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.

Phospholipid Levels at Seroconversion Are Associated With Resolution of Persistent Islet Autoimmunity: The Diabetes Autoimmunity Study in the Young.

Reversion of islet autoimmunity (IA) may point to mechanisms that prevent IA progression. We followed 199 individuals who developed IA during the Diabetes Autoimmunity Study in the Young. Untargeted metabolomics was performed in serum samples following IA. Cox proportional hazards models were used to test whether the metabolites (2,487) predicted IA reversion: two or more consecutive visits negative for all autoantibodies. We conducted a principal components analysis (PCA) of the top metabolites; |hazard ratio (HR) >1.25| and nominal P < 0.01. Phosphatidylcholine (16:0_18:1(9Z)) was the strongest individual metabolite (HR per 1 SD 2.16, false discovery rate (FDR)-adjusted P = 0.0037). Enrichment analysis identified four clusters (FDR P < 0.10) characterized by an overabundance of sphingomyelin (d40:0), phosphatidylcholine (16:0_18:1(9Z)), phosphatidylcholine (30:0), and l-decanoylcarnitine. Overall, 63 metabolites met the criteria for inclusion in the PCA. PC1 (HR 1.4, P < 0.0001), PC2 (HR 0.85, P = 0.0185), and PC4 (HR 1.28, P = 0.0103) were associated with IA reversion. Given the potential influence of diet on the metabolome, we investigated whether nutrients were correlated with PCs. We identified 20 nutrients that were correlated with the PCs (P < 0.05). Total sugar intake was the top nutrient. Overall, we identified an association between phosphatidylcholine, sphingomyelin, and carnitine levels and reversion of IA.

Measurement of Femoral Version by MRI is as Reliable and Reproducible as CT in Children and Adolescents With Hip Disorders.

BACKGROUND: Femoral version measurement techniques based on magnetic resonance imaging (MRI) studies have been developed as an alternative to the high levels of ionizing radiation associated with computed tomography (CT)-based methods. Previous studies have not evaluated the reliability, repeatability, and accuracy of MRI-based femoral version measurements in an adolescent population. METHODS: Subjects who underwent MRI and CT studies for clinical suspicion of hip pain secondary to hip dysplasia or femoroacetabular impingement between 2011 and 2013 were identified. Rapid sequence femoral version images were obtained from MRI Hip dGEMRIC and/or postarthrogram studies. Femoral version images were also obtained from bilateral CT lower extremity, without contrast, studies. Measurements were made by 1 fellowship-trained, pediatric hip preservation attending surgeon, 2 pediatric orthopaedic surgical fellows, and 1 fellowship-trained musculoskeletal radiologist on 2 separate occasions. Linear mixed models were used to estimate the reliability and repeatability associated with CT-based and MRI-based measurements (intraclass correlation coefficients) and to estimate the agreement (CT-MRI) between the 2 techniques. RESULTS: The mean age of 36 subjects was 15.4 years (±4.1 y). Interrater reliability was 0.91 (95% CI, 0.86-0.95) for the CT technique compared with 0.90 (95% CI, 0.86-0.94) for the rapid sequence MRI technique. Intrarater reliability for the CT technique was 0.96 (95% CI, 0.91-0.98) compared with 0.95 (95% CI, 0.90-0.97) for the MRI technique. The agreement between the MRI-based and CT-based techniques (bias: 1.9 degrees, limits of agreement: -11.3 to 14.9 degrees) was similar to the agreement between consecutive MRI measurements (bias: 0.4 degrees, limits of agreement: -7.8 to 8.6 degrees) as well as consecutive CT measurements (bias: 0.5 degrees, limits of agreement: -8.8 to 9.9 degrees). CONCLUSIONS: The interrater and intrarater reliability and repeatability estimates (intraclass correlation coefficient values) associated with both techniques was excellent (>0.90). Acquirement of axial images at the pelvis and knee during MRI for investigation of adolescents with hip pain allows for reliable measurement of femoral version. LEVEL OF EVIDENCE: Level II-diagnostic study.

Return to Play Following Open Treatment of Femoroacetabular Impingement in Adolescent Athletes.

INTRODUCTION: After treatment of femoroacetabular impingement (FAI) in adolescent competitive athletes, the rate, timing, and level of return to play have not been well reported. METHODS: Adolescent athletes who underwent open FAI treatment were assessed at a minimum 1-year follow-up. Patients completed a self-reported questionnaire centered on the time and level of return to play. Pain and functional outcomes were assessed using the modified Harris Hip Score (mHHS) and the Hip Disability and Osteoarthritis Outcome Score (HOOS). RESULTS: Among the 24 athletes included, 21 (87.5%) (95% confidence interval [CI], 67.6% to 97.3%) successfully returned to play after open FAI treatment. The median time to return to play was 7 months (95% CI, 6 to 10 months). Of the 21 who returned to play, 19 (90%) returned at a level that was equivalent to or greater than their level of play before surgery. Three athletes (12.5%) did not return to play and indicated that failure to return to play was unrelated to their hip. There was significant improvement in the mHHS (P < 0.0001), HOOS (P < 0.0001), α angle (P < 0.0001), and offset (P < 0.0001). DISCUSSION: Most adolescent athletes can expect to return to the same or better level of sports participation during the first year after open treatment of FAI.

Incidence of Deep Vein Thrombosis and Pulmonary Embolism in the Elective Pediatric Orthopaedic Patient.

BACKGROUND: Although venous thromboembolism (VTE) has been well studied in the pediatric trauma population, rates of VTE associated with elective pediatric orthopaedic procedures have not been addressed in current literature. The purpose of this retrospective study was to identify the incidence of VTE in the elective pediatric orthopaedic surgical population and delineate subsets of this population at greatest risk. This study may provide valuable data to begin the process of resolving the controversy surrounding deep vein thrombosis prophylaxis in the pediatric orthopaedic population. METHODS: The Pediatric Health Information System was queried for patients admitted on an ambulatory or inpatient basis, aged below 18 years, from January 2006 to March 2011 during which an elective orthopaedic surgery was the principal procedure performed. Patients with diagnoses or procedures related to infection, trauma, malignancy, or coagulopathies were excluded. Patients admitted through the emergency department or whose orthopaedic procedure was not performed on the admission date were excluded. Age, sex, ethnicity, race, admission year, and all procedures/diagnoses were recorded. The presence of VTE at the index admission or any subsequent readmission within 90 days was recorded. All criteria were coded using ICD-9-CM codes. Generalized logistic regression analyses were used to identify factors related to VTE. RESULTS: A total of 143,808 admissions (117,676 patients) matched the inclusion criteria. Thirty-three had a VTE during the index admission with an additional 41 at subsequent readmissions, for a total incidence of 0.0515% by admission and 0.0629% by patient. In the multivariable model, variables significantly (P<0.05) related to VTE included increasing age, admission type, diagnosis of metabolic conditions, obesity, and/or syndromes, and complications of implanted devices and/or surgical procedures. No procedure variables were significantly related to VTE in the multivariable model. CONCLUSIONS: The incidence of VTE in this cohort of pediatric patients undergoing elective orthopaedic surgery was 0.0515%. In children, underlying diagnosis seems to be a stronger predictor of VTE than procedures performed. Diagnosis with a metabolic condition, syndrome, and/or obesity, complications of implanted devices and/or surgical procedures, older age, and admission as an inpatient were significantly related to the development of a VTE. LEVEL OF EVIDENCE: Level IV­case series.

Operative versus nonoperative treatment of displaced proximal humeral physeal fractures: a matched cohort.

BACKGROUND: Displaced proximal humeral physeal fractures (PHPF) are rare injuries. Because of the lack of comparative studies, treatment has historically been based on surgeon preference. The purpose of this study was to compare treatment outcomes among skeletally immature patients who underwent operative versus nonoperative treatment for Neer-Horwitz (NH) III or IV PHPF. METHODS: Skeletally immature patients who underwent treatment for a displaced PHPF from 2003 to 2012 were identified. Eligible subjects were invited to complete a validated shoulder outcome instrument (QuickDASH) and a phone survey. A propensity score matching approach was utilized to match subjects who underwent operative treatment to subjects who underwent nonoperative treatment on the basis of age at injury and NH classification. RESULTS: Seventy patients were identified with a NH III or IV PHPF, of whom 32 subjects completed the study. There was also no difference (P=0.5637) in the proportion of subjects who developed a less than desirable treatment outcome in operative group (57.14%, 4/7) as compared with the nonoperative group (42.86%, 3/7). There was also no difference (P=0.5637) in the proportion of subjects who developed a less than desirable treatment outcome in operative group (57.14%, 4/7) as compared with the nonoperative group. Differences in rate of return to preinjury level of activity (P>0.9999), or cosmetic appearance scores (P>0.999) were not significantly different. QuickDASH scores were 1.9 points (95% CI, 3.0-6.9; P=0.3699) higher overall in the nonoperative group as opposed to the operative group. A less than desirable treatment outcome was noted in 4/23 (17.4%) subjects who underwent nonoperative treatment. Subgroup analysis of the nonoperative cases showed that, for every 1 year increase in age at initial injury, the odds of less than desirable outcome increased by a factor of 3.81 (95% CI, 1.31-21.0). CONCLUSIONS: In a matched cohort of patients with proximal humerus physeal fractures, there was no difference in occurrence of complications, rate of return to activity, or cosmetic satisfaction. Functional outcomes were also nonsignificant, but tended to be higher among fractures that underwent nonoperative treatment. Among nonoperatively treated fractures, less than desirable outcomes were more common in older patients, particularly those older than 12 years of age. LEVEL OF EVIDENCE: Level III-therapeutic.

Intra-articular Radial Head Fractures In the Skeletally Immature Patient: Complications and Management.

BACKGROUND: Intra-articular (IARH) and extra-articular (EARH) radial head fractures in skeletally immature patients are rare injuries that have not been well studied. The objective of this study was to investigate the rate of complications associated with IARH fractures relative to EARH fractures in pediatric patients treated at a tertiary referral children's hospital. METHODS: With IRB approval, Current-Procedural Terminology codes were used to identify all patients who underwent management of radial head and/or neck fractures between 2005 and 2012. A retrospective chart review was used to collect variables related to: demographics, fracture type, treatment method(s), complications, need for physical/occupational therapy, and the need for subsequent surgery. Mid-P exact tests and logistic regression analyses were used to compare differences in the incidence of complications, need for physical therapy (PT), and need for revision surgery between the IARH and EARH fracture groups. RESULTS: Among the 311 patients included in the cohort, 12 (3.86%) were affected by IARH fractures and 299 (96.14%) were affected by EARH fractures. The mean age at the time of injury was 11.46 (±3.09) years and 8.32 (±3.31) years in the IARH and EARH group, respectively. The estimated incidence of complications was significantly (P<0.0001) higher in the IARH group (50 per 100) compared with the EARH group (1.34 per 100). A significantly (P<0.0001) greater proportion of the subjects with IARH fractures also required revision surgery (25% IARH vs. 0% EARH) and PT (50% IARH vs. 19.59% EARH). CONCLUSIONS: Compared with EARH fractures, IARH fractures were associated with a significantly higher rate of complications, greater need for PT, and greater need for surgical intervention. The significant complication rate associated with pediatric IARH fractures necessitates an increased awareness of this fracture pattern and prompt, aggressive diagnostic and treatment modalities. LEVEL OF EVIDENCE: Therapeutic studies: Level III.