The Optimal Age for Surgical Management of DDH Differs by Treatment Method.

BACKGROUND: There is a lack of consensus on the optimal age for specific surgical interventions for developmental dysplasia of the hip. We compared radiographic and clinical outcomes among patients who were treated with closed reduction (CR), open reduction (OR), and open reduction with concomitant pelvic osteotomy (ORP) for the treatment of a dislocated hip. We sought to identify the optimal age at treatment within each of these groups. METHODS: We retrospectively reviewed 256 hips (n=195 patients) who underwent CR (n=96), OR (n=116), or an ORP (n=44) as their index procedure at a single institution between January 1, 2004 and September 23, 2020. Radiographic outcomes included acetabular index, The International Hip Dysplasia Institute classification, and acetabular depth ratio. The incidence of further corrective surgery (FCS), defined as the need for an additional femoral and/or pelvic osteotomy before skeletal maturity, and the optimal age cutoffs for index surgery within each surgical group were determined. RESULTS: After adjusting for age and sex, the incidence of FCS was 13.8% in the CR group, 29.2% in the OR group, and 9.2% in the ORP group. Earlier surgery was protective against FCS in the CR and OR groups. In contrast, patients in the ORP group who were older at index procedure were less likely to undergo FCS. Optimal age at surgery was 9.9 months (CR), 11.5 months (OR), and 21.4 months (ORP). Compared with older patients, younger patients were associated with a larger average decrease in the acetabular index and a larger average increase in acetabular width during the first 5 years post surgery. CONCLUSIONS: Age at index surgical procedure was correlated with both clinical and radiographic outcomes. Age at index procedure did impact the risk of subsequent FCS, particularly in the CR and ORP groups. Based on our analysis, CR should be considered before 9.9 months of age and OR considered before 11.5 months of age to minimize the risk of FCS during childhood. This work highlights the importance of considering age-related heterogeneity in developmental dysplasia of the hip treatment outcomes. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Propensity scores as a novel method to guide sample allocation and minimize batch effects during the design of high throughput experiments.

BACKGROUND: We developed a novel approach to minimize batch effects when assigning samples to batches. Our algorithm selects a batch allocation, among all possible ways of assigning samples to batches, that minimizes differences in average propensity score between batches. This strategy was compared to randomization and stratified randomization in a case-control study (30 per group) with a covariate (case vs control, represented as ß1, set to be null) and two biologically relevant confounding variables (age, represented as ß2, and hemoglobin A1c (HbA1c), represented as ß3). Gene expression values were obtained from a publicly available dataset of expression data obtained from pancreas islet cells. Batch effects were simulated as twice the median biological variation across the gene expression dataset and were added to the publicly available dataset to simulate a batch effect condition. Bias was calculated as the absolute difference between observed betas under the batch allocation strategies and the true beta (no batch effects). Bias was also evaluated after adjustment for batch effects using ComBat as well as a linear regression model. In order to understand performance of our optimal allocation strategy under the alternative hypothesis, we also evaluated bias at a single gene associated with both age and HbA1c levels in the 'true' dataset (CAPN13 gene). RESULTS: Pre-batch correction, under the null hypothesis (ß1), maximum absolute bias and root mean square (RMS) of maximum absolute bias, were minimized using the optimal allocation strategy. Under the alternative hypothesis (ß2 and ß3 for the CAPN13 gene), maximum absolute bias and RMS of maximum absolute bias were also consistently lower using the optimal allocation strategy. ComBat and the regression batch adjustment methods performed well as the bias estimates moved towards the true values in all conditions under both the null and alternative hypotheses. Although the differences between methods were less pronounced following batch correction, estimates of bias (average and RMS) were consistently lower using the optimal allocation strategy under both the null and alternative hypotheses. CONCLUSIONS: Our algorithm provides an extremely flexible and effective method for assigning samples to batches by exploiting knowledge of covariates prior to sample allocation.

DNA Methylation Near DLGAP2 May Mediate the Relationship between Family History of Type 1 Diabetes and Type 1 Diabetes Risk.

Given the differential risk of type 1 diabetes (T1D) in offspring of affected fathers versus affected mothers and our observation that T1D cases have differential DNA methylation near the imprinted DLGAP2 gene compared to controls, we examined whether methylation near DLGAP2 mediates the association between T1D family history and T1D risk. In a nested case-control study of 87 T1D cases and 87 controls from the Diabetes Autoimmunity Study in the Young, we conducted causal mediation analyses at 12 DLGAP2 region CpGs to decompose the effect of family history on T1D risk into indirect and direct effects. These effects were estimated from two regression models adjusted for the human leukocyte antigen DR3/4 genotype: a linear regression of family history on methylation (mediator model) and a logistic regression of family history and methylation on T1D (outcome model). For 8 of the 12 CpGs, we identified a significant interaction between T1D family history and methylation on T1D risk. Accounting for this interaction, we found that the increased risk of T1D for children with affected mothers compared to those with no family history was mediated through differences in methylation at two CpGs (cg27351978, cg00565786) in the DLGAP2 region, as demonstrated by a significant pure natural indirect effect (odds ratio (OR) = 1.98, 95% confidence interval (CI): 1.06-3.71) and nonsignificant total natural direct effect (OR = 1.65, 95% CI: 0.16-16.62) (for cg00565786). In contrast, the increased risk of T1D for children with an affected father or sibling was not explained by DNA methylation changes at these CpGs. Results were similar for cg27351978 and robust in sensitivity analyses. Lastly, we found that DNA methylation in the DLGAP2 region was associated (P<0:05) with gene expression of nearby protein-coding genes DLGAP2, ARHGEF10, ZNF596, and ERICH1. Results indicate that the maternal protective effect conferred through exposure to T1D in utero may operate through changes to DNA methylation that have functional downstream consequences.

Pediatric Pelvic and Acetabular Fractures: Discerning Severity by Classification and Clinical Management.

BACKGROUND: Existing classification systems may not adequately describe the injury patterns seen pelvic ring and acetabular fractures in the skeletally immature population. Pediatric patients, once stabilized, are often transferred for these injuries. We evaluated which commonly used systems correlate with clinical management in pediatric patients, including transfer patterns based on injury severity. METHODS: A retrospective review of patients aged 1 to 15 treated for traumatic pelvic or acetabular fractures over a 10-year period at an academic level I Pediatric Trauma Center reviewed demographic, radiographic, and clinical data. RESULTS: A total of 188 pediatric patients (average age 10.1 y) were included. Increasing injury severity based on classification Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA P <0.001; Young and Burgess P <0.001; Torode/Zieg P <0.001), increasing Injury Severity Score ( P =0.0017), and decreasing hemoglobin levels ( P =0.0144) were significantly associated with operative management. Injury characteristics did not differ between patients who were transferred versus patients who were brought in directly from the field. Air transport was significantly associated with surgical treatment, pediatric intensive care unit admission, polytrauma, and Torode/Zieg classification ( P =0.036, <0.0001, 0.0297, 0.0003, respectively). CONCLUSIONS: Although not fully descriptive of skeletally immature fracture patterns, the AO/OTA and Young and Burgess classification systems adequately assess the severity of pelvic rings and injuries in pediatric patients and predict management patterns. The Torode and Zieg classification also predicts management. In a large cohort, air transport was significantly associated with surgical treatment, need for pediatric intensive care unit stay, the presence of an additional injury, and instability in the Torode and Zieg classification. These findings suggest that air transfers are being utilized to expedite advanced-level care in more severe injuries. Further studies with long-term follow-up are required to assess the clinical outcomes of both nonoperatively and operatively treated pediatric pelvic fractures and to guide both triage and treatment decisions for these rare but severe injuries. LEVEL OF EVIDENCE: Level III.

Prediction of Late Dysplasia Based on Ultrasound and Plain X-Ray at 6 Months.

BACKGROUND: Developmental dysplasia of the hip represents a spectrum of deformity. Residual dysplasia at 2 years of age is associated with an increased risk for osteoarthritis and functional limitations. We compared the prognostic value of 6-month imaging modalities and aimed to identify optimal diagnostic metrics for the prediction of residual dysplasia. METHODS: After IRB approval, patients who underwent Pavlik treatment between 2009 and 2018 with 2-year follow-up were identified. Sonographs [ultrasound (US)] and radiographs (x-ray) were obtained at 6-month and 2-year-old visits. Dysplasia at 2 years was defined as an acetabular index (AI) >24 degrees. Receiver operating characteristic curves were constructed to quantitatively compare the prognostic ability of US and x-ray-based measures at 6 months. Youden's index [(YI) (values range from 0 (poor test) to 1 (perfect test)] was used to evaluate existing cutoffs at 6 months of age (normal measurements: alpha angle (AA) ≥60 degrees, femoral head coverage (FHC) ≥50%, and AI <30 degrees) relative to newly proposed limits. RESULTS: Fifty-nine patients were included, of which 28.8% of patients (95% CI: 17.3 to 40.4%) had acetabular dysplasia at 2 years. After adjusting for sex, AA [Area under the Curve (AUC): 80] and AI (AUC: 79) at 6 months of age were better tests than FHC (AUC: 0.77). Current diagnostic cutoffs for AA (YI: 0.08), AI (YI: 0.0), and FHC (YI: 0.06) at 6 months had poor ability to predict dysplasia at 2 years. A composite test of all measures based on proposed cutoffs (AA ≥73 degrees, FHC > 62% and AI ≤24 degrees) was a better predictor of dysplasia at 2 years (Youden's index (YI): 0.63) than any single metric. CONCLUSIONS: The rate of residual dysplasia remains concerning. The 6-month x-ray and US both play a role in the ongoing management of the developmental dysplasia of the hip. The prediction of dysplasia is maximized when all metrics are considered collectively. Existing parameters were not accurate; We recommend the following cutoffs: AA ≥73 degrees, FHC > 62%, and AI ≤24 degrees. These cutoffs must be validated. LEVEL OF EVIDENCE: Prognostic Level II.

Application of Accepted Use Criteria for the Treatment of Developmental Dysplasia of the Hip Decreases the Number of Infants Treated With a Pavlik Harness.

BACKGROUND: This analysis examined how the application of the American Academy of Orthopedic Surgeons appropriate use criteria (AUC) for developmental dysplasia of the hip in infants would change treatment patterns and outcomes for Graf IIA hips at a single quaternary pediatric hospital. METHODS: After Institutional Review Board approval, patient medical records were reviewed and data were collected. Graf IIa hips were defined as alpha angle (AA) 50 to 59 degrees. AA and femoral head coverage (FHC) were measured from initial and 6-month ultrasounds and acetabular index (AI) was measured from radiographs at 6 months of age. Instability (positive Ortolani and Barlow tests) was noted. On the basis of the American Academy of Orthopedic Surgeons AUC for managing developmental dysplasia of the hip, hips were further categorized as normal (FHC ≥45%), borderline (FHC 35% to 44%), or dysplastic (FHC <35%). RESULTS: Overall, 13% (49/371) of Graf IIa hips (AA 50 to 59 degrees) were dysplastic (FHC <35%). Total 24% (89/371) were clinically unstable. Total 42% (37/89) of unstable Graf IIa hips were dysplastic. Only 4% of stable Graf IIa hips were dysplastic (12/282). Out of 371 Graf IIa hips, 256 were treated with Pavlik harness (n=250) or Rhino brace (n=6). Among stable, nondysplastic (SND) hips (those with normal and borderline FHC≥35%), 33% (52/158) were treated because of a more severe contralateral side. If the AUC had been applied, 67% (106/158) of SND Graf IIa hips would not have been treated. Among the n=162 hips that returned for a 6-month radiograph, there was no difference in AI in the 115 treated and 47 untreated SND hips (mean difference treatment vs. no treatment: -1.5, 95% CI, -3.1 to 0.2, P =0.0808). CONCLUSIONS: Using AUC recommendations, our center could reduce the number of SND Graf IIa hips we treat by 67%. Although 24% of Graf IIa hips were clinically unstable and 13% were dysplastic based on FHC, most Graf IIa hips had normal or borderline FHC per the AUC and may do well with observation and follow-up ultrasound at 12 weeks old. LEVEL OF EVIDENCE: Level III-diagnostic study.

Inverse probability weighting is an effective method to address selection bias during the analysis of high dimensional data.

Omics studies frequently use samples collected during cohort studies. Conditioning on sample availability can cause selection bias if sample availability is nonrandom. Inverse probability weighting (IPW) is purported to reduce this bias. We evaluated IPW in an epigenome-wide analysis testing the association between DNA methylation (261,435 probes) and age in healthy adolescent subjects (n = 114). We simulated age and sex to be correlated with sample selection and then evaluated four conditions: complete population/no selection bias (all subjects), naïve selection bias (no adjustment), and IPW selection bias (selection bias with IPW adjustment). Assuming the complete population condition represented the "truth," we compared each condition to the complete population condition. Bias or difference in associations between age and methylation was reduced in the IPW condition versus the naïve condition. However, genomic inflation and type 1 error were higher in the IPW condition relative to the naïve condition. Postadjustment using bacon, type 1 error and inflation were similar across all conditions. Power was higher under the IPW condition compared with the naïve condition before and after inflation adjustment. IPW methods can reduce bias in genome-wide analyses. Genomic inflation is a potential concern that can be minimized using methods that adjust for inflation.

Ligament-Sparing Volar Radiocarpal Arthrotomy During Distal Radius Fracture Repair: Biomechanical Implications on Wrist Stability in a Cadaveric Model.

PURPOSE: Distal radius (DR) fracture fixation with volar locked plating typically uses indirect fracture reduction without direct visualization of the articular surface in an attempt to preserve the volar radiocarpal ligaments and prevent iatrogenic radiocarpal instability. This study assessed the biomechanical stability after a volar radiocarpal arthrotomy for direct articular visualization for DR fracture repair compared to a standard trans-flexor carpi radialis approach without arthrotomy in a cadaver model. METHODS: Ten fresh-frozen upper extremity matched-pair cadaveric specimens were tested. For each pair, one limb underwent trans-FCR approach with a volar arthrotomy that partially sectioned the long and short radiolunate ligaments to visualize the DR articular surface (Group 1). The contralateral limb underwent standard trans-FCR approach without arthrotomy (Group 2). Following capsular repair (Group 1), all specimens (Groups 1 and 2) underwent biomechanical testing, including axial loading (22.2 N, 44.5 N, 89.0 N, 177.9 N), volar translational, and dorsal translation loading (22.2 N, 44.5 N, 89.0 N) to assess carpal stability using both fluoroscopy and motion capture. Ulnar carpal translation was assessed using the Gilula method, measuring radiographic lunate overhang from the ulnar edge of the lunate fossa relative to the full width of the lunate. Dorsal and volar translation were assessed by measuring lunate overhang with respect to the dorsal or volar radial cortex. To simulate fractures with dorsal radiocarpal ligament disruption, the dorsal capsule was sectioned, and the biomechanical comparisons were repeated. RESULTS: Ulnar translation of the lunate remained below 2 mm for both groups in all testing scenarios. No significant differences were identified in ulnar, volar, or dorsal translation with increasing loads between the groups. CONCLUSIONS: This volar ligament-sparing radiocarpal arthrotomy did not cause biomechanical radiocarpal instability. CLINICAL RELEVANCE: This arthrotomy may provide enhanced visualization of the DR articular surface during fracture fixation without causing iatrogenic wrist instability.

Pediatric Supracondylar Humerus Fracture AAOS Appropriate Use Criteria: Does Treatment at a Pediatric Level I Trauma Center Comply?

BACKGROUND: The primary purpose of this analysis was to compare supracondylar humerus fracture (SCHF) treatment patterns at a single quaternary pediatric hospital relative to the American Academy of Orthopedic Surgeons (AAOS) appropriate use treatment recommendation(s). METHODS: Among all fractures included in the cohort (n=571), the observed treatment approach was evaluated relative to the AAOS "Appropriate" treatment recommendation(s). The proportion, and corresponding 95% confidence interval, of cases that agreed with the "Appropriate" treatment recommendation was estimated. Demographics and clinical characteristics among cases that were managed in accordance with the "Appropriate," "May be Appropriate," or "Rarely Appropriate" were compared. RESULTS: All fractures were treated according to the "Appropriate," "May be Appropriate," or "Rarely Appropriate" AAOS treatment guidelines. The observed treatment among fractures included in the cohort agreed with AAOS "Appropriate" recommendations in 92.1% [95% confidence interval (CI): 89.6%-94.2%] of the cases. Fracture type differed significantly between patients treated according to AAOS "Appropriate" recommendations compared to those treated according to "May be Appropriate," or "Rarely Appropriate" recommendation. CONCLUSIONS: The treatment approach implemented at a single level 1 trauma center was in concordance with the appropriate use criteria treatment recommendations in a significant majority of cases. Fractures not treated according to "Appopriate" recommendations were primarily type IIA injuries, and were treated with closed reduction and casting instead of the recommended closed reduction and percutaneous pinning. LEVEL OF EVIDENCE: Level III.

How Do We Best Educate Our Patients' Caregivers? Comparing the Efficacy of Print Versus Media-based Education Materials in Peripheral Nerve Catheter and Pain Pump Education.

BACKGROUND: Media-based educational materials (EMs) are becoming prominent. The purpose of this study was to compare print versus media-based EMs given to caregivers of pediatric and young adult patients undergoing surgery. We aimed to see whether print or media-based EMs lead to greater caregiver satisfaction, comfort, and preparedness for outpatient peripheral nerve catheter and pain pump management. We also assessed caregiver preference for EM modality. HYPOTHESIS: We hypothesized that media-based EMs would demonstrate greater overall efficacy and thus generate higher caregiver preference. STUDY DESIGN: Randomized control trial. METHODS: After IRB approval, clinicaltrials.gov registration (17-0638), and informed consent, caregivers were randomized to either media or print-based EM groups. Caregivers reviewed their assigned EM and completed a standardized assessment of their comprehension. We assessed caregiver satisfaction, preparedness, and comfort level with the content on a 5-point Likert scale. On postoperative days 1 to 2, caregivers reported satisfaction, comfort, and preference for EM modality. An intent-to-treat analysis was used to compare the 2 groups. RESULTS: From our final cohort of 135 caregivers, we found no difference [P>0.05] in satisfaction, comfort level, level of preparedness, or discharge readiness scores between groups. After the caregivers were given both EMs, they were evenly split in their preference for print (49.6%) versus video (50.4%) based methods. CONCLUSIONS: We did not detect a significant difference in caregiver preference or feelings of preparedness between groups. Interestingly, a significant proportion of caregivers (25%) did not feel comfortable managing the peripheral nerve catheter and its pain pump at home. Future studies should work to improve caregiver comfort with educational content before patient discharge. CLINICAL RELEVANCE: Providers and institutions should feel comfortable providing both print and media-based patient and caregiver education. Caregiver education may be best suited based on caregiver preference of one EM modality versus the other. LEVEL OF EVIDENCE: Level I.

The oxylipin profile is associated with development of type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY).

AIMS/HYPOTHESIS: Oxylipins are lipid mediators derived from polyunsaturated fatty acids. Some oxylipins are proinflammatory (e.g. those derived from arachidonic acid [ARA]), others are pro-resolving of inflammation (e.g. those derived from α-linolenic acid [ALA], docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) and others may be both (e.g. those derived from linoleic acid [LA]). The goal of this study was to examine whether oxylipins are associated with incident type 1 diabetes. METHODS: We conducted a nested case-control analysis in the Diabetes Autoimmunity Study in the Young (DAISY), a prospective cohort study of children at risk of type 1 diabetes. Plasma levels of 14 ARA-derived oxylipins, ten LA-derived oxylipins, six ALA-derived oxylipins, four DHA-derived oxylipins and two EPA-related oxylipins were measured by ultra-HPLC-MS/MS at multiple timepoints related to autoantibody seroconversion in 72 type 1 diabetes cases and 71 control participants, which were frequency matched on age at autoantibody seroconversion (of the case), ethnicity and sample availability. Linear mixed models were used to obtain an age-adjusted mean of each oxylipin prior to type 1 diabetes. Age-adjusted mean oxylipins were tested for association with type 1 diabetes using logistic regression, adjusting for the high risk HLA genotype HLA-DR3/4,DQB1*0302. We also performed principal component analysis of the oxylipins and tested principal components (PCs) for association with type 1 diabetes. Finally, to investigate potential critical timepoints, we examined the association of oxylipins measured before and after autoantibody seroconversion (of the cases) using PCs of the oxylipins at those visits. RESULTS: The ARA-related oxylipin 5-HETE was associated with increased type 1 diabetes risk. Five LA-related oxylipins, two ALA-related oxylipins and one DHA-related oxylipin were associated with decreased type 1 diabetes risk. A profile of elevated LA- and ALA-related oxylipins (PC1) was associated with decreased type 1 diabetes risk (OR 0.61; 95% CI 0.40, 0.94). A profile of elevated ARA-related oxylipins (PC2) was associated with increased diabetes risk (OR 1.53; 95% CI 1.03, 2.29). A critical timepoint analysis showed type 1 diabetes was associated with a high ARA-related oxylipin profile at post-autoantibody-seroconversion but not pre-seroconversion. CONCLUSIONS/INTERPRETATION: The protective association of higher LA- and ALA-related oxylipins demonstrates the importance of both inflammation promotion and resolution in type 1 diabetes. Proinflammatory ARA-related oxylipins may play an important role once the autoimmune process has begun.

Predictors of oxylipins in a healthy pediatric population.

BACKGROUND: Oxylipins are formed from oxidation of omega-6 (n6) and omega-3 (n3) fatty acids (FAs). Evidence for inflammatory effects comes mostly from adults. METHODS: Oxylipins from n6 FA (27 n6-oxylipins) and n3 FA (12 n3-oxylipins) were measured through ultra-high-performance liquid chromatography-mass spectrometry (LC-MS/MS) in plasma from 111 children at risk of type 1 diabetes (age 1-17 years) studied longitudinally. Oxylipin precursor FAs (arachidonic acid, linoleic acid, alpha-linolenic acid, docosahexaenoic acid, eicosapentaenoic acid) were measured in red blood cell (RBC) membrane and plasma. Precursor FAs dietary intake was measured through food frequency questionnaire and environmental tobacco smoke (ETS) through questionnaires. Linear mixed models were used to test oxylipins with predictors. RESULTS: Age associated with 15 n6- and 6 n3-oxylipins; race/ethnicity associated with 3 n6- and 1 n3-oxylipins; sex associated with 2 n6-oxylipins. ETS associated with lipoxin-A4. Oxylipins associated with precursor FAs in plasma more often than RBC. RBC levels and dietary intake of precursor FAs more consistently associated with n3-oxylipins than with n6-oxylipins. CONCLUSIONS: In healthy children, oxylipin levels change with age. Oxylipins associated with precursor FAs more often in plasma than RBC or diet, suggesting that inflammatory regulation leading to FA release into plasma may also be a determinant of oxylipin generation. IMPACT: This is the first study to examine predictors of oxylipins in healthy children at risk of type 1 diabetes. In healthy children at risk of type 1 diabetes, many oxylipins change with age, and most oxylipins do not differ by sex or race/ethnicity. Environmental tobacco smoke exposure was associated with the presence of lipoxin A4. Omega-6- and omega-3-related oxylipin levels were consistently associated with their respective precursor fatty acid levels measured in the plasma. Proportionally more omega-3 compared to omega-6 oxylipins were associated with dietary intake and red blood cell membrane levels of the respective precursor fatty acid.

Comparison of 2D, 3D, and radially reformatted MR images in the detection of labral tears and acetabular cartilage injury in young patients.

OBJECTIVE: The purpose of this study was to compare the utility of two-dimensional high-resolution (2D), 3-dimensional with multiplanar reconstruction (3D MPR), and radially reformatted (RR) MRIs when evaluating the complexities of the hip joint in patients with femoroacetabular impingement (FAI). We hypothesized RR would be superior in detecting labral pathology and 2D would be superior in detecting transition zone and acetabular cartilage injury. MATERIALS AND METHODS: 2D, 3D MPR, and RR MRIs of 33 patients, who later underwent surgical treatment for FAI, were evaluated for sensitivity, specificity, and accuracy. Bland-Altman methods were used to estimate agreement between each method and the gold-standard, arthroscopic visualization of the hip joint, regarding the percentage of the hip joint affected by each injury type. RESULTS: 3D MPR and RR groupings were associated with the highest sensitivity and accuracy for labral injury. 3D MPR demonstrated the smallest bias in assessing the percentage of joint affected by labral injury and was the most accurate in identifying acetabular cartilage injury, whereas RR had the smallest mean difference in assessing the percentage of joint affected by acetabular cartilage injury. 2D was the most accurate in identifying transition zone injuries, while RR was superior in assessing the percentage of the joint affected by transition zone injury. CONCLUSIONS: Our results suggest that including both 3D MPR and RR MRI groupings is favorable for accurate joint visualization and well-informed treatment planning, especially given that labral injury is a main source of pain and dysfunction for FAI patients.

Isometric Cervical Muscular Strength in Pediatric Athletes With Multiple Concussions.

OBJECTIVE: To compare maximal cervical muscle strength among athletes with a history of 2 or more concussions relative to athletes with no history of a previous concussion. DESIGN: Athletes in the 2 groups were frequency-matched. Linear mixed models were used to test for differences in peak isometric flexion, extension, left lateral flexion, and right lateral flexion cervical muscle torque between groups. SETTING: Pediatric sports medicine clinic. PARTICIPANTS: Athletes with a history of multiple concussions (n = 16) and athletes with no previous concussion history (n = 17). INTERVENTIONS (OR ASSESSMENT OF RISK FACTORS OR INDEPENDENT VARIABLES):: Concussion history (group), age, sex, neck girth, and height. MAIN OUTCOME MEASURES: Peak isometric torque measured with a stationary isokinetic dynamometer during a 3-second isometric hold. RESULTS: There was no significant difference in peak flexion [mean difference: 21.2%, 95% confidence interval (CI): -6.6% to 57.4%, P = 0.1413], extension (mean difference: 17%, 95% CI, -6.8% to 47.1%, P = 0.1667), left lateral (mean difference: 4.4%, 95% CI, -16.9% to 31.1%, P = 0.7011), or right lateral (mean difference: 9.3%, 95% CI, -14.5% to 39.8%, P = 0.4627) isometric torque in the concussion group relative to the control group. Across all muscle actions, neck torque was significantly (P < 0.05) higher in male compared with female athletes. Increasing neck girth was also associated with a significant (P < 0.05) increase in neck torque. CONCLUSIONS: There was no evidence of a consistent cervical muscle strength deficit among athletes with a history of 2 or more concussions relative to athletes with no previous history of a concussion. Age, neck girth, and sex were significantly associated with cervical muscle strength. CLINICAL RELEVANCE: Isometric cervical muscle strength testing may not be a reliable test for differentiating athletes with a history of multiple concussions relative to athletes with no history of concussions in the pediatric and adolescent population. Our study presents a reliable methodology for testing cervical muscle strength among young athletes.

Hip Morphology in Early-stage LCPD: Is There an Argument for Anatomic-specific Containment?

BACKGROUND: Early containment surgery has become increasingly popular in Legg-Calvé-Perthes Disease (LCPD), especially for older children. These procedures treat the proximal femur, the acetabulum, or both, and most surgeons endorse the same surgical option regardless of an individual patient's anatomy. This "one-surgery-fits-all" approach fails to consider potential variations in baseline anatomy that may make one option more sensible than another. We sought to describe hip morphology in a large series of children with newly diagnosed LCPD, hypothesizing that variation in anatomy may support the concept of anatomic-specific containment. METHODS: A retrospective review of a prospectively collected multicenter database was conducted for patients aged 6 to 11 at diagnosis. To assess anatomy before significant morphologic changes secondary to the disease itself, only patients in Waldenström stages IA/IB were included. Standard hip radiographic measurements including acetabular index, lateral center-edge angle, proximal femoral neck-shaft angle (NSA), articulotrochanteric quartiles, and extrusion index (EI) were made on printed anteroposterior pelvis radiographs. Age-specific percentiles were calculated for these measures using published norms. Significant outliers (≤10th/≥90th percentile) were reported where applicable. RESULTS: A total of 168 patients with mean age at diagnosis of 8.0±1.3 years met inclusion criteria (81.5% male). Mean acetabular index for the entire cohort was 16.8±4.1 degrees; 58 hips (34.5%) were significantly dysplastic compared with normative data. Mean lateral center-edge angle was 15.9±5.2 degrees at diagnosis; 110 (65.5%) were ≤10th percentile indicating dysplasia (by this metric). Mean NSA overall was 136.5±7.0 degrees. Fifty-one (30.4%) and 20 (11.9%) hips were significantly varus (≤10th percentile) or valgus (≥90th percentile), respectively. Thirty-five hips (20.8%) were the third articulo-trochanteric quartiles or higher suggesting a higher-riding trochanter at baseline. Mean EI was 15.5%±9.0%, while 63 patients (37.5%) had an EI ≥20%. CONCLUSIONS: The present study finds significant variation in baseline anatomy in children with early-stage LCPD, including a high prevalence of coexisting acetabular dysplasia as well as high/low NSAs. These variations suggest that the "one-surgery-fits-all" approach may lack specificity for a particular patient; a potentially wiser option may be an anatomic-specific containment operation (eg, acetabular-sided osteotomy for coexisting dysplasia, varus femoral osteotomy for valgus NSA). LEVEL OF EVIDENCE: Level IV.

DNA methylation near the INS gene is associated with INS genetic variation (rs689) and type 1 diabetes in the Diabetes Autoimmunity Study in the Young.

OBJECTIVE: Mechanisms underlying the role of non-human leukocyte antigen (HLA) genetic risk variants in type 1 diabetes (T1D) are poorly understood. We aimed to test the association between methylation and non-HLA genetic risk. METHODS: We conducted a methylation quantitative trait loci (mQTL) analysis in a nested case-control study from the Dietary Autoimmunity Study in the Young. Controls (n = 83) were frequency-matched to T1D cases (n = 83) based on age, race/ethnicity, and sample availability. We evaluated 13 non-HLA genetic markers known be associated with T1D. Genome-wide methylation profiling was performed on peripheral blood samples collected prior to T1D using the Illumina 450 K (discovery set) and infinium methylation EPIC beadchip (EPIC validation) platforms. Linear regression models, adjusting for age and sex, were used to test to each single nucleotide polymorphism (SNP) -probe combination. Logistic regression models were used to test the association between T1D and methylation levels among probes with a significant mQTL. A meta-analysis was used to combine odds ratios from the two platforms. RESULTS: We identified 10 SNP-methylation probe pairs (false discovery rate (FDR) adjusted P < .05 and validation P < .05). Probes were associated with the GSDMB, C1QTNF6, IL27, and INS genes. The cg03366382 (OR: 1.9, meta-P = .0495), cg21574853 (OR: 2.5, meta-P = .0232), and cg25336198 (odds ratio: 6.6, meta-P = .0081) probes were significantly associated with T1D. The three probes were located upstream from the INS transcription start site. CONCLUSIONS: We confirmed an association between DNA methylation and rs689 that has been identified in related studies. Measurements in our study preceded the onset of T1D suggesting methylation may have a role in the relationship between INS variation and T1D development.

No Difference in Return to Sport and Other Outcomes Between Operative and Nonoperative Treatment of Medial Epicondyle Fractures in Pediatric Upper-Extremity Athletes.

OBJECTIVE: Compare outcomes of operative and nonoperatively managed medial epicondyle fractures in upper-extremity athletes. DESIGN: Retrospective chart review and phone survey. SETTING: Level 1, tertiary-referral pediatric hospital. PATIENTS: Propensity scores (probability of operative treatment) were estimated from a logistic regression model that included sex, age, displacement, limb dominance, and injury severity (presence of an additional fracture, nerve injury, or elbow dislocation). These were used to match subjects in the operative group to the nonoperative group. MAIN OUTCOME MEASURES: Return to sport, duration of time required to return to sport, pain, range of motion (ROM), need for physical therapy, and complications were recorded for both groups. RESULTS: Twenty-eight nonoperative subjects were matched to 14 operative subjects. There was no significant difference in the proportion of subjects who returned to the same sport (92.9% in each group), performance at preinjury level of competition, or median time to return to play (P = 0.7106). There was no significant difference in functional limitations in social-/work-related activities (P > 0.9999), pain in the past 30 days (P = 0.0640), need for physical therapy (P = 0.5680), ROM limitations (P = 0.0988), difficulty in sleeping (P = 0.4773), or complications (P = 0.4081). CONCLUSIONS: Our study found no statistical difference in outcomes or complications between operative and nonoperatively treated moderately displaced medial epicondyle fractures in adolescent upper-extremity athletes. Our data show that similar outcomes may be achieved with both treatment groups for medial epicondyle fractures in upper-extremity athletes.

Can EOS Imaging Substitute for Conventional Radiography in Measurement of Acetabular Morphology in the Young Dysplastic Hip?

BACKGROUND: EOS imaging offers a low-radiation alternative to conventional radiography (CR) and has little to no magnification effects. However, it is unclear how radiographic measures may be affected using EOS. The present study aims to determine the reproducibility of measures of acetabular morphology on EOS images as compared with CR, and to directly compare the 2 imaging modalities. METHODS: A total of 21 consecutive patients (66.7% female; 14.4±4.7 y) indicated for an open hip preservation procedure with both an anterior-posterior pelvis radiograph and EOS image performed preoperatively were included. Three orthopaedic surgeons measured Tönnis angle, lateral center edge angle (LCEA), acetabular depth-width ratio (ADR), and extrusion index (EI). Measurements were performed twice, 2 weeks apart. Reliability between observers and time points was measured using intraclass correlation coefficients, and agreement between time points and modalities was measured using Bland-Altman analysis. RESULTS: On EOS images, inter-rater reliability was 0.86 for Tönnis angle, 0.86 for LCEA, 0.74 for ADR, and 0.93 for EI. On CR, inter-rater reliability was 0.86 for Tönnis anlge, 0.90 for LCEA, 0.82 for ADR, and 0.84 for EI. In the agreement analysis, biases between imaging modalities were observed. On average, raters measured Tönnis angle and EI higher on EOS images than CR (2.22 degrees, 1.09%, respectively); and LCEA and ADR lower on EOS images than CR (1.54 degrees, 1.14% respectively). Limits of agreement (LOA) between modalities were similar to that of LOA observed in intra-rater analysis. CONCLUSIONS: Measures of acetabular morphology performed on EOS images have similarly high intra-rater and inter-rater reliability compared with CR. Measures performed on EOS also have similar intra-rater agreement as compared with CR. Intermodality agreement had similar LOA as intra-rater agreement on either individual imaging modality. Small biases between imaging modalities were detected. LEVELS OF EVIDENCE: Level I-diagnostic study: investigating a diagnostic test.

Fassier-Duval Rod Failure: Is It Related to Positioning in the Distal Epiphysis?

BACKGROUND: The relationship between Fassier-Duval (FD) rod placement and rod failure rates has not previously been quantified. METHODS: Retrospective review was conducted on patients with osteogenesis imperfecta treated with FD rods between 2005 and 2017. Age at first surgery, sex, Sillence type of osteogenesis imperfecta, bisphosphonate treatment, location of rod (side of body and specific bone), and dates of surgeries, radiographs, and rod failures were collected. C-arm images determined rod fixation within the distal epiphysis at the time of surgery. C-arm variables included rod deviation (percent deviation from the midline of the distal epiphysis) and anatomical direction of deviation (anterior/posterior and medial/lateral). X-ray images were examined for rod failure, which was defined as bending, pulling out of the physis, protrusion out of the bone, and/or failure to telescope. Cox proportional hazards regression models were used to compare failure rates with location of placement within the distal epiphysis allowing for clustering of the data by side (left or right) and bone (femur or tibia). RESULTS: The cohort was 13 patients (11 female individuals and 2 male individuals) with a total of 66 rods and 75 surgeries. Mean time from the first surgery to the last follow-up visit was 8.9 years (SD=5 y). There was a 7% increase in hazard of failure per 1-mm increase in antero-posterior (AP) deviation [hazard ratio (HR), 1.07; 95% confidence interval (CI), 1.01-1.14; P=0.029)]. Similarly, there was a 9% increase in hazard of failure for every 1-mm increase in lateral deviation (HR, 1.09; 95% CI, 1.01-1.18; P=0.019). A 12% increase in hazard of failure per 10% increase in deviation from the midline for both AP and lateral radiograph views was also found, although this was only statistically significant for lateral deviation on the AP radiograph view (HR, 1.12; 95% CI, 1.01-1.25; P=0.030). CONCLUSIONS: FD rod placement within the distal epiphysis has significant impact on increasing rod survival. LEVEL OF EVIDENCE: Level III-therapeutic study.

A Pediatric Medial Epicondyle Fracture Cadaveric Study Comparing Standard AP Radiographic View With the Distal Humerus Axial View.

BACKGROUND: Controversy exists with regard to the amount of fracture displacement that warrants surgical fixation of medial epicondyle fractures. Inaccurate determination of degree of displacement on plain radiographs may account for the disputed management. Recently, a novel distal humerus axial radiograph technique has been developed to improve the accuracy of radiographs. The purposes of the study are 2-fold; to identify the anatomic orientation of the medial elbow epicondyle physis in children and to compare the accuracy of determining fracture displacement between axial radiographs and standard anterior-posterior (AP) radiographs in a cadaveric medial epicondyle fracture model. METHODS: Twelve pediatric elbow computed tomographic scans and 19 pediatric elbow magnetic resonance imaging scans were analyzed for the orientation of the medial elbow physis. After determining the correct orientation, 15 adult cadaveric medial epicondyle fracture models were created at displacements of 2, 5, 10 mm, and maximum displacement with elbow at 90 degrees of flexion. A linear mixed model regression analysis was used to compare displacement based on the axial versus the AP radiographic methods. RESULTS: The medial epicondyle physis was found to be a posterior structure angled distally at ~36 degrees (range, 10.7 to 49.6) and angled posteriorly at 45 degrees (range, 32.2 to 59). The AP radiograph significantly underestimated displacement relative to the axial radiograph at 5 mm [mean difference, -1.6; 95% confidence interval (CI), -2.9 to -0.3], at 10 mm (mean difference, -4.5; 95% CI, -5.8 to -3.2 mm), and at maximal displacement (mean, 15 mm; range, 13 to 20 mm) (mean difference, -7.1; 95% CI, -8.3 to -5.8). CONCLUSIONS: The medial epicondyle physis of the distal humerus is a posterior structure angled distally and posteriorly. When displacement was >5 mm, the distal humerus axial radiograph technique was significantly more accurate than the AP radiograph technique at determining actual fracture displacement in our adult cadaveric fracture models. Therefore, we recommend clinicians to include the axial radiograph view during the evaluation of patients with medial epicondyle fractures. CLINICAL RELEVANCE: This study provides further insight into the location and orientation of the medial humeral epicondyle physis, and further supports the improved accuracy of the distal humerus axial radiograph at detecting displacement in medial epicondyle fractures.