Male epispadias repair: Outcomes at three sites prior to the establishment of a multi-institutional collaboration.

INTRODUCTION: Epispadias, which occurs on the more mild end of the Bladder Exstrophy Epispadias Complex (BEEC) spectrum, presents still with a wide range of severity in boys, from mild glanular epispadias to penopubic epispadias with severe urethral and bladder neck defects. Surgical management ranges from isolated epispadias repair to epispadias repair with bladder neck reconstruction (BNR) with or without pelvic osteotomies. OBJECTIVES: We aimed to evaluate outcomes in epispadias treated at three institutions prior to formation of a formal collaboration. In addition, we sought to delineate outcomes based on anatomic severity at time of diagnosis, and initial procedure performed in cases of penopubic epispadias. METHODS: IRB approved databases were retrospectively queried at three institutions for patients who underwent repair of epispadias between 1/1993 and 1/2013. Degree of epispadias, age and technique at initial repair, and self-reported continence status at last follow-up were recorded. Continence was categorized as: wet, intermediate (dry 2-3 h), or dry, while also distinguishing those who void and those who require clean intermittent catheterization (CIC). Those not seen since 1/1/2015, younger than 10 years at last follow up, or in whom continence data were not recorded were excluded. RESULTS: A total of 48 boys were identified; 36 met inclusion criteria. The epispadias cohort consisted of 8 glanular epispadias (GE) (22%); 8 penile epispadias (PE) (22%), and 20 penopubic epispadias (PPE) (56%) with a median follow-up of 11.3 years (3.2-26.2 years). Overall, 33 of 36 (92%) boys void per urethra. Within the group that voids, 19/33 (58%) are completely dry, while 6/33 (18%) are wet. Among patients who underwent initial epispadias repair without concurrent or subsequent bladder neck reconstruction, continence rates were: GE 63% (5/8); PE 75% (6/8); PPE 71% (5/7). Among the 9 boys with PPE who underwent initial epispadias repair with concurrent BNR, 22% (2/9) were dry with no further surgeries. Overall, 8/20 (40%) of boys with PPE void with complete dryness. DISCUSSION: This multi-center retrospective review of continence in epispadias demonstrates that even some boys with glanular and penile epispadias can have challenges with continence, and boys with penopubic epispadias may remain wet despite careful preoperative assessment of bladder neck functionality and concurrent BNR. CONCLUSION: Continence outcomes in boys with all degrees of epispadias can be variable. Even boys with more distal defects may have significant bladder neck deficiency. And those with the most severe form of epispadias may require bladder neck reconstruction to achieve continence.

Incorporating patient-specific hip orientation from weightbearing computed tomography affects discrete element analysis-computed regional joint contact mechanics in individuals treated with periacetabular osteotomy for hip dysplasia.

Computational models of the hip often omit patient-specific functional orientation when placing imaging-derived bony geometry into anatomic landmark-based coordinate systems for application of joint loading schemes. The purpose of this study was to determine if this omission meaningfully alters computed contact mechanics. Discrete element analysis models were created from non-weightbearing (NWB) clinical CT scans of 10 hip dysplasia patients (11 hips) and oriented in the International Society of Biomechanics (ISB) coordinate system (NWB-ISB). Three additional models were generated for each hip by adding patient-specific stance information obtained via weightbearing CT (WBCT) to each ISB-oriented model: (1) patient-specific sagittal tilt added (WBCT-sagittal), (2) coronal and axial rotation from optical motion capture added to (1; WBCT-combo), and (3) WBCT-derived axial, sagittal, and coronal rotation added to (1; WBCT-original). Identical gait cycle loading was applied to all models for a given hip, and computed contact stress and contact area were compared between model initialization techniques. Addition of sagittal tilt did not significantly change whole-joint peak (p = 0.922) or mean (p = 0.871) contact stress or contact area (p = 0.638). Inclusion of motion-captured coronal and axial rotation (WBCT-combo) decreased peak contact stress (p = 0.014) and slightly increased average contact area (p = 0.071) from WBCT-sagittal models. Including all WBCT-derived rotations (WBCT-original) further reduced computed peak contact stress (p = 0.001) and significantly increased contact area (p = 0.001). Variably significant differences (p = 0.001-1.0) in patient-specific acetabular subregion mechanics indicate the importance of functional orientation incorporation for modeling applications in which local contact mechanics are of interest.

A New Method for Creating Impact-Induced Intra-Articular Fractures in a Rabbit Model Induces Severe Post-Traumatic Osteoarthritis.

OBJECTIVES: The objective of this work was to develop a model of intra-articular fracture (IAF) in a rabbit and document the speed and severity of degenerative joint changes after fracture fixation. METHODS: With Institutional Animal Care & Use Committee approval, impact-induced IAFs were created in the distal tibia of 16 New Zealand White rabbits. Fractures were fixed with a plate and screws. Pain and function were monitored at regular postoperative intervals with limb loading analysis. Twelve or 26 weeks after fracture, animals were euthanized for histological assessment of cartilage degeneration and micro-computed tomography analysis of bone histomorphometry. RESULTS: Eleven animals successfully completed the study. Maximum foot force in the fractured limb was 41% ± 21% lower than preoperative values ( P = 0.006) 12 weeks after fracture and remained 25% ± 13% lower ( P = 0.081) after 26 weeks. Cortical bone mineral density in micro-computed tomography images was 34% ± 13% lower 12 weeks after fracture ( P < 0.001) and remained (42% ± 8%) lower 26 weeks after fracture ( P < 0.001). Twelve weeks after fracture, Mankin scores of cartilage degeneration were significantly higher in the medial talus ( P = 0.007), lateral talus ( P < 0.001), medial tibia ( P = 0.017), and lateral tibia ( P = 0.002) of the fractured limb compared with the uninjured contralateral limb. Average Mankin scores in the talus increased from 12 to 26 weeks (5.9 ± 0.9 to 9.4 ± 0.4; P < 0.001 lateral; 5.4 ± 1.8 to 7.8 ± 2.0; P = 0.043 medial), indicating substantial and progressive joint degeneration. CONCLUSIONS: The ankle joint of the New Zealand White rabbit provides the smallest available model of impact-induced IAF that can be treated with clinically relevant techniques and replicates key features of healing and degeneration found in human patients.

The Effects of Residual Femoral Deformity on Computed Contact Mechanics in Patients Treated With In Situ Fixation for Slipped Capital Femoral Epiphysis.

OBJECTIVE: In situ fixation for treatment of slipped capital femoral epiphysis (SCFE) can stabilize the epiphysis and prevent further joint deformation but often leaves residual deformity that may adversely affect intra-articular contact mechanics. The purpose of this study was to investigate the relationship between residual deformity and contact mechanics in the post-SCFE hip. METHODS: Patient-specific hip models were created for 19 patients with SCFE treated with in situ fixation. For each model, discrete element analysis was used to compute cumulative acetabular and femoral contact stress exposure during a walking gait cycle. Slip severity was evaluated for each patient using the two-dimensional Southwick angle and a novel three-dimensional (3D) assessment of multiplanar femoral deformity (3D slip angle). RESULTS: Of the SCFE cases, 2/7 mild (Southwick angle ≤30 degrees) had peak cumulative femoral exposures equivalent to that of severe (Southwick angle ≥60 degrees) cases. Severe SCFE cases had higher peak ( P = 0.015) and mean ( P = 0.028) femoral contact stress exposure and lower cumulative femoral contact area ( P = 0.003) than mild (Southwick angle ≤30 degrees) SCFE cases. Mean femoral contact stress exposure was also higher in severe SCFE cases than in moderate SCFE cases ( P = 0.027). Acetabular and femoral contact mechanics metrics typically demonstrated stronger correlations with 3D slip angle than two-dimensional Southwick angle. CONCLUSIONS: Increased slip severity adversely impacts intra-articular femoral contact mechanics. Contact mechanics metrics demonstrate higher correlations with 3D slip angle, indicating that this novel measurement may better describe global deformity and its relationship to intra-articular mechanics; however, the modest strength of these correlations may also imply that global impingement-generating deformity is not the primary factor driving contact mechanics in the post-SCFE hip. CLINICAL RELEVANCE: Greater slip severity adversely impacts contact mechanics in the post-SCFE hip. However, focal regions of high contact stress were seen even in mild SCFE deformities, suggesting some type of deformity correction should be considered even for mild slips to alleviate secondary impingement, address focal incongruities, and reduce osteoarthritis development/progression.

Providing a computationally derived, mechanically optimised target correction during preoperative planning can improve joint contact mechanics of hip dysplasia treated with periacetabular osteotomy.

AIM: Preoperative identification of acetabular corrections that optimally improve joint stability and reduce elevated contact stresses could further reduce osteoarthritis progression in patients with hip dysplasia who are treated with periacetabular osteotomy (PAO). The purpose of this study was to investigate how providing patient-specific, mechanically optimal acetabular reorientations to the surgeon during preoperative planning affected the surgically achieved correction. METHODS: Preoperative CT scans were used to create patient-specific hip models for 6 patients scheduled for PAO. A simulated acetabular fragment was extracted from the preoperative pelvis model and computationally rotated to simulate candidate acetabular reorientations. For each candidate, discrete element analysis was used to compute contact stresses during walking, which were summed over the gait cycle and scaled by patient age to obtain chronic contact stress-time exposure. The ideal patient-specific reorientation was identified using a cost function that balances minimising chronic stress exposures and achieving surgically acceptable acetabular coverage angles. The optimal reorientation angles and associated contact mechanics were provided to the surgeon preoperatively. After PAO was performed, a model of the surgically achieved correction was created from a postoperative CT scan. Radiographic coverage and contact mechanics were compared between preoperative, optimal, and surgically achieved orientations. RESULTS: While surgically achieved reorientations were not significantly different from optimal reorientations in radiographically measured lateral (p = 0.094) or anterior (p = 0.063) coverage, surgically achieved reorientations had significantly (p = 0.031) reduced total contact area compared to optimal reorientations. The difference in lateral coverage and peak chronic exposure between surgically achieved and optimal reorientations decreased with increasing surgeon experience using the models (R² = 0.758, R2 = 0.630, respectively). CONCLUSIONS: Providing hip surgeons with a patient-specific, computationally optimal reorientation during preoperative planning may improve contact mechanics after PAO, which may help reduce osteoarthritis progression in patients with hip dysplasia.

Altered Ulnar Variance With Full-Body Weight-bearing During Handstands With Upper Extremity Weight-bearing CT.

PURPOSE: Ulnar variance (UV) is a radiographic measurement relating the articular surface heights of the distal radius and ulna. Abnormal UV increases the risk for wrist pathology; however, it only provides a static measurement of an inherently dynamic bony relationship that changes with wrist position and loading. The purpose of this study was to investigate how full-body weight-bearing affects UV using weight-bearing computed tomography (WBCT). METHODS: Ten gymnasts completed two 45-second scans inside a WBCT machine while performing a handstand on a flat platform (H) and parallettes (P). A non-weight-bearing CT scan was collected to match clinical practice (N). Differences in UV between weight-bearing conditions were evaluated separately for dominant and nondominant sides, and then, UV was compared between weight-bearing conditions on pooled dominant/nondominant data. RESULTS: Pooled analyses comparing weight-bearing conditions revealed a significant increase in UV for H versus N (0.58 mm) and P versus N (1.00 mm), but no significant change in UV for H versus P (0.43 mm). Significant differences in UV were detected for H versus N, P versus N, and H versus P for dominant and nondominant extremities. The change from N to H was significantly greater in the dominant versus nondominant side, but greater in the nondominant side from N to P. CONCLUSIONS: Ulnar variance changed with the application of load and position of the wrist. Differences in UV were found between dominant and nondominant extremities. CLINICAL RELEVANCE: Upper extremity loading patterns are affected by hand dominance as defined by a cartwheel and suggest skeletal consequences from repetitive load on a dominantly used wrist. Although statistically significant, subtle changes detected in this investigational study do not necessarily bear clinical significance. Future WBCT research can lead to improved diagnostic measures for wrist pathologies affected by active loading and rotational wrist behavior.

NPS MedicineWise application in supporting medication adherence in chronic heart failure: an acceptability and feasibility pilot study.

Introduction: Heart failure (HF) is an increasing global concern. Despite evidence-based pharmacotherapy, associated morbidity and mortality remain high. This study aimed to assess the acceptability, feasibility, and value of the NPS MedicineWise dose reminder app in a tiered, pharmacist-led intervention to address medication non-adherence in patients with HF. Methods: This prospective, single-blinded, randomised controlled trial recruited 55 patients with HF between September 2019 and October 2020. Participants were randomly assigned to either the intervention or control arms. Intervention participants used the app which prompted medication administration at each dosing interval. Control participants received standard care and remained blinded to the app throughout the study. Treatment non-adherence prompted a tiered, pharmacist-led intervention. Comparison of the Self-Efficacy for Appropriate Medication Use Scale (SEAMS) at baseline and 6-months measured the app's value in supporting medication adherence. Secondary outcome measures included self-reported medication knowledge, health-related quality of life, psychological wellbeing, and signs and symptoms of HF. Data were analysed using standard statistical tests with significance set at α 0.05. Results: Approximately half of respondents reported managing HF and medications better by using the MedicineWise app (Tier 1). Most respondents expressed satisfaction with the in-app messages (Tier 2) and pharmacists' phone calls (Tier 3). The intervention participants demonstrated a significant improvement in the SEAMS between baseline and 6-months follow-up. Discussion: It is feasible and potentially of value to use the MedicineWise app with a tiered, pharmacist-led intervention to support medication adherence in patients with HF. Our findings provide clinicians with "real-world" information on the practicality and potential value of using mobile health to support treatment adherence in patients with HF. Trial registration number: Australian New Zealand Clinical Trials Registry Clinical trial registration number: ACTRN12619000289112p (http://www.ANZCTR.org.au/ACTRN12619000289112p.aspx).

Effects of Radiotherapy Upon Bone Structure-Strength Relationships Vary With Sex and Fractionation of Dosing.

Background: Radiotherapy for tumor treatment in or near bones often causes osteopenia and/or osteoporosis, and the resulting increased bone fragility can lead to pathologic fractures. Bone mineral density (BMD) is often used to screen for fracture risk, but no conclusive relationship has been established between BMD and the microstructural/ biomechanical changes in irradiated bone. Understanding the effects of radiation dosing regimen on the bone structure-strength relationship would improve the ability to reduce fracture-related complications resulting from cancer treatment. Methods: Thirty-two C57B6J mice aged 10 - 12 weeks old were randomized to single dose (1 x 25 Gy) and fractionated dose (5 x 5 Gy) irradiation groups. Right hindlimbs were irradiated while the contralateral hindlimbs served as the non-irradiated control. Twelve weeks after irradiation, BMD and bone microstructure were assessed with micro-computed tomography, and mechanical strength/stiffness was assessed with a torsion test. The effects of radiation dosing regimen on bone microstructure and strength were assessed using ANOVA, and bone strength-structure relationships were investigated through correlation analysis of microstructural and mechanical parameters. Results: Fractionated irradiation induced significantly greater losses in BMD in the femur (23% - male mice, p=0.016; 19% - female mice) and the tibia (18% - male mice; 6% - female mice) than the single-dose radiation. The associated reductions in trabecular bone volume (-38%) and trabecular number (-34% to -42%), and the increase in trabecular separation (23% to 29%) were only significant in the male mice with fractionated dosing. There was a significant reduction in fracture torque in the femurs of male (p=0.021) and female (p=0.0017) mice within the fractionated radiation group, but not in the single dose radiation groups. There was moderate correlation between bone microstructure and mechanical strength in the single-dose radiation group (r = 0.54 to 0.73), but no correlation in the fractionated dosing group (r=0.02 to 0.03). Conclusion: Our data indicate more detrimental changes in bone microstructure and mechanical parameters in the fractionated irradiation group compared to the single dose group. This may suggest the potential for protecting bone if a needed therapeutic radiation dose can be delivered in a single session rather than administered in fractions.

Finite Element Model-Computed Mechanical Behavior of Femurs with Metastatic Disease Varies Between Physiologic and Idealized Loading Simulations.

Background and objectives: Femurs affected by metastatic bone disease (MBD) frequently undergo surgery to prevent impending pathologic fractures due to clinician-perceived increases in fracture risk. Finite element (FE) models can provide more objective assessments of fracture risk. However, FE models of femurs with MBD have implemented strain- and strength-based estimates of fracture risk under a wide variety of loading configurations, and "physiologic" loading models typically simulate a single abductor force. Due to these variations, it is currently difficult to interpret mechanical fracture risk results across studies of femoral MBD. Our aims were to evaluate (1) differences in mechanical behavior between idealized loading configurations and those incorporating physiologic muscle forces, and (2) differences in the rankings of mechanical behavior between different loading configurations, in FE simulations to predict fracture risk in femurs with MBD. Methods: We evaluated 9 different patient-specific FE loading simulations for a cohort of 54 MBD femurs: strain outcome simulations-physiologic (normal walking [NW], stair ascent [SA], stumbling), and joint contact only (NW contact force, excluding muscle forces); strength outcome simulations-physiologic (NW, SA), joint contact only, offset torsion, and sideways fall. Tensile principal strain and femur strength were compared between simulations using statistical analyses. Results: Tensile principal strain was 26% higher (R 2 = 0.719, P < .001) and femur strength was 4% lower (R 2 = 0.984, P < .001) in simulations excluding physiologic muscle forces. Rankings of the mechanical predictions were correlated between the strain outcome simulations (ρ = 0.723 to 0.990, P < .001), and between strength outcome simulations (ρ = 0.524 to 0.984, P < .001). Conclusions: Overall, simulations incorporating physiologic muscle forces affected local strain outcomes more than global strength outcomes. Absolute values of strain and strength computed using idealized (no muscle forces) and physiologic loading configurations should be used within the appropriate context when interpreting fracture risk in femurs with MBD.

Radiographically successful periacetabular osteotomy does not achieve optimal contact mechanics in dysplastic hips.

BACKGROUND: Optimal correction of hip dysplasia via periacetabular osteotomy may reduce osteoarthritis development by reducing damaging contact stress. The objective of this study was to computationally determine if patient-specific acetabular corrections that optimize contact mechanics can improve upon contact mechanics resulting from clinically successful, surgically achieved corrections. METHODS: Preoperative and postoperative hip models were retrospectively created from CT scans of 20 dysplasia patients treated with periacetabular osteotomy. A digitally extracted acetabular fragment was computationally rotated in 2-degree increments around anteroposterior and oblique axes to simulate candidate acetabular reorientations. From discrete element analysis of each patient's set of candidate reorientation models, a mechanically optimal reorientation that minimized chronic contact stress exposure and a clinically optimal reorientation that balanced improving mechanics with surgically acceptable acetabular coverage angles was selected. Radiographic coverage, contact area, peak/mean contact stress, and peak/mean chronic exposure were compared between mechanically optimal, clinically optimal, and surgically achieved orientations. FINDINGS: Compared to actual surgical corrections, computationally derived mechanically/clinically optimal reorientations had a median[IQR] 13[4-16]/8[3-12] degrees and 16[6-26]/10[3-16] degrees more lateral and anterior coverage, respectively. Mechanically/clinically optimal reorientations had 212[143-353]/217[111-280] mm2 more contact area and 8.2[5.8-11.1]/6.4[4.5-9.3] MPa lower peak contact stresses than surgical corrections. Chronic metrics demonstrated similar findings (p ≤ 0.003 for all comparisons). INTERPRETATION: Computationally selected orientations achieved a greater mechanical improvement than surgically achieved corrections; however, many predicted corrections would be considered acetabular over-coverage. Identifying patient-specific corrections that balance optimizing mechanics with clinical constraints will be necessary to reduce the risk of osteoarthritis progression after periacetabular osteotomy.

Biomechanical guidance can improve accuracy of reduction for intra-articular tibia plafond fractures and reduce joint contact stress.

Articular fracture malreduction increases posttraumatic osteoarthritis (PTOA) risk by elevating joint contact stress. A new biomechanical guidance system (BGS) that provides intraoperative assessment of articular fracture reduction and joint contact stress based solely on a preoperative computed tomography (CT) and intraoperative fluoroscopy may facilitate better fracture reduction. The objective of this proof-of-concept cadaveric study was to test this premise while characterizing BGS performance. Articular tibia plafond fractures were created in five cadaveric ankles. CT scans were obtained to provide digital models. Indirect reduction was performed in a simulated operating room once with and once without BGS guidance. CT scans after fixation provided models of the reduced ankles for assessing reduction accuracy, joint contact stresses, and BGS accuracy. BGS was utilized 4.8 ± 1.3 (mean ± SD) times per procedure, increasing operative time by 10 min (39%), and the number of fluoroscopy images by 31 (17%). Errors in BGS reduction assessment compared to CT-derived models were 0.45 ± 0.57 mm in translation and 2.0 ± 2.5° in rotation. For the four ankles that were successfully reduced and fixed, associated absolute errors in computed mean and maximum contact stress were 0.40 ± 0.40 and 0.96 ± 1.12 MPa, respectively. BGS reduced mean and maximum contact stress by 1.1 and 2.6 MPa, respectively. BGS thus improved the accuracy of articular fracture reduction and significantly reduced contact stress. Statement of Clinical Significance: Malreduction of articular fractures is known to lead to PTOA. The BGS described in this work has potential to improve quality of articular fracture reduction and clinical outcomes for patients with a tibia plafond fracture.

Joint contact stress improves in dysplastic hips after periacetabular osteotomy but remains higher than in normal hips.

AIM: The purpose of this study was to use computational modeling to determine if surgical correction of hip dysplasia restores hip contact mechanics to those of asymptomatic, radiographically normal hips. METHODS: Discrete element analysis (DEA) was used to compute joint contact stresses during the stance phase of normal walking gait for 10 individuals with radiographically normal, asymptomatic hips and 10 age- and weight-matched patients with acetabular dysplasia who underwent periacetabular osteotomy (PAO). RESULTS: Mean and peak contact stresses were higher (p < 0.001 and p = 0.036, respectively) in the dysplastic hips than in the matched normal hips. PAO normalised standard radiographic measurements and medialised the location of computed contact stress within the joint. Mean contact stress computed in dysplastic hips throughout the stance phase of gait (median 5.5 MPa, [IQR 3.9-6.1 MPa]) did not significantly decrease after PAO (3.7 MPa, [IQR 3.2-4.8]; p = 0.109) and remained significantly (p < 0.001) elevated compared to radiographically normal hips (2.4 MPa, [IQR 2.2-2.8 MPa]). Peak contact stress demonstrated a similar trend. Joint contact area during the stance phase of gait in the dysplastic hips increased significantly (p = 0.036) after PAO from 395 mm2 (IQR 378-496 mm2) to 595 mm2 (IQR 474-660 mm2), but remained significantly smaller (p = 0.001) than that for radiographically normal hips (median 1120 mm2, IQR 853-1444 mm2). CONCLUSIONS: While contact mechanics in dysplastic hips more closely resembled those of normal hips after PAO, the elevated contact stresses and smaller contact areas remaining after PAO indicate ongoing mechanical abnormalities should be expected even after radiographically successful surgical correction.

Mechanical Gains Associated With Virtual Prophylactic Intramedullary Nail Fixation in Femurs With Metastatic Disease.

Background: Many patients with metastatic bone disease (MBD) of the femur undergo prophylactic surgical fixation for impending pathologic fractures; intramedullary nailing (IMN) being the most common fixation type. However, surgeons often question if IMN fixation provides sufficient improvements in mechanical strength for particular metastatic lesions. Our goal was to use patient-specific finite element (FE) modeling to computationally evaluate the effects of simulated IMN fixation on the mechanics of femurs affected with MBD. Methods: Computed tomography (CT) scans were available retrospectively from 48 patients (54 femurs) with proximal femoral metastases. The CT scans were used to create patient-specific, non-linear, voxel-based FE models of the femur, simulating the instant of peak hip joint contact force during normal walking. FE analyses were repeated after incorporating virtual IMN fixation (Smith and Nephew, TRIGEN INTERTAN) into the same femurs. Femur strength and load-to-strength ratio (LSR; lower LSR indicates lower fracture risk) were compared between untreated and IMN conditions using statistical analyses. Results: IMN fixation resulted in a very modest average 10% increase in mechanical strength (p<0.001), which was associated with a slight 7% reduction in fracture risk (p<0.001). However, there was considerable variation in fracture risk reduction between individual femurs (0.13-50%). In femurs with the largest reduction in fracture risk (>10%), IMN hardware directly passed through a considerable section of that femur's metastatic lesion. Femurs with lytic (10%) and diffuse (9%) metastases tended to have greater reductions in fracture risk compared to femurs with blastic (5%) and mixed (4%) metastases (p=0.073). Conclusion: Given the mechanically strong baseline condition of most femurs in this cohort, evident by the low fracture risk at the time of CT scanning, the relative increase in stiffness with the addition of the IMN hardware may not make a substantial contribution to overall mechanical strength. The mechanical gains of IMN fixation in femurs with MBD appear most beneficial when the hardware traverses an adequate section of the lesion. Level of Evidence: III.

The Relationship Between Lesion Size and Load to Failure After Stabilization of Simulated Metastatic Lesions of the Proximal Femur.

Background: As overall cancer survival continues to improve, the incidence of metastatic lesions to the bone continues to increase. The subsequent skeletal related events that can occur with osseous metastasis can be debilitating. Complete and impending pathologic femur fractures are common with patients often requiring operative fixation. However, the efficacy of an intramedullary nail construct, on providing stability, continue to be debated. Therefore, the purpose of this study was to utilize a synthetic femur model to determine 1) how proximal femur defect size and cortical breach impact femur load to failure (strength) and stiffness, and 2) and how the utilization of an IMN, in a prophylactic fashion, subsequently alters the overall strength and stiffness of the proximal femur. Methods: A total of 21 synthetic femur models were divided into four groups: 1) intact (no defect), 2) 2 cm defect, 3) 2.5 cm defect, and 4) 4 cm defect. An IMN was inserted in half of the femur specimens that had a defect present. This procedure was performed using standard antegrade technique. Specimens were mechanically tested in offset torsion. Force-displacement curves were utilized to determine each constructs load to failure and overall torsional stiffness. The ultimate load to failure and construct stiffness of the synthetic femurs with defects were compared to the intact synthetic femur, while the femurs with the placement of the IMN were directly compared to the synthetic femurs with matching defect size. Results: The size of the defect invertedly correlated with the load the failure and overall stiffness. There was no difference in load to failure or overall stiffness when comparing intact models with no defect and the 2 cm defect group (p=0.98, p=0.43). The 2.5 cm, and 4.5 cm defect groups demonstrated significant difference in both load to failure and overall stiffness when compared to intact models with results demonstrating 1313 N (95% CI: 874-1752 N; p<0.001) and 104 N/mm (95% CI: 98-110 N/mm; p=0.03) in the 2.5 cm defect models, and 512 N (95% CI: 390-634 N, p<0.001) and 21 N/mm (95% CI: 9-33 N/mm, p<0.001) in the models with a 4 cm defect. Compared to the groups with defects, the placement an IMN increased overall stiffness in the 2.5 cm defect group (125 N/mm; 95% CI:114-136 N/mm; p=0.003), but not load to failure (p=0.91). In the 4 cm defect group, there was a significant increase in load to failure (1067 N; 95% CI: 835-1300 N; p=0.002) and overall stiffness (57 N/mm; 95% CI:46-69 N/mm; p=0.001). Conclusion: Prophylactic IMN fixation significantly improved failure load and overall stiffness in the group with the largest cortical defects, but still demonstrated a failure loads less than 50% of the intact model. This investigation suggests that a cortical breach causes a loss of strength that is not completely restored by intramedullary fixation. Level of Evidence: II.

Finite element analysis potentially identifies nonessential prophylactic stabilization in femurs with metastatic disease.

Metastatic bone disease (MBD) is often managed by non-specialized orthopedic surgeons who rely on Mirels' criteria to predict pathologic fracture risk. However, low specificity of Mirels' criteria implies many lesions are scored at high fracture risk when the actual mechanical fracture risk is minimal. Our goal was to retrospectively compare mechanical fracture risk in MBD patients to Mirels' score and clinical treatment received. Using a CT-based finite element (FE) model of the proximal femur affected by MBD, femur strength and load-to-strength ratio (LSR) were determined for 52 femurs from 48 patients. Associations of femur strength with pain and Mirels' scores (Pearson r/Spearman ρ correlations), and the decision to operate (percentile analysis), and associations of LSR with pain and Mirels' scores (Spearman correlations) were determined. Nineteen of 52 femurs (37%) had a very low computed mechanical fracture risk (LSR < 0.4); 5 of those 19 underwent prophylactic stabilization, suggesting that clinical decision-making in MBD is substantially influenced by non-mechanical factors that likely overestimate pathologic fracture risk. Of the 30 femurs managed non-operatively, 24 had a low computed mechanical fracture risk (LSR ≤ 0.5), none of which (0%) experienced a fracture within 9 months. Patient-reported pain did not correlate with femur strength (r = -0.05, p = 0.748) nor with LSR (ρ = 0.07, p = 0.632). Mirels' score correlated weakly with femur strength (ρ = -0.32, p = 0.019) and with LSR (ρ = 0.29, p = 0.034). Computational mechanical tools like this FE model could be used as a clinical decision aid when considering non-surgical management in appropriate patients, potentially alleviating nonessential surgical treatment in some patients with femur MBD.

Extracellular biomolecular free radical formation during injury.

OBJECTIVE: Determine if oxidative damage increases in articular cartilage as a result of injury and matrix failure and whether modulation of the local redox environment influences this damage. Osteoarthritis is an age associated disease with no current disease modifying approaches available. Mechanisms of cartilage damage in vitro suggest tissue free radical production could be critical to early degeneration, but these mechanisms have not been described in intact tissue. To assess free radical production as a result of traumatic injury, we measured biomolecular free radical generation via immuno-spin trapping (IST) of protein/proteoglycan/lipid free radicals after a 2 J/cm2 impact to swine articular cartilage explants. This technique allows visualization of free radical formation upon a wide variety of molecules using formalin-fixed, paraffin-embedded approaches. Scoring of extracellular staining by trained, blinded scorers demonstrated significant increases with impact injury, particularly at sites of cartilage cracking. Increases remain in the absence of live chondrocytes but are diminished; thus, they appear to be a cell-dependent and -independent feature of injury. We then modulated the extracellular environment with a pulse of heparin to demonstrate the responsiveness of the IST signal to changes in cartilage biology. Addition of heparin caused a distinct change in the distribution of protein/lipid free radicals at sites of failure alongside a variety of pertinent redox changes related to osteoarthritis. This study directly confirms the production of biomolecular free radicals from articular trauma, providing a rigorous characterization of their formation by injury.

Effect of modeling femoral version and head-neck offset correction on computed contact mechanics in dysplastic hips treated with periacetabular osteotomy.

While correction of dysplastic acetabular deformity has been a focus of both clinical treatment and research, concurrent femoral deformities have only more recently received serious attention. The purpose of this study was to determine how including abnormalities in femoral head-neck offset and femoral version alter computationally derived contact stresses in patients with combined dysplasia and femoroacetabular impingement (FAI). Hip models with patient-specific bony anatomy were created from preoperative and postoperative CT scans of 20 hips treated with periacetabular osteotomy and femoral osteochondroplasty. To simulate performing only a PAO, a third model was created combining each patient's postoperative pelvis and preoperative femur geometry. These three models were initialized with the femur in two starting orientations: (1) standardized template orientation, and (2) using patient-specific anatomic landmarks. Hip contact stresses were computed in all 6 model sets during an average dysplastic gait cycle, an average FAI gait cycle, and an average stand-to-sit activity using discrete element analysis. No significant differences in peak contact stress (p = 0.190 to 1), mean contact stress (p = 0.273 to 1), or mean contact area (p = 0.050 to 1) were identified during any loading activity based on femoral alignment technique or inclusion of femoral osteochondroplasty. These findings suggest that presence of abnormal femoral version and/or head-neck offset deformities are not themselves predominant factors in intra-articular contact mechanics during gait and stand-to-sit activities. Inclusion of modified movement patterns caused by these femoral deformities may be necessary for models to adequately capture the mechanical effects of these clinically recognized risk factors for negative outcomes.

The Effect of Progressive Lateral Column Lengthening in a Novel Stage II-B Flatfoot Cadaveric Model Evaluated Using Software-Guided Radiographic Measurements of Foot Alignment.

BACKGROUND: This work used software-guided radiographic measurement to assess the effects of progressive lateral column lengthening (LCL) on restoring alignment in a novel cadaveric model of stage II-B flatfoot deformity. METHODS: A stage II-B flatfoot was created in 8 cadaveric specimens by transecting the spring ligament complex, anterior deltoid, and interosseous talocalcaneal and cervical ligaments. Weightbearing computed tomographic (WBCT) scans were performed with specimens under 450 N of compressive load in the intact, flat, and 6-, 8-, and 10-mm lateral column-lengthening conditions. Custom software-guided radiographic measurements of the lateral talo-first metatarsal (Meary) angle, anteroposterior talo-first metatarsal angle, naviculocuneiform overlap, and 2 new measures (plantar fascia [PF] distance and angle) were recorded on digitally reconstructed radiographs. Four anonymized analysts performed measurements twice. Intra- and interobserver agreement was assessed using intraclass correlation coefficients (ICCs). RESULTS: Six-millimeter LCL restored alignment closest to the intact foot in this new cadaveric model, whereas 10-mm lengthening tended toward overcorrection. The PF line displaced laterally in the flatfoot condition, and LCL restored the PF line to a location beneath the talonavicular joint. Interobserver agreement was excellent for PF distance (ICC = 0.99) and naviculocuboid overlap (ICC = 0.91), good for Meary angle (ICC = 0.81) and PF angle (ICC = 0.69), and acceptable for the talonavicular coverage angle (ICC = 0.65). CONCLUSION: In this stage II-B cadaveric flatfoot model, cervical ligament transection was essential to create deformity after the medial hindfoot ligaments were transected. Software-guided radiographic measurement proved reliable; standardized implementation should improve comparability between studies of flatfoot deformity. The novel PF distance performed most consistently (ICC = 0.99) and warrants further study. With this model, we found that a 6-mm LCL restored alignment closest to the intact foot, whereas 10-mm lengthening tended toward overcorrection. CLINICAL RELEVANCE: Future joint-sparing flatfoot corrections may consider using a relatively small LCL combined with other bony and/or anatomic ligament/tendon reconstructions.

Do Relaxin Levels Impact Hip Injury Incidence in Women? A Scoping Review.

Purpose: The aim of this review is to assess the current evidence regarding the impact of relaxin on incidence of soft tissue hip injuries in women. Methods: A trained research librarian assisted with searches of PubMed, Embase, CINAHL, and SPORTDiscus, with a preset English language filter. The review was completed per the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis methodology. Included studies required assessment of relaxin effects on musculoskeletal health, pelvic girdle stability, or hip joint structures in human subjects. Letters, texts, and opinion papers were excluded. Results: Our screen yielded 82 studies. Molecularly, relaxin activates matrix metalloproteinases (MMPs) including collagenases MMP-1/-13 and gelatinases MMP-2/-9 to loosen pelvic ligaments for parturition. However, relaxin receptors have also been detected in female periarticular tissues, such as the anterior cruciate ligament, which tears significantly more often during the menstrual cycle peak of relaxin. Recently, high concentrations of relaxin-activated MMP-9 receptors have been found on the acetabular labrum; their expression upregulated by estrogen. Conclusions: Menstrual cycle peaks of relaxin activate MMPs, which locally degrade collagen and gelatine. Women have relaxin receptors in multiple joints including the hip and knee, and increased relaxin correlates with increased musculoskeletal injuries. Relaxin has paracrine effects in the female pelvis on ligaments adjacent to hip structures, such as acetabular labral cells which express high levels of relaxin-targeted MMPs. Therefore, it is imperative to investigate the effect of relaxin on the hip to determine if increased levels of relaxin are associated with an increased risk of acetabular labral tears.

Objective evaluation of chondrocyte density & cloning after joint injury using convolutional neural networks.

Variations in chondrocyte density and organization in cartilage histology sections are associated with osteoarthritis progression. Rapid, accurate quantification of these two features can facilitate the evaluation of cartilage health and advance the understanding of their significance. The goal of this work was to adapt deep-learning-based methods to detect articular chondrocytes and chondrocyte clones from safranin-O-stained cartilage to evaluate chondrocyte cellularity and organization. The U-net and "you-only-look-once" (YOLO) models were trained and validated for identifying chondrocytes and chondrocyte clones, respectively. Validated models were then used to quantify chondrocyte and clone density in talar cartilage from Yucatan minipigs sacrificed 1 week, 3, 6, and 12 months after fixation of an intra-articular fracture of the hock joint. There was excellent/good agreement between expert researchers and the developed models in identifying chondrocytes/clones (U-net: R2 = 0.93, y = 0.90x-0.69; median F1 score: 0.87/YOLO: R2 = 0.79, y = 0.95x; median F1 score: 0.67). Average chondrocyte density increased 1 week after fracture (from 774 to 856 cells/mm2 ), decreased substantially 3 months after fracture (610 cells/mm2 ), and slowly increased 6 and 12 months after fracture (638 and 683 cells/mm2 , respectively). Average detected clone density 3, 6, and 12 months after fracture (11, 11, 9 clones/mm2 ) was higher than the 4-5 clones/mm2 detected in normal tissue or 1 week after fracture and show local increases in clone density that varied across the joint surface with time. The accurate evaluation of cartilage cellularity and organization provided by this deep learning approach will increase objectivity of cartilage injury and regeneration assessments.