BMPER variants associated with a novel, attenuated subtype of diaphanospondylodysostosis.

Diaphanospondylodysostosis (DSD), caused by loss of bone morphogenetic protein-binding endothelial regulator (BMPER), has been considered a lethal skeletal dysplasia characterized by severe deficiency of vertebral body and sacral ossification, reduced rib number and cystic kidneys. In this study, however, we have demonstrated that variants in BMPER may cause a milder disorder, without renal anomalies, that is compatible with long-term survival. Four siblings, three males and one female, presented with severe congenital scoliosis associated with rib and vertebral malformations as well as strikingly delayed ossification of the pedicles. The female was stillborn from an unrelated cause. Stabilization of the scoliosis with expandable titanium rods was successful in the three boys, all of whom have short stature. An autosomal recessive mode of inheritance was hypothesized. Single nucleotide polymorphism microarray analysis was performed for three of the siblings to identify autosomal genes with shared allele patterns, suggesting possible linkage. Exome sequencing of one sibling was then performed. Rare variants were identified in 347 genes with shared alleles. Only one of these genes had bi-allelic variants in a gene strongly expressed in paraxial mesenchyme: BMPER, which is the cause of DSD, an autosomal recessive disorder. The disorder described herein could represent an attenuated form of DSD or could be designated a separate entity such as spondylopedicular dysplasia.

The use of tissue sealants to deliver antibiotics to an orthopaedic surgical site with a titanium implant.

BACKGROUND: Orthopaedic surgery is associated with unacceptable infection rates that respond poorly to systemic antibiotics. The objective of this study was to use an animal model for orthopaedic implant infection to examine the ability of a new-generation fibrin tissue sealant to effectively deliver antibiotics to the surgical site. METHODS: The antibiotics cefazolin, fusidic acid or 5-fluorouracil were blended into Vitagel tissue sealant. The release rate of the drugs was measured using HPLC methods and bioactivity was measured by the zone of inhibition method with pathogenic Staphylococcus aureus. The antibiotic activity of the drug-loaded sealant was then tested in rats using infected orthopaedic surgical sites (titanium clip on spine). Efficacy was evaluated by residual bacterial counts on clips, clinical observations of infection, and histological findings. RESULTS: The drugs were released in a controlled manner over 2-4 days. All three antibiotics demonstrated strong antibacterial activity when released from the sealants. None of the treated animals demonstrated systemic illness. Post mortem dissection revealed a well-encapsulated abscess surrounding the titanium clip with erosion of the bony process. Using an inoculum of 1-5 × 10(3) CFU, treatment with antibiotic-loaded fibrin sealant demonstrated reduced infective swelling and reduced bacterial counts on surgical clip swabs compared to control rats or rats treated with antibiotic only. This model allowed for almost 100 % infectivity with a 0 % mortality rate due to infection, mimicking the clinical features of human implant infection. CONCLUSION: The results support the use of antibiotic-loaded commercially available fibrin sealants to prevent infection after implant surgery.

The epidemiology of nonaccidental trauma in children.

BACKGROUND: Abuse of children is abhorrent in Western society and, yet, is not uncommon. Nonaccidental trauma (NAT) is the result of a complex sociopathology. Not all of the causative factors of NAT are known, many are incompletely described, not all function in each case, and many are secondary to preexisting pathology in other areas. QUESTIONS/PURPOSES: We therefore addressed the following questions in this review: (1) what is the general incidence of NAT; (2) what factors are intrinsic to the abused child, family, and society; and (3) what orthopaedic injuries are common in NAT? METHODS: We searched Medline, Medline In Process & Other Non-Indexed Citations, and Embase using OVID. Only one article fit our inclusion criteria; therefore, this is a descriptive generalized review of the epidemiology of NAT. RESULTS: The general incidence of NAT ranges from 0.47 per 100,000 to 2000 per 100,000. Younger children are at greater risk of NAT than older children. Parents are often the perpetrators of the abuse. Rib fractures are highly indicative of NAT in young children. CONCLUSIONS: It is important to consider child, family, and societal factors when confronted with suspicions of child abuse. Our review demonstrates the currently limited information on the true incidence of NAT. To determine a much more accurate incidence of NAT, there needs to be a population-based surveillance program conducted through primary care providers.

Inter-observer and intra-observer agreement in the radiographic diagnosis of avascular necrosis of the femoral head following slipped capital femoral epiphysis.

INTRODUCTION: Slipped capital femoral epiphysis (SCFE) is a common pediatric hip disorder. Avascular necrosis (AVN) of the femoral head is a devastating complication of SCFE. The frequency of this complication reported in the literature has been variable. It was the objective of this study to estimate the inter- and intra-observer agreement between two experienced pediatric orthopaedic surgeons for the radiographic diagnosis of AVN following SCFE. METHODS: A retrospective review of all cases of SCFE treated at our center between 1995 and 2005 was performed. All cases of AVN and a random sample of 19 of the remaining cases were selected for study. The most recent anteroposterior and lateral radiographs were presented to two experienced pediatric orthopaedic surgeons in a random order. Inter-observer reliability was determined by calculating the kappa statistic to assess for clinical agreement. Each observer repeated this process two weeks after the initial review. RESULTS: There were a total of 103 cases of SCFE, of which four were diagnosed with AVN. The inter-observer agreement in the first trial was 0.79. The intra-observer agreement for the first observer was 0.9 and for the second observer, it was 0.88. CONCLUSION: The agreement, both inter- and intra-observer, for the radiographic diagnosis of AVN amongst adolescents with previous SCFE is very high. The results of this study suggest that the reported discrepancy of AVN in the literature following SCFE is not likely due to the lack of inter- and intra-observer agreement.

The effect of surgical timing on operative duration and quality of reduction in Type III supracondylar humeral fractures in children.

PURPOSE: To determine the influence of the time from injury to surgery of Type III supracondylar fractures on operative duration and quality of reduction. METHODS: A retrospective review of Type III supracondylar fractures treated by closed reduction and percutaneous pinning over a 3-year period was performed. RESULTS: The subjects were divided into two groups based on the time from injury to surgery (IST): Group 1 (<8 h) 48 subjects and Group 2 (>8 h) 39 subjects. There was no difference in the mean age or gender ratio between the two groups. There were no cases of compartment syndrome or conversion to open reduction in either group. The mean IST was 669 min. The mean IST for Group 1 was 340 min and it was 1,074 min for Group 2. The operative duration for Group 1 was 32.56 min and for Group 2 it was 31.72 min (P = 0.77). There were no significant differences in the quality of reduction. CONCLUSIONS: There was no difference in the operative duration demonstrated between IST <8 h and IST >8 h. This failure to demonstrate a difference should not be interpreted as demonstrating equivalence. This study does not conclude that all displaced supracondylar fractures should be delayed, though it does inform the surgeon that, if compelled to delay surgery, this series did not demonstrate an increased risk of complications, nor a worsened quality of reduction.

Pediatric and adult three-dimensional cervical spine kinematics: effect of age and sex through overall motion.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To determine the effect of age and sex on the three-dimensional kinematics of the cervical spine. SUMMARY OF BACKGROUND DATA: Spine kinematics information has important implications for biomechanical model development, anthropomorphic test device development, injury prevention, surgical treatment, and safety equipment design. There is a paucity of data of this type available for children, and it is unknown whether cervical spine kinematics of the pediatric population is different than that of adults. The helical axis of motion (HAM) of the spine provides unique information about the quantity and quality (coupling etc.) of the measured motion. METHODS: Ninety subjects were recruited and divided into 6 groups based on sex and age (young children aged 4-10 years, older children aged 11-17 years, adults aged 25+ years). Subjects actively moved their head in axial rotation, lateral bending, and flexion/extension. An optoelectronic motion analysis system recorded the position of infrared markers placed on the first thoracic vertebrae (T1) and on tight-fitting headgear worn by the subjects. HAM parameters were calculated for the head motion with respect to T1. RESULTS: HAM location in axial rotation and flexion/extension was more anterior in young females compared to adult females. Young females had a more anterior HAM location in flexion/extension compared to young males, indicating an effect of sex. For females, the HAM locations of adults were superior to those of children in flexion/extension and lateral bending whereas in males the HAM locations of adults were inferior to those of children. Age-related differences in HAM orientation were also observed in axial rotation and lateral bending. CONCLUSION.: Cervical spine kinematics vary with age and sex. The variation in spine mechanics based on age and sex found in the present study may indicate general trends that would grow stronger in even younger children (age <4 years).

Pediatric lumbar Chance fractures in British Columbia: chart review and analysis of the use of shoulder restraints in MVAs.

Chance fractures of the skeletally immature spine classically occur in frontal motor vehicle accidents (MVAs) when the occupants are restrained by a lap belt only and undergo traumatic hyperflexion of the torso during the impact. We retrospectively examined all MVA-related Chance fractures at British Columbia's Children's Hospital since 1986, by collecting injury and seat-belt use information from chart data and imaging studies. Twenty-six patients were included in the study, 14 wore a lap belt only, seven wore a three-point restraint properly, and five were reportedly misusing the shoulder portion of a three-point restraint. The subjects ranged in age from 3 to 16 with a mean age of 10.6 years. Eleven of the 26 (42%) patients sustained abdominal viscera injuries, seven of the 26 patients suffered neurologic injury (spinal cord and/or spinal nerve injury) associated with their spinal fracture, with two cases of complete paralysis, and there was a 38% incidence of head injury. Concomitant injuries (i.e. to the head, abdomen and abdominal contents) tended to be mitigated by the presence of a properly worn shoulder restraint. This leads to the conclusion that Chance fractures can be sustained even when the occupant is using a shoulder belt to restrain their torso. The mechanism responsible for this is unknown. This may indicate that Chance fractures can be caused by a lesser degree of torso hyperflexion than previously thought. Alternatively, we also speculate that Chance fractures can occur while the torso is restrained by the shoulder belt if the hips submarine beneath the lap belt and the torso experiences hyperflexion secondary to forward excursion of the pelvis and legs during the collision. Future work is necessary to confirm these mechanisms and to find ways to prevent them. These studies will need to use computational or experimental child surrogates that can sit in a slouched posture and submarine during a collision.

[A Jehovah's Witness child with hemophilia B and factor IX inhibitors undergoing scoliosis surgery].

PURPOSE: To describe the successful perioperative hemostatic management of a Jehovah's Witness patient with hemophilia B and anaphylactic inhibitors to factor IX, undergoing scoliosis surgery. CLINICAL FEATURES: A 14 (1/2)-yr-old boy with severe hemophilia B who had a history of anaphylactic inhibitors to factor IX was scheduled to undergo corrective scoliosis surgery. He was initially started on epoetin alfa and iron supplementation to maximize preoperative red cell mass. Additionally, he was placed on a desensitization protocol of recombinant coagulation factor IX (rFIX) and was then treated with activated recombinant coagulation factor VII (rFVIIa) during the postoperative period. Tranexamic acid was given concomitantly. The intraoperative blood loss was approximately 350 mL. The nadir hemoglobin concentration was 111 g.L(-1) on postoperative days one and two. On postoperative day 11, the patient was stable and discharged home with a hemoglobin of 138 g.L(-1). He did not require blood transfusion and no adverse events were observed. CONCLUSIONS: The use of rFIX, rFVIIa, erythropoetin, iron, and tranexamic acid before, during and after scoliosis surgery may be a viable and safe option for hemophilia patients with inhibitors, who refuse blood products.

Outcome analysis of chance fractures of the skeletally immature spine.

STUDY DESIGN: Observational. OBJECTIVE: The authors present a detailed description of 25 skeletally immature patients with Chance fractures with a mean follow-up of 6.4 years. SUMMARY OF BACKGROUND DATA: Since the legislation mandating seat belt usage in Canada was first introduced, the fatality rate of automobile collisions has decreased significantly. However, seat belts do not result in the complete elimination of injury. Fractures of the lumbar spine due to seat belts are well recognized in adolescents and adults but there are few reports in young children. METHODS: Radiographic images and patient records were analyzed for information on patient demographics and injury details. RESULTS: Treatment involved either posterior instrumentation (n = 16) or a conservative approach using casting or bracing (n = 9). Concomitant injuries were documented. A deformity index was developed as a simple value to take into account the severity of both anterior loss of vertebral height and posterior distraction. CONCLUSION: The deformity index was significantly higher in patients with a concomitants abdominal injury and significantly higher in patients managed operatively. Functional outcome scores were completed on 14 of the patients. Patients scored within the reported norms on the SF-36 version 2 but scored poorly on the pain and disability component of the AAOS lumbar specific questionnaire. These outcomes indicate a need for using an injury specific score to accurately quantify disability.

A clinicoradiologic study of the shoulder in Apert syndrome.

UNLABELLED: To provide a comprehensive radiographic, clinical, and functional description of the shoulder in Apert syndrome. METHODS: A cohort of 9 Apert syndrome patients (ages, 9-27 years) followed at a tertiary care facility was included in this prospective study. Patients were clinically assessed with physical examination and completion of 2 validated functional assessment tools, the Shoulder Pain and Disability Index (SPADI) and American Academy of Orthopaedic Surgeons Pediatric Outcomes Data Collection Instrument (AAOS PODCI). Radiographs were obtained of both shoulders, and standardized-protocol magnetic resonance imaging was performed on the dominant shoulder of all participants. RESULTS: All patients had some degree of functional impairment attributable to their shoulder pathologic abnormality. Physical examination consistently revealed reduced forward flexion and abduction. Radiographic findings were similar to previous reports, with pervasive osseous dysplasia of the shoulder joint. Medial humeral head hypoplasia was seen in 8 of 9 patients and greater tuberosity overgrowth in 7 of 9 patients. Magnetic resonance imaging of the shoulder, not previously performed in a cohort of Apert patients, allowed better delineation of abnormalities seen radiographically such as a central glenoid cleft seen in 8 of 9 patients. It also revealed a new finding of inferior glenoid inclination (7/9 patients) that has not been described in the literature. Very few soft tissue or degenerative abnormalities were demonstrated. CONCLUSIONS: The findings of this study confirm that patients with Apert syndrome are functionally impaired by their shoulder pathologic abnormality, which may have a similar clinical impact as the more well-described hand and foot anomalies. The global functioning of patients with Apert syndrome is equivalent to patients with juvenile rheumatoid arthritis. The shoulder range of motion in Apert patients is decreased, most significantly in flexion and abduction. Radiographs confirmed previous imaging findings of glenohumeral dysplasia. The novel magnetic resonance imaging component demonstrated consistent inferior glenoid inclination, which may be a significant factor in their shoulder impairment. Magnetic resonance imaging revealed no significant soft tissue or degenerative abnormalities to account for their clinical disability. These findings have potential relevance in the surgical and clinical management of these patients. LEVEL OF EVIDENCE: Level IV.

The mutant guppy syndrome curveback as a model for human heritable spinal curvature.

STUDY DESIGN: This study investigated the morphology, pathogenesis, and inheritance of idiopathic-like spinal curvature in the guppy syndrome, curveback. OBJECTIVE: To determine whether curveback could be applied as a model for the primary factors that contribute to heritable spinal curvature in humans, specifically, the etiopathogenesis of human familial idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Although a genetic basis is accepted, phenotypic complexity and the lack of an animal model with noninduced curvature have made identification of idiopathic scoliosis etiology difficult. It is well established that humans and fish share many genes with similar tissue and temporal expression characteristics, and comparisons between human and fish genomes have proven to be valuable for understanding the genetics of diseases affecting humans. METHODS: The curveback lineage of guppies was constructed from a single curved male crossed to a normal female. Offspring (103) from the original cross were scored from birth until death for the presence and magnitude of spinal curvature. Genetic architecture was investigated through selective inbreeding, analysis of the distribution of curve magnitude in the mature population, and assessment of curve dynamics during development. Computed tomography assessed vertebral detail. RESULTS: Computed tomography reveals that vertebral breakage or fusion is not associated with the curveback syndrome. Inbreeding demonstrates a strong genetic influence on curveback, and the distribution of curve magnitude among adult fish suggests polygenic inheritance. There is a female bias for curves of high magnitude and curves that resolve before maturity. There is developmental variability for the age of curve onset, curve progression, and final curve magnitude. CONCLUSIONS: Observed parallels between the curveback syndrome and human idiopathic scoliosis suggest that the guppy model is an unexploited resource for the identification of primary etiological factors involved in curvature. As models for biomedical research, teleosts offer great potential regarding spinal stability and deformity.

Post-surgical telehealth support for children and family care-givers.

Early discharge of children following surgery shifts the burden of care from professionals in hospital to family care-givers at home. We evaluated the relative effectiveness of telephone and videophone follow-up for children and families after a child's scoliosis surgery. Fourty-three patients and their families were enrolled in the study with 21 dyads receiving videophone and 22 dyads telephone support. At discharge, those in the intervention arm were provided with a videophone operating on the ordinary telephone network (PSTN). Data were gathered during telehealth contact on post-discharge day 3 and during extra calls with the clinic nurse, and during sessions with a research assistant comprising a follow-up call and an interview at the six-week post-surgical visit. Calls and interviews were recorded and transcribed. Data were analysed using constant comparative analysis. The results showed that videophone and telephone use provided care continuity for patients and their families following a child's back surgery. The relative effect of the videophone and telephone technology depended on the fit between the characteristics of the patients and families and the capacities of the technology. When implementing telehealth for follow-up care, a participatory process is recommended to ensure a fit between user characteristics and technology.

Use of fibrin sealants for the localized, controlled release of cefazolin.

BACKGROUND: Fibrin sealants are used increasingly in surgery to reduce bleeding and improve wound healing. They have great potential as biocompatible, biodegradable drug delivery systems, because the sealant may adhere to the target tissue and allow controlled release of the drug over an extended period. We investigated the encapsulation, stability and controlled release of erythromycin and cefazolin from Beriplast fibrin sealants (Aventis Behring Canada). METHODS: Drug-loaded clots were cast in glass vials and allowed to set. We observed the clots for drug precipitation and aggregation, and we assessed the effect of drug encapsulation on clot strength. Drug stability and release from the clots in phosphate buffered saline (PBS) was quantified by ultraviolet and visible violet absorbance spectroscopy and high-performance liquid chromatography. RESULTS: Erythromycin was found to release slowly from the fibrin clots over the first 2 hours but then degrade rapidly. Cefazolin was found to be very stable in clots in PBS (97% stable at 2 d and 93% stable at 5 d). The drug released in a controlled manner over 2 days, with most being released during the first day. The dose of drug released could be varied by changing the amount placed in the thrombin solution. Clot thickness had no effect on the rate of cefazolin release. CONCLUSION: Overall, the 2-day release profile and the excellent stability of the drug suggest that cefazolin-loaded fibrin sealants may offer an effective route of postoperative antibiotic delivery.

Abdominal aortic injuries associated with chance fractures in pediatric patients.

Injury to the abdominal aortic artery from blunt trauma is an infrequent event with few cases reported in either the adult or the pediatric literature. Injury to the thoracic aorta after blunt abdominal trauma is more common. It has been estimated that 95% to 99% of all aortic disruptions are in the thoracic region. Injury to the abdominal aorta is rarely seen in association with fractures of the lumbar spine secondary to seat belt use in motor vehicle accidents; there are few cases in the literature of these injuries in pediatric patients. Nevertheless, the overall mortality rate of this injury has been reported to be between 18% and 37%. It is therefore important to be aware of the possible association to allow prompt diagnosis and management of multitraumatized patients because extensive injuries to the abdominal viscera may mask aortic dissection and prognosis is significantly improved with early intervention.

The effect of interbody cage positioning on lumbosacral vertebral endplate failure in compression.

STUDY DESIGN: A biomechanical investigation using a human cadaver, multisegmental lumbosacral spine model. OBJECTIVES: To determine if 2 small, posterolaterally positioned titanium mesh interbody cages would provide superior construct strength and stiffness in compression compared to central cage placement. In addition, determine construct stiffness with interbody cages as opposed to an intact spine and assess the effect of bone mineral density (BMD). SUMMARY OF BACKGROUND DATA: Previous work has shown that the posterolateral corners of the lumbosacral endplates are stronger than the anterior and central regions. Information to suggest appropriate interbody cage positioning to avoid subsidence into adjacent vertebrae would be valuable for spine surgeons and implant designers. METHODS: A total of 27 functional spinal units from L3 to S1 were dual x-ray absorptiometry scanned for BMD, instrumented with pedicle screw systems, and tested to failure in compression with titanium mesh interbody cages placed in 1 of 3 positions: 2 small posterolateral, 2 small central, or 1 large central. Analysis of covariance was conducted to compare failure load and stiffness across the different cage configurations. Repeated measures analysis of variance was used to analyze stiffness between functional spinal units with intact disc, discectomy, or interbody cages. Failure load was correlated against BMD. RESULTS: Of the 3 placement patterns, 2 small titanium mesh cages in the posterolateral corners had 20% higher failure loads, although the difference was not significant (P = 0.20). Stiffness in compression for the 3 cage positions was not significantly different (P = 0.82). All intact discs with posterior instrumentation were significantly stiffer than any of the cage patterns (P = 0.0001). BMD of the vertebrae significantly correlated with failure loads (P = 0.007). CONCLUSIONS: The placement of 2 small interbody cages posterolaterally tended to result in higher failure loads than central cage placement, although the results were not statistically significant. It is noteworthy that cage placement in any position resulted in a less stiff construct in compression than with an intact disc.

Clinical usefulness of somatosensory evoked potentials for detection of brachial plexopathy secondary to malpositioning in scoliosis surgery.

STUDY DESIGN: A retrospective longitudinal study of 434 consecutive pediatric patients who underwent surgical correction of scoliosis, while being monitored for positional brachial plexopathy. OBJECTIVE: To evaluate the effectiveness of intermittent monitoring of ulnar nerve somatosensory evoked potentials (SSEPs) for detecting brachial plexus injury caused by malpositioning during scoliosis surgery. SUMMARY OF BACKGROUND DATA: Continuous intraoperative SSEP monitoring for spinal cord function has been well reported, and is widely accepted as the standard for spinal deformity correction surgery to detect and avoid neurologic injury. The use of SSEPs for the monitoring of ulnar nerve function intraoperatively as an indicator of brachial plexus function is becoming more accepted as a valid and useful technique to minimize intraoperative neurologic injuries during deformity corrections. METHODS: A review was conducted to assess the effect of ulnar nerve SSEP monitoring, as a measure of brachial plexus function, during anterior, posterior, or combined approach surgeries. The type of scoliosis, type of surgery and positioning, and surgical event at noted amplitude decrease were included in an analysis of variance for repeated measures, and a Student t test was performed for significant differences. RESULTS: A total of 27 patients had ulnar nerve amplitude decreases of > or =30%, resulting in a point prevalence of 6.2% for positional brachial plexopathy during positioning for all scoliosis surgeries. A significant difference was noted between the types of positioning, with prone positioning accounting for a higher rate of brachial plexopathy compared with anterior approach positioning (P < 0.01). No statistical difference exists as to the type of scoliosis present and the incidence of brachial plexopathy (P < 0.01). CONCLUSIONS: Avoidance of neurologic injury to the brachial plexus during scoliosis surgery is possible by early detection with ulnar nerve SSEP monitoring.

Sternal split approach to the cervicothoracic junction in children.

STUDY DESIGN: We present a descriptive case series outlining the surgical technique and outcome in six patients managed with a combined anterior neck and sternal splitting approach. OBJECTIVES: To describe a surgical approach used in the management of severe cervicothoracic kyphosis and/or scoliosis in pediatric patients. SUMMARY OF BACKGROUND DATA: There are few reports in the literature that address the problem of accessing multileveled spinal deformities around the cervicothoracic junction requiring stabilization in the pediatric population. METHODS: A detailed chart and radiographic review was completed of six consecutive patients managed at our center with a combined anterior neck and sternal splitting approach. The indications, surgical technique, and outcome are reviewed for each case. This technique was employed in 6 pediatric patients, aged 3-15 years, at the authors' institution. Diagnoses included Klippel-Feil Syndrome (2 patients), Proteus Syndrome, Larsen Syndrome, and neurofibromatosis type I (2 patients). All patients had severe cervicothoracic kyphosis requiring surgical instrumentation. This technique allowed surgical access from C5-T6. RESULTS: This approach was invaluable in gaining access to the cervicothoracic junction to address complex spinal deformities in pediatric patients. In one patient, a separate thoracotomy was performed to access the lower thoracic spine. The only significant complication related to the approach was recurrent laryngeal nerve palsy experienced by one patient. This approach allowed stabilization of severe scoliotic and/or kyphotic deformities to impede curve progression. CONCLUSIONS: This approach was invaluable in gaining multileveled access to the cervicothoracic junction to address complex spinal deformities in pediatric patients.