Evolutionary Selection and Constraint on Human Knee Chondrocyte Regulation Impacts Osteoarthritis Risk.

During human evolution, the knee adapted to the biomechanical demands of bipedalism by altering chondrocyte developmental programs. This adaptive process was likely not without deleterious consequences to health. Today, osteoarthritis occurs in 250 million people, with risk variants enriched in non-coding sequences near chondrocyte genes, loci that likely became optimized during knee evolution. We explore this relationship by epigenetically profiling joint chondrocytes, revealing ancient selection and recent constraint and drift on knee regulatory elements, which also overlap osteoarthritis variants that contribute to disease heritability by tending to modify constrained functional sequence. We propose a model whereby genetic violations to regulatory constraint, tolerated during knee development, lead to adult pathology. In support, we discover a causal enhancer variant (rs6060369) present in billions of people at a risk locus (GDF5-UQCC1), showing how it impacts mouse knee-shape and osteoarthritis. Overall, our methods link an evolutionarily novel aspect of human anatomy to its pathogenesis.

Protocol and validity testing of femoroacetabular posterior translation with dynamic hip ultrasonography.

OBJECTIVE: To describe femoroacetabular posterior translation (FAPT) using dynamic hip ultrasonography (DHUS), and to determine the inter- and intra-rater reliability of hip ultrasound measurements of FAPT. MATERIALS AND METHODS: The study design was a feasibility study of 13 healthy young adults (26 hips) using test-retest analysis. The data was collected prospectively over a 2-week time period. Three DHUS measurements (posterior neutral (PN), flexion, adduction, and internal rotation (PFADIR), and stand and load (PStand) were measured by four independent raters (2 senior who divided the cohort, 1 intermediate, 1 junior) at two time points for bilateral hips of each participant. Reliability was assessed by calculating the intraclass correlation coefficient (ICC) along with 95% confidence intervals (CIs) for each rater and across all raters. RESULTS: A total of 468 US scans were completed. The mean age of the cohort was 25.7 years (SD 5.1 years) and 54% were female. The inter-rater reliability was excellent for PFADIR (ICC 0.85 95% CI 0.76-0.91), good for PN (ICC 0.69 95% CI 0.5-0.81), and good for PStand (ICC 0.72 95% CI 0.55-0.83). The intra-rater reliability for all raters was good for PFADIR (ICC 0.60 95% CI 0.44-0.73), fair for PN (ICC 0.42 95% CI 0.21-0.59), and fair for PStand (ICC 0.42 95% CI 0.22-0.59). CONCLUSION: This is the first study to present a protocol using dynamic ultrasonography to measure FAPT. DHUS measure for FAPT was shown to be reliable across raters with varying levels of ultrasound experience.

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.

Telehealth Potential in Pediatric Orthopaedics and Sports Medicine Care is Comparable to In-Person Care But Disparities Remain.

BACKGROUND: Understanding the challenges and potential of telehealth visits (THVs) in a large population can inform future practice and policy discussion for pediatric orthopaedic and sports medicine (OSM) care. We comprehensively assess telehealth challenges and potential in a large pediatric OSM population based on access, visit completion, patient satisfaction, and technological challenges. METHODS: Demographics, address, insurance, visit information, patient feedback, experience with video visits, and technical challenges of all 2019 to 2020 visits at our hospital were assessed (3,278,006 visits). We evaluated the differences in rate of telehealth utilization, rate of patient adherence, disparities in care access and patient satisfaction, and technological issues. RESULTS: Compared with in-person prepandemic visits, THVs had lower ratios of non-White patients (by 5.8%; P <0.001), Hispanic patients (by 2.8%; P <0.001) and patients with public insurance (by 1.8%; P <0.001), and a higher mean distance between the patient's residence and clinic (by 18.8 miles; P <0.001). There were minimal differences in median household income (average $2297 less in THV; P <0.001) and social vulnerability index (average 0.01 points lower in THV; P <0.001) between groups. THVs had comparable patient satisfaction to in-person visits. Non-White patients, Hispanics, and those with public insurance had lower ratings for both in-person visits and THVs and had more technical difficulties during their THV. CONCLUSIONS: Telehealth is a viable method of care for a range of pediatric OSM conditions, providing a similar quality of care as in-person visits with a greater geographic reach. However, in its current format, reduced disparities were not observed in pediatric OSM THVs. LEVEL OF EVIDENCE: Level III.

Early MRI-based quantitative outcomes are associated with a positive functional performance trajectory from 6 to 24 months post-ACL surgery.

PURPOSE: Quantitative magnetic resonance imaging (qMRI) has been used to determine the failure properties of ACL grafts and native ACL repairs and/or restorations. How these properties relate to future clinical, functional, and patient-reported outcomes remain unknown. The study objective was to investigate the relationship between non-contemporaneous qMRI measures and traditional outcome measures following Bridge-Enhanced ACL Restoration (BEAR). It was hypothesized that qMRI parameters at 6 months would be associated with clinical, functional, and/or patient-reported outcomes at 6 months, 24 months, and changes from 6 to 24 months post-surgery. METHODS: Data of BEAR patients (n = 65) from a randomized control trial of BEAR versus ACL reconstruction (BEAR II Trial; NCT02664545) were utilized retrospectively for the present analysis. Images were acquired using the Constructive Interference in Steady State (CISS) sequence at 6 months post-surgery. Single-leg hop test ratios, arthrometric knee laxity values, and International Knee Documentation Committee (IKDC) subjective scores were determined at 6 and 24 months post-surgery. The associations between traditional outcomes and MRI measures of normalized signal intensity, mean cross-sectional area (CSA), volume, and estimated failure load of the healing ACL were evaluated based on bivariate correlations and multivariable regression analyses, which considered the potential effects of age, sex, and body mass index. RESULTS: CSA (r = 0.44, p = 0.01), volume (r = 0.44, p = 0.01), and estimated failure load (r = 0.48, p = 0.01) at 6 months were predictive of the change in single-leg hop ratio from 6 to 24 months in bivariate analysis. CSA (ßstandardized = 0.42, p = 0.01), volume (ßstandardized = 0.42, p = 0.01), and estimated failure load (ßstandardized = 0.48, p = 0.01) remained significant predictors when considering the demographic variables. No significant associations were observed between MRI variables and either knee laxity or IKDC when adjusting for demographic variables. Signal intensity was also not significant at any timepoint. CONCLUSION: The qMRI-based measures of CSA, volume, and estimated failure load were predictive of a positive functional outcome trajectory from 6 to 24 months post-surgery. These variables measured using qMRI at 6 months post-surgery could serve as prospective markers of the functional outcome trajectory from 6 to 24 months post-surgery, aiding in rehabilitation programming and return-to-sport decisions to improve surgical outcomes and reduce the risk of reinjury. LEVEL OF EVIDENCE: Level II.

Natural language processing: using artificial intelligence to understand human language in orthopedics.

Natural language processing (NLP) describes the broad field of artificial intelligence by which computers are trained to understand and generate human language. Within healthcare research, NLP is commonly used for variable extraction and classification/cohort identification tasks. While these tools are becoming increasingly popular and available as both open-source and commercial products, there is a paucity of the literature within the orthopedic space describing the key tasks within these powerful pipelines. Curation and navigation of the electronic medical record are becoming increasingly onerous, and it is important for physicians and other healthcare professionals to understand potential methods of harnessing this large data resource. The purpose of this study is to provide an overview of the tasks required to develop an NLP pipeline for orthopedic research and present recent examples of successful implementations.

Supervised machine learning and associated algorithms: applications in orthopedic surgery.

Supervised learning is the most common form of machine learning utilized in medical research. It is used to predict outcomes of interest or classify positive and/or negative cases with a known ground truth. Supervised learning describes a spectrum of techniques, ranging from traditional regression modeling to more complex tree boosting, which are becoming increasingly prevalent as the focus on "big data" develops. While these tools are becoming increasingly popular and powerful, there is a paucity of literature available that describe the strengths and limitations of these different modeling techniques. Typically, there is no formal training for health care professionals in the use of machine learning models. As machine learning applications throughout medicine increase, it is important that physicians and other health care professionals better understand the processes underlying application of these techniques. The purpose of this study is to provide an overview of commonly used supervised learning techniques with recent case examples within the orthopedic literature. An additional goal is to address disparities in the understanding of these methods to improve communication within and between research teams.

Effects of joint loading on the development of capital femoral epiphysis morphology.

INTRODUCTION: The deleterious influence of increased mechanical forces on capital femoral epiphysis development is well established; however, the growth of the physis in the absence of such forces remains unclear. The hips of non-ambulatory cerebral palsy (CP) patients provide a weight-restricted (partial weightbearing) model which can elucidate the influence of decreased mechanical forces on the development of physis morphology, including features related to development of slipped capital femoral epiphysis (SCFE). Here we used 3D image analysis to compare the physis morphology of children with non-ambulatory CP, as a model for abnormal hip loading, with age-matched native hips. MATERIALS AND METHODS: CT images of 98 non-ambulatory CP hips (8-15 years) and 80 age-matched native control hips were used to measure height, width, and length of the tubercle, depth, width, and length of the metaphyseal fossa, and cupping height across different epiphyseal regions. The impact of age on morphology was assessed using Pearson correlations. Mixed linear model was used to compare the quantified morphological features between partial weightbearing hips and full weightbearing controls. RESULTS: In partial weightbearing hips, tubercle height and length along with fossa depth and length significantly decreased with age, while peripheral cupping height increased with age (r > 0.2, P < 0.04). Compared to normally loaded (full weightbearing) hips and across all age groups, partially weightbearing hips' epiphyseal tubercle height and length were smaller (P < .05), metaphyseal fossa depth was larger (P < .01), and posterior, inferior, and anterior peripheral cupping heights were smaller (P < .01). CONCLUSIONS: Smaller epiphyseal tubercle and peripheral cupping with greater metaphyseal fossa size in partial weightbearing hips suggests that the growing capital femoral epiphysis requires mechanical stimulus to adequately develop epiphyseal stabilizers. Deposit low prevalence and relevance of SCFE in CP, these findings highlight both the role of normal joint loading in proper physis development and how chronic abnormal loading may contribute to various pathomorphological changes of the proximal femur (i.e., capital femoral epiphysis).

The development and deployment of machine learning models.

Applications of artificial intelligence, specifically machine learning, are becoming increasingly popular in Orthopaedic Surgery, and medicine as a whole. This growing interest is shared by data scientists and physicians alike. However, there is an asymmetry of understanding of the developmental process and potential applications of machine learning. As new technology will undoubtedly affect clinical practice in the coming years, it is important for physicians to understand how these processes work. The purpose of this paper is to provide clarity and a general framework for building and assessing machine learning models.

Limited Hip Flexion and Internal Rotation Resulting From Early Hip Impingement Conflict on Anterior Metaphysis of Patients With Untreated Severe SCFE Using 3D Modelling.

INTRODUCTION: Slipped capital femoral epiphysis (SCFE) is the most common hip disorder in adolescent patients that can result in complex 3 dimensional (3D)-deformity and hip preservation surgery (eg, in situ pinning or proximal femoral osteotomy) is often performed. But there is little information about location of impingement.Purpose/Questions: The purpose of this study was to evaluate (1) impingement-free hip flexion and internal rotation (IR), (2) frequency of impingement in early flexion (30 to 60 degrees), and (3) location of acetabular and femoral impingement in IR in 90 degrees of flexion (IRF-90 degrees) and in maximal flexion for patients with untreated severe SCFE using preoperative 3D-computed tomography (CT) for impingement simulation. METHODS: A retrospective study involving 3D-CT scans of 18 patients (21 hips) with untreated severe SCFE (slip angle>60 degrees) was performed. Preoperative CT scans were used for bone segmentation of preoperative patient-specific 3D models. Three patients (15%) had bilateral SCFE. Mean age was 13±2 (10 to 16) years and 67% were male patients (86% unstable slip, 81% chronic slip). The contralateral hips of 15 patients with unilateral SCFE were evaluated (control group). Validated software was used for 3D impingement simulation (equidistant method). RESULTS: (1) Impingement-free flexion (46±32 degrees) and IRF-90 degrees (-17±18 degrees) were significantly ( P <0.001) decreased in untreated severe SCFE patients compared with contralateral side (122±9 and 36±11 degrees).(2) Frequency of impingement was significantly ( P <0.001) higher in 30 and 60 degrees flexion (48% and 71%) of patients with severe SCFE compared with control group (0%).(3) Acetabular impingement conflict was located anterior-superior (SCFE patients), mostly 12 o'clock (50%) in IRF-90 degrees (70% on 2 o'clock for maximal flexion). Femoral impingement was located on anterior-superior to anterior-inferior femoral metaphysis (between 2 and 6 o'clock, 40% on 3 o'clock and 40% on 5 o'clock) in IRF-90 degrees and on anterior metaphysis (40% on 3 o'clock) in maximal flexion and frequency was significantly ( P <0.001) different compared with control group. CONCLUSION: Severe SCFE patients have limited hip flexion and IR due to early hip impingement using patient-specific preoperative 3D models. Because of the large variety of hip motion, individual evaluation is recommended to plan the osseous correction for severe SCFE patients. LEVEL OF EVIDENCE: Level III.

Does the Capital Femoral Physis Bony MorphologyDiffer in Children with Symptomatic Cam-type Femoroacetabular Impingement.

BACKGROUND: The epiphyseal tubercle, the corresponding metaphyseal fossa, and peripheral cupping are key stabilizers of the femoral head-neck junction. Abnormal development of these features in the setting of supraphysiologic physeal stress under high forces (for example, forces that occur during sports activity) may result in a cam morphology. Although most previous studies on cam-type femoroacetabular impingement (FAI) have mainly focused on overgrowth of the peripheral cupping, little is known about detailed morphologic changes of the epiphyseal and metaphyseal bony surfaces in patients with cam morphology. QUESTIONS/PURPOSES: (1) Does the CT-based bony morphology of the peripheral epiphyseal cupping differ between patients with a cam-type morphology and asymptomatic controls (individuals who did not have hip pain)? (2) Does the CT-based bony morphology of the epiphyseal tubercle differ between patients with a cam-type morphology and asymptomatic controls? (3) Does the CT-based bony morphology of the metaphyseal fossa differ between patients with a cam-type morphology and asymptomatic controls? METHODS: After obtaining institutional review board approval for this study, we retrospectively searched our institutional database for patients aged 8 to 15 years with a diagnosis of an idiopathic cam morphology who underwent a preoperative CT evaluation of the affected hip between 2005 and 2018 (n = 152). We excluded 96 patients with unavailable CT scans and 40 patients with prior joint diseases other than cam-type FAI. Our search resulted in 16 patients, including nine males. Six of 16 patients had a diagnosis of bilateral FAI, for whom we randomly selected one side for the analysis. Three-dimensional (3-D) models of the proximal femur were generated to quantify the size of the peripheral cupping (peripheral growth of the epiphysis around the metaphysis), epiphyseal tubercle (a beak-like prominence in the posterosuperior aspect of the epiphysis), and metaphyseal fossa (a groove on the metaphyseal surface corresponding to the epiphyseal tubercle). A general linear model was used to compare the quantified anatomic features between the FAI cohort and 80 asymptomatic hips (aged 8 to 15 years; 50% male) after adjusting for age and sex. A secondary analysis using the Wilcoxon matched-pairs signed rank test was performed to assess side-to-side differences in quantified morphological features in 10 patients with unilateral FAI. RESULTS: After adjusting for age and sex, we found that patients with FAI had larger peripheral cupping in the anterior, posterior, superior, and inferior regions than control patients who did not have hip symptoms or radiographic signs of FAI (by 1.3- to 1.7-fold; p < 0.01 for all comparisons). The epiphyseal tubercle height and length were smaller in patients with FAI than in controls (by 0.3- to 0.6-fold; p < 0.02 for all comparisons). There was no difference in tubercle width between the groups. Metaphyseal fossa depth, width, and length were larger in patients with FAI than in controls (by 1.8- to 2.3-fold; p < 0.001 for all comparisons). For patients with unilateral FAI, we saw similar peripheral cupping but smaller epiphyseal tubercle (height and length) along with larger metaphyseal fossa (depth) in the FAI side compared with the uninvolved contralateral side. CONCLUSION: Consistent with prior studies, we observed more peripheral cupping in patients with cam-type FAI than control patients without hip symptoms or radiographic signs of FAI. Interestingly, the epiphyseal tubercle height and length were smaller and the metaphyseal fossa was larger in hips with cam-type FAI, suggesting varying inner bone surface morphology of the growth plate. The docking mechanism between the epiphyseal tubercle and the metaphyseal fossa is important for epiphyseal stability, particularly at early ages when the peripheral cupping is not fully developed. An underdeveloped tubercle and a large fossa could be associated with a reduction in stability, while excessive peripheral cupping growth would be a factor related to improved physeal stability. This is further supported by observed side-to-side differences in tubercle and fossa morphology in patients with unilateral FAI. Further longitudinal studies would be worthwhile to study the causality and compensatory mechanisms related to epiphyseal and metaphyseal bony morphology in pathogenesis cam-type FAI. Such information will lay the foundation for developing imaging biomarkers to predict the risk of FAI or to monitor its progress, which are critical in clinical care planning. LEVEL OF EVIDENCE: Level III, prognostic study.

What Is the Association Among Epiphyseal Rotation, Translation, and the Morphology of the Epiphysis and Metaphysis in Slipped Capital Femoral Epiphysis?

BACKGROUND: Contemporary studies have described the rotational mechanism in patients with slipped capital femoral epiphysis (SCFE). However, there have been limited patient imaging data and information to quantify the rotation. Determining whether the epiphysis is rotated or translated and measuring the epiphyseal displacement in all planes may facilitate planning for surgical reorientation of the epiphysis. QUESTIONS/PURPOSES: (1) How does epiphyseal rotation and translation differ among mild, moderate, and severe SCFE? (2) Is there a correlation between epiphyseal rotation and posterior or inferior translation in hips with SCFE? (3) Does epiphyseal rotation correlate with the size of the epiphyseal tubercle or the metaphyseal fossa or with epiphyseal cupping? METHODS: We identified 51 patients (55% boys [28 of 51]; mean age 13 ± 2 years) with stable SCFE who underwent preoperative CT of the pelvis before definitive treatment. Stable SCFE was selected because unstable SCFE would not allow for accurate assessment of rotation given the complete displacement of the femoral head in relation to the neck. The epiphysis and metaphysis were segmented and reconstructed in three-dimensions (3-D) for analysis in this retrospective study. One observer (a second-year orthopaedic resident) performed the image segmentation and measurements of epiphyseal rotation and translation relative to the metaphysis, epiphyseal tubercle, metaphyseal fossa, and the epiphysis extension onto the metaphysis defined as epiphyseal cupping. To assess the reliability of the measurements, a randomly selected subset of 15 hips was remeasured by the primary examiner and by the two experienced examiners independently. We used ANOVA to calculate the intraclass and interclass correlation coefficients (ICCs) for intraobserver and interobserver reliability of rotational and translational measurements. The ICC values for rotation were 0.91 (intraobserver) and 0.87 (interobserver) and the ICC values for translation were 0.92 (intraobserver) and 0.87 (intraobserver). After adjusting for age and sex, we compared the degree of rotation and translation among mild, moderate, and severe SCFE. Pearson correlation analysis was used to assess the associations between rotation and translation and between rotation and tubercle, fossa, and cupping measurements. RESULTS: Hips with severe SCFE had greater epiphyseal rotation than hips with mild SCFE (adjusted mean difference 21° [95% CI 11° to 31°]; p < 0.001) and hips with moderate SCFE (adjusted mean difference 13° [95% CI 3° to 23°]; p = 0.007). Epiphyseal rotation was positively correlated with posterior translation (r = 0.33 [95% CI 0.06 to 0.55]; p = 0.02) but not with inferior translation (r = 0.16 [95% CI -0.12 to 0.41]; p = 0.27). There was a positive correlation between rotation and metaphyseal fossa depth (r = 0.35 [95% CI 0.08 to 0.57]; p = 0.01), width (r = 0.41 [95% CI 0.15 to 0.61]; p = 0.003), and length (r = 0.56 [95% CI 0.38 to 0.75]; p < 0.001). CONCLUSION: This study supports a rotational mechanism for the pathogenesis of SCFE. Increased rotation is associated with more severe slips, posterior epiphyseal translation, and enlargement of the metaphyseal fossa. The rotational nature of the deformity, with the center of rotation at the epiphyseal tubercle, should be considered when planning in situ fixation and realignment surgery. Avoiding placing a screw through the epiphyseal tubercle-the pivot point of rotation- may increase the stability of the epiphysis. The realignment of the epiphysis through rotation rather than simple translation is recommended during the open subcapital realignment procedure. Enlargement of the metaphyseal fossa disrupts the interlocking mechanism with the tubercle and increases epiphyseal instability. Even in the setting of a stable SCFE, an increased fossa enlargement may indicate using two screws instead of one screw, given the severity of epiphyseal rotation and the risk of instability. Further biomechanical studies should investigate the number and position of in situ fixation screws in relation to the epiphyseal tubercle and metaphyseal fossa. LEVEL OF EVIDENCE: Level III, prognostic study.

Impact of broad regulatory regions on Gdf5 expression and function in knee development and susceptibility to osteoarthritis.

OBJECTIVES: Given the role of growth and differentiation factor 5 (GDF5) in knee development and osteoarthritis risk, we sought to characterise knee defects resulting from Gdf5 loss of function and how its regulatory regions control knee formation and morphology. METHODS: The brachypodism (bp) mouse line, which harbours an inactivating mutation in Gdf5, was used to survey how Gdf5 loss of function impacts knee morphology, while two transgenic Gdf5 reporter bacterial artificial chromosome mouse lines were used to assess the spatiotemporal activity and function of Gdf5 regulatory sequences in the context of clinically relevant knee anatomical features. RESULTS: Knees from homozygous bp mice (bp/bp) exhibit underdeveloped femoral condyles and tibial plateaus, no cruciate ligaments, and poorly developed menisci. Secondary ossification is also delayed in the distal femur and proximal tibia. bp/bp mice have significantly narrower femoral condyles, femoral notches and tibial plateaus, and curvier medial femoral condyles, shallower trochlea, steeper lateral tibial slopes and smaller tibial spines. Regulatory sequences upstream from Gdf5 were weakly active in the prenatal knee, while downstream regulatory sequences were active throughout life. Importantly, downstream but not upstream Gdf5 regulatory sequences fully restored all the key morphological features disrupted in the bp/bp mice. CONCLUSIONS: Knee morphology is profoundly affected by Gdf5 absence, and downstream regulatory sequences mediate its effects by controlling Gdf5 expression in knee tissues. This downstream region contains numerous enhancers harbouring human variants that span the osteoarthritis association interval. We posit that subtle alterations to morphology driven by changes in downstream regulatory sequence underlie this locus' role in osteoarthritis risk.

Biomechanical Outcomes of Bridge-enhanced Anterior Cruciate Ligament Repair Are Influenced by Sex in a Preclinical Model.

BACKGROUND: Despite the well-established role of sex on the anterior cruciate ligament (ACL) injury risk, its effects on ACL surgical outcomes remain controversial. This is particularly critical when developing novel surgical techniques to treat the injury because there are limited data existing on how these procedures will respond in each sex. One such approach is bridge-enhanced ACL repair, in which primary suture repair of the ACL is augmented with a bioactive scaffold saturated with autologous blood. It has shown comparable biomechanical outcomes to ACL reconstruction in preclinical models. QUESTIONS/PURPOSES: We asked (1) whether sex affects the biomechanical outcomes of bridge-enhanced ACL repair; and (2) if suture type (absorbable or nonabsorbable), used to repair the torn ACL, can minimize the potential sex discrepancies in outcomes after 15 weeks of healing in a large animal preclinical model. METHODS: Seventeen (eight males, nine females) Yorkshire pigs (Parson's Farms, Hadley, MA, USA) underwent bilateral ACL transection and received bridge-enhanced ACL repair with an absorbable suture (n=17) on one side and with a nonabsorbable suture (n=17) on the other side. The leg receiving the absorbable suture was randomized within each animal. ACL structural properties and AP knee laxity for each knee were measured after 15 weeks of healing. Mixed linear models were used to compare the biomechanical outcomes between sexes and suture groups. RESULTS: When treated with absorbable suture, females had a lower ACL linear stiffness (females, 11 N/mm [range, 8-42]; males, 31 N/mm [range, 12-56]; difference, 20 N/mm [95% confidence interval {CI}, 4-36]; p=0.032), ACL yield (females, 121 N [range, 56-316]; males, 224 N [range, 55-538]; difference, 103 N [95% CI, 6-200]; p=0.078), and maximum load (females, 128 N [range, 63-332]; males, 241 N [range, 82-538]; difference, 114 N [95% CI, 15-212]; p=0.052) than males after 15 weeks of healing. Female knees treated with absorbable suture had a lower linear stiffness (absorbable, 11 N/mm [range, 8-42]; nonabsorbable, 25 N/mm [range, 8-64]; difference, 14 [95% CI, 2-26] N; p=0.054), ACL yield (absorbable, 121 N [range, 56-316]; nonabsorbable, 230 N [range, 149-573]; difference, 109 N [95% CI, 56-162]; p=0.002), and maximum load (absorbable, 128 N [range, 63-332]; nonabsorbable, 235 N [range, 151-593]; difference, 107 N [95% CI, 51-163]; p=0.002) along with greater AP knee laxity at 30° (absorbable, 9 mm [range, 5-12]; nonabsorbable, 7 mm [range, 2-13]; difference, 2 mm [95% CI, 1-4]; p=0.034) than females treated with nonabsorbable suture. When repaired using nonabsorbable suture, the biomechanical outcomes were similar between female and male knees (p>0.10). CONCLUSIONS: Females had significantly worse biomechanical outcomes than males when the repairs were performed using absorbable sutures. However, the use of nonabsorbable sutures ameliorated these differences between males and females. CLINICAL RELEVANCE: The current findings highlight the critical role of sex on the biomechanical outcomes of bridge-enhanced ACL repair in a relevant large animal model. Better understanding of the mechanisms responsible for these observations using preclinical models and concomitant clinical studies in human patients may allow for additional development of sex-specific surgical and rehabilitative strategies with potentially improved outcomes in women.

Validation of porcine knee as a sex-specific model to study human anterior cruciate ligament disorders.

BACKGROUND: Animal models have long been considered an important modality for studying ACL injuries. However, to our knowledge, the value of these preclinical models to study sex-related phenomena associated with ACL injury and recovery has not been evaluated. QUESTIONS/PURPOSES: We asked whether (1) prominent anatomic and (2) biomechanical factors differ between female and male porcine knees, particularly those known to increase the risk of ACL injury. METHODS: Eighteen intact minipig knees (nine males, nine females) underwent MRI to determine the femoral bicondylar width, intercondylar notch size (width, area and index), medial and lateral tibial slope, ACL size (length, cross-sectional area, and volume), and medial compartment tibiofemoral cartilage thickness. AP knee laxity at 30°, 60°, and 90° flexion and ACL tensile structural properties were measured using custom-designed loading fixtures in a universal tensile testing apparatus. Comparisons between males and females were performed for all anatomic and biomechanical measures. The findings then were compared with published data from human knees. RESULTS: Female pigs had smaller bicondylar widths (2.9 mm, ratio=0.93, effect size=-1.5) and intercondylar notches (width: 2.0 mm, ratio=0.79, effect size=-2.8; area: 30.8 mm2, ratio=0.76, effect size=-2.1; index: 0.4, ratio=0.84, effect size=-2.0), steeper lateral tibial slope (4.3°, ratio=1.13, effect size=1.1), smaller ACL (length: 2.7 mm, ratio=0.91, effect size=-1.1; area: 6.8 mm2, ratio=0.74, effect size=-1.5; volume: 266.2 mm3, ratio=0.68, effect size=-1.5), thinner medial femoral cartilage (0.4 mm, ratio=0.8, effect size=-1.1), lower ACL yield load (275 N, ratio=0.81, effect size=-1.1), and greater AP knee laxity at 30° (0.7 mm, ratio=1.32, effect size=1.1) and 90° (0.5 mm, ratio=1.24, effect size=1.1) flexion compared with their male counterparts. These differences were significant for all parameters (p≤0.04). Observed sex-related differences were similar to those reported for the human knee. CONCLUSIONS: Significant differences exist between knees of male and female pigs with respect to prominent anatomic and biomechanical factors. Our findings strongly agreed with published data regarding human knees. CLINICAL RELEVANCE: The findings highlight the use of the porcine large animal model to study the role of sex on ACL injuries and surgical outcome. This validated preclinical model may facilitate the development of novel, sex-specific interventions to prevent and treat ACL injuries for male and female patients.

Biomechanical evaluation of the pedicle screw insertion depth effect on screw stability under cyclic loading and subsequent pullout.

STUDY DESIGN: A biomechanical ex vivo study of the human lumbar spine. OBJECTIVE: To evaluate the effects of transpedicular screw insertion depth on overall screw stability and pullout strength following cyclic loading in the osteoporotic lumbar spine. SUMMARY OF BACKGROUND DATA: Although much is known about the clinical outcomes of spinal fusion, questions remain in our understanding of the biomechanical strength of lumbar pedicle screw fixation as it relates to screw sizing and placement. Biomechanical analyses examining ideal pedicle screw depth with current pedicle screw technology are limited. In the osteoporotic spine, optimized pedicle screw insertion depth may improve construct strength, decreasing the risk of loosening or pullout. METHODS: A total of 100 pedicles from 10 osteoporotic lumbar spines were randomly instrumented with pedicle screws in mid-body, pericortical, and bicortical depths. Instrumented specimens underwent cyclic loading (5000 cycles of ±2 N m pure flexion moment) and subsequent pullout. Screw loosening, failure loads, and energy absorption were calculated. RESULTS: Cyclic loading significantly (P<0.001) reduced screw-bone angular stiffness between prefatigue and postfatigue conditions by 25.6%±17.9% (mid-body), 20.8%±14.4% (pericortical), and 14.0%±13.0% (bicortical). Increased insertion depth resulted in lower levels of reduction in angular stiffness, which was only significant between mid-body and bicortical screws (P=0.009). Pullout force and energy of 583±306 N and 1.75±1.98 N m (mid-body), 713±321 N and 2.40±1.79 N m (pericortical), and 797±285 N and 2.97±2.33 N m (bicortical) were observed, respectively. Increased insertion depth resulted in higher magnitudes of both pullout force and energy, which was significant only for pullout force between mid-body and bicortical screws (P=0.005). CONCLUSION: Although increased screw depth led to increased fixation and decreased loosening, additional purchase of the stiff anterior cortex is essential to reach superior screw-bone construct stability and stiffness.

Finite element model of the knee for investigation of injury mechanisms: development and validation.

Multiple computational models have been developed to study knee biomechanics. However, the majority of these models are mainly validated against a limited range of loading conditions and/or do not include sufficient details of the critical anatomical structures within the joint. Due to the multifactorial dynamic nature of knee injuries, anatomic finite element (FE) models validated against multiple factors under a broad range of loading conditions are necessary. This study presents a validated FE model of the lower extremity with an anatomically accurate representation of the knee joint. The model was validated against tibiofemoral kinematics, ligaments strain/force, and articular cartilage pressure data measured directly from static, quasi-static, and dynamic cadaveric experiments. Strong correlations were observed between model predictions and experimental data (r > 0.8 and p < 0.0005 for all comparisons). FE predictions showed low deviations (root-mean-square (RMS) error) from average experimental data under all modes of static and quasi-static loading, falling within 2.5 deg of tibiofemoral rotation, 1% of anterior cruciate ligament (ACL) and medial collateral ligament (MCL) strains, 17 N of ACL load, and 1 mm of tibiofemoral center of pressure. Similarly, the FE model was able to accurately predict tibiofemoral kinematics and ACL and MCL strains during simulated bipedal landings (dynamic loading). In addition to minimal deviation from direct cadaveric measurements, all model predictions fell within 95% confidence intervals of the average experimental data. Agreement between model predictions and experimental data demonstrates the ability of the developed model to predict the kinematics of the human knee joint as well as the complex, nonuniform stress and strain fields that occur in biological soft tissue. Such a model will facilitate the in-depth understanding of a multitude of potential knee injury mechanisms with special emphasis on ACL injury.

Biomechanical analysis of various footprints of transforaminal lumbar interbody fusion devices.

STUDY DESIGN: A biomechanical finite element modeling study of the human lumbar spine. OBJECTIVE: To evaluate the effects of a transforaminal interbody device's footprint on lumbar spine biomechanics to further examine the potential subtle biomechanical differences not captured in previous studies. SUMMARY OF BACKGROUND DATA: In recent years, the evolution of interbody fusion devices has provided the surgeons with a multitude of options. An articulating transforaminal lumbar interbody fusion (TLIF) device is developed to overcome the surgical challenges associated with insertion of a large footprint interbody device through a small incision. METHODS: A finite element model of the L3-S1 lumbar segment was modified to simulate replacement of various TLIF constructs with different cage designs including an articulating vertebral interbody (AVID) TLIF device and a generic TLIF device placed in different configurations. The instrumented models were subjected to a 400 N follower load along with a 10 N m bending moment at different physiological planes. The kinematics, loads, and stresses were compared among various models. RESULTS: Simulated cage designs provided similar kinematical stability within the treated segments. However, the articulating and double TLIF implants allowed for better load sharing through the anterior column. These implants resulted in lower endplate and pedicle screw stresses and in more homogenous stress distribution across the peripheral region of the endplate. CONCLUSIONS: An articulating, large footprint, peripherally placed TLIF device affords substantial biomechanical advantages. This device may be able to reduce the incidence of subsidence because of its ability to reduce and distribute the endplate stresses in the stronger peripheral region. It may also reduce the posterior hardware failure incidence owing to its ability to reduce the screw stresses as compared with traditional TLIF. Although double TLIF has been demonstrated to have similar biomechanical advantages as the AVID, complications associated with double TLIF (ie, larger surgical incision, longer surgical procedure, placement and alignment challenges) support AVID as a better optimized alternative.

Systematic evaluation of common natural language processing techniques to codify clinical notes.

Proper codification of medical diagnoses and procedures is essential for optimized health care management, quality improvement, research, and reimbursement tasks within large healthcare systems. Assignment of diagnostic or procedure codes is a tedious manual process, often prone to human error. Natural Language Processing (NLP) has been suggested to facilitate this manual codification process. Yet, little is known on best practices to utilize NLP for such applications. With Large Language Models (LLMs) becoming more ubiquitous in daily life, it is critical to remember, not every task requires that level of resource and effort. Here we comprehensively assessed the performance of common NLP techniques to predict current procedural terminology (CPT) from operative notes. CPT codes are commonly used to track surgical procedures and interventions and are the primary means for reimbursement. Our analysis of 100 most common musculoskeletal CPT codes suggest that traditional approaches can outperform more resource intensive approaches like BERT significantly (P-value = 4.4e-17) with average AUROC of 0.96 and accuracy of 0.97, in addition to providing interpretability which can be very helpful and even crucial in the clinical domain. We also proposed a complexity measure to quantify the complexity of a classification task and how this measure could influence the effect of dataset size on model's performance. Finally, we provide preliminary evidence that NLP can help minimize the codification error, including mislabeling due to human error.

Changes in Functional Meniscal Morphology During Skeletal Growth and Maturation.

Background: Little is known on how meniscal morphology develops during skeletal growth and maturation and its subsequent relationship with the corresponding bony anatomy. Hypotheses: (1) Meniscal dimensions and morphology would change by age during skeletal growth and maturation in different ways in boys compared with girls. (2) Morphological features of the medial and lateral menisci would correlate to medial and lateral femoral condyle curvatures. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Anatomic features of the medial and lateral menisci were measured on magnetic resonance imaging scans from 269 unique knees (age, 3-18 years; 51% female) with no prior history of injury, congenital or growth-related skeletal disorders, or bony deformities. Morphological shape-based measurements were normalized to tibial plateau width or determined as ratios of meniscal dimensions. The association between age and anatomy was analyzed with linear regression. Two-way analysis of variance with the Holm-Sídák post hoc method was used to compare anatomy between sexes in different age groups. Linear regression was used to evaluate the relationship between femoral condyle curvature radius and meniscal morphology in each compartment after adjusting for age and sex. Results: Meniscal length, width, horn distance, mean cross-sectional area (CSA), and mean height increased with age in both sexes (R2 > 0.1; P < .001). Age-related changes in meniscal morphology were seen in normalized length, width, horn distance, and mean height; width-to-length ratio; horn distance-to-length ratio (lateral meniscus only); normalized mean CSA (except lateral meniscus in girls); and mean tip angle (R2 > 0.04; P < .02). Sex-based differences were also found, with some morphological differences (normalized length and height) throughout development (P < .03) and size differences (length, width, and mean CSA) in later development (P < .01). After adjusting for age and sex, there were significant correlations between medial condyle curvature radius and normalized width, width-to-length ratio, horn distance, horn distance-to-length ratio, mean CSA, and mean height of the medial meniscus (P≤ .041) and between lateral condyle curvature radius and normalized length, mean height, and mean tip angle of the lateral meniscus (P≤ .004). Conclusion: Age-related changes in meniscal dimensions and morphology, most notably a nonuniform growth pattern in meniscal geometry, occurred during skeletal growth and maturation, with different trends in boys than in girls.