dysplasia with a minimum 1-year radiographic follow-up. We developed and validated a technique to measure the superior ramus osteotomy location on anterior-posterior (AP) pelvis radiographs and computed tomography. Logistic regression with generalized estimating equations was used to evaluate the relationships between odds of non-union and potential demographic and radiographic predictor variables in univariate and multivariate analyses. Twenty-nine (9.2%) hips developed superior ramus non-union. Age {median [interquartile range (IQR)] 23 years (18-35) healed versus 35 years (26-40) non-united, P = 0.001}, pre-operative lateral center-edge angle (LCEA) [16° (11-20) healed versus 10° (6-13) non-united, P < 0.001] and the distance from the superior ramus osteotomy to the ilioishial line [15.8 mm (13.2-18.7) healed versus 18.1 mm (16.2-20.5) non-united, P < 0.001] varied significantly between groups. Using multivariate analysis, moderate-to-severe dysplasia [LCEA < 15°, odds ratio (OR) 5.95, standard error (SE) 3.32, 95% confidence interval (CI) 1.99-17.79, P = 0.001], increased age (5-year increase, OR 1.29, SE 3.32, 95% CI 1.105-1.60, P-value = 0.018) and distance from the ilioishial line (3-mm increase, OR 1.67, SE 0.22, 95% CI 1.29-2.18, P < 0.001) were at increased risk of developing non-union. Superior ramus osteotomy non-union is common after PAO. Older age, moderate-to-severe dysplasia, and more medial osteotomy location were independent risk factors for non-union. Consideration should be made in high-risk patients for a more lateral superior ramus osteotomy and adjuvant medical and surgical interventions.
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    Emerging Technologies within Spine Surgery
    (MDPI, 2023-10-09) Foley, David; Hardacker, Pierce; McCarthy, Michael; Orthopaedic Surgery, School of Medicine
    New innovations within spine surgery continue to propel the field forward. These technologies improve surgeons’ understanding of their patients and allow them to optimize treatment planning both in the operating room and clinic. Additionally, changes in the implants and surgeon practice habits continue to evolve secondary to emerging biomaterials and device design. With ongoing advancements, patients can expect enhanced preoperative decision-making, improved patient outcomes, and better intraoperative execution. Additionally, these changes may decrease many of the most common complications following spine surgery in order to reduce morbidity, mortality, and the need for reoperation. This article reviews some of these technological advancements and how they are projected to impact the field. As the field continues to advance, it is vital that practitioners remain knowledgeable of these changes in order to provide the most effective treatment possible.
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    In situ forming biomaterials as muscle void fillers for the provisional treatment of volumetric muscle loss injuries
    (Elsevier, 2023-09-02) Clark, Andrew; Kulwatno, Jonathan; Kanovka, Sergey S.; McKinley, Todd O.; Potter, Benjamin K.; Goldman, Stephen M.; Dearth, Christopher L.; Orthopaedic Surgery, School of Medicine
    Volumetric muscle loss (VML) represents a devastating extremity injury which leads to chronic functional deficits and disability and is unrecoverable through normal healing pathways. When left untreated, the VML pathophysiology creates many challenges towards successful treatment, such as altered residual muscle architecture, excessive fibrosis, and contracture(s). As such, innovative approaches and technologies are needed to prevent or reverse these adverse sequelae. Development of a rationally designed biomaterial technology which is intended to be acutely placed within a VML defect – i.e., to serve as a muscle void filler (MVF) by maintaining the VML defect – could address this clinical unmet need by preventing these adverse sequelae as well as enabling multi-staged treatment approaches. To that end, three biomaterials were evaluated for their ability to serve as a provisional MVF treatment intended to stabilize a VML defect in a rat model for an extended period (28 days): polyvinyl alcohol (PVA), hyaluronic acid and polyethylene glycol combination (HA + PEG), and silicone, a clinically used soft tissue void filler. HA + PEG biomaterial showed signs of deformation, while both PVA and silicone did not. There were no differences between treatment groups for their effects on adjacent muscle fiber count and size distribution. Not surprisingly, silicone elicited robust fibrotic response resulting in a fibrotic barrier with a large infiltration of macrophages, a response not seen with either the PVA or HA + PEG. Taken together, PVA was found to be the best material to be used as a provisional MVF for maintaining VML defect volume while minimizing adverse effects on the surrounding muscle.
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    Idiopathic Slipped Capital Femoral Epiphysis: Demographic Differences and Similarities between Stable, Unstable, and Valgus Types
    (MDPI, 2023-09-15) Loder, Randall T.; Gunderson, Zachary; Sun, Seungyup; Orthopaedic Surgery, School of Medicine
    Idiopathic slipped capital femoral epiphysis (SCFE) is a known disorder in pre/adolescent children with vague hip/knee pain. We wished to study the demographic differences between stable varus, unstable varus, and valgus idiopathic SCFEs using a retrospective review over a 10-year period of SCFE children seen at a tertiary children’s hospital. Standard demographic data was collected, and radiographs were measured to determine the Southwick angle and status of the tri-radiate cartilage. There were 190 patients; 138 had stable varus SCFEs, 45 unstable varus SCFEs, and 7 valgus SCFEs. All unstable SCFEs were varus, and all valgus SCFEs were stable. There were significant differences between the three groups by age at diagnosis, sex, race, SCFE severity, weight percentile, and duration of symptoms. The average age at diagnosis was 11.0 ± 1.2, 11.8 ± 1.8, and 12.3 ± 1.7 years for the valgus, unstable varus, and stable varus groups (p = 0.019), and similarly, SCFE severity was 25° ± 15°, 48° ± 18°, and 35° ± 19° (p = 0.0002) for the three same groups. Patients with valgus SCFEs were mostly female (86%) compared to the stable varus (39.9%) and unstable (47%) groups (p = 0.05) and mostly non-White (86%) (0.011). The duration of symptoms was 4.1 ± 4.1, 2.3 ± 5.0, and 4.5 ± 5.0 months for the valgus, unstable varus, and stable varus groups (p = 0.00005). These three types of idiopathic SCFEs demonstrated differences by age at diagnosis, sex, race, weight percentile, and duration of symptoms.
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    Bone healing: Advances in biology and technology
    (Wolters Kluwer, 2021-04-15) Mullis, Brian H.; Gudeman, Andrew S.; Borrelli, Joseph, Jr.; Crist, Brett D.; Lee, Mark A.; Evans, Andrew R.; Orthopaedic Surgery, School of Medicine
    Fracture healing is a complex cascade of cellular and molecular processes. These processes require the appropriate cellular and molecular environment to ensure the restoration of skeletal stability and resolution of inflammation. In order for fracture healing to occur, the necessary building blocks for bone metabolism and synthesis must be supplied through proper nutrition. Pharmacologic therapies aimed at modulating the inflammatory response to fractures have the potential to interfere with the synthesis of molecules needed for the production of bone. Infection can interfere with, and even prevent normal fracture healing from occurring. Cellular and genetic treatment strategies are actively being developed to target deficiencies, and bridge gaps that can influence how fractures heal. Evolving technologies, including nutritional supplementation, pharmacotherapies, antibiotics, surgical techniques, as well as genetic and cellular therapies, have the potential to enhance, optimize, and even revolutionize the process of fracture healing.
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    Halicin Is Effective Against Staphylococcus aureus Biofilms In Vitro
    (Wolters Kluwer, 2022) Higashihira, Shota; Simpson, Stefanie Jan; Collier, Christopher David; Natoli, Roman Michael; Kittaka, Mizuho; Greenfield, Edward Michael; Orthopaedic Surgery, School of Medicine
    Background: Biofilms protect bacteria from the host immune system and many antibiotics, making the treatment of orthopaedic infections difficult. Halicin, a recently discovered antibiotic, has potent activity against nonorthopaedic infections in mice and the planktonic, free-living forms of many bacterial species, including Staphylococcus aureus , a common cause of orthopaedic infections. Importantly, halicin did not induce resistance in vitro and was effective against drug-resistant bacteria and proliferating and quiescent bacteria. Quiescence is an important cause of antibiotic tolerance in biofilms. However, whether halicin acts on biofilms has not been tested. Questions/purposes: (1) Does halicin reduce the viability of S. aureus in less mature and more mature biofilms as it does in planktonic cultures? (2) How do the relative effects of halicin on S. aureus biofilms and planktonic cultures compare with those of conventional antibiotics (tobramycin, cefazolin, vancomycin, or rifampicin) that are commonly used in clinical orthopaedic infections? Methods: To measure minimal biofilm eradication concentrations (MBECs) with less mature 3-day and more mature 7-day biofilms, we used 96-well peg plates that provided high throughput and excellent reproducibility. After S. aureus -Xen36 biofilm formation, planktonic bacteria were removed from the cultures, and the biofilms were exposed to various concentrations of halicin, tobramycin, cefazolin, vancomycin, or rifampicin for 20 hours. Biofilm viability was determined by measuring resazurin reduction or by counting colony-forming units after sonication. To determine effects of halicin and the conventional antibiotics on biofilm viability, we defined MBEC 75 as the lowest concentration that decreased viability by 75% or more. To determine effects on bacterial viability in planktonic cultures, minimum inhibitory concentrations (MICs) were determined with the broth dilution method. Each result was measured in four to 10 independent experiments. Results: We found no differences between halicin's effectiveness against planktonic S. aureus and 3-day biofilms (MIC and MBEC 75 for 3-day biofilms was 25 μM [interquartile range 25 to 25 and 25 to 25, respectively]; p > 0.99). Halicin was eightfold less effective against more mature 7-day biofilms (MBEC 75 = 200 μM [100 to 200]; p < 0.001). Similarly, tobramycin was equally effective against planktonic culture and 3-day biofilms (MIC and MBEC 75 for 3-day biofilms was 20 μM [20 to 20 and 10 to 20, respectively]; p > 0.99). Tobramycin's MBEC 75 against more mature 7-day biofilms was 320 μM (320 to 480), which is 16-fold greater than its planktonic MIC (p = 0.03). In contrast, the MBEC 75 for cefazolin, vancomycin, and rifampicin against more mature 7-day biofilms were more than 1000-fold (> 1000; p < 0.001), 500-fold (500 to 875; p < 0.001), and 3125-fold (3125 to 5469; p = 0.004) greater than their planktonic MICs, respectively, consistent with those antibiotics' relative inactivity against biofilms. Conclusion: Halicin was as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but eightfold higher concentrations were needed for more mature 7-day biofilms. Tobramycin, an antibiotic whose effectiveness depends on biofilm maturity, was also as effective against S. aureus in less mature 3-day biofilms as those in planktonic cultures, but 16-fold higher concentrations were needed for more mature 7-day biofilms. In contrast, cefazolin, vancomycin, and rifampicin were substantially less active against both less and more mature biofilms than against planktonic cultures. Clinical relevance: Halicin is a promising antibiotic that may be effective against S. aureus osteomyelitis and infections on orthopaedic implants. Future studies should assess the translational value of halicin by testing its effects in animal models of orthopaedic infections; on the biofilms of other bacterial species, including multidrug-resistant bacteria; and in combination therapy with conventional antibiotics.
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    Age-related Cellular and Microstructural Changes in the Rotator Cuff Enthesis
    (Wiley, 2022) Long, Zeling; Nakagawa, Koichi; Wang, Zhanwen; Amadio, Peter C.; Zhao, Chunfeng; Gingery, Anne; Orthopaedic Surgery, School of Medicine
    Rotator cuff injuries increase with age. The enthesis is the most frequent site of rotator cuff injury and degeneration. Understanding age-related changes of the enthesis are essential to determine the mechanism of rotator cuff injuries, degeneration, and to guide mechanistically driven therapies. In this study, we explored age-related cellular changes of the rotator cuff enthesis in young, mature, and aged rats. Here we found that the aged enthesis is typified by an increased mineralized zone and decreased non-mineralized zone. Proliferation, migration, and colony forming potential of rotator cuff derived cells (RCECs) was attenuated with aging. The tenogenic and chondrogenic potential were significantly reduced, while the osteogenic potential increased in aged RCECs. The adipogenic potential increased in RCECs with age. This study explores the cellular differences found between young, mature, and aged rotator cuff enthesis cells and highlights the importance of using age appropriate models, as well as provides a basis for further delineation of mechanisms and potential therapeutics for rotator cuff injuries.
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    Post-traumatic osteoarthritis: A review of pathogenic mechanisms and novel targets for mitigation
    (Elsevier, 2023-01-30) Dilley, Julian E.; Bello, Margaret Anne; Roman, Natoli; McKinley, Todd; Sankar, Uma; Orthopaedic Surgery, School of Medicine
    Post-traumatic osteoarthritis (PTOA) develops secondary to a joint injury and accounts for 12 % of all osteoarthritis. These injuries, often of the lower extremity joints, occur due to trauma or accidents related to athletic or military activities. They primarily affect younger individuals although PTOA can occur across the spectrum of age. Pain and functional disability caused by PTOA confer a heavy economic toll on patients, in addition to detrimentally affecting their quality of life. Both high energy injuries that cause articular surface fracture with or without subchondral bone disruption and low-energy injuries involving joint dislocations or ligamentous injury cause PTOA, albeit through different mechanisms. Regardless, chondrocyte death, mitochondrial dysfunction, reactive oxygen species production, subchondral bone remodeling, inflammation and cytokine release in the cartilage and synovium play integral roles in the pathogenesis of PTOA. Evolving surgical methods are focused on stabilizing articular surface and joint structure congruity. However, to date there are no disease modifying medical therapies against PTOA. Increased recent understanding of the pathogenesis of the subchondral bone and synovial inflammation as well as that of chondrocyte mitochondrial dysfunction and apoptosis have led to the investigation of new therapeutics targeting these mechanisms to prevent or delay PTOA. This review discusses new advances in our understanding of cellular mechanisms underlying PTOA, and therapeutic approaches that are potentially effective in reducing the self-propagating cycle of subchondral bone alterations, inflammation, and cartilage degradation. Within this context, we focus therapeutic options involving anti-inflammatory and anti-apoptotic candidates that could prevent PTOA.
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    Plating versus Intramedullary Nailing of OTA/AO 43C1 and C2 Intra-articular Distal Tibia Fractures: A Propensity Score and Multivariate Analysis
    (Wolters Kluwer, 2024-01) Jang, Yohan; Wilson, Nathaniel; Jones, Jenna; Alchaide, Doriann; Szatkowski, Jan; Sorkin, Anthony; Slaven, James E.; Natoli, Roman; Orthopaedic Surgery, School of Medicine
    OBJECTIVE: To compare rates of reduction loss, nonunion, and infection in intra-articular distal tibia fractures (IADTF) treated with limited open reduction internal fixation and intramedullary nailing (IMN) as compared to open reduction internal fixation with plate and screws (plate fixation [PF]). METHODS: Design: Retrospective review. Setting: Level-I academic trauma center. Patient Selection Criteria: Patients age ≥ 18 with OTA/AO 43C1 and C2 IADTF treated with IMN or PF between 2013-2021. Outcome Measures and Comparisons: Loss of reduction, surgical site infection (SSI), nonunion, and patient-reported outcomes (PROs) were compared for IMN versus PF treatments. RESULTS: One hundred ten patients met the inclusion criteria (IMN 33 and PF 77). There was no loss of reduction found. Seventeen nonunions (15% overall; IMN 4/33 and PF 13/77) and 13 SSIs (12% overall; IMN 2/33 and PF11/77) were identified. Despite several risk factors being identified for nonunion and SSI in bivariate analysis, only open fracture remained significant as a risk factor for both nonunion (odds ratio 0.09 for closed fracture, 95% confidence interval, 0.02–0.56, P = 0.009) and SSI (odds ratio 0.07 for closed fracture, 95% confidence interval, 0.06–0.26, P = 0.012) in the multivariate model. Propensity scoring based on presurgical variables was significantly different between patients who received IMN versus PF (P = 0.03); however, logistic regression incorporating the propensity score revealed no significant association with nonunion and SSI. Adjusting for the propensity score, there remained no association comparing IMN versus PF with nonunion and SSI (P = 0.54 and P = 0.17, respectively). There was also no difference in PROs between IMN and PF (physical function: P = 0.25 and pain interference: P = 0.21). CONCLUSIONS: Overall nonunion and SSI prevalence was 15% and 12%, respectively, in operatively treated OTA/AO 43C1 and C2 IADTF. An open fracture was a significant risk factor for nonunion and SSI. Metaphyseal fixation through IMN or PF did not affect loss of reduction, nonunion, SSI, or PROs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.