Association between genetic polymorphisms and risk of adolescent idiopathic scoliosis in case-control studies: a systematic review.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a structural lateral spinal curvature of ≥10° with rotation. Approximately 2%-3% of children across populations are affected with AIS, and this condition is responsible for ~$3 billion in costs within the USA. Although AIS is believed to have a strong genetic contribution, clinical translation of identified genetic variants has stalled. METHODS: The databases MEDLINE (via PubMed), Embase, Google Scholar and Ovid MEDLINE were searched and limited to articles in English. Title and abstract, full-text and data extraction screening was conducted through Covidence, followed by data transfer to a custom REDCap database. Studies containing variant-level data using genome-wide methodology as well as validation studies of genome-wide methods were considered. Quality assessment was conducted using Q-Genie. RESULTS: 33 studies were included, including 9 genome-wide association studies, 4 whole exome sequencing and 20 validation studies. Combined, these studies included data from >35,000 cases and >67,000 controls, not including validation cohorts. Additionally, results from six meta-analyses containing novel cohorts were also reported. All included study cohorts were from populations of primarily East Asian or Caucasian descent. Quality assessment found that overall study quality was high and control group selection was moderate. The highest number of reported associations were in single nucleotide polymorphisms (SNPs) in or near LBX1, LBX1-AS1, GPR126/ADGRG6 or BNC2. CONCLUSION: AIS risk may be influenced by specific SNPs, particularly those in/near LBX1 and GPR126. Translatability of study findings is unknown due to an underrepresentation of most ethnic groups as well as few identified genome-wide studies. Further studies may benefit from increased cohort diversity and thorough evaluation of control cohort groups.

Optimized Patient Outcomes With the Novel Modality of Corrective Chemical Peel and Neurotoxin on Same-Day Treatment.

BACKGROUND: This study was conducted to improve standards of care in the cosmetic treatment of sun damage, fine lines, and wrinkles. Chemical Peels and Neurotoxins have been traditionally used cosmetically as monotherapies. This study aimed to confirm that the same-day combination created no additional side effects while also improving outcomes. METHODS: The multi-generational study enrolled 30 patients with Fitzpatrick I-VI representation. The Roberts Skin Type Classification System was used to establish baseline patient information. Patients were treated with a VI Peel®, followed by Botox®. Objectively, photographic matching, Wrinkle Severity Scale, Uniformity of Pigment Scale, and Skin Tone Scales were used to evaluate skin improvement. Patient questionnaires were issued to assess satisfaction. RESULTS: Safety of the same-day combination was established with no adverse events reported. Improvements on the Wrinkle Severity Scale showed an average rating dropping from 1.46 to 0.59 representing a 60% improvement. Improvements on the Uniformity of Pigment Scale showed an average rating dropping from 2.27 to 0.92 representing a 59% improvement. Improvements on the Skin Tone Scale showed an average rating dropping from 2.35 to 0.71 representing a 70% improvement. Questionnaires correlated with objective findings with high satisfaction.  Conclusion: This study confirmed the safety of the same-day combination. The efficacy of VI Peel & Botox same-day treatment was clinically proven by the improvements to Wrinkle Severity, Uniformity of Pigment, and Skin Tone via photographic matching. While perception studies indicated strong patient satisfaction with the combination. J Drugs Dermatol. 2024;23(1):1349-1354.   doi:10.36849/JDD.7194R1.

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.

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.

Pandemic Response Requires Research Samples: A U.S. Safety-Net Hospital's Experience and Call for National Action.

Biorepositories provide a critical resource for gaining knowledge of emerging infectious diseases and offer a mechanism to rapidly respond to outbreaks; the emergence of the novel coronavirus, SARS-CoV-2, has proved their importance. During the COVID-19 pandemic, the absence of centralized, national biorepository efforts meant that the onus fell on individual institutions to establish sample repositories. As a safety-net hospital, Boston Medical Center (BMC) recognized the importance of creating a COVID-19 biorepository to both support critical science at BMC and ensure representation in research for its urban patient population, most of whom are from underserved communities. This article offers a realistic overview of the authors' experience in establishing this biorepository at the onset of the COVID-19 pandemic during the height of the first surge of cases in Boston, Massachusetts, with the hope that the challenges and solutions described are useful to other institutions. Going forward, funders, policymakers, and infectious disease and public health communities must support biorepository implementation as an essential element of future pandemic preparedness.

Mutations in KIF7 implicated in idiopathic scoliosis in humans and axial curvatures in zebrafish.

Idiopathic scoliosis (IS) is a spinal disorder affecting up to 3% of otherwise healthy children. IS has a strong familial genetic component and is believed to be genetically complex due to significant variability in phenotype and heritability. Previous studies identified putative loci and variants possibly contributing to IS susceptibility, including within extracellular matrix, cilia, and actin networks, but the genetic architecture and underlying mechanisms remain unresolved. Here, we used whole-exome sequencing from three affected individuals in a multigenerational family with IS and identified 19 uncommon variants (minor allele frequency < 0.05). Genotyping of additional family members identified a candidate heterozygous variant (H1115Q, G>C, rs142032413) within the ciliary gene KIF7, a regulator within the hedgehog (Hh) signaling pathway. Resequencing of the second cohort of unrelated IS individuals and controls identified several severe mutations in KIF7 in affected individuals only. Subsequently, we generated a mutant zebrafish model of kif7 using CRISPR-Cas9. kif7co63/co63 zebrafish displayed severe scoliosis, presenting in juveniles and progressing through adulthood. We observed no deformities in the brain, Reissner fiber, or central canal cilia in kif7co63/co63 embryos, although alterations were seen in Hh pathway gene expression. This study suggests defects in KIF7-dependent Hh signaling, which may drive pathogenesis in a subset of individuals with IS.

A Laboratory Medicine Best Practices Systematic Review and Meta-analysis of Nucleic Acid Amplification Tests (NAATs) and Algorithms Including NAATs for the Diagnosis of Clostridioides (Clostridium) difficile in Adults.

The evidence base for the optimal laboratory diagnosis of Clostridioides (Clostridium) difficile in adults is currently unresolved due to the uncertain performance characteristics and various combinations of tests. This systematic review evaluates the diagnostic accuracy of laboratory testing algorithms that include nucleic acid amplification tests (NAATs) to detect the presence of C. difficile The systematic review and meta-analysis included eligible studies (those that had PICO [population, intervention, comparison, outcome] elements) that assessed the diagnostic accuracy of NAAT alone or following glutamate dehydrogenase (GDH) enzyme immunoassays (EIAs) or GDH EIAs plus C. difficile toxin EIAs (toxin). The diagnostic yield of NAAT for repeat testing after an initial negative result was also assessed. Two hundred thirty-eight studies met inclusion criteria. Seventy-two of these studies had sufficient data for meta-analysis. The strength of evidence ranged from high to insufficient. The uses of NAAT only, GDH-positive EIA followed by NAAT, and GDH-positive/toxin-negative EIA followed by NAAT are all recommended as American Society for Microbiology (ASM) best practices for the detection of the C. difficile toxin gene or organism. Meta-analysis of published evidence supports the use of testing algorithms that use NAAT alone or in combination with GDH or GDH plus toxin EIA to detect the presence of C. difficile in adults. There is insufficient evidence to recommend against repeat testing of the sample using NAAT after an initial negative result due to a lack of evidence of harm (i.e., financial, length of stay, or delay of treatment) as specified by the Laboratory Medicine Best Practices (LMBP) systematic review method in making such an assessment. Findings from this systematic review provide clarity to diagnostic testing strategies and highlight gaps, such as low numbers of GDH/toxin/PCR studies, in existing evidence on diagnostic performance, which can be used to guide future clinical research studies.

Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis.

INTRODUCTION: Adolescent idiopathic scoliosis (AIS) is a common musculoskeletal disorder with strong evidence for a genetic contribution. CNVs play an important role in congenital scoliosis, but their role in idiopathic scoliosis has been largely unexplored. METHODS: Exome sequence data from 1197 AIS cases and 1664 in-house controls was analysed using coverage data to identify rare CNVs. CNV calls were filtered to include only highly confident CNVs with >10 average reads per region and mean log-ratio of coverage consistent with single-copy duplication or deletion. The frequency of 55 common recurrent CNVs was determined and correlated with clinical characteristics. RESULTS: Distal chromosome 16p11.2 microduplications containing the gene SH2B1 were found in 0.7% of AIS cases (8/1197). We replicated this finding in two additional AIS cohorts (8/1097 and 2/433), resulting in 0.7% (18/2727) of all AIS cases harbouring a chromosome 16p11.2 microduplication, compared with 0.06% of local controls (1/1664) and 0.04% of published controls (8/19584) (p=2.28×10-11, OR=16.15). Furthermore, examination of electronic health records of 92 455 patients from the Geisinger health system showed scoliosis in 30% (20/66) patients with chromosome 16p11.2 microduplications containing SH2B1 compared with 7.6% (10/132) of controls (p=5.6×10-4, OR=3.9). CONCLUSIONS: Recurrent distal chromosome 16p11.2 duplications explain nearly 1% of AIS. Distal chromosome 16p11.2 duplications may contribute to scoliosis pathogenesis by directly impairing growth or by altering expression of nearby genes, such as TBX6. Individuals with distal chromosome 16p11.2 microduplications should be screened for scoliosis to facilitate early treatment.

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.

Impact of Adding Telephone-Based Care Coordination to Standard Telephone-Based Smoking Cessation Counseling Post-hospital Discharge: a Randomized Controlled Trial.

BACKGROUND: Cessation counseling and pharmacotherapy are recommended for hospitalized smokers, but better coordination between cessation counselors and providers might improve utilization of pharmacotherapy and enhance smoking cessation. OBJECTIVE: To compare smoking cessation counseling combined with care coordination post-hospitalization to counseling alone on uptake of pharmacotherapy and smoking cessation. DESIGN: Unblinded, randomized clinical trial PARTICIPANTS: Hospitalized smokers referred from primarily rural hospitals INTERVENTIONS: Counseling only (C) consisted of telephone counseling provided during the hospitalization and post-discharge. Counseling with care coordination (CCC) provided similar counseling supplemented by feedback to the smoker's health care team and help for the smoker in obtaining pharmacotherapy. At 6 months post-hospitalization, persistent smokers were re-engaged with either CCC or C. MAIN MEASURES: Utilization of pharmacotherapy and smoking cessation at 3, 6, and 12 months post-discharge. KEY RESULTS: Among 606 smokers randomized, 429 (70.8%) completed the 12-month assessment and 580 (95.7%) were included in the primary analysis. Use of any cessation pharmacotherapy between 0 and 6 months (55.2%) and between 6 and 12 months (47.1%) post-discharge was similar across treatment arms though use of prescription-only pharmacotherapy between months 6-12 was significantly higher in the CCC group (30.1%) compared with the C group (18.6%) (RR, 1.61 (95% CI, 1.08, 2.41)). Self-reported abstinence rates of 26.2%, 20.3%, and 23.4% at months 3, 6, and 12, respectively, were comparable across the two treatment arms. Of those smoking at month 6, 12.5% reported abstinence at month 12. Validated smoking cessation at 12 months was 19.3% versus 16.9% in the CCC and C groups, respectively (RR, 1.13 (95% CI, 0.80, 1.61)). CONCLUSION: Supplemental care coordination, provided by counselors outside of the health care team, failed to improve smoking cessation beyond that achieved by cessation counseling alone. Re-engagement of smokers 6 months post-discharge can lead to new quitters, at which time care coordination might facilitate use of prescription medications. TRIAL REGISTRATION: NCT01063972.

Point-of-care influenza testing does not significantly shorten time to disposition among patients with an influenza-like illness.

INTRODUCTION: Availability of anti-viral agents and need to isolate infected patients increases the need to confirm the diagnosis of influenza before determining patient disposition. OBJECTIVES: We sought to determine if time-to-disposition (TTD) was shorter among patients tested for influenza using an Emergency Department (ED) Point-of-care (POC) test compared to core laboratory (lab) test and to determine difference in antibiotic use between groups. METHODS: We prospectively enrolled a convenience sample of ED patients for whom influenza testing was ordered during influenza season 2017. Participants were randomized to POC or lab. Data collected included demographics, chief complaint, influenza test results, turnaround time (TAT), whether antibiotics were given, and TTD. Descriptive statistics were calculated and group comparisons conducted using chi squared and Wilcoxon Rank Sum tests. RESULTS: Study population included 100 in the POC group and 97 in the lab group. Demographics were similar between POC and lab participants. More flu positive results were reported in the POC group compared to the lab group (51.0% vs. 33.0% p = 0.01). The median TTD was 146.5 min (IQR 98.5) for POC group and 165.5 min (IQR 127) for lab group (p = 0.26). The median TAT was 30.5 min (IQR 7.5) for POC group and 106.0 min (IQR 55) for core lab group (p = 0.001). Antibiotics were given to 14.0% of POC participants and 14.4% of lab participants (p = 0.93). CONCLUSIONS: Although use of a POC influenza test provided more rapid TAT than use of a core lab test, there was no significant difference in TTD or antibiotic use between groups.

Clubfoot and Tethered Cord Syndrome: Results of Treatment With the Ponseti Method.

BACKGROUND: The Ponseti technique has demonstrated high success rates worldwide for the treatment of idiopathic clubfoot. The purpose of this study was to determine whether clubfoot associated with tethered cord syndrome (TCS) was more resistant to Ponseti treatment than isolated clubfoot. METHODS: An IRB-approved retrospective cohort study of subjects undergoing Ponseti treatment of clubfoot between 2002 and 2013 was conducted. Subjects with TCS were matched to subjects with isolated clubfoot (1:2) on the basis of laterality, date of birth, sex, and age at presentation. Subject demographics, number of casts placed (pretenotomy and posttenotomy), and recurrence data were collected. Generalized logistic regression and linear mixed model regression analyses were used to compare recurrence within 2 years of the initiation of casting and the log number of casts needed to achieve an acceptable correction, respectively. RESULTS: Data from 24 subjects (16 isolated clubfeet, 8 with TCS) with clubfoot (12 bilateral, 12 unilateral) were analyzed. The isolated clubfoot group was the same age at presentation on average (21.9±4.7 d) as the TCS group (28.3±9.6 d) (P=0.55). The number of casts required to achieve an acceptable correction was 54% higher (95% CI, 7.8%-120.3%; P=0.0217) in the TCS group compared with the isolated clubfoot group. The cumulative crude incidence of deformity recurrence within the first 2 years after casting initiation was 8% in the isolated clubfoot group compared with 42% in the TCS group. The odds of deformity recurrence in the TCS group were 5.6 (95% CI, 0.7-45.2; P=0.1054) times the odds of deformity recurrence in the isolated clubfoot group. Furthermore, the incidence of deformity recurrence was higher among subjects who had a tethered cord release posttenotomy (56%, 5/9) as compared with pretenotomy (0%, 0/3). CONCLUSION: Clubfoot associated with TCS required more casts to achieve an acceptable correction. Subjects with tethered cord were also at an increased risk of deformity recurrence compared with subjects with isolated clubfoot. LEVEL OF EVIDENCE: Level II-retrospective prognostic study.

Dimeglio Score Predicts Treatment Difficulty During Ponseti Casting for Isolated Clubfoot.

BACKGROUND: The Dimeglio score (DS) is widely used to assess clubfoot severity, but its ability to predict long-term outcomes following Ponseti treated isolated clubfoot (IC) is controversial. This study tested the association between the initial DS and its individual parameters with the number of Ponseti clubfoot casts required to achieve correction and the rate of early recurrence following treatment. METHODS: Data were retrospectively collected from patients who underwent treatment of IC between March 2012 and March 2015 and were followed for ≥2 years. DSs were collected at the initial casting visit. The number of Ponseti casts required to achieve clubfoot correction before tenotomy and recurrence of deformity were collected as the primary outcome variables. Recurrence was defined as any loss of correction leading to repeat casting or tenotomy during the bracing phase. Negative binomial and logistic regression analyses were used to test the association between the 8 Dimeglio parameters and number of casts and incidence of recurrence, respectively. RESULTS: A total of 53 patients (37 male and 16 female) were included in the study. The median number of casts required to achieve an acceptable correction was 5 (range, 2 to 16). The incidence of recurrence was 24.53% (13/53). An increase in derotation, varus, equinus, muscle condition, and total DSs at the initial cast visit were associated with a significant (P<0.05) increase in the number of casts required to achieve an acceptable correction. The derotation parameter [rate ratio: 1.30, 95% confidence interval (CI): 1.13-1.50, P=0.0003] was most strongly associated with number of casts. Total DSs at initial visit was the only variable significantly associated with the incidence of deformity recurrence (odds ratio: 1.36, 95% confidence interval: 1.01-1.84, P=0.0482). CONCLUSION: Initial DS is correlated with the number of casts required for correction in Ponseti treated IC. DS may help physicians establish realistic expectations for families with regard to the length of treatment and the possibility of recurrence following Ponseti treatment. LEVEL OF EVIDENCE: Level II-retrospective prognostic study.

Fassier-Duval Rods are Associated With Superior Probability of Survival Compared With Static Implants in a Cohort of Children With Osteogenesis Imperfecta Deformities.

BACKGROUND: The survival of Fassier-Duval (FD) telescoping rods as compared with static implants in children affected by osteogenesis imperfecta is not well characterized. The purpose of this study was to compare risk of lower extremity implant failure in FD rods versus static implants. METHODS: Data were retrospectively collected from patients with osteogenesis imperfecta who underwent surgical treatment using either FD rods or static implants (Rush rods, flexible nails, or Steinmann pins) between 1995 and 2015. The timing of implant failure was the primary outcome variable of interest. Comparisons were limited to limbs with no previous history of implants. Cox-proportional hazards regression analyses were used to compare the hazard of implant failure across implants. Negative binomial regression analyses were used to compare the incidence of surgical procedures in the 2 implant groups. RESULTS: The final cohort consisted of 64 limbs (n=21 patients). The static implant group (n=38) consisted of 24 Rush rods (63%), 14 flexible nails (37%), and 2 Steinmann pins (5%). The hazard of implant failure in the static implant group was 13.2 times [95% confidence interval (CI), 2.5-69.6; P=0.0024] the hazard of implant failure in the FD rod group. The hazard of implant failure among females was 4.8 (95% CI, 1.4-16.7; P=0.0125) times the hazard of implant failure among males. The total surgery rate in the static implant group was 7.8 (95% CI, 1.8-33.0; P=0.0056) times the total surgery rate in the FD group. CONCLUSIONS: Among surgically naive limbs, FD rods were associated with significantly improved probability of survival compared with static implants. LEVEL OF EVIDENCE: Level II-retrospective study.

A polygenic burden of rare variants across extracellular matrix genes among individuals with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a complex inherited spinal deformity whose etiology has been elusive. While common genetic variants are associated with AIS, they explain only a small portion of disease risk. To explore the role of rare variants in AIS susceptibility, exome sequence data of 391 severe AIS cases and 843 controls of European ancestry were analyzed using a pathway burden analysis in which variants are first collapsed at the gene level then by Gene Ontology terms. Novel non-synonymous/splice-site variants in extracellular matrix genes were significantly enriched in AIS cases compared with controls (P = 6 × 10(-9), OR = 1.7, CI = 1.4-2.0). Specifically, novel variants in musculoskeletal collagen genes were present in 32% (126/391) of AIS cases compared with 17% (146/843) of in-house controls and 18% (780/4300) of EVS controls (P = 1 × 10(-9), OR = 1.9, CI = 1.6-2.4). Targeted resequencing of six collagen genes replicated this association in combined 919 AIS cases (P = 3 × 10(-12), OR = 2.2, CI = 1.8-2.7) and revealed a highly significant single-gene association with COL11A2 (P = 6 × 10(-9), OR = 3.8, CI = 2.6-7.2). Importantly, AIS cases harbor mainly non-glycine missense mutations and lack the clinical features of monogenic musculoskeletal collagenopathies. Overall, our study reveals a complex genetic architecture of AIS in which a polygenic burden of rare variants across extracellular matrix genes contributes strongly to risk.

Summary of the first inaugural joint meeting of the International Consortium for scoliosis genetics and the International Consortium for vertebral anomalies and scoliosis, March 16-18, 2017, Dallas, Texas.

Scoliosis represents the most common musculoskeletal disorder in children and affects approximately 3% of the world population. Scoliosis is separated into two major phenotypic classifications: congenital and idiopathic. Idiopathic scoliosis is defined as a curvature of the spine of 10° or greater visualized on plane radiograph and does not have associated vertebral malformations (VM). "Congenital" scoliosis (CS) due to malformations in vertebrae is frequently associated with other birth defects. Recently, significant advances have been made in understanding the genetic basis of both conditions. There is evidence that both conditions are etiologically related. A 2-day conference entitled "Genomic Approaches to Understanding and Treating Scoliosis" was held at Scottish Rite Hospital for Children in Dallas, Texas, to synergize research in this field. This first combined, multidisciplinary conference featured international scoliosis researchers in basic and clinical sciences. A major outcome of the conference advancing scoliosis research was the proposal and subsequent vote in favor of merging the International Consortium for Vertebral Anomalies and Scoliosis (ICVAS) and International Consortium for Scoliosis Genetics (ICSG) into a single entity called International Consortium for Spinal Genetics, Development, and Disease (ICSGDD). The ICSGDD is proposed to meet annually as a forum to synergize multidisciplinary spine deformity research.

Prevalence of Persistent Median Arteries in the Pediatric Population on Ultrasonography.

OBJECTIVES: To use real-time ultrasonography to estimate the prevalence of persistent median arteries in a cohort of pediatric orthopedic patients. METHODS: With Institutional Review Board approval, patients between the ages of 3 months and 19 years were recruited for this cross-sectional study. Variables of interest included demographics, underlying diagnoses, and the presence of a Doppler-confirmed median artery. Ultrasonographic examinations were performed on both upper extremities by a single investigator. Patient- and limb-level analyses were performed. A multivariable generalized logistic regression analysis was used to test the association between the prevalence of limb-specific persistent median arteries and age. A generalized estimating equation was used to adjust for the inclusion of multiple limbs from the same patient. RESULTS: A total of 135 patients (270 limbs) were evaluated. The patient-specific prevalence rate (persistent median arteries present in 1 or both limbs) was 26.7%. Among these patients (n = 36), a persistent median artery was present bilaterally in 55.6% (n = 20). The limb-specific prevalence rate (proportion of limbs with a persistent median artery) was 20.7%. After adjusting for race, for every 1-year increase in age, the odds of a persistent median artery decreased by 4.4%. After adjusting for age, African Americans were significantly more likely to present with a persistent median artery (odds ratio, 3.78; 95% confidence interval, 1.25-11.48). CONCLUSIONS: Ultrasonography can effectively visualize anatomic variants, such as persistent median arteries, in the pediatric population. The prevalence of persistent median arteries was higher than anticipated, especially among African American patients.

Clinical and Radiographic Outcomes After Submuscular Plating (SMP) of Pediatric Femoral Shaft Fractures.

BACKGROUND: To evaluate lower extremity strength and alignment among children who underwent submuscular plating (SMP). METHODS: Subjects who underwent SMP for a length unstable femoral fracture returned for isokinetic strength testing ≥2 years after surgery. Extensor and flexor strength deficits (percent difference) between the operative and nonoperative limbs were evaluated. Radiographic measurements of mechanical alignment [anatomic lateral distal femoral angle (aLDFA)] and qualitative measurements (The Pediatric Outcomes Data Collection Instrument, PODCI) were obtained from all subjects. The upper 97.5% confidence interval approach to establishing clinical equivalency was utilized to compare differences in strength and alignment between the operative and nonoperative limbs. An extensor strength deficit of >19% and an aLDFA discrepancy of >5 degrees were considered to be clinically significant. RESULTS: The average age at surgery of the 10 subjects included in the study was 8.7 years. The hardware was placed an average of 27.9 mm from the distal femoral physis and was removed 6.4 months postsurgery. Among all subjects, the median PODCI scores were ≥97 according to all subscales. There was no significant difference in extension torque between the operative versus nonoperative limbs at 60 degrees/s (P=0.5400), 120 degrees/s (P=0.4214), or 180 degrees/s (P=0.8166). More importantly, extension strength deficits between the operative and nonoperative limbs were not clinically significant at 60 degrees/s [upper 97.5% confidence interval (CI), 10.9%], 120 degrees/s (upper 97.5% CI, 11.0%), or 180 degrees/s (upper 97.5% CI, 10.7%). The difference in aLDFA between the operative and nonoperative limb was less than the predefined clinically significant threshold of 5 degrees for all subjects. CONCLUSIONS: SMP achieves satisfactory clinical and functional results. In this series, extensor strength deficits and/or lower extremity malalignment were not clinically meaningful. High patient satisfaction can be expected after implant removal. LEVEL OF EVIDENCE: Level IV-case series.

Outcomes of Isolated Varus Derotational Osteotomy in Children With Cerebral Palsy Hip Dysplasia and Predictors of Resubluxation.

BACKGROUND: The appropriate intervention for hip subluxation or dislocation in children affected by cerebral palsy (CP) remains controversial. The purpose of this retrospective study was to report radiographic and clinical outcomes following isolated femoral varus derotational osteotomy (VDRO) in children with CP hip dysplasia. Risk factors for resubluxation and avascular necrosis (AVN) were also examined. METHODS: A cohort of 100 patients (199 hips) with CP treated with isolated VDRO between 2003 and 2009 was reviewed. All but 1 patient received bilateral surgery. Patients were followed for an average of 5.4 years (range, 1.03 to 10.20 y). Anteroposterior pelvic radiographs were used to assess migration percentage (MP), Shenton's line, and presence of AVN. Resubluxation was defined as a postoperative break in Shenton's line. Radiographic outcomes and risk analysis was performed in the 91 subjects (179 hips) with radiographic follow-up >1 year. RESULTS: Significant improvement was observed in MP, and all hips had a reconstituted Shenton's line following surgery. Over the course of follow-up, 16% of hips were noted to have a repeat break in Shenton's line. Univariate risk analysis showed preoperative MP, Gross Motor Function Classification System (GMFCS) level, and age at surgery were risk factors for a recurrent line break. Preoperative MP and GMFCS level were found to be predictors of resubluxation in multivariate analysis. AVN was detected in 10 hips (5.7%). GMFCS level V patients were more at risk for resubluxation, but less at risk for AVN when compared with ambulatory (GMFCS I/II/II) patients and GMFCS level IV patients. CONCLUSIONS: Performing a VDRO without additional procedures provided a stable and concentrically reduced hip joint in this population of children with CP. Attention should be paid to initial ambulatory status during the postoperative period. Concomitant procedures such as pelvic osteotomy should be considered for patients of GMFCS level IV and V, as these patients were more at risk for recurrent subluxation. LEVEL OF EVIDENCE: Level III-retrospective comparative study.