Use of the flat panel detector fluoroscope reduces radiation exposure during periacetabular osteotomy.

The Periacetabular Osteotomy is a technically demanding procedure that requires precise intraoperative evaluation of pelvic anatomy. Fluoroscopic images pose a radiation risk to operating room staff, scrubbed personnel, and the patient. Most commonly, a Standard Fluoroscope with an Image Intensifier is used. Our institution recently implemented the novel Fluoroscope with a Flat Panel Detector. The purpose of this study was to compare radiation dosage and accuracy between the two fluoroscopes. A retrospective review of a consecutive series of patients who underwent Periacetabular Osteotomy for symptomatic hip dysplasia was completed. The total radiation exposure dose (mGy) was recorded and compared for each case from the standard fluoroscope (n = 27) and the flat panel detector (n = 26) cohorts. Lateral center edge angle was measured and compared intraoperatively and at the six-week postoperative visit. A total of 53 patients (96% female) with a mean age and BMI of 17.84 (± 6.84) years and 22.66 (± 4.49) kg/m2 (standard fluoroscope) and 18.23 (± 4.21) years and 21.99 (± 4.00) kg/m2 (flat panel detector) were included. The standard fluoroscope averaged total radiation exposure to be 410.61(± 193.02) mGy, while the flat panel detector averaged 91.12 (± 49.64) mGy (p < 0.0001). The average difference (bias) between intraoperative and 6-week postoperative lateral center edge angle measurement was 0.36° (limits of agreement: - 3.19 to 2.47°) for the standard fluoroscope and 0.27° (limits of agreement: - 2.05 to 2.59°) for the flat panel detector cohort. Use of fluoroscopy with flat panel detector technology decreased the total radiation dose exposure intraoperatively and produced an equivalent assessment of intraoperative lateral center edge angle. Decreasing radiation exposure to young patients is imperative to reduce the risk of future comorbidities.

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.

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.

Investigating iron intake in risk of progression from islet autoimmunity to type 1 diabetes: The diabetes autoimmunity study in the young.

Background: Studies of the role of iron in the risk of type 1 diabetes (T1D) have been inconsistent. Given that iron generates reactive oxygen radicals, which can lead to oxidative damage and apoptosis in the beta cells of the pancreas, we examined whether iron intake was associated with the risk of progressing to T1D in individuals with islet autoimmunity (IA), the pre-clinical phase of T1D. Methods: DAISY is a prospective cohort following 2,547 children at increased risk for IA and progression to T1D. IA is defined as at least two consecutive serum samples positive for at least one autoantibody (insulin, GAD, IA-2, or ZnT8). We measured dietary intake at the time of IA seroconversion in 175 children with IA, and of these, 64 progressed to T1D. We used Cox regression to examine the association between energy-adjusted iron intake and progression to T1D, adjusting for HLA-DR3/4 genotype, race/ethnicity, age at seroconversion, presence of multiple autoantibodies at seroconversion, and multiple vitamin use. In addition, we tested whether this association was modified by vitamin C or calcium intake. Results: In children with IA, high iron intake (as defined as above the 75th percentile, > 20.3 mg/day) was associated with decreased risk of progression to T1D compared to moderate iron intake (as defined by the middle 25-75th percentiles, 12.7-20.3 mg/day) (adjusted hazard ratio (HR): 0.35; 95% confidence interval (CI): 0.15, 0.79). The association between iron intake and T1D was not modified by vitamin C nor calcium intake. In a sensitivity analysis, the removal of six children who had been diagnosed with celiac disease prior to IA seroconversion did not affect this association. Conclusion: Higher iron intake at the time of IA seroconversion is associated with a lower risk of progression to T1D, independent of multivitamin supplement use. Further research that includes plasma biomarkers of iron status is needed to investigate the relationship between iron and the risk of T1D.

Genome-wide analysis of oxylipins and oxylipin profiles in a pediatric population.

Background: Oxylipins are inflammatory biomarkers derived from omega-3 and-6 fatty acids implicated in inflammatory diseases but have not been studied in a genome-wide association study (GWAS). The aim of this study was to identify genetic loci associated with oxylipins and oxylipin profiles to identify biologic pathways and therapeutic targets for oxylipins. Methods: We conducted a GWAS of plasma oxylipins in 316 participants in the Diabetes Autoimmunity Study in the Young (DAISY). DNA samples were genotyped using the TEDDY-T1D Exome array, and additional variants were imputed using the Trans-Omics for Precision Medicine (TOPMed) multi-ancestry reference panel. Principal components analysis of 36 plasma oxylipins was used to capture oxylipin profiles. PC1 represented linoleic acid (LA)- and alpha-linolenic acid (ALA)-related oxylipins, and PC2 represented arachidonic acid (ARA)-related oxylipins. Oxylipin PC1, PC2, and the top five loading oxylipins from each PC were used as outcomes in the GWAS (genome-wide significance: p < 5×10-8). Results: The SNP rs143070873 was associated with (p < 5×10-8) the LA-related oxylipin 9-HODE, and rs6444933 (downstream of CLDN11) was associated with the LA-related oxylipin 13 S-HODE. A locus between MIR1302-7 and LOC100131146, rs10118380 and an intronic variant in TRPM3 were associated with the ARA-related oxylipin 11-HETE. These loci are involved in inflammatory signaling cascades and interact with PLA2, an initial step to oxylipin biosynthesis. Conclusion: Genetic loci involved in inflammation and oxylipin metabolism are associated with oxylipin levels.

Rare Coding Variants in Patients with Non-Syndromic Vestibular Dysfunction.

Vertigo due to vestibular dysfunction is rare in children. The elucidation of its etiology will improve clinical management and the quality of life of patients. Genes for vestibular dysfunction were previously identified in patients with both hearing loss and vertigo. This study aimed to identify rare, coding variants in children with peripheral vertigo but no hearing loss, and in patients with potentially overlapping phenotypes, namely, Meniere's disease or idiopathic scoliosis. Rare variants were selected from the exome sequence data of 5 American children with vertigo, 226 Spanish patients with Meniere's disease, and 38 European-American probands with scoliosis. In children with vertigo, 17 variants were found in 15 genes involved in migraine, musculoskeletal phenotypes, and vestibular development. Three genes, OTOP1, HMX3, and LAMA2, have knockout mouse models for vestibular dysfunction. Moreover, HMX3 and LAMA2 were expressed in human vestibular tissues. Rare variants within ECM1, OTOP1, and OTOP2 were each identified in three adult patients with Meniere's disease. Additionally, an OTOP1 variant was identified in 11 adolescents with lateral semicircular canal asymmetry, 10 of whom have scoliosis. We hypothesize that peripheral vestibular dysfunction in children may be due to multiple rare variants within genes that are involved in the inner ear structure, migraine, and musculoskeletal disease.

Epidemiology of Physeal Fractures and Clinically Significant Growth Disturbances Affecting the Distal Tibia, Proximal Tibia, and Distal Femur: A Retrospective Cohort Study.

INTRODUCTION: Childhood fractures involving the physis potentially result in premature physeal closure that can lead to growth disturbances. Growth disturbances are challenging to treat with associated complications. Current literature focusing on physeal injuries to lower extremity long bones and risk factors for growth disturbance development is limited. The purpose of this study was to provide a review of growth disturbances among proximal tibial, distal tibial, and distal femoral physeal fractures. METHODS: Data were retrospectively collected from patients undergoing fracture treatment at a level I pediatric trauma center between 2008 and 2018. The study was limited to patients 0.5 to 18.9 years with a tibial or distal femoral physeal fracture, injury radiograph, and appropriate follow-up for determination of fracture healing. The cumulative incidence of clinically significant growth disturbance (CSGD) (a growth disturbance requiring subsequent physeal bar resection, osteotomy, and/or epiphysiodesis) was estimated, and descriptive statistics were used to summarize demographics and clinical characteristics among patients with and without CSGD. RESULTS: A total of 1,585 patients met the inclusion criteria. The incidence of CSGD was 5.0% (95% confidence interval, 3.8% to 6.6%). All cases of growth disturbance occurred within 2 years of initial injury. The risk of CSGD peaked at 10.2 years for males and 9.1 years for females. Complex fractures that required surgical treatment, distal femoral and proximal tibial fractures, age, and initial treatment at an outside hospital were significantly associated with an increased risk of a CSGD. DISCUSSION: All CSGDs occurred within 2 years of injury, indicating that these injuries should be followed for a period of at least 2 years. Patients with distal femoral or proximal tibial physeal fractures that undergo surgical treatment are at highest risk for developing a CSGD. LEVEL OF EVIDENCE: Level III Retrospective Cohort Study.

Pediatric and Adult Fracture Incidence: A Decreasing Trend With Increasing Hospital Admissions.

Large-scale studies examining fracture trends and epidemiological data are lacking. The purpose of this study was to evaluate the incidence of fractures presenting to US emergency departments using the National Electronic Injury Surveillance System. A total of 7,109,078 pediatric and 13,592,548 adult patients presenting to US emergency departments with a fracture between 2008 and 2017 were analyzed for patterns. Fractures accounted for 13.9% of pediatric injuries and 15% of adult injuries. Among children, fracture incidence was highest in the group 10 to 14 years old and most frequently involved the forearm (19.0%). Fracture incidence was highest in adults 80 years and older and most frequently involved the lower trunk (16.2%). On average, the rate of pediatric fractures decreased by 2.34% per year (95% CI, 0.25% increase to 4.88% decrease; P=.0757). Among adults, fracture incidence increased 0.33% per year (95% CI, 2.34% decrease to 2.85% increase; P=.7892). This change was significantly different between the pediatric and adult populations (P=.0152). There was an increase in the annual proportion of adults with fractures who were admitted (odds ratio per 1-year increase, 1.05; 95% CI, 1.03-1.07; P<.0001). There was no change in the proportion of pediatric patients with fractures who were admitted (odds ratio, 1.02; 95% CI, 0.99-1.05; P=.0606). The incidence of fractures decreased in pediatric patients yet was relatively stable in adult patients. Conversely, the proportion of patients with fractures who were admitted increased, particularly among adults. These findings may suggest that less severe fractures are presenting elsewhere, falsely inflating the observed rise in admissions. [Orthopedics. 2023;46(6):e369-e375.].

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.

An Oxylipin-Related Nutrient Pattern and Risk of Type 1 Diabetes in the Diabetes Autoimmunity Study in the Young (DAISY).

Oxylipins, pro-inflammatory and pro-resolving lipid mediators, are associated with the risk of type 1 diabetes (T1D) and may be influenced by diet. This study aimed to develop a nutrient pattern related to oxylipin profiles and test their associations with the risk of T1D among youth. The nutrient patterns were developed with a reduced rank regression in a nested case-control study (n = 335) within the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal cohort of children at risk of T1D. The oxylipin profiles (adjusted for genetic predictors) were the response variables. The nutrient patterns were tested in the case-control study (n = 69 T1D cases, 69 controls), then validated in the DAISY cohort using a joint Cox proportional hazards model (n = 1933, including 81 T1D cases). The first nutrient pattern (NP1) was characterized by low beta cryptoxanthin, flavanone, vitamin C, total sugars and iron, and high lycopene, anthocyanidins, linoleic acid and sodium. After adjusting for T1D family history, the HLA genotype, sex and race/ethnicity, NP1 was associated with a lower risk of T1D in the nested case-control study (OR: 0.44, p = 0.0126). NP1 was not associated with the risk of T1D (HR: 0.54, p-value = 0.1829) in the full DAISY cohort. Future studies are needed to confirm the nested case-control findings and investigate the modifiable factors for oxylipins.

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.

Rectus femoris transfers with and without a hamstring lengthening will not change hip kinematics in children with cerebral palsy.

BACKGROUND: A rectus femoris transfer (RFT) surgery with and without a hamstring lengthening (HSL) is used to treat stiff-knee gait in children with cerebral palsy (CP). While current literature has reported that a RFT surgery improves the kinematics at the knee, little is known about the kinematic changes at the hip. RESEARCH QUESTION: Does a RFT surgery change hip joint kinematics in children with CP? METHODS: This retrospective study included children (<18 years old) diagnosed with CP, who underwent a RFT procedure, and who were seen at our institution's accredited clinical motion laboratory. Patients with both pre- and post-operative gait analysis were identified and comparison between those analyses were performed to identify kinematic differences at the hip and knee. A total of 66 legs from 46 children (mean age: 11.1 ± 3.6) met the inclusion criteria. RESULTS: Overall results revealed that a RFT did not change kinematics at the hip [p > 0.05], however, a RFT did increase the maximum knee flexion during the swing period [Mean Difference Post - Pre: 8.3°, 95% CI: 4.9-11.8, p < 0.0001]. Additionally, it was found that changes in hip extension during the terminal stance phase were significantly different between the combined RFT and HSL compared to solely an RFT. The results of this study also revealed that children whose stiff-knee gait did not improve, tended to have increased hip external rotation during terminal stance and swing and greater hip extension during terminal stance, compared to children whose stiff-knee gait did improve. SIGNIFICANCE: Overall, a RFT with and without a HSL surgery improves hip and knee kinematics in the sagittal plane, however, improvements at the hip were not clinically significant. As a result, a RFT or a combined RFT with HSL should not be used to change hip kinematics in children with CP.

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.

7.7% Prevalence of neural axis abnormalities on routine magnetic resonance imaging in patients with presumed adolescent idiopathic scoliosis scheduled for spine surgery: a consecutive single surgeon retrospective cohort of 182 patients.

PURPOSE: The purpose of this study was to use a Delphi analysis to identify a clinically relevant threshold for the prevalence of neural axis abnormalities (NAAs) that would warrant routine preoperative screening. METHODS: A panel of experienced physicians specializing in pediatric spine surgery, pediatric neurosurgery, and pediatric neuroradiology was formed to establish consensus using a Delphi process to identify a minimum prevalence of NAAs that would initiate the implementation of preoperative MRIs as standard of care. Following the Delphi analysis, patients scheduled for PSF (Posterior Spinal Fusion) from 2010 to 2018 were retrospectively identified. Patients were included based on the following criteria: (1) 10-18 years old at time of MRI (inclusive), (2) AIS diagnosis prior to preoperative MRI (no concerning curve pattern, rate of progression, or neurologic signs/symptoms to suggest alternative diagnosis to AIS), and (3) standard preoperative MRI of the cervical, thoracic, and lumbar spine undergone. The prevalence of NAAs on preoperative MRI was recorded for all patients. RESULTS: There were 182 eligible patients. 14 had NAAs on MRI. The prevalence of NAAs was 7.7% [95% CI 4.27-12.57%]. This prevalence was significantly [p < 0.0001] higher than the clinically relevant threshold of 1.3% established by the Delphi panel. Of the 14 patients with NAAs noted on preoperative MRI, neurosurgical intervention was recommended for 4 patients, 2.2% [95% CI 0.6-5.5%] of the total cohort. CONCLUSIONS: Delphi panelists reported a low tolerance for NAAs among patients undergoing PSF for presumed AIS. Group consensus recommended routine screening should be implemented if the prevalence of NAAs is greater than 1.3%. The prevalence of NAAs in our cohort as well as related studies was significantly higher than this threshold. LEVEL OF EVIDENCE: Diagnostic-level III.

Adolescent athletes return to sports rapidly after posterior spine fusion for idiopathic scoliosis: a prospective cohort study.

PURPOSE: No consensus exists regarding the timing for return to sports after PSF for patients with AIS. Return-to-play protocols are based on expert opinion and vary widely. The purpose of this study was to determine how rapidly athletes return to baseline sports activity following posterior spinal fusion for adolescent idiopathic scoliosis. METHODS: Athletes were consecutively enrolled. Inclusion criteria included competition at a junior varsity level or greater for ≥ 3 months yearly, major Cobb angle of 40-75°, age 10-18 years, and one year of follow-up. Athletes completed preoperative sports performance and Patient Reported Outcomes Measurement Information System (PROMIS) physical activity, pain interference, and depressive symptoms questionnaires. Self-assessments were repeated monthly until one year after PSF. RESULTS: Twenty-six athletes were enrolled. The median time to return to sport was 2.7 months [range: 0.6-13 months]. At twelve months, 24 of 26 [90.1%; 95% CI 36.9-74.9%] athletes reported they had returned to the sport at their presurgical level of play. Participation in contact sports was associated with a longer return to sport relative to participation in non-contact/limited contact sports [Hazard Ratio: 0.37, 95% 95% CI 0.14-0.97, p = 0.0427]. Conditioning and flexibility were the most common barriers to return to sport. CONCLUSIONS: When released to unrestricted activity at 4-8 weeks, athletes rapidly return to baseline levels of sports performance, with over half achieving this metric by 3 months.

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.

Changes in the Coexpression of Innate Immunity Genes During Persistent Islet Autoimmunity Are Associated With Progression of Islet Autoimmunity: Diabetes Autoimmunity Study in the Young (DAISY).

Longitudinal changes in gene expression during islet autoimmunity (IA) may provide insight into biological processes that explain progression to type 1 diabetes (T1D). We identified individuals from Diabetes Autoimmunity Study in the Young (DAISY) who developed IA, autoantibodies present on two or more visits. Illumina's NovaSeq 6000 was used to quantify gene expression in whole blood. With linear mixed models we tested for changes in expression after IA that differed across individuals who progressed to T1D (progressors) (n = 25), reverted to an autoantibody-negative stage (reverters) (n = 47), or maintained IA positivity but did not develop T1D (maintainers) (n = 66). Weighted gene coexpression network analysis was used to identify coexpression modules. Gene Ontology pathway analysis of the top 150 differentially expressed genes (nominal P < 0.01) identified significantly enriched pathways including leukocyte activation involved in immune response, innate immune response, and regulation of immune response. We identified a module of 14 coexpressed genes with roles in the innate immunity. The hub gene, LTF, is known to have immunomodulatory properties. Another gene within the module, CAMP, is potentially relevant based on its role in promoting ß-cell survival in a murine model. Overall, results provide evidence of alterations in expression of innate immune genes prior to onset of T1D.

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.

Lower extremity physeal fractures and post-traumatic surgical deformities; National Trauma Data Bank and institutional cohorts.

Background: Pediatric lower extremity physeal fractures carry a risk of developing deformities. Most epidemiological evidence is over 25 years old, single institution, and lacks follow-up, while recent studies report variable results. Understanding their epidemiology and deformity risk is important for patient counseling and follow-up. Methods: The National Trauma Data Bank (NTDB) from 2016 was queried to describe the modern epidemiology of physeal fractures. This was contrasted with our 10-year experience of surgically treated deformities. Basic descriptive statistics, Chi-square analysis, prevalence ratios and multivariable linear regression were used to interpret results. Results: The NTDB contained 22,048 non-physeal and 1,929 physeal fractures of the femur, tibia, and fibula. Physeal fracture prevalence rose after 8 years of age but decreased for girls 2 years sooner than boys. Salter Harris (SH) type 2 fractures predominated. Physeal fractures were more commonly associated with lower energy mechanisms of injury. Distal tibia fractures were more prevalent in the NTDB cohort, while distal femur and SH-1 fractures were more prevalent in the operative cohort. Over 10 years, only 52 (5.3%) of the deformity-correcting surgeries at our institution were for physeal fracture sequelae. Age at injury and intraarticular fractures were associated with shorter times from injury to deformity correction. Conclusion: Lower extremity physeal fractures are uncommon. Fracture pattern prevalence differs from an operative cohort. Proximal tibia physeal fractures appear to be an underappreciated source of deformity. The risk of developing deformity requiring operative intervention appears to be low and is generally treated within 2 years of initial injury.

Twelve-week standard of care protocol longer than median time to normalization among IIc hips treated with Pavlik harness.

Best treatment protocols for infants with developmental dysplasia of the hip (DDH) are poorly defined. This study estimates the time to normalization among Graf IIc hips undergoing Pavlik harness treatment. Following institutional review board approval, patients referred for DDH evaluation at a pediatric institution between 2009 and 2018 (n = 1424 hips/712 patients) were identified. We isolated all Graf IIc hips that underwent Pavlik harness treatment (n = 132 hips/n = 106 patients). Demographic and outcome measures were collected. Normalization was defined as alpha angle greater than or equal to 60° and femoral head coverage greater than or equal to 50%. Kaplan-Meier and Cox proportional hazards regression analyses modeled time to normalization and identified factors associated with earlier normalization. Median time to normalization was 7.0 weeks. At 12 weeks standard treatment, 85.8% [95% confidence interval (CI): 80.2-91.9%] had normalized. Greater femoral head coverage [hazard ratio (HR) per 1% increase: 1.03; 95% CI: 1.01-1.05; P = 0.0068] and hip stability at treatment initiation (HR unstable vs. stable: 0.64; 95% CI: 0.44-0.93; P = 0.0192) were associated with longer time to normalization. Some patients may not need 12 weeks of Pavlik bracing, particularly those with stable presentation who normalize before week 12. Shorter treatment lengths offer benefit without sacrificing long-term outcomes. Findings reinforce growing evidence that femoral head coverage should be a more significant consideration during diagnosis and instability is a concerning finding on examination.