Injury-related cell death and proteoglycan loss in articular cartilage: Numerical model combining necrosis, reactive oxygen species, and inflammatory cytokines.

Osteoarthritis (OA) is a common musculoskeletal disease that leads to deterioration of articular cartilage, joint pain, and decreased quality of life. When OA develops after a joint injury, it is designated as post-traumatic OA (PTOA). The etiology of PTOA remains poorly understood, but it is known that proteoglycan (PG) loss, cell dysfunction, and cell death in cartilage are among the first signs of the disease. These processes, influenced by biomechanical and inflammatory stimuli, disturb the normal cell-regulated balance between tissue synthesis and degeneration. Previous computational mechanobiological models have not explicitly incorporated the cell-mediated degradation mechanisms triggered by an injury that eventually can lead to tissue-level compositional changes. Here, we developed a 2-D mechanobiological finite element model to predict necrosis, apoptosis following excessive production of reactive oxygen species (ROS), and inflammatory cytokine (interleukin-1)-driven apoptosis in cartilage explant. The resulting PG loss over 30 days was simulated. Biomechanically triggered PG degeneration, associated with cell necrosis, excessive ROS production, and cell apoptosis, was predicted to be localized near a lesion, while interleukin-1 diffusion-driven PG degeneration was manifested more globally. Interestingly, the model also showed proteolytic activity and PG biosynthesis closer to the levels of healthy tissue when pro-inflammatory cytokines were rapidly inhibited or cleared from the culture medium, leading to partial recovery of PG content. The numerical predictions of cell death and PG loss were supported by previous experimental findings. Furthermore, the simulated ROS and inflammation mechanisms had longer-lasting effects (over 3 days) on the PG content than localized necrosis. The mechanobiological model presented here may serve as a numerical tool for assessing early cartilage degeneration mechanisms and the efficacy of interventions to mitigate PTOA progression.

Accuracy of volumetric bone mineral density measurement in weight bearing, cone beam computed tomography.

BACKGROUND: Weight bearing computed tomography (WBCT) utilizes cone beam CT technology to provide assessments of lower limb joint structures while they are functionally loaded. Grey-scale values indicative of X-ray attenuation that are output from cone beam CT are challenging to calibrate, and their use for bone mineral density (BMD) measurement remains debatable. To determine whether WBCT can be reliably used for cortical and trabecular BMD assessment, we sought to establish the accuracy of BMD measurements at the knee using modern WBCT by comparing them to measurements from conventional CT. METHODS: A hydroxyapatite phantom with three inserts of varying densities was used to systematically quantify signal uniformity and BMD accuracy across the acquisition volume. We evaluated BMD in vivo (n = 5, female) using synchronous and asynchronous calibration techniques in WBCT and CT. To account for variation in attenuation along the height (z-axis) of acquisition volumes, we tested a height-dependent calibration approach for both WBCT and CT images. RESULTS: Phantom BMD measurement error in WBCT was as high as 15.3% and consistently larger than CT (up to 5.6%). Phantom BMD measures made under synchronous conditions in WBCT improved measurement accuracy by up to 3% but introduced more variability in measured BMD. We found strong correlations (R = 0.96) as well as wide limits of agreement (-324 mgHA/cm3 to 183 mgHA/cm3) from Bland-Altman analysis between WBCT and CT measures in vivo that were not improved by height-dependent calibration. CONCLUSION: Whilst BMD accuracy from WBCT was found to be dependent on apparent density, accuracy was independent of the calibration technique (synchronous or asynchronous) and the location of the measurement site within the field of view. Overall, we found strong correlations between BMD measures from WBCT and CT and in vivo measures to be more accurate in trabecular bone regions. Importantly, WBCT can be used to distinguish between anatomically relevant differences in BMD, however future work is necessary to determine the repeatability and sensitivity of BMD measures in WBCT.

The Inflamma-type: a patient phenotype characterized by a dysregulated inflammatory response after lower extremity articular fracture.

Synovial fluid was collected from 113 patients who had suffered tibial plateau (n = 48), tibial plafond (n = 29), or rotational ankle fractures (n = 36). Concentrations of IL-1ß, IL-1RA, IL-6, IL-8, IL-10, and MMP-1, -3, and -13 were quantified using multiplex assays. A cluster analysis of synovial fluid biomarker concentrations was performed. Patient demographics, fracture type, Injury Severity Score (ISS), Charlson Comorbidity Index (CCI), and biomarker concentrations were compared between clusters. A subset of patients demonstrated a dysregulated inflammatory response after articular fracture including elevated pro-inflammatory cytokines and degradative enzymes previously linked to the development of post-traumatic osteoarthritis.

Surgical Skill Can be Objectively Measured From Fluoroscopic Images Using a Novel Image-based Decision Error Analysis (IDEA) Score.

BACKGROUND: To advance orthopaedic surgical skills training and assessment, more rigorous and objective performance measures are needed. In hip fracture repair, the tip-apex distance is a commonly used summative performance metric with clear clinical relevance, but it does not capture the skill exercised during the process of achieving the final implant position. This study introduces and evaluates a novel Image-based Decision Error Analysis (IDEA) score that better captures performance during fluoroscopically-assisted wire navigation. QUESTIONS/PURPOSES: (1) Can wire navigation skill be objectively measured from a sequence of fluoroscopic images? (2) Are skill behaviors observed in a simulated environment also exhibited in the operating room? Additionally, we sought to define an objective skill metric that demonstrates improvement associated with accumulated surgical experience. METHODS: Performance was evaluated both on a hip fracture wire navigation simulator and in the operating room during actual fracture surgery. After examining fluoroscopic image sequences from 176 consecutive simulator trials (performed by 58 first-year orthopaedic residents) and 21 consecutive surgical procedures (performed by 19 different orthopaedic residents and one attending orthopaedic surgeon), three main categories of erroneous skill behavior were identified: off-target wire adjustments, out-of-plane wire adjustments, and off-target drilling. Skill behaviors were measured by comparing wire adjustments made between consecutive images against the goal of targeting the apex of the femoral head as part of our new IDEA scoring methodology. Decision error metrics (frequency, magnitude) were correlated with other measures (image count and tip-apex distance) to characterize factors related to surgical performance on both the simulator and in the operating room. An IDEA composite score integrating decision errors (off-target wire adjustments, out-of-plane wire adjustments, and off-target drilling) and the final tip-apex distance to produce a single metric of overall performance was created and compared with the number of hip wire navigation cases previously completed (such as surgeon experience levels). RESULTS: The IDEA methodology objectively analyzed 37,000 images from the simulator and 688 images from the operating room. The number of decision errors (7 ± 5 in the operating room and 4 ± 3 on the simulator) correlated with fluoroscopic image count (33 ± 14 in the operating room and 20 ± 11 on the simulator) in both the simulator and operating room environments (R2 = 0.76; p < 0.001 and R2 = 0.71; p < 0.001, respectively). Decision error counts did not correlate with the tip-apex distance (16 ± 4 mm in the operating room and 12 ± 5 mm on the simulator) for either the simulator or the operating room (R2 = 0.08; p = 0.15 and R2 = 0.03; p = 0.47, respectively), indicating that the tip-apex distance is independent of decision errors. The IDEA composite score correlated with surgical experience (R2 = 0.66; p < 0.001). CONCLUSION: The fluoroscopic images obtained in the course of placing a guide wire contain a rich amount of information related to surgical skill. This points the way to an objective measure of skill that also has potential as an educational tool for residents. Future studies should expand this analysis to the wide variety of procedures that rely on fluoroscopic images. CLINICAL RELEVANCE: This study has shown how resident skill development can be objectively assessed from fluoroscopic image sequences. The IDEA scoring provides a basis for evaluating the competence of a resident. The score can be used to assess skill at key timepoints throughout residency, such as when rotating onto/off of a new surgical service and before performing certain procedures in the operating room, or as a tool for debriefing/providing feedback after a procedure is completed.

Influence of subscapularis stiffness with glenosphere lateralization on physiological external rotation limits after reverse shoulder arthroplasty.

BACKGROUND: Repair of the subscapularis following reverse shoulder arthroplasty (RSA) remains a controversial topic among surgeons. Poor rotator cuff muscle quality is associated with increased musculotendinous stiffness, and the subsequent effect of compromised tissue repair on RSA functional outcomes remains unclear. The objective was to investigate the influence of subscapularis stiffness together with glenoid component lateralization on pre- and postimpingement joint mechanics during external rotation after RSA. METHODS: A validated finite element model incorporating the Zimmer Trabecular Metal reverse system was used. The deltoid and subscapularis tendon were tensioned and wrapped around the joint prior to controlled shoulder external rotation. Baseline subscapularis stiffness, determined from cadaveric testing, was varied to 80%, 120% and 140% of baseline, to simulate a range of pliability associated with fatty infiltration and fibrosis. We evaluated the effects of varying subscapularis stiffness and the corresponding variation in joint tension with varying glenosphere lateralization (2, 4, and 10 mm) on the torque required to externally rotate the shoulder and the impingement/subluxation risk. RESULTS: Prior to any impingement, the torques required to externally rotate the shoulder ranged from 22-47 Nm across the range of parameters studied, with the greatest torques required for the 10-mm glenosphere lateralization. The impact of increasing subscapularis stiffness on torque requirements was most pronounced at the 10-mm lateralization, as well. A 20% increase in subscapularis stiffness necessitated a 7%-14% increase in preimpingement torque, whereas a 40% stiffness increase was associated with a 12%-27% increase in torque. Torque was proportional to lateralization. When lateralization was increased from 2 to 4 mm, the preimpingement torque increased by 10%-13%, whereas a 10-mm lateralization necessitated a 35%-62% torque increase relative to 2 mm of lateralization. Increased subscapularis stiffness did not limit impingement-free range of motion or substantially decrease postimpingement subluxation in this model. DISCUSSION: Mechanical gains achieved through lateralization may be hindered by increased torque demands, especially when a stiffer subscapularis is repaired. As lateralization increases subscapularis tension, greater torque is required to externally rotate the shoulder. The torque required for external rotation has been reported between 15-50 Nm. Subscapularis repair with the simulated increases in stiffness requires relative increases in torque that the reconstructed shoulder may not be able to physically produce to rotate the glenohumeral joint, particularly at 10-mm lateralization. These results suggest that subscapularis repair may not be indicated in cases where a lateralized glenoid component is used and the subscapularis is compromised.

Do Skills Acquired from Training with a Wire Navigation Simulator Transfer to a Mock Operating Room Environment?

BACKGROUND: Skills training and simulation play an increasingly important role in orthopaedic surgical education. The intent of simulation is to improve performance in the operating room (OR), a trait known as transfer validity. No prior studies have explored how simulator-based wire navigation training can transfer to higher-level tasks. Additionally, there is a lack of knowledge on the format in which wire navigation training should be deployed. QUESTIONS/PURPOSES: (1) Which training methods (didactic content, deliberate practice, or proficiency-based practice) lead to the greatest improvement in performing a wire navigation task? (2) Does a resident's performance using a wire navigation simulator correlate with his or her performance on a higher-level simulation task in a mock OR involving a C-arm, a radiopaque femur model, and a large soft tissue surrogate surrounding the femur? METHODS: Fifty-five residents from four different medical centers participated in this study over the course of 2 years. The residents were divided into three groups: traditional training (included first-year residents from the University of Iowa, University of Minnesota, and the Mayo Clinic), deliberate practice (included first-year residents from the University of Nebraska and the University of Minnesota), and proficiency training (included first-year residents from the University of Minnesota and the Mayo Clinic). Residents in each group received a didactic introduction covering the task of placing a wire to treat an intertrochanteric fracture, and this was considered traditional training. Deliberate practice involved training on a radiation-free simulator that provided specific feedback throughout the practice sessions. Proficiency training used the same simulator to train on specific components of wire navigation, like finding the correct starting point, to proficiency before moving to assessment. The wire navigation simulator uses a camera system to track the wire and provide computer-generated fluoroscopy. After training, task performance was assessed in a mock OR. Residents from each group were assessed in the mock OR based on their use of fluoroscopy, total time, and tip-apex distance. Correlation analysis was performed to examine the relationship between resident performance on the simulator and in the mock OR. RESULTS: Residents in the two simulation-based training groups had a lower tip-apex distance than those in the traditional training group (didactic training tip-apex distance: 24 ± 7 mm, 95% CI, 20-27; deliberate practice tip-apex distance: 16 ± 5 mm, 95% CI, 13-19, p = 0.001; proficiency training tip-apex distance: 15 ± 4 mm, 95% CI, 13-18, p < 0.001). Residents in the proficiency training group used more images than those in the other groups (didactic training: 22 ± 12 images, p = 0.041; deliberate practice: 19 ± 8 images; p = 0.012, proficiency training: 31 ± 14 images). In the two simulation-based training groups, resident performance on the simulator, that is, tip-apex distance, image use, and overall time, was correlated with performance in the mock OR (r-square = 0.15 [p = 0.030], 0.61 [p < 0.001], and 0.43 [p < 0.001], respectively). CONCLUSIONS: As residency programs are designing their curriculum to train wire navigation skills, emphasis should be placed on providing an environment that allows for deliberate practice with immediate feedback about their performance. Simulators such as the one presented in this study offer a safe environment for residents to learn this key skill. LEVEL OF EVIDENCE: Level II, therapeutic study.

Test-retest reliability of tibiofemoral joint space width measurements made using a low-dose standing CT scanner.

OBJECTIVE: To determine the test-retest reliability of knee joint space width (JSW) measurements made using standing CT (SCT) imaging. SUBJECTS AND METHODS: This prospective two-visit study included 50 knees from 30 subjects (66% female; mean ± SD age 58.2 ± 11.3 years; BMI 29.1 ± 5.6 kg/m2; 38% KL grade 0-1). Tibiofemoral geometry was obtained from bilateral, approximately 20° fixed-flexed SCT images acquired at visits 2 weeks apart. For each compartment, the total joint area was defined as the area with a JSW <10 mm. The summary measurements of interest were the percentage of the total joint area with a JSW less than 0.5-mm thresholds between 2.0 and 5.0 mm in each tibiofemoral compartment. Test-retest reliability of the summary JSW measurements was assessed by intraclass correlation coefficients (ICC 2,1) for the percentage area engaged at each threshold of JSW and root-mean-square errors (RMSE) were calculated to assess reproducibility. RESULTS: The ICCs were excellent for each threshold assessed, ranging from 0.95 to 0.97 for the lateral and 0.90 to 0.97 for the medial compartment. RMSE ranged from 1.1 to 7.2% for the lateral and from 3.1 to 9.1% for the medial compartment, with better reproducibility at smaller JSW thresholds. CONCLUSION: The knee joint positioning protocol used demonstrated high day-to-day reliability for SCT 3D tibiofemoral JSW summary measurements repeated 2 weeks apart. Low-dose SCT provides a great deal of information about the joint while maintaining high reliability, making it a suitable alternative to plain radiographs for evaluating JSW in people with knee OA.

The effect of glenoid component version and humeral polyethylene liner rotation on subluxation and impingement in reverse shoulder arthroplasty.

BACKGROUND: A previously validated finite element modeling approach was used to determine how changes in glenoid component version and polyethylene liner rotation within the humeral component affect the arm abduction angle at which impingement between the inferior glenoid and the polyethylene liner occurs as well as the amount of subluxation generated by that impingement. MATERIALS AND METHODS: Five glenoid component versions (5° anteversion; neutral; 5°, 10°, and 20° retroversion) and 7 polyethylene liner rotations (20° and 10° anterior; neutral; 10°, 20°, 30°, and 40° posterior) were considered, resulting in 35 different clinically representative models. The humerus was internally and externally rotated and extended and flexed, and the resulting impingement and subluxation were measured. To further analyze more global trends and to identify implantations least prone to subluxation, polyethylene liner rotation was additionally varied in coarser 30° increments across the entire 360° range. RESULTS: All subluxation caused by impingement occurred during external rotation and extension, and external rotation produced nearly 10-fold more subluxation than extension. Neutral glenoid component version was associated with the least amount of subluxation for all polyethylene liner rotations. Posteriorly rotated polyethylene liners, which place the thick inferior region of the component away from the scapula, produced the least amount of subluxation. The 90° and 120° posterior liner rotations produced no subluxation, whereas the 30° and 60° anterior liner rotations produced the greatest amount of subluxation. CONCLUSION: These results indicate that rotating modern radially asymmetric humeral polyethylene liners posteriorly can reduce the risk of subluxation leading to dislocation and increase external rotation range of motion.

Objective Structured Assessments of Technical Skills (OSATS) Does Not Assess the Quality of the Surgical Result Effectively.

BACKGROUND: Performance assessment in skills training is ideally based on objective, reliable, and clinically relevant indicators of success. The Objective Structured Assessment of Technical Skill (OSATS) is a reliable and valid tool that has been increasingly used in orthopaedic skills training. It uses a global rating approach to structure expert evaluation of technical skills with the experts working from a list of operative competencies that are each rated on a 5-point Likert scale anchored by behavioral descriptors. Given the observational nature of its scoring, the OSATS might not effectively assess the quality of surgical results. QUESTIONS/PURPOSES: (1) Does OSATS scoring in an intraarticular fracture reduction training exercise correlate with the quality of the reduction? (2) Does OSATS scoring in a cadaveric extraarticular fracture fixation exercise correlate with the mechanical integrity of the fixation? METHODS: Orthopaedic residents at the University of Iowa (six postgraduate year [PGY]-1s) and at the University of Minnesota (seven PGY-1s and eight PGY-2s) undertook a skills training exercise that involved reducing a simulated intraarticular fracture under fluoroscopic guidance. Iowa residents participated three times during 1 month, and Minnesota residents participated twice with 1 month between their two sessions. A fellowship-trained orthopaedic traumatologist rated each performance using a modified OSATS scoring scheme. The quality of the articular reduction obtained was then directly measured. Regression analysis was performed between OSATS scores and two metrics of articular reduction quality: articular surface deviation and estimated contact stress. Another skills training exercise involved fixing a simulated distal radius fracture in a cadaveric specimen. Thirty residents, distributed across four PGY classes (PGY-2 and PGY-3, n = 8 each; PGY-4 and PGY-5, n = 7 each), simultaneously completed the exercise at individual stations. One of three faculty hand surgeons independently scored each performance using a validated OSATS scoring system. The mechanical integrity of each fixation construct was then assessed in a materials testing machine. Regression analysis was performed between OSATS scores and two metrics of fixation integrity: stiffness and failure load. RESULTS: In the intraarticular fracture model, OSATS scores did not correlate with articular reduction quality (maximum surface deviations: R = 0.17, p = 0.25; maximum contact stress: R = 0.22, p = 0.13). Similarly in the cadaveric extraarticular fracture model, OSATS scores did not correlate with the integrity of the mechanical fixation (stiffness: R = 0.10, p = 0.60; failure load: R = 0.30, p = 0.10). CONCLUSIONS: OSATS scoring methods do not effectively assess the quality of the surgical result. Efforts must be made to incorporate assessment metrics that reflect the quality of the surgical result. CLINICAL RELEVANCE: New objective, reliable, and clinically relevant measures of the quality of the surgical result obtained by a trainee are urgently needed. For intraarticular fracture reduction and extraarticular fracture fixation, direct physical measurement of reduction quality and of mechanical integrity of fixation, respectively, meet this need.

Use of mutant 125I-perfringolysin O to probe transport and organization of cholesterol in membranes of animal cells.

Animal cells strictly control the distribution of cholesterol in their organelle membranes. This regulation requires an efficient machinery to transport insoluble cholesterol between organelles. In the present study, we generate an (125)I-labeled mutant version of Perfringolysin O (PFO), a cholesterol-binding protein, and use it to measure cholesterol in the plasma membrane of intact cells. We also purify plasma membranes from the same cells, which allows us to directly relate cholesterol concentration to (125)I-PFO binding. We show that cholesterol is organized in the plasma membrane in a manner that makes it inaccessible to PFO until its concentration exceeds a threshold of 35 mol% of total lipids. This 35% threshold is in striking contrast to the 5% threshold previously found for PFO binding to endoplasmic reticulum membranes. The (125)I-PFO probe also proved useful in monitoring the movement of LDL-derived cholesterol from lysosomes to plasma membranes. Using three different mutant cell lines, we show that this transport requires receptor-mediated uptake of LDL, hydrolysis of LDL-cholesteryl esters in lysosomes, and transfer of the liberated cholesterol to the plasma membrane.

Mechanical tradeoffs associated with glenosphere lateralization in reverse shoulder arthroplasty.

BACKGROUND: Scapular notching in reverse shoulder arthroplasty occurs in up to 97% of patients. Notching is associated with decreased strength and reduced motion and may lead to long-term failure due to polyethylene wear. Many implant systems lateralize the glenosphere to address scapular notching, but the mechanical tradeoffs of lateralization have not been rigorously evaluated. We hypothesized that lateralization would decrease bony impingement but also decrease the mechanical advantage of the deltoid. METHODS: Finite element models were created using the same implants with different amounts of glenoid lateralization: 5 mm of medialization to replicate glenoid erosion, as well as 2.5, 5, 7.5, and 10 mm of lateralization. Tests were performed with static and dynamic scapulae for motion in either the coronal or scapular plane. The angle of impingement between the scapula and the humeral polyethylene was recorded, as was the deltoid force required to elevate the arm. RESULTS: Increasing lateralization decreased impingement while increasing the deltoid force required to elevate the arm. Differences were found between the static and dynamic scapulae, with the dynamic scapula model having increased humeral adduction before impinging. The impingement angle was also substantially affected by the bony prominences on the inferior scapula, showing how individual bony anatomy can affect impingement. CONCLUSION: Lateralization is effective in increasing impingement-free range of motion but also increases the deltoid force required to perform identical tasks. In addition, impingement is determined by scapular motion, which should be included in all shoulder models.

Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria.

The de novo and salvage dTTP pathways are essential for maintaining cellular dTTP pools to ensure the faithful replication of both mitochondrial and nuclear DNA. Disregulation of dTTP pools results in mitochondrial dysfunction and nuclear genome instability due to an increase in uracil misincorporation. In this study, we identified a de novo dTMP synthesis pathway in mammalian mitochondria. Mitochondria purified from wild-type Chinese hamster ovary (CHO) cells and HepG2 cells converted dUMP to dTMP in the presence of NADPH and serine, through the activities of mitochondrial serine hydroxymethyltransferase (SHMT2), thymidylate synthase (TYMS), and a novel human mitochondrial dihydrofolate reductase (DHFR) previously thought to be a pseudogene known as dihydrofolate reductase-like protein 1 (DHFRL1). Human DHFRL1, SHMT2, and TYMS were localized to mitochondrial matrix and inner membrane, confirming the presence of this pathway in mitochondria. Knockdown of DHFRL1 using siRNA eliminated DHFR activity in mitochondria. DHFRL1 expression in CHO glyC, a previously uncharacterized mutant glycine auxotrophic cell line, rescued the glycine auxotrophy. De novo thymidylate synthesis activity was diminished in mitochondria isolated from glyA CHO cells that lack SHMT2 activity, as well as mitochondria isolated from wild-type CHO cells treated with methotrexate, a DHFR inhibitor. De novo thymidylate synthesis in mitochondria prevents uracil accumulation in mitochondrial DNA (mtDNA), as uracil levels in mtDNA isolated from glyA CHO cells was 40% higher than observed in mtDNA isolated from wild-type CHO cells. These data indicate that unlike other nucleotides, de novo dTMP synthesis occurs within mitochondria and is essential for mtDNA integrity.

A Method to Represent Heterogeneous Materials for Rapid Prototyping: The Matryoshka Approach.

PURPOSE: The purpose of this paper is to present a new method for representing heterogeneous materials using nested STL shells, based, in particular, on the density distributions of human bones. DESIGN/METHODOLOGY/APPROACH: Nested STL shells, called Matryoshka models, are described, based on their namesake Russian nesting dolls. In this approach, polygonal models, such as STL shells, are "stacked" inside one another to represent different material regions. The Matryoshka model addresses the challenge of representing different densities and different types of bone when reverse engineering from medical images. The Matryoshka model is generated via an iterative process of thresholding the Hounsfield Unit (HU) data using computed tomography (CT), thereby delineating regions of progressively increasing bone density. These nested shells can represent regions starting with the medullary (bone marrow) canal, up through and including the outer surface of the bone. FINDINGS: The Matryoshka approach introduced can be used to generate accurate models of heterogeneous materials in an automated fashion, avoiding the challenge of hand-creating an assembly model for input to multi-material additive or subtractive manufacturing. ORIGINALITY/VALUE: This paper presents a new method for describing heterogeneous materials: in this case, the density distribution in a human bone. The authors show how the Matryoshka model can be used to plan harvesting locations for creating custom rapid allograft bone implants from donor bone. An implementation of a proposed harvesting method is demonstrated, followed by a case study using subtractive rapid prototyping to harvest a bone implant from a human tibia surrogate.

Research Toward Understanding the Benefits and Limitations of Orthotic Use To Improve Mobility and Balance for Individuals With Neuropathic Conditions.

Background: Walking is a vital activity often compromised in individuals with neuropathic conditions. Charcot-Marie-Tooth (CMT) disease and Cerebral Palsy (CP) are two common neurodevelopmental disabilities affecting gait, predisposing to the risk of falls. With guiding scientific evidence limited, there is a critical need to better understand how surgical correction affects mobility, balance confidence, and gait compared to ankle foot orthosis (AFO) bracing. A systematic approach will enable rigorous collaborative research to advance clinical care. Methods: Key elements of this vision include 1) prospective studies in select patient cohorts to systematically compare conservative vs. surgical management, 2) objective laboratory-based evaluation of patient mobility, balance, and gait using reliable methods, and 3) use of patient-centric outcome measures related to health and mobility. Results: Valid and reliable standardized tests of physical mobility and balance confidence have been described in the literature. They include 1) the four-square step test, a widely used test of balance and agility that predicts fall risk, 2) the self-selected walking velocity, a measure of general mobility able to detect function change with orthosis use, and 3) the activity specific balance confidence scale, a survey instrument that assesses an individual's level of balance confidence during activity. Additionally, motion capture and ground reaction force data can be used to evaluate whole-body motion and loading, with discriminative biomechanical measures including toe clearance during the swing phase of gait, plantarflexion at 50% of swing, peak ankle plantarflexor moment, and peak ankle push-off power. Conclusion: The tools needed to support evidence-based practice and inform clinical decision making in these challenging patient populations are all available. Research must now be conducted to better understand the potential benefits and limitations of AFO use in the context of mobility and balance during gait for individuals with neuropathic conditions, particularly relative to those offered by surgical correction. Clinical Relevance: Following this path of research will provide comparative baseline data on mobility, balance confidence, and gait that can be used to inform an objective criterion-based approach to AFO prescription and the impact of surgical intervention.

Fluoroscopic image-based behavior analysis can objectively explain subjective expert assessment of wire navigation skill.

Psychomotor skill and decision-making efficiency in surgical wire navigation can be objectively evaluated by analysis of intraoperative fluoroscopic image sequences. Prior work suggests that such image-based behavior analysis of operating room (OR) performance can predict performer experience level (R2 = 0.62) and agree with expert opinion (the current standard) on the quality of a final implant construct (R2 = 0.59). However, it is unclear how objective image-based evaluation compares with expert assessments for entire technical OR performances. This study examines the relationships between three key variables: (1) objective image-based criteria, (2) expert opinions, and (3) performing surgeon experience level. A paired-comparison survey of seven experts, based upon eight OR fluoroscopic wire navigation image sequences, shows that the experts' preferences are best explained by objective metrics that reflect psychomotor and decision-making behaviors which are counter-productive to successful implant placement, like image count (R2 = 0.83) and behavior tally (R2 = 0.74). One such behavior, adjustments away from goal, uniquely correlated well with all three key variables: a fluoroscopic image-based analysis composite score (R2 = 0.40), expert consensus (R2 = 0.76), and performer experience (R2 = 0.41). These results confirm that experts view less efficient technical behavior as indicative of lesser technical proficiency. While expert assessments of technical skill were reliable and consistent, neither individual nor consensus expert opinion appears to correlate with performer experience (R2 = 0.11).

Influence of sidewall retention and interference fit in total ankle replacement on implant-bone micromotion: A finite element study.

The success of uncemented total ankle replacement (TAR) is linked to initial stability because bony ingrowth depends upon limited early micromotion. Tibial implant design fixation features resist micromotion aided by bony sidewall retention and interference fit. Our goal was to investigate factors influencing implant-bone micromotion in TAR. Two TAR tibial components were virtually inserted into CT-derived computer models of two distal tibias from patients with end-stage ankle arthritis. Density-based inhomogeneous material assignment was used to model bone compaction during press-fit. Finite element analysis (FEA) was used to simulate three fixation cases: (1) no sidewalls + line-to-line fit, (2) sidewalls + line-to-line fit, and (3) sidewalls + 50, 100, or 200 µm interference fit. Kinetic profiles from the stance phase of gait were simulated and micromotions computed from FEA output. Without sidewalls or interference fit, micromotions were largest in early and late stance, with largest micromotions (averaging ~150-250 µm) observed near heel strike. Micromotions decreased 39%-62% when sidewalls were retained. When interference fit was also modeled, micromotions decreased another 37%-61% to ~10 µm. Micromotion differences between patients persisted with sidewall retention but largely disappeared with interference fit. This study presents new insights into the effects of TAR fixation features on implant-bone micromotion. Stability appeared to be influenced by surrounding bone quality, but this influence was greatly diminished when interference fit was introduced. More complete understanding of TAR implant features and performance is needed, but our results show the importance of bone quality and interference fit in the stability of uncemented TAR.

Foot offloading associated with carbon fiber orthosis use: A pilot study.

BACKGROUND: Traumatic lower limb injuries can result in chronic pain. Orthotic interventions are a leading conservative approach to reduce pain, manage loading, and protect the foot. Robust carbon fiber custom dynamic orthoses (CDOs) designed for military service members have been shown to reduce foot loading. However, the effect of carbon fiber orthosis design, including designs widely used in the civilian sector, on foot loading is unknown. RESEARCH QUESTION: Determine if carbon fiber orthoses alter foot loading during gait. METHODS: Loadsol insoles were used to measure peak forces and force impulse acting on the forefoot, midfoot, hindfoot, and total foot. Nine healthy, able-bodied individuals participated. Force impulse was quantified as cumulative loading throughout stance phase. Participants walked without an orthosis and with three carbon fiber orthoses of differing designs: a Firm stiffness CDO, a Moderate stiffness CDO, and a medial and lateral strut orthosis (MLSO). RESULTS: There were significant main effects of orthosis condition on peak forefoot forces as well as forefoot and hindfoot force impulse. Peak forefoot forces were significantly lower in the Moderate and Firm CDOs compared to no orthosis and MLSO. Compared to walking without an orthosis, forefoot force impulse was significantly lower and hindfoot force impulse was significantly greater in all carbon fiber orthoses. Additionally, hindfoot force impulse in the Firm CDO was significantly higher than in the MLSO and Moderate CDO. SIGNIFICANCE: The three carbon fiber orthosis designs differed regarding foot loading, with more robust orthoses providing greater forefoot offloading. Orthosis-related changes in forefoot loading suggest that carbon fiber orthoses could reduce loading-associated pain during gait. However, increased hindfoot force impulse suggests caution should be used when considering carbon fiber orthoses for individuals at risk of skin breakdown with repetitive loading.

Distal femur fractures: basic science and international perspectives.

Distal femur fractures are challenging injuries to manage, and complication rates remain high. This article summarizes the international and basic science perspectives regarding distal femoral fractures that were presented at the 2022 Orthopaedic Trauma Association Annual Meeting. We review a number of critical concepts that can be considered to optimize the treatment of these difficult fractures. These include biomechanical considerations for distal femur fixation constructs, emerging treatments to prevent post-traumatic arthritis, both systemic and local biologic treatments to optimize nonunion management, the relative advantages and disadvantages of plate versus nail versus dual-implant constructs, and finally important factors which determine outcomes. A robust understanding of these principles can significantly improve success rates and minimize complications in the treatment of these challenging injuries.

Competition between sumoylation and ubiquitination of serine hydroxymethyltransferase 1 determines its nuclear localization and its accumulation in the nucleus.

Serine hydroxymethyltransferase 1 (SHMT1) expression limits rates of de novo dTMP synthesis in the nucleus. Here we report that SHMT1 is ubiquitinated at the small ubiquitin-like modifier (SUMO) consensus motif and that ubiquitination at that site is required for SHMT1 degradation. SHMT1 protein levels are cell cycle-regulated, and Ub-SHMT1 levels are lowest at S phase when SHMT1 undergoes SUMO modification and nuclear transport. Mutation of the SUMO consensus motif increases SHMT1 stability. SHMT1 interacts with components of the proteasome in both the nucleus and cytoplasm, indicating that degradation occurs in both compartments. Ubc13-mediated ubiquitination is required for SHMT1 nuclear export and increases stability of SHMT1 within the nucleus, whereas Ubc9-mediated modification with Sumo2/3 is involved in nuclear degradation. These data demonstrate that SUMO and ubiquitin modification of SHMT1 occurs on the same lysine residue and determine the localization and accumulation of SHMT1 in the nucleus.