Hemiepiphysiodesis for Genu Valgum in Patients With Multiple Hereditary Exostoses.

BACKGROUND: Genu valgum is a well-known feature of multiple hereditary exostoses (MHE). Though prior reports have demonstrated successful treatment with hemiepiphysiodesis, details regarding the correction rate and comparison to an idiopathic population are lacking. This study aimed to detail our institution's experience with guided growth of the knee in patients with MHE and compare this to an idiopathic population. METHODS: All pediatric patients (age 18 and younger) with MHE who underwent lower extremity hemiepiphysiodesis at a tertiary care medical center between January 2016 and December 2022 were retrospectively reviewed. Preoperative and postoperative mechanical lateral distal femoral angle (mLDFA) and medial proximal tibial angle (MPTA, the primary outcomes) were measured in addition to mechanical axis deviation (MAD) and hip-knee-ankle angle (HKA). Patients were 1:2 matched based on age, sex, and physes instrumented to a cohort with idiopathic genu valgum. RESULTS: A total of 21 extremities in 16 patients with MHE underwent hemiepiphysiodesis of the distal femur, proximal tibia, and/or distal tibia. The mean age at surgery was 11.7±2.2 years. Mean MAD corrected from zone 1.9±0.7 to -0.3±1.5, while mLDFA corrected from 83.4±2.9 to 91.7±5.2 degrees and MPTA corrected from 95.3±3.6 to 90.5±4.0 degrees in distal femurs and proximal tibias undergoing guided growth, respectively. Three extremities (14.3%) experienced overcorrection ≥5 degrees managed with observation. There were no differences in correction rates per month for mLDFA (0.54±0.34 vs. 0.51±0.29 degrees, P =0.738) or MPTA (0.31±0.26 vs. 0.50±0.59 degrees, P =0.453) between MHE and idiopathic groups. For 11 extremities in the MHE group with open physes at hardware removal, they experienced a mean recurrence of HKA of 4.0±3.4 degrees at 19-month follow-up. CONCLUSION: Hemiepiphysiodesis corrects lower extremity malalignment in patients with MHE at a similar rate compared with an idiopathic coronal plane deformity population. Rebound deformity of 4 degrees at 19 months after hardware removal in patients with remaining open growth plates should make surgeons conscious of the remaining growth potential when planning deformity correction. LEVEL OF EVIDENCE: Level III.

Simultaneous MPFL reconstruction and guided growth result in low rates of recurrent patellofemoral instability.

PURPOSE: Implant-mediated guided growth (IMGG) is used to address coronal plane deformity in skeletally immature patients. Few studies have reported on IMGG and simultaneous medial patellofemoral ligament (MPFL) reconstruction for paediatric patients with concurrent genu valgum and patellofemoral instability (PFI). This study aimed to report on the outcomes of these simultaneous procedures. MATERIALS AND METHODS: This was a retrospective review of paediatric patients undergoing simultaneous MPFL reconstruction and IMGG between 2016 and 2023. Mechanical lateral distal femoral angle (mLDFA), hip-knee-ankle angle (HKA) and mechanical axis deviation (MAD) were measured on full-length hip-to-ankle plain radiographs. Measurements were taken preoperatively, prior to implant removal and/or at final follow-up with minimum 1-year clinical follow-up. RESULTS: A total of 25 extremities in 22 patients (10 female) underwent simultaneous IMGG and MPFL reconstruction. The mean age at surgery was 12.6 ± 1.7 years. The mean duration of implant retention was 18.6 ± 11.3 months. Nineteen extremities (76%) underwent implant removal by final follow-up. Preoperative HKA corrected from a mean of 5.8 ± 2.3° to -0.8 ± 4.5° at implant removal or final follow-up (p < 0.001), with mLDFA and MAD similarly improving (both p < 0.001). HKA corrected a mean of 0.7 ± 0.9° per month, while mLDFA and MAD corrected a mean of 0.5 ± 0.6°/month and 2 ± 3 mm/month, respectively. At the time of implant removal or final follow-up, 88% of patients demonstrated alignment within 5° of neutral. Only one extremity experienced subsequent PFI (4%). For 14 patients who underwent implant removal with further imaging at a mean of 7.8 ± 4.9 months, only one patient (7%) had a valgus rebound to an HKA > 5°. CONCLUSION: Simultaneous MPFL reconstruction and IMGG provided successful correction of lower extremity malalignment with only one recurrence of PFI. This approach is a reliable surgical option for skeletally immature patients with genu valgum and PFI. LEVEL OF EVIDENCE: Level 4 case series.

Comparative Analysis of Patient-Reported Outcome Measures for Proximal Hamstring Injuries: A Systematic Review.

Background: There is controversy regarding which patient-reported outcome measures (PROMs) should be used for proximal hamstring tendon injuries. Hypothesis: It was hypothesized that (1) most (>50%) of the questions on the 13 most common PROMs for proximal hamstring injuries would demonstrate extensive overlap in the health domains and question categories and (2) each of the PROMs would contain a variable distribution of questions within each health domain. Study Design: Systematic review. Methods: We conducted a literature review through PubMed, Scopus, and CINAHL and identified the 13 most common PROMs for proximal hamstring injuries: Lower Extremity Functional Scale (LEFS), Marx activity rating scale (MARS), 12-item Short Form Survey (SF-12), Tegner activity scale (TAS), Single Assessment Numeric Evaluation (SANE), Perth Hamstring Assessment Tool (PHAT), Proximal Hamstring Injury Questionnaire (PHIQ), modified Harris Hip Score (mHHS), University of California, Los Angeles activity score (UCLA), International Hip Outcome Tool (iHOT-12), Hip Outcome Score (HOS), Sydney Hamstring Origin Rupture Evaluation (SHORE), and Non-Arthritic Hip Score (NAHS). All PROM questions were sorted into 5 health domains (pain, symptoms, activities of daily living, sports, and mindset) and further divided into question categories if they referred to similar tasks or aspects of health. Questions in the same health domain and question category were considered overlapping, and those within a health domain that did not fit into a question category were considered unique. For each PROM, we analyzed the distribution of questions within particular health domains and question categories as well as the amount of overlapping and unique questions. Results: Of the 165 questions evaluated, 116 (70.3%) were overlapping, and 49 (29.7%) were unique. The SF-12 contained the most unique questions (9/12 [75.0%]). The MARS, TAS, SANE, and UCLA had 0 unique questions. The PHIQ and iHOT-12 contained questions in all 5 health domains. The PHAT, SHORE, and NAHS contained questions in every health domain except mindset. The LEFS, MARS, SF-12, TAS, mHHS, SANE, UCLA, and HOS contained questions in ≤3 health domains. Conclusion: The evaluated PROMs had a high degree of overlapping questions (≥50%) and demonstrated a statistically significant variance in the distribution of questions within each health domain.

Comparing Outcomes in Cemented and Press-Fit Hemiarthroplasty.

INTRODUCTION: Arthroplasty has become the standard of care for displaced femoral neck fractures in the geriatric cohort. However, details regarding optimal implant design and fixation strategy continue to be debated. We sought to determine whether cemented or press-fit hemiarthroplasties were more advantageous in terms of revision surgery, contralateral hip fractures, hospital length of stay, mortality rates, and survival. METHODS: All geriatric fragility hip fractures at a level 1 trauma center (2014 to 2019) were retrospectively reviewed for the fracture pattern, fixation methodology, and outcome, yielding 707 femoral neck fractures treated with hemiarthroplasty (309 cemented and 398 press fit). The final follow-up was either date of death or final encounter. Major end points were revision surgery, contralateral fracture, and death. A Z-score test of two proportions was used for dichotomous variables, and a two-tailed t -test was used for continuous variables. Cox proportional hazard was used for revision surgery-free survival between groups, adjusting for age, sex, and American Society of Anesthesiologists status. RESULTS: Patients who underwent press-fit hemiarthroplasty had a significantly higher rate of revision surgery (7.8% vs 3.9%; P = 0.006). Press-fit cases had a trend toward a decreased risk of contralateral fracture (13% vs 9.8%; P = 0.12), although this did not reach significance. Both groups had similar length of stay ( P = 0.08) and death rates ( P = 0.39). Of those who died, there was a trend toward longer survival in patients who received a press-fit hemiarthroplasty (413 vs 615 days; P < 0.001). There was a trend toward longer survival without repeat surgery in the cemented group without reaching significance (hazard ratio, 0.66 [0.34 to 1.23]; P = 0.201). CONCLUSION: In this study, we found a markedly longer survival time after press-fit hemiarthroplasty, which we believe reflects surgeons' tendencies to cement the femoral prosthesis in patients with more comorbidities. However, press-fit hemiarthroplasties were more likely to result in repeat procedures on the same hip. Displaced geriatric femoral neck fractures may benefit from a cemented rather than press-fit hemiarthroplasty.

A Novel MRI Mapping Technique for Evaluating Bone Bruising Patterns Associated With Noncontact ACL Ruptures.

Background: Bone bruise patterns in the knee can aid in understanding the mechanism of injury in anterior cruciate ligament (ACL) ruptures. There is no universally accepted magnetic resonance imaging (MRI) mapping technique to describe the specific locations of bone bruises. Hypothesis: The authors hypothesized that (1) our novel mapping technique would show high interrater and intrarater reliability for the location of bone bruises in noncontact ACL-injured knees and (2) the bone bruise patterns reported from this technique would support the most common mechanisms of noncontact ACL injury, including valgus stress, anterior tibial translation, and internal tibial rotation. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Included were 43 patients who underwent ACL reconstruction between 2018 and 2020, with MRI within 30 days of the injury on a 3.0-T scanner, documentation of a noncontact mechanism of injury, and no concomitant or previous knee injuries. Images were retrospectively reviewed by 2 radiologists blinded to all clinical data. The locations of bone bruises were mapped on fat-suppressed T2-weighted coronal and sagittal images using a novel technique that combined the International Cartilage Repair Society (ICRS) tibiofemoral articular cartilage surgical lesions diagram and the Whole-Organ Magnetic Resonance Imaging Scoring (WORMS) mapping system. Reliability between the reviewers was assessed using the intraclass correlation coefficient (ICC), where ICC >0.90 indicated excellent agreement. Results: The interrater and intrarater ICCs were 0.918 and 0.974, respectively, for femoral edema mapping and 0.979 and 0.978, respectively, for tibial edema mapping. Significantly more bone bruises were seen within the lateral femoral condyle compared with the medial femoral condyle (67% vs 33%; P < .0001), and more bruises were seen within the lateral tibial plateau compared with the medial tibial plateau (65% vs 35%; P < .0001). Femoral bruises were almost exclusively located in the anterior/central regions (98%) of the condyles as opposed to the posterior region (2%; P < .0001). Tibial bruises were localized to the posterior region (78%) of both plateaus as opposed to the anterior/central regions (22%; P < .0001). Conclusion: The combined mapping technique offered a standardized and reliable method for reporting bone bruises in noncontact ACL injuries. The contusion patterns identified using this technique were indicative of the most commonly reported mechanisms for noncontact ACL injuries.

Examining the Bone Bruise Patterns in Multiligament Knee Injuries With Peroneal Nerve Injury.

BACKGROUND: Tibiofemoral bone bruise patterns seen on magnetic resonance imaging (MRI) are associated with ligamentous injuries in the acutely injured knee. Bone bruise patterns in multiligament knee injuries (MLKIs) and particularly their association with common peroneal nerve (CPN) injuries are not well described. PURPOSE: To analyze the tibiofemoral bone bruise patterns in MLKIs with and without peroneal nerve injury. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We retrospectively identified 123 patients treated for an acute MLKI at a level 1 trauma center between January 2001 and March 2021. Patients were grouped into injury subtypes using the Schenck classification. Within this cohort, patients with clinically documented complete (motor and sensory loss) and/or partial CPN palsies on physical examination were identified. Imaging criteria required an MRI scan on a 1.5 or 3 Tesla scanner within 30 days of the initial MLKI. Images were retrospectively interpreted for bone bruising patterns by 2 board-certified musculoskeletal radiologists. The location of the bone bruises was mapped on fat-suppressed T2-weighted coronal and sagittal images. Bruise patterns were compared among patients with and without CPN injury. RESULTS: Of the 108 patients with a MLKI who met the a priori inclusion criteria, 26 (24.1%) were found to have a CPN injury (N = 20 complete; N = 6 partial) on physical examination. For CPN-injured patients, the most common mechanism of injury was high-energy trauma (N = 19 [73%]). The presence of a grade 3 posterolateral corner (PLC) injury (N = 25; odds ratio [OR], 23.81 [95% CI, 3.08-184.1]; P = .0024), anteromedial femoral condyle bone bruising (N = 24; OR, 21.9 [95% CI, 3.40-202.9]; P < .001), or a documented knee dislocation (N = 16; OR, 3.45 [95% CI, 1.38-8.62]; P = .007) was significantly associated with the presence of a CPN injury. Of the 26 patients with CPN injury, 24 (92.3%) had at least 1 anteromedial femoral condyle bone bruise. All 20 (100%) patients with complete CPN injury also had at least 1 anteromedial femoral condyle bone bruise on MRI. In our MLKI cohort, the presence of anteromedial femoral condyle bone bruising had a sensitivity of 92.3% and a specificity of 64.6% for the presence of CPN injury on physical examination. CONCLUSION: In our MLKI cohort, the presence of a grade 3 PLC injury had the greatest association with CPN injury. Additionally, anteromedial femoral condyle bone bruising on MRI was a highly sensitive finding that was significantly correlated with CPN injury on physical examination. The high prevalence of grade 3 PLC injuries and anteromedial tibiofemoral bone bruising suggests that these MLKIs with CPN injuries most commonly occurred from a hyperextension-varus mechanism caused by a high-energy blow to the anteromedial knee.

Measuring Proximal Tibial Metaphyseal Width and Lateral Epiphyseal Height Improves Determination of Remaining Growth in Children.

BACKGROUND: Accurate assessments of skeletal maturity is of critical importance to guide type and timing of orthopaedic surgical interventions. Several quantitative markers of the proximal tibia were recently developed using historical knee radiographs. The purpose of the present study was to determine which marker would be most effective in assessment of full-length radiographs in a modern pediatric patient population. METHODS: All full-length radiographs at our institutions between 2013 and 2018 were reviewed. Inclusion criteria for our study required that the child reached final height as defined by 2 consecutive unchanged heights, at least 6 months apart, after age 16 for boys and 14 for girls. Patients with metabolic bone disease, prior surgery such as epiphysiodesis, or previous infections around the knee were excluded. Summary statistics for each of the 3 proximal tibial ratios were calculated and multiple linear regression was performed with percent of growth remaining as a dependent variable. A recommended regression model is presented and evaluated. RESULTS: A total of 692 full-length radiographs met inclusion criteria. Proximal tibial ratios were calculated and averaged values for each percent of growth remaining was presented. Multiple linear regression demonstrated that using all 3 variables led to overfitting of the model so tibial metaphyseal width/lateral tibial epiphyseal height was selected as the optimal ratio for use by clinicians. The optimal model for determining growth was found to have R2=0.723 in the developmental set and R2=0.762 in an excluded validation set. CONCLUSIONS: This study demonstrates that the proximal tibial metaphyseal width/lateral tibial epiphyseal height is the ideal measurement for clinicians seeking to determine growth remaining in children. It presents average values between 0% and 25% of growth remaining. This study also develops and validates a multivariable regression model for determining percentage of growth remaining in children that will allow for quantitative determination of growth using full-length radiographs. LEVEL OF EVIDENCE: Level III.

The Relationship of Olecranon Apophyseal Ossification and Sanders Hand Scores with the Timing of Peak Height Velocity in Adolescents.

BACKGROUND: The onset of peak height velocity (PHV) guides the timing of interventions in the growing child. The purpose of the present study was to validate the Diméglio olecranon grading system and to compare these scores with the Risser/triradiate closure (TRC), proximal humerus, and Sanders hand scores. METHODS: Eighty children with annual serial radiographs were selected from the Bolton-Brush collection. The olecranon apophysis was graded with use of lateral radiographs of the elbow. The mean age to PHV was determined for each stage, and reliability was calculated with use of an intraclass correlation coefficient (ICC). Olecranon stage was combined with age, sex, and height in a generalized estimating equation (GEE) model to predict PHV. Predictive performance of this model was evaluated with use of tenfold cross-validation such that the model was trained on 90% of the radiographs and was asked to predict the PHV of the remaining 10%. RESULTS: PHV is closely associated with olecranon stage, with stage 1 occurring 3.0 years before PHV and stage 7 occurring 3.4 years after PHV. Stage 5 was found to occur at PHV. Scoring system reliability was high across an array of observers (ICC = 0.85 ± 0.07). The GEE model showed that this olecranon system outperforms the Risser/TRC system in predicting PHV and is comparable with the humerus and Sanders hand systems. When combined with age and sex, the olecranon system successfully predicted PHV such that 62% of PHV predictions were accurate within 6 months and 90% of PHV predictions were accurate within a year. CONCLUSIONS: Our data show that stage 5 occurs at PHV, contrary to previously published data. When combined with age and sex, the olecranon system successfully predicts PHV within a year in 90% of cases, establishing a single lateral view of the olecranon as a simple alternative to more complex grading systems. Last, we describe novel 3 variations in olecranon morphology and provide a guide for accurate olecranon staging. CLINICAL RELEVANCE: Understanding PHV is critical in the treatment of many pediatric orthopaedic disorders. The revised olecranon staging system will allow for more accurate determination of this variable.

Modification and application of the proximal humerus ossification system to adolescent idiopathic scoliosis patients.

PURPOSE: We have previously demonstrated that proximal humeral ossification patterns are reliable for assessing peak height velocity in growing patients. Here, we sought to modify the system by including medial physeal closure and evaluate whether this system combined with the Cobb angle correlates with progression to surgery in patients with adolescent idiopathic scoliosis. METHODS: We reviewed 616 radiographs from 79 children in a historical collection to integrate closure of the medial physis into novel stages 3A and 3B. We then analyzed radiographs from the initial presentation of 202 patients with adolescent idiopathic scoliosis who had either undergone surgery or completed monitoring at skeletal maturity. Summary statistics for the percentage of patients who progressed to the surgical range were calculated for each category of humerus and Cobb angle. RESULTS: The intra-observer and inter-observer ICC for assessment of the medial physis was 0.6 and 0.8, respectively. Only 3.4% of radiographs were unable to be assessed for medial humerus closure. The medial humerus physis begins to close about 1 year prior to the lateral physis and patients with a closing medial physis, but an open lateral physis were found to be the closest to PHV (0.7 years). Stratifying patients by Cobb angle and modified humerus stage yield categories with low and high risks of progression to the surgical range. CONCLUSION: The medial humerus can be accurately evaluated and integrated into a new modified proximal humerus ossification system. Patients with humerus stage 3A or below have a higher rate of progression to the surgical range than those with humerus stage 3B or above.

Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake.

TUG tethering proteins bind and sequester GLUT4 glucose transporters intracellularly, and insulin stimulates TUG cleavage to translocate GLUT4 to the cell surface and increase glucose uptake. This effect of insulin is independent of phosphatidylinositol 3-kinase, and its physiological relevance remains uncertain. Here we show that this TUG cleavage pathway regulates both insulin-stimulated glucose uptake in muscle and organism-level energy expenditure. Using mice with muscle-specific Tug (Aspscr1)-knockout and muscle-specific constitutive TUG cleavage, we show that, after GLUT4 release, the TUG C-terminal cleavage product enters the nucleus, binds peroxisome proliferator-activated receptor (PPAR)γ and its coactivator PGC-1α and regulates gene expression to promote lipid oxidation and thermogenesis. This pathway acts in muscle and adipose cells to upregulate sarcolipin and uncoupling protein 1 (UCP1), respectively. The PPARγ2 Pro12Ala polymorphism, which reduces diabetes risk, enhances TUG binding. The ATE1 arginyltransferase, which mediates a specific protein degradation pathway and controls thermogenesis, regulates the stability of the TUG product. We conclude that insulin-stimulated TUG cleavage coordinates whole-body energy expenditure with glucose uptake, that this mechanism might contribute to the thermic effect of food and that its attenuation could promote obesity.

The More the Merrier: Integrating Multiple Models of Skeletal Maturity Improves the Accuracy of Growth Prediction.

BACKGROUND: Multiple systems using radiographic skeletal markers to measure development have been described, including the Greulich and Pyle Atlas (GP), the Fels Method (Fels), and the Sanders Hand Classification (Sanders). The purpose of this study was to quantitatively assess whether the integration of skeletal maturity assessment methods and demographic variables improves the accuracy of pediatric growth predictions over the use of skeletal markers or chronologic age alone. METHODS: The Brush Inquiry contains prospectively collected longitudinal data on children who lived in Cleveland, Ohio between 1926 and 1942. A total of 16 boys and 29 girls were selected for study. All had age, height, and an anteroposterior radiograph of the hand at each of 3 visits. Those visits occurred at 85%, 90%, and 95% of final height. We determined the growth completed at each visit by dividing the height observed by the final height at skeletal maturity. Boys and girls were analyzed separately using chronologic age, height, GP, Fels, and Sanders. The residual difference between the height predicted and actual height, as well as the SD of the prediction error of the cohort at each time point was calculated. To account for multiple visits from each subject, all linear models were produced using the generalized estimating equations (GEEs) procedure. RESULTS: For boys, age, GP, and Fels performed similarly in predicting growth remaining at all 3 time points. For girls, age, GP, and Fels performed similarly in predicting growth remaining at the 85% and 95% time points; however, the Fels Method demonstrated improved performance at the 90% time point compared with chronologic age (P = 0.0076) and GP alone (P = 0.0155). For both boys and girls, the most accurate multivariate GEE model with the lowest SD of prediction error integrated Fels, age, GP, Sanders, and height. CONCLUSIONS: The most accurate multivariate GEE model of growth prediction for both boys and girls integrated Fels, age, GP, Sanders, and height. When calculating the amount of growth remaining, it is prudent to integrate multiple systems for greater predictive accuracy. LEVEL OF EVIDENCE: Level III.

Reliable skeletal maturity assessment for an AIS patient cohort: external validation of the proximal humerus ossification system (PHOS) and relevant learning methodology.

STUDY DESIGN: Validation of classification system. OBJECTIVES: To externally validate the Proximal Humerus Ossification System (PHOS) as a reliable skeletal maturity scoring system and to assess the learning curve associated with teaching the procedure to individuals of varying levels of experience. BACKGROUND: Assessment of skeletal maturity is essential for treatment decisions in Adolescent Idiopathic Scoliosis (AIS). PHOS is a five-stage system that uses the proximal humeral physis in assessing skeletal maturity and has been shown to reliably grade skeletal age leading up to and beyond peak growth age (PGA). This system is advantageous in the AIS patient, as it is often captured in standard scoliosis films. METHODS: A medical student, an orthopedic surgery resident (PGY-2), spine fellow, and experienced scoliosis surgeon in his 25th year in practice were given a three-slide PHOS learning module. Each participant rated 100 X-rays on two separate occasions, separated by 1 week. Intra- and inter-observer reliability, as well as cross-institutional reliability, were calculated using intraclass correlation coefficients (ICC) with 95% confidence intervals [CI95]. RESULTS: Average intra-observer reliability ICC between scoring sessions was 0.94 [0.92, 0.96] and inter-observer reliability by level of training were 0.94 [0.91, 0.96], 0.93 [0.9, 0.95], 0.94 [0.91, 0.96], 0.96 [0.94, 0.97] for the medical student, PGY-2, fellow, and attending, respectively. Reliability across institutions was 0.99 [0.98, 0.99]. Combined rating observations (n = 400) showed 82% exact matches, as well as 17% and 1% mismatches by 1 and 2 stages, respectively. Similar to the PHOS developers, we found PHOS stage 3 to occur immediately after PGA. CONCLUSION: PHOS is easily learned and employed by raters with varying levels of training. It comprises a five-stage system to reliably measure bone age leading up to PGA and thereafter. This new system relies on visualization of the proximal humerus, which is readily available on standard scoliosis X-rays. LEVEL OF EVIDENCE: Level III.

Predicting Growth Quantitatively Through Proximal Tibia Radiograph Markers.

BACKGROUND: The creation of accurate markers for skeletal maturity has been of significant interest to orthopaedic surgeons. They guide the management of diverse disorders such as adolescent idiopathic scoliosis, leg length discrepancy, cruciate ligament injuries, and slipped capital femoral epiphysis. Multiple systems have been described to predict growth using radiographic skeletal markers; however, no such system has yet been developed for the proximal tibia. The purpose of this study was to establish quantitative radiographic parameters within the proximal tibia that can be used to assess degree of skeletal maturity. METHODS: From the Bolton Brush collection, 94 children, consisting of 49 girls and 4 boys between the ages of 3 and 18 years old, were followed annually throughout growth with serial radiographs and physical examinations. Final height at maturity was used to calculate the growth remaining at each visit. Multiple measurements for each knee radiograph were performed and correlated with the percentage of growth remaining. Tibial epiphysis width, tibial metaphysis width, and height of the lateral tibial epiphysis were measured on each film and the composite ratios between each of these sets of variables along with their respective accuracy and reliability were calculated. Single and multiple linear regression models were constructed to determine accuracy of prediction. Interobserver and intraobserver studies were performed with 4 investigators ranging from medical student to senior attending and calculated using the intraclass correlation coefficient. All 4 examiners measured all of the subjects and the ratios created were averaged. RESULTS: Tibial epiphysis width, tibial metaphysis width, and height of the lateral tibial epiphysis were all found to be strongly correlated with growth remaining with R values ranging from 0.57 to 0.84. In addition, all 3 ratios were found to be reliable with intraobserver and interobserver intraclass correlation coefficients ranging from 0.92 to 0.94 and 0.80 to 0.94, respectively. A multiple linear regression model demonstrated that combining these 3 ratios allows for a predictive R value of 0.917, showing that these ratios when combined were highly predictive of growth remaining. All findings were independent of sex (P=0.996). CONCLUSIONS: We describe 3 measurements that can easily be obtained on an anteroposterior radiograph of the knee. We demonstrate that ratios of these variables can be measured reliably and correlate closely with remaining growth, independent of sex. Together, we believe that these factors will improve the accuracy of determining growth from lower extremity radiographs that include the proximal tibia. CLINICAL RELEVANCE: This study provides a new quantitative technique to evaluate growth in the lower extremity, which can inform a range of conditions including adolescent idiopathic scoliosis, leg length discrepancy, cruciate ligament injury, and slipped capital femoral epiphyses.

Reliability of Radiographic Union Scoring in Humeral Shaft Fractures.

OBJECTIVES: To establish the reliability of 2 radiographic union scoring systems for nonoperative humeral shaft fractures. DESIGN: Retrospective medical record review. Patients identified had humeral shaft fractures and radiographs at various follow-up time points, which were graded according to the both the standard (RUST) and modified radiographic union scoring systems (mRUST). SETTING: A single North American Level-1 Trauma center in Connecticut, including emergency department and clinic follow-up visits. PATIENTS/PARTICIPANTS: Forty-five adult patients (162 image sets) met the following inclusion criteria: diaphyseal humerus fracture, initial nonoperative management, and greater than 2 weeks of follow-up with imaging. INTERVENTION: All 162 image sets of anterior-posterior and lateral radiographs were scored and divided into 4 tiers based on increasing score. Anterior-posterior and lateral image sets were randomly selected from each tier for a total of 50 that were then scored by 7 different reviewers using both the RUST and mRUST systems. MAIN OUTCOME MEASURES: The intraclass correlation coefficients for the cortical and system scores for the RUST and mRUST systems. RESULTS: Interobserver reliability was 0.795 for the RUST system and 0.801 for mRUST. Intraobserver reliability was 0.909 for RUST and 0.949 for mRUST. For mRUST, 92% of values were within ± 1 point from each other. CONCLUSIONS: The RUST and mRUST systems can be applied to humeral shaft fractures with excellent reliability. They have the potential to assist in the diagnosis of humeral shaft union by providing an objective and standardized method to assess healing of bone over time.

Vasopressin inactivation: Role of insulin-regulated aminopeptidase.

The physiological importance of vasopressin inactivation has long been appreciated, but the mechanisms and potential pathophysiologic roles of this process remain active subjects of research. Human Placental Leucine Aminopeptidase (P-LAP, encoded by the LNPEP gene) is an important determinant of vasopressinase activity during pregnancy and is associated with gestational diabetes insipidus and preeclampsia. Insulin-Regulated Aminopeptidase (IRAP), the rodent homologue of P-LAP, is coregulated with the insulin-responsive glucose transporter, GLUT4, in adipose and muscle cells. Recently, the Tether containing a UBX domain for GLUT4 (TUG) protein was shown to mediate the coordinated regulation of water and glucose homeostasis. TUG sequesters IRAP and GLUT4 intracellularly in the absence of insulin. Insulin and other stimuli cause the proteolytic cleavage of TUG to mobilize these proteins to the cell surface, where IRAP acts to terminate the activity of circulating vasopressin. Intriguingly, genetic variation in LNPEP is associated with the vasopressin response and mortality during sepsis, and increased copeptin, a marker of vasopressin secretion, is associated with cardiovascular and metabolic disease. We propose that in the setting of insulin resistance in muscle, increased cell-surface IRAP and accelerated vasopressin degradation cause a compensatory increase in vasopressin secretion. The increased vasopressin concentrations present at the kidneys then contribute to hypertension in the metabolic syndrome. Further analyses of metabolism and of vasopressin and copeptin may yield novel insights into a unified pathophysiologic mechanism linking insulin resistance and hypertension, and potentially other components of the metabolic syndrome, in humans.

The Proximal Humeral Ossification System Improves Assessment of Maturity in Patients with Scoliosis.

BACKGROUND: We recently developed a classification system to assess skeletal maturity by scoring proximal humeral ossification in a similar way to the canonical Risser sign. The purpose of the present study was to determine whether our system can be used to reliably assess radiographs of the spine for modern patients with idiopathic scoliosis, whether it can be used in combination with the Sanders hand system, and whether the consideration of patient factors such as age, sex, and standing height improves the accuracy of predictions. METHODS: We retrospectively reviewed 414 randomized radiographs from 216 modern patients with scoliosis and measured reliability with use of the intraclass correlation coefficient (ICC). We then analyzed 606 proximal humeral radiographs for 70 children from a historical collection to determine the value of integrating multiple classification systems. The age of peak height velocity (PHV) was predicted with use of linear regression models, and performance was evaluated with use of tenfold cross-validation. RESULTS: The proximal humeral ossification system demonstrated excellent reliability in modern patients with scoliosis, with an ICC of 0.97 and 0.92 for intraobserver and interobserver comparisons, respectively. The use of our system in combination with the Sanders hand system yielded 7 categories prior to PHV and demonstrated better results compared with either system alone. Linear regression algorithms showed that integration of the proximal part of the humerus, patient factors, and other classification systems outperformed models based on canonical Risser and triradiate-closure methods. CONCLUSIONS: Humeral head ossification can be reliably assessed in modern patients with scoliosis. Furthermore, the system described here can be used in combination with other parameters such as the Sanders hand system, age, sex, and height to predict PHV and percent growth remaining with high accuracy. CLINICAL RELEVANCE: The proximal humeral ossification system can improve the prediction of PHV in patients with scoliosis on the basis of a standard spine radiograph without a hand radiograph for the determination of bone age. This increased accuracy for predicting maturity will allow physicians to better assess patient maturity relative to PHV and therefore can help to guide treatment decision-making without increasing radiation exposure, time, or cost. The present study demonstrates that assessment of the proximal humeral physis is a viable and valuable aid in the determination of skeletal maturity as obtained from radiographs of the spine that happen to include the shoulder in adolescent patients with idiopathic scoliosis.

GLUT4 Storage Vesicles: Specialized Organelles for Regulated Trafficking.

Fat and muscle cells contain a specialized, intracellular organelle known as the GLUT4 storage vesicle (GSV). Insulin stimulation mobilizes GSVs, so that these vesicles fuse at the cell surface and insert GLUT4 glucose transporters into the plasma membrane. This example is likely one instance of a broader paradigm for regulated, non-secretory exocytosis, in which intracellular vesicles are translocated in response to diverse extracellular stimuli. GSVs have been studied extensively, yet these vesicles remain enigmatic. Data support the view that in unstimulated cells, GSVs are present as a pool of preformed small vesicles, which are distinct from endosomes and other membrane-bound organelles. In adipocytes, GSVs contain specific cargoes including GLUT4, IRAP, LRP1, and sortilin. They are formed by membrane budding, involving sortilin and probably CHC22 clathrin in humans, but the donor compartment from which these vesicles form remains uncertain. In unstimulated cells, GSVs are trapped by TUG proteins near the endoplasmic reticulum - Golgi intermediate compartment (ERGIC). Insulin signals through two main pathways to mobilize these vesicles. Signaling by the Akt kinase modulates Rab GTPases to target the GSVs to the cell surface. Signaling by the Rho-family GTPase TC10α stimulates Usp25m-mediated TUG cleavage to liberate the vesicles from the Golgi. Cleavage produces a ubiquitin-like protein modifier, TUGUL, that links the GSVs to KIF5B kinesin motors to promote their movement to the cell surface. In obesity, attenuation of these processes results in insulin resistance and contributes to type 2 diabetes and may simultaneously contribute to hypertension and dyslipidemia in the metabolic syndrome.

Changes in Proximal Femoral Shape During Fetal Development.

BACKGROUND: Walker and Goldsmith's classic article on fetal hip joint development reported that neck/shaft angle did not change from 12 weeks of gestational age through term while version increased from 0 to 40 degrees. This suggests no change in coronal alignment during development, a conclusion we dispute. By re-examining their data, we found that the true neck/shaft angle (tNSA) decreased by 7.5 degrees as version increased by 40 degrees from 12 weeks of gestational age to term. METHODS: Four investigators measured both femoral version and neck-shaft angle from photographs published by the authors of femurs at multiple stages of maturation from 12 weeks of gestational age to term. The tNSAs and inclination angles were calculated for each femur illustrated using previously validated formula. Changes in the morphology of the femur over time were analyzed using a Student t test. Interobserver and intraobserver reliability were also determined by the Pearson R coefficient. RESULTS: As reported by Walker and Goldsmith, apparent neck/shaft angle (aNSA) did not significantly change during maturation, whereas version increased by 40 degrees. However, tNSA decreased by 7.5 degrees during maturation, while the inclination increased by 32 degrees over the same period. This paper demonstrates angular changes in both the coronal and transverse planes with a 4:1 ratio of angular change in the transverse and coronal planes respectively. Interobserver Pearson coefficient R=0.98 and an intraobserver Pearson coefficient R=0.99. CONCLUSIONS: Although Walker and Goldsmith reported angular changes only in the transverse plane, we conclude that they identified angular changes in both the coronal and transverse planes. Here we show it is mathematically necessary for tNSA to decrease, if aNSA remains constant as version increases. CLINICAL RELEVANCE: A reader who is not well versed in the difference between aNSA and tNSA or version and inclination cannot appreciate what Walker and Goldsmith presented. Surgeons operating on the proximal femur also benefit from understanding these distinctions.

Humeral Head Ossification Predicts Peak Height Velocity Timing and Percentage of Growth Remaining in Children.

BACKGROUND: Understanding skeletal maturity is important in the management of idiopathic scoliosis. Iliac apophysis, triradiate cartilage, hand, and calcaneal ossification patterns have previously been described to assess both peak height velocity (PHV) and percent growth remaining; however, these markers may not be present on standard spine radiographs. The purpose of this study was to describe a novel maturity assessment method based on proximal humeral epiphyseal ossification patterns. METHODS: Ninety-four children were followed at least annually throughout growth with serial radiographs and physical examinations. The PHV of each child was determined by measuring the change in height observed at each visit and adjusting for the interval between visits. Percent growth remaining was determined by comparing current to final standing height. The humeral head periphyseal ossification was grouped into stages by 8 investigators ranging from medical student to attending surgeon. RESULTS: The morphologic changes involving the proximal humeral physis were categorized into 5 stages based on development of the humeral head epiphysis and fusion of the lateral margin of the physis. Our novel classification scheme was well distributed around the PHV and reliably correlated with age of peak growth and percent growth remaining with >70% nonoverlapping interquartile ranges. Furthermore, the scheme was extremely reliable with intraclass correlation coefficients of 0.96 and 0.95 for intraobserver and interobserver comparisons, respectively. CONCLUSIONS: The humeral head classification system described here was strongly correlated with age of PHV as well as percentage growth remaining. Furthermore, the staging system was extremely reliable in both interobserver and intraobserver correlations suggesting that it can be easily generalized. CLINICAL RELEVANCE: As a view of the humeral head is almost always present on standard scoliosis spine x-ray at our institution, our classification can be easily adapted by surgeons to gain additional insight into skeletal maturity of patients with scoliosis. We believe that our method will significantly improve the evaluation of the child with scoliosis without increasing radiation exposure, time, or cost.

Usp25m protease regulates ubiquitin-like processing of TUG proteins to control GLUT4 glucose transporter translocation in adipocytes.

Insulin stimulates the exocytic translocation of specialized vesicles in adipocytes, which inserts GLUT4 glucose transporters into the plasma membrane to enhance glucose uptake. Previous results support a model in which TUG (Tether containing a UBX domain for GLUT4) proteins trap these GLUT4 storage vesicles at the Golgi matrix and in which insulin triggers endoproteolytic cleavage of TUG to translocate GLUT4. Here, we identify the muscle splice form of Usp25 (Usp25m) as a protease required for insulin-stimulated TUG cleavage and GLUT4 translocation in adipocytes. Usp25m is expressed in adipocytes, binds TUG and GLUT4, dissociates from TUG-bound vesicles after insulin addition, and colocalizes with TUG and insulin-responsive cargoes in unstimulated cells. Previous results show that TUG proteolysis generates the ubiquitin-like protein, TUGUL (for TUGubiquitin-like). We now show that TUGUL modifies the kinesin motor protein, KIF5B, and that TUG proteolysis is required to load GLUT4 onto these motors. Insulin stimulates TUG proteolytic processing independently of phosphatidylinositol 3-kinase. In nonadipocytes, TUG cleavage can be reconstituted by transfection of Usp25m, but not the related Usp25a isoform, together with other proteins present on GLUT4 vesicles. In rodents with diet-induced insulin resistance, TUG proteolysis and Usp25m protein abundance are reduced in adipose tissue. These effects occur soon after dietary manipulation, prior to the attenuation of insulin signaling to Akt. Together with previous data, these results support a model whereby insulin acts through Usp25m to mediate TUG cleavage, which liberates GLUT4 storage vesicles from the Golgi matrix and activates their microtubule-based movement to the plasma membrane. This TUG proteolytic pathway for insulin action is independent of Akt and is impaired by nutritional excess.