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.

Management of Clubfoot Relapses With the Ponseti Method: Results of a Survey of the POSNA Members.

BACKGROUND: Despite the high rate of initial success using the Ponseti method to manage idiopathic clubfoot deformity, relapse continues to be a problem. We surveyed the Pediatric Orthopedic Society of North America (POSNA) members about their experience with relapsed deformity following the initial correction of clubfeet. METHODS: We created a survey to focus on the management of clubfeet after initial correction of deformity. The survey included questions on postcorrective bracing, clinical findings used to identify relapse, the observed frequency of relapsed deformity, and how relapses are managed. The questionnaire was approved by the POSNA Evidence Based Committee and was sent electronically to all POSNA members. RESULTS: We received responses from 321 members (26%). Of those, 94% were fellowship trained in pediatric orthopaedics. The Ponseti method was used by 98% of respondents. The Mitchell-Ponseti orthosis was most commonly used (51%), followed by the Denis-Browne brace (25%). The duration of bracing used varied among members with 23% recommending only 2 years, 33% recommending 3 years, and 34% recommending 4 years. A tight heel cord was felt to be the first sign of relapse by 59% of respondents, and dynamic supination by 30%. The rate of relapse was observed to be <10% by 22% of the respondents, 10% to 20% by 52%, and 20% to 40% by 25%. Manipulation and cast treatment alone (55%) and cast treatment with tenotomy (23%) were reported as the 2 most common initial treatment approaches for a relapsed deformity. Cast treatment to correct relapsed deformity before tibialis anterior tendon transfer was reported by 62% of respondents. Heel cord tenotomy (75%) and posterior capsular release (43%) were the 2 most common procedures used in addition to tibialis anterior tendon transfer for the treatment of clubfoot relapse. CONCLUSION: This study highlights the wide variation with which clubfoot relapses are evaluated and treated among the POSNA membership with differences in the recommended duration of bracing, identification of relapses, and their management. These wide differences highlight the need for future research and educational programs to inform and standardize the management of clubfoot using the Ponseti Method. LEVEL OF EVIDENCE: Not applicable.

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.

The 2018 Nicholas Andry Award: The Evidence Base for the Treatment of Developmental Dysplasia of the Hip: The Iowa Contribution.

This review summarizes evidence developed at the University of Iowa concerning the management and outcomes of developmental dysplasia of the hip beginning with the observations and analyses of Dr Arthur Steindler in the early 1900s. The strong evidence-based practice tradition established by Steindler 100 years ago continues as we critically evaluate our procedures and patient outcomes, only altering approaches when warranted by strong personal and research evidence. Our practice continues to be conservative in that we strive to produce the best environment possible for the hip to develop on its own and operate only when less invasive methods have failed.

Joint hyperlaxity prevents relapses in clubfeet treated by Ponseti method-preliminary results.

PURPOSE: The aim of the study was to evaluate the role of joint hyperlaxity (by Beighton score) as a protective factor for clubfoot relapse. METHODS: Patients with idiopathic clubfoot treated with the Ponseti method between January 2004 and December 2012, without other congenital foot deformity, and not previously treated by open surgery were included in either the Relapse group (n = 23) if it was a clubfoot relapse or the Control group (n = 19) if no relapse was noted. Joint laxity was evaluated using the Beighton score at the latest follow-up against the Normal group (n = 22, children matched by sex and age without clubfoot deformity). RESULTS: We found a significantly higher joint laxity in the Control group (4.58, 95% confidence interval [CI]: 2.1-7.06) as compared to the Relapse (3.17, 95% CI: 1.53-4.81, p = 0.032) and Normal (3.14, 95% CI: 1.78-4.5, p = 0.03) groups. The univariate logistic regression showed a 5.28-times increase in the risk of relapse for a Beighton score lower than 4/9 points (odds ratio = 5.28; 95% CI = 1.29-21.5; p = 0.018). CONCLUSIONS: Joint hyperlaxity could be a protective factor for clubfoot relapse.

Results of Ponseti Brasil Program: Multicentric Study in 1621 Feet: Preliminary Results.

BACKGROUND: The Ponseti method has been shown to be the most effective treatment for congenital clubfoot. The current challenge is to establish sustainable national clubfoot treatment programs that utilize the Ponseti method and integrate it within a nation's governmental health system. The Brazilian Ponseti Program (Programa Ponseti Brasil) has increased awareness of the utility of the Ponseti method and has trained >500 Brazilian orthopaedic surgeons in it. METHODS: A group of 18 of those surgeons had been able to reproduce the Ponseti clubfoot treatment, and compiled their initial results through structured spreadsheet. RESULTS: The study compiled 1040 patients for a total of 1621 feet. The average follow-up time was 2.3 years with an average correction time of approximately 3 months. Patients required an average of 6.40 casts to achieve correction. CONCLUSIONS: This study demonstrates that good initial correction rates are reproducible after training; from 1040 patients only 1.4% required a posteromedial release. LEVEL OF EVIDENCE: Level IV.

Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) causes spinal deformity in 3% of children. Despite a strong genetic basis, few genes have been associated with AIS and the pathogenesis remains poorly understood. In a genome-wide rare variant burden analysis using exome sequence data, we identified fibrillin-1 (FBN1) as the most significantly associated gene with AIS. Based on these results, FBN1 and a related gene, fibrillin-2 (FBN2), were sequenced in a total of 852 AIS cases and 669 controls. In individuals of European ancestry, rare variants in FBN1 and FBN2 were enriched in severely affected AIS cases (7.6%) compared with in-house controls (2.4%) (OR = 3.5, P = 5.46 × 10(-4)) and Exome Sequencing Project controls (2.3%) (OR = 3.5, P = 1.48 × 10(-6)). Scoliosis severity in AIS cases was associated with FBN1 and FBN2 rare variants (P = 0.0012) and replicated in an independent Han Chinese cohort (P = 0.0376), suggesting that rare variants may be useful as predictors of curve progression. Clinical evaluations revealed that the majority of AIS cases with rare FBN1 variants do not meet diagnostic criteria for Marfan syndrome, though variants are associated with tall stature (P = 0.0035) and upregulation of the transforming growth factor beta pathway. Overall, these results expand our definition of fibrillin-related disorders to include AIS and open up new strategies for diagnosing and treating severe AIS.

Long-term results of comprehensive clubfoot release versus the Ponseti method: which is better?

BACKGROUND: Clubfoot can be treated nonoperatively, most commonly using a Ponseti approach, or surgically, most often with a comprehensive clubfoot release. Little is known about how these approaches compare with one another at longer term, or how patients treated with these approaches differ in terms of foot function, foot biomechanics, or quality-of-life from individuals who did not have clubfoot as a child. QUESTIONS/PURPOSES: We compared (1) focused physical and radiographic examinations, (2) gait analysis, and (3) quality-of-life measures at long-term followup between groups of adult patients with clubfoot treated either with the Ponseti method of nonsurgical management or a comprehensive surgical release through a Cincinnati incision, and compared these two groups with a control group without clubfoot. METHODS: This was a case control study of individuals treated for clubfoot at two separate institutions with different methods of treatment between 1983 to 1987. One hospital used only the Ponseti method and the other mainly used a comprehensive clubfoot release. There were 42 adults (24 treated surgically, 18 treated with Ponseti method) with isolated clubfoot along with 48 healthy control subjects who agreed to participate in a detailed analysis of physical function, foot biomechanics, and quality-of-life metrics. RESULTS: Both treatment groups had diminished strength and motion compared with the control subjects on physical examination measures; however, the Ponseti group had significantly greater ankle plantar flexion ROM (p < 0.001), greater ankle plantar flexor (p = 0.031) and evertor (p = 0.012) strength, and a decreased incidence of osteoarthritis in the ankle and foot compared with the surgical group. During gait the surgical group had reduced peak ankle plantar flexion (p = 0.002), and reduced sagittal plane hindfoot (p = 0.009) and forefoot (p = 0.008) ROM during the preswing phase compared with the Ponseti group. The surgical group had the lowest overall ankle power generation during push off compared with the control subjects (p = 0.002). Outcome tools revealed elevated pain levels in the surgical group compared with the Ponseti group (p = 0.008) and lower scores for physical function and quality-of-life for both clubfoot groups compared with age-range matched control subjects (p = 0.01). CONCLUSIONS: Although individuals in each treatment group experienced pain, weakness, and reduced ROM, they were highly functional into early adulthood. As adults the Ponseti group fared better than the surgically treated group because of advantages including increased ROM observed at the physical examination and during gait, greater strength, and less arthritis. This study supports efforts to correct clubfoot with Ponseti casting and minimizing surgery to the joints, and highlights the need to improve methods that promote ROM and strength which are important for adult function. LEVEL OF EVIDENCE: Level III, prognostic study.

Perception about braces in parents of children with clubfoot.

OBJECTIVE: To access the acceptability of Steenbeek brace by children undergoing clubfoot correction and their parents to ensure long-term compliance. METHODS: The cross-sectional study was conducted at the Indus Hospital, Karachi from October 2013 to March 2014. A trained researcher interviewed the person primarily responsible for bracing the child using a pre-coded questionnaire. Modified Orthotics Prosthetics User Survey for satisfaction with either the Mitchell brace of the Steenbeek brace was used. It included 11 questions in the Parent Bracing Satisfaction Survey. SPSS 21 was used for statistical analysis. RESULTS: Interviews were completed with 110 primary caregivers among whom 90(81.8%) were mothers. Overall, 32(29.1%) children were using the Mitchell brace, 30(27.3%) the Steenbeek brace, 46(41.8%) had shifted from Mitchell to Steenbeek brace, and 2(1.8%) had shifted from Steenbeek to Mitchell brace. Median duration of current brace usage was 4 and 3.5 months for Steenbeek and Mitchell braces respectively. The mean age of the child was 1.4 ±0.7 years, and the mean of 4-point Likerts cale score of parent bracing satisfaction was 28.7±2.2 in children on the Mitchell brace versus 28.5±1.9 for those on Steenbeek brace (p=0.505). Overall, 82(74.5%) parents had favourable attitude towards braces in general, but there were no significant differences in the items except "brace is easy to put on" (p=0.040) and "durability between Mitchell and Steenbeek groups" (p=0.017). CONCLUSIONS: There were no differences in satisfaction levels between the two types of brace users.

A mouse model of osteochondromagenesis from clonal inactivation of Ext1 in chondrocytes.

We report a mouse model of multiple osteochondromas (MO), an autosomal dominant disease in humans, also known as multiple hereditary exostoses (MHE or HME) and characterized by the formation of cartilage-capped osseous growths projecting from the metaphyses of endochondral bones. The pathogenesis of these osteochondromas has remained unclear. Mice heterozygous for Ext1 or Ext2, modeling the human genotypes that cause MO, occasionally develop solitary osteochondroma-like structures on ribs [Lin et al. (2000) Dev Biol 224(2):299-311; Stickens et al. (2005) Development 132(22):5055-5068]. Rather than model the germ-line genotype, we modeled the chimeric tissue genotype of somatic loss of heterozygosity (LOH), by conditionally inactivating Ext1 via head-to-head loxP sites and temporally controlled Cre-recombinase in chondrocytes. These mice faithfully recapitulate the human phenotype of multiple metaphyseal osteochondromas. We also confirm homozygous disruption of Ext1 in osteochondroma chondrocytes and their origin in proliferating physeal chondrocytes. These results explain prior modeling failures with the necessity for somatic LOH in a developmentally regulated cell type.

Online information exchanges for parents of children with a rare health condition: key findings from an online support community.

BACKGROUND: The Internet provides new opportunities for parents of children with difficult illnesses and disabilities to find information and support. The Internet is particularly important for caregivers of children with special needs due to numerous health-related decisions they face. For at-risk populations, online support communities can become key settings and channels for health promotion and communication. OBJECTIVE: This study is an initial exploration of the information-seeking and information-provision processes present in an online support community, which is an area of opportunity and interest for Internet-based medical research and practice. The aim of this study was to explore and describe information-related processes of uncertainty management in relationship to clubfoot. Specifically, the study explored interpersonal communication (information seeking and provision) in an online support community serving the needs of parents of children with clubfoot. METHODS: The study population consisted of messages posted to an online community by caregivers (parents) of children with clubfoot. The theoretical framework informing the study was the Uncertainty Management Theory (UMT). The study used content analysis to explore and categorize the content of 775 messages. RESULTS: Women authored 664 of 775 messages (86%) and men authored 47 messages (6%). Caregivers managed uncertainty through information seeking and provision behaviors that were dynamic and multilayered. The ratio of information-seeking messages to information-provision responses was 1 to 4. All five types of information-seeking behaviors proposed by Brashers' schema were identified, most of them being correlated. Information seeking using direct questions was found to be positively correlated to self-disclosure (r=.538), offering of a candidate answer (r=.318), and passive information seeking (r=.253). Self-disclosure was found to be positively correlated to provision of a candidate answer (r=.324), second-guessing (r=.149), and passive information seeking (r=.366). Provision of a candidate answer was found to be positively correlated with second-guessing (r=.193) and passive information seeking (r=.223). Second-guessing was found to be positively correlated to passive information seeking (r=.311). All correlations reported above were statistically significant (P<0.01). Of the 775 messages analyzed, 255 (33%) identified a medical professional or institution by name. Detailed medical information was provided in 101 (13%) messages, with the main source of information identified being personal experience rather than medical sources. CONCLUSION: Online communities can be an effective channel for caregivers, especially women, to seek and offer information required for managing clubfoot-related uncertainty. To enhance communication with parents, health care institutions may need to invest additional resources in user-friendly online information sources and online interactions with caregivers of children with special illnesses such as clubfoot. Furthermore, explorations of information-seeking and information-provision behaviors in online communities can provide valuable data for interdisciplinary health research and practice.

Exploring the link between dystonia genes and idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is characterized by a complex curvature of the spine of unknown etiology. Unknown genetic factors likely play a role in disease pathogenesis. Recent studies suggest that AIS could result from central nervous system dysfunction and be related to dystonia. On the basis of this information, we hypothesized that genes linked to dystonia contribute to the pathogenesis of AIS. METHODS: To test this hypothesis, we evaluated the potential association between sequence variants in candidate dystonia genes and AIS. We sequenced the coding region of 5 selected dystonia-causing genes in 24 subjects with AIS, followed by targeted confirmation in additional 89 patients and 73 controls. RESULTS: No mutations were identified in any of the dystonia genes studied. CONCLUSIONS: We found no genetic link between dystonia and AIS. CLINICAL RELEVANCE: This investigation is a genetic evaluation of the association between dystonia and AIS. Despite the support in the literature for a pathogenic link between both the disorders, we have not identified any mutations in dystonia genes in patients with AIS.

Prereferral MRI use in patients with musculoskeletal tumors is not excessive.

BACKGROUND: Inappropriate MRI use has been targeted as a particular area of concern in orthopaedics, but it is unclear whether and to what extent its use is inappropriate in musculoskeletal oncology. QUESTIONS/PURPOSES: We therefore evaluated the incidence and cost of inappropriate prereferral MRI among patients with musculoskeletal tumors. METHODS: We retrospectively identified 920 patients treated in a musculoskeletal oncology clinic between 2009 and 2010. We accepted as necessary any MRI for a primary bone sarcoma, for biopsy-proven soft tissue sarcomas, for soft tissue masses greater than 5 cm in diameter, for soft tissue masses deep to the fascia, for painful soft tissue masses, and for growing soft tissue masses. Patients without these criteria were reviewed by a team of musculoskeletal oncologists to determine the necessity. The criteria for a repeat MRI were failure to show the tumor, lack of gadolinium contrast, lack of T1 or T2 MRI sequence, or poor image quality. Cost was determined using 2010 Medicare reimbursement rates. RESULTS: Of 920 patients, 320 (35%) arrived with a prereferral MRI study. Eight of the 320 (3%) studies were unnecessary, and 12 (4%) were necessary but were repeated. The cost was $11,474, which averages to $574 per study and $36 of waste per patient referred with an MRI study. CONCLUSIONS: Based on our data, we judged MRI use before referral to our tertiary center as not excessive. This is likely attributable, in part, to the relatively low use of MRI in our referral base. Inappropriate MRI use in patients with tumors may not be as widespread as previously reported. LEVEL OF EVIDENCE: Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.

Radiological findings for hip dysplasia at skeletal maturity. Validation of digital and manual measurement techniques.

OBJECTIVE: To report on intra-observer, inter-observer, and inter-method reliability and agreement for radiological measurements used in the diagnosis of hip dysplasia at skeletal maturity, as obtained by a manual and a digital measurement technique. MATERIALS AND METHODS: Pelvic radiographs from 95 participants (56 females) in a follow-up hip study of 18- to 19-year-old patients were included. Eleven radiological measurements relevant for hip dysplasia (Sharp's, Wiberg's, and Ogata's angles; acetabular roof angle of Tönnis; articulo-trochanteric distance; acetabular depth-width ratio; femoral head extrusion index; maximum teardrop width; and the joint space width in three different locations) were validated. Three observers measured the radiographs using both a digital measurement program and manually in AgfaWeb1000. Inter-method and inter- and intra-observer agreement were analyzed using the mean differences between the readings/readers, establishing the 95% limits of agreement. We also calculated the minimum detectable change and the intra-class correlation coefficient. RESULTS: Large variations among different radiological measurements were demonstrated. However, the variation was not related to the use of either the manual or digital measurement technique. For measurements with greater absolute values (Sharp's angle, femoral head extrusion index, and acetabular depth-width ratio) the inter- and intra-observer and inter-method agreements were better as compared to measurements with lower absolute values (acetabular roof angle, teardrop and joint space width). CONCLUSION: The inter- and intra-observer variation differs notably across different radiological measurements relevant for hip dysplasia at skeletal maturity, a fact that should be taken into account in clinical practice. The agreement between the manual and digital methods is good.

Relapse after tibialis anterior tendon transfer in idiopathic clubfoot treated by the Ponseti method.

BACKGROUND: The Ponseti method for clubfoot correction has demonstrated excellent results. However, relapses are common and continue to be the most important problem facing clubfoot practitioners. Relapses usually require repeated casting and/or surgical intervention with tibialis anterior tendon transfer (TATT). However, recent data on relapses suggest that performing a successful TATT may not be a definitive cure as there may be other processes, such as neuromuscular deficits, that may result in subsequent relapses. METHODS: The authors reviewed 66 patients (102 clubfeet) treated by TATT for clubfoot relapses after successful initial treatment by the Ponseti method. Ten patients (15 clubfeet) experienced a subsequent relapse. Demographic, clinical, and treatment data was recorded. RESULTS: These patients had a tendency toward a greater number of casts at initial treatment (P=0.14) and they underwent relapse surgery earlier than those who did not relapse after TATT (P=0.05). Two of these patients had a neuromyopathy, diagnosed by muscle biopsy. The treatment of post-TATT relapse included casting (6 patients), ankle foot orthotic (4 patients), physical therapy (2 patients), or bracing (1 patient). One patient was treated by osteotomies of the cuboid and medial cuneiform and 1 patient had a peroneus longus to peroneus brevis tendon transfer. CONCLUSIONS: Performing a TATT may not be the definitive treatment for clubfoot relapses as neuromuscular deficits may be involved. In addition, these patients may be at an increased risk of relapse due to the earlier age at which TATT was performed. When there is a high index of suspicion, prompt diagnosis with muscle biopsy is warranted. LEVEL OF EVIDENCE: Level III (Case-control study).

Treatment results of late-relapsing idiopathic clubfoot previously treated with the Ponseti method.

BACKGROUND: Idiopathic clubfoot has a stubborn tendency for relapse, with most relapses happening within the first few years. However, a few patients relapse later, adding to the complexity of management. This study investigates the treatment results of relapsing clubfoot deformity after age 4. METHODS: Thirty-nine patients (60 feet) met the inclusion criteria. Age at initial treatment, previous treatment, number of casts and tenotomies, length of bracewear, and relapse presentation were recorded. Treatment of late relapse followed 1 of the 5 courses: (1) observation only (4 feet); (2) bracing (26 feet); (3) casting followed by bracing (7 feet); (4) casting followed by tibialis anterior tendon transfer (TATT) with or without open tendo Achilles lengthening (TAL) (8 feet); or (5) primary TATT±TAL (15 feet). Of the 37 feet treated initially with observation, bracing, or casting, 33 went on to have TATT (89%). Multiple other concurrent procedures were performed according to the specific deformities. These included plantar fasciotomy (6 feet), extensor hallicus longus recession (5 feet), limited posterior release 5 feet, and others (3 feet). Five feet underwent revision surgery after TATT, 2 of which ended in triple arthrodeses. RESULTS: Average age at final follow-up was 23.3 years (range, 8.5 to 50.6 y). Ninety percent of patients wore regular shoes, 41% had pain with activities, but only 18% were limited in function by their feet. Average ankle dorsiflexion was 6 degrees (range, -15 to 25 degrees). Mild residual deformities were noted in 55% of feet. CONCLUSIONS: This challenging group of patients with apparently persistent deforming biology achieves acceptable results with individualized evaluation and treatment of their foot deformities. LEVEL OF EVIDENCE: Therapeutic level IV.

Development of a surrogate biomodel for the investigation of clubfoot bracing.

Congenital talipes equinovarus (clubfoot) is a complex deformity of the lower extremity and foot occurring in 1/1000 live births. Regardless of treatment, whether conservative or surgical, clubfoot has a stubborn tendency to relapse, thus requiring postcorrection bracing. However, to date, there are no investigations specifically focused on clubfoot bracing from a bioengineering perspective. This study applied engineering principles to clubfoot bracing through construction of a surrogate biomodel. The surrogate was developed to represent an average 5-year-old human subject capable of biomechanical characteristics including joint articulation and kinematics. The components include skeleton, articulating joints, muscle-tendon systems, and ligaments. A protocol was developed to measure muscle-tendon tension in resting and braced positions of the surrogate. Measurement error ranged from 1% to 6% and was considered variance due to brace and investigator. In conclusion, this study shows that surrogate biomodeling is an accurate and repeatable method to investigate clubfoot bracing. The methodology is an effective means to evaluate wide ranging brace options and can be used to assist in future brace development and the tuning of brace parameters. Such patient-specific brace tuning may also lead to advanced braces that increase compliance.

The current management of idiopathic clubfoot revisited: results of a survey of the POSNA membership.

BACKGROUND: In 2001, the members of the Pediatric Orthopaedic Society of North America (POSNA) were surveyed regarding their approach to treating idiopathic clubfoot deformity. Since that time, several studies have advocated a change in the approach to treating this deformity, moving away from surgical release and toward less invasive methods. The purpose of this study was to assess the recent approach to treating clubfoot among the POSNA membership. METHODS: A survey was emailed to all POSNA members to define their current treatment of idiopathic clubfoot deformity. RESULTS: We received 323 responses. Ninety-three percent of participants were fellowship trained and were in practice for an average of 17.2 years. On an average, physicians reported each treating 23.5 new clubfoot patients during the year of survey. Nearly all (96.7%) of those surveyed stated that they use the Ponseti treatment method. The average time to initial correction was estimated at 7.1 weeks. Eighty-one percent of patients were estimated to require a tenotomy; 52.7% were performed under general anesthesia or conscious sedation, whereas 39.4% were done under local. Those surveyed estimated that 22% of clubfeet relapsed and 7% required a comprehensive release. Seventy-five percent of the respondents stated that their current treatment approach differed from how they were trained, and 82.7% were trained in the Ponseti method in the last few years. CONCLUSIONS: Our study provides convincing evidence that a large majority of pediatric orthopaedic surgeons now prefer the Ponseti method to treat idiopathic clubfoot and indicates that the move away from extensive release surgery occurred during the past decade. LEVEL OF EVIDENCE: Not applicable.

Putative multifunctional signature of lung metastases in dedifferentiated chondrosarcoma.

Chondrosarcomas are among the most malignant skeletal tumors. Dedifferentiated chondrosarcoma is a highly aggressive subtype of chondrosarcoma, with lung metastases developing within a few months of diagnosis in 90% of patients. In this paper we performed comparative analyses of the transcriptomes of five individual metastatic lung lesions that were surgically resected from a patient with dedifferentiated chondrosarcoma. We document for the first time a high heterogeneity of gene expression profiles among the individual lung metastases. Moreover, we reveal a signature of "multifunctional" genes that are expressed in all metastatic lung lesions. Also, for the first time, we document the occurrence of massive macrophage infiltration in dedifferentiated chondrosarcoma lung metastases.

Common polymorphisms in human lysyl oxidase genes are not associated with the adolescent idiopathic scoliosis phenotype.

BACKGROUND: Although adolescent idiopathic scoliosis affects approximately 3% of adolescents, the genetic contributions have proven difficult to identify. Work in model organisms, including zebrafish, chickens, and mice, has implicated the lysyl oxidase family of enzymes in the development of scoliosis. We hypothesized that common polymorphisms in the five human lysyl oxidase genes (LOX, LOXL1, LOXL2, LOXL3, and LOXL4) may be associated with the phenotype of adolescent idiopathic scoliosis. METHODS: This was a case-control genetic association study. A total of 112 coding and tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 were genotyped in a discovery cohort of 138 cases and 411 controls. Genotypes were tested for association with adolescent idiopathic scoliosis by logistic regression with a two degree of freedom genotypic model and gender as a covariate. Fourteen SNPs with p < 0.1 in the discovery phase were genotyped in an independent replication cohort of 400 cases and 506 controls. RESULTS: No evidence for significant association was found between coding or tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 and the phenotype of adolescent idiopathic scoliosis. CONCLUSIONS: Despite suggestive evidence in model organisms, common variants and known coding SNPs in the five human lysyl oxidase genes do not confer increased genotypic risk for adolescent idiopathic scoliosis. The above methodology does not address rare variants or individually private mutations in these genes, and future research may focus on this area.