Robert K. Lark

Abnormal bone turnover in cystic fibrosis adults.

Abstract: Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption. The CF subjects had moderate lung disease (FEV1: 46.1 ± 18.6% predicted) and malnutrition (BMI: 20.0 ± 3.3 kg/m2). Only 3 subjects had normal BMD. CF subjects had higher urinary N-telopeptides of type I collagen (81.0 ± 60.0 vs 49.0 ± 24.2 nm BCE/mmol creatinine, p= 0.0006) and free deoxypyridinoline (7.3 ± 5.0 vs 5.3 ± 1.9 nM/mM, p= 0.004) levels than controls. Serum osteocalcin levels were similar in the two groups, a result confirmed by two immunoassays that recognize different epitopes on osteocalcin. Serum bone-specific alkaline phosphatase levels were elevated in CF patients (32.0 ± 11.3 vs 21.8 ± 7.0 U/l, p<0.0001), but were much more closely associated with serum total alkaline phosphatase levels (r = 0.51, p = 0.001) than with age or gender. Parathyroid hormone levels were elevated (p= 0.007) and 25-hydroxyvitamin D levels were depressed (p= 0.0002) in the CF patients in comparison with controls. These results indicate that adults with CF have increased bone resorption with little change in bone formation. Medications that decrease bone resorption or improve calcium homeostasis may be effective therapies for CF bone disease.

Neuromuscular Scoliosis: Current Concepts.

Scoliosis is a common deformity in neuromuscular disorders. This spinal deformity usually presents at an early age, rapidly progresses during growth, and continues to progress even after skeletal maturity. Neuromuscular scoliosis classically involves the entire thoracolumbar spine, often extending to the pelvis and causing pelvic obliquity. Physical examination can be challenging, but it is important to assess the flexibility of the spinal curve and associated joint contractures. Upright anteroposterior and lateral radiographs are the preferred imaging. When formulating a treatment plan, it is important to take into account not only the degree of curvature, but also each patients needs and quality of life, the potentially high perioperative complication rates, and the natural history of the underlying neuromuscular disorder. Different neuromuscular conditions behave differently and should therefore be treated differently. With the exception of steroids for Duchenne muscular dystrophy, bracing remains the only reliable nonoperative intervention available. Preoperative optimization of medical comorbidities is crucial given the relatively high complication rate. Posterior segmental instrumentation has revolutionized the surgical management of neuromuscular scoliosis and is the most commonly used technique today. Despite reported improvement in postoperative quality of life, there are several limitations with currently used outcome measures that prevent a well-informed discussion on the outcomes after surgery.

Bovine xenograft failures in pediatric foot reconstructive surgery.

Background: Structural bone grafting serves an important and necessary role during pediatric foot reconstruction. Different bone grafts have been used for such reconstructions including corticocancellous autografts, allografts, and synthetic grafts. Bovine xenografts represent a novel option with multiple potential advantages; however, there are limited clinical data on the efficacy and success of such grafts. This retrospective case series was performed to review the anecdotally recognized high failure rate of bovine xenograft transplantation in pediatric foot reconstruction at a tertiary institution. Materials and Methods: Ten pediatric patients with 13 feet underwent reconstructive procedures involving implantation of bovine xenografts for various foot deformities. The mean age at time of surgery was 14.1 years with an average clinical follow-up of 21.6 months. All patients received lateral column lengthening with additional various other reconstructive procedures performed by 3 separate orthopaedic surgeons in a similar step-wise manner. Clinical outcomes were obtained through a retrospective chart review of standard preoperative and postoperative clinical and radiographic data. Results: Seven of 13 (53.8%) bovine xenografts implanted resulted in clinical symptoms of failure with corresponding radiographic failed graft incorporation. The most common presenting symptom was foot pain with activity and each failure was easily identified on plain radiographs by lucency surrounding the graft sites. All 7 failures required a subsequent revision surgery to remove the bovine graft followed by placement of human iliac crest allograft. After revision surgery, each patient reported subjective improvement in pain and return to daily activity with radiographic evidence of complete incorporation of the graft. Conclusions: Bovine xenografts used as structural grafts in pediatric foot reconstruction resulted in unacceptably high rates of failure and the need for further revision surgery. For this reason, surgeons should be cautioned against the use of bovine xenograft material in the surgical management of pediatric foot deformity. Level of Evidence: Level IV case series.

Adding thoracic fusion levels in Lenke 5 curves: risks and benefits.

Study Design. Multicenter; review of prospectively collected data. Objective. To determine the risks and potential benefits of nonselective versus selective fusion in a matched set of patients with Lenke 5 curves. Summary of Background Data. The Lenke classification suggests a limited thoracolumbar/lumbar fusion for type 5 curves, although many experienced adolescent idiopathic scoliosis surgeons, at times, include a fusion of the thoracic curve. Methods. Prospectively collected cases from a multicenter database were analyzed. Patients with Lenke type 5 scoliosis curves were divided into 2 groups: 109 selective or short (only thoracolumbar/lumbar curve fused), and 41 nonselective or long (both thoracolumbar/lumbar and thoracic curves fused). Patients were then matched on the basis of the preoperative radiographical and clinical measures. Two-year postoperative radiographical and clinical outcomes were compared, using analysis of variance, with Bonferroni correction (P < 0.008). Results. Twenty-nine matched pairs (58 patients) with Lenke 5 curves were identified. There were no preoperative differences between groups in age, thoracic or lumbar Cobb angle, curve flexibility, thoracic kyphosis, clinical trunk flexibility, or Scoliosis Research Society outcomes questionnaire scores. Postoperatively, patients in the nonselective group exhibited greater coronal correction for thoracic (residual Cobb; 22° vs. 12°) and lumbar curves (residual Cobb; 19° vs. 13°). However, the longer fusions had significantly less thoracic kyphosis (27° vs. 18°), truncal side bending (14 vs. 10 cm), and rotational flexibility (53° vs. 42°). There was no difference in clinical balance or Scoliosis Research Society questionnaire, version 22, scores. Conclusion. Adolescent idiopathic scoliosis surgeons attempt to achieve balanced correction with the fewest motion segments fused. Our data suggest that fusion of the thoracic curve in primary thoracolumbar scoliosis may improve coronal correction, but at the cost of decreased thoracic kyphosis and clinical flexibility 2 years postoperatively.

Prevalence of Painful Peroneal Tubercles in the Pediatric Population

Pain isolated to the lateral aspect of the heel can be difficult to diagnose, particularly in the growing child. Peroneal tendinopathy or frank tears of the peroneal tendons secondary to an enlarged peroneal tubercle has been implicated as a potential source of pain in adults. Neither the prevalence of enlarged peroneal tubercles in the pediatric population nor the number of symptomatic tubercles in children has been elucidated. We conducted a review of children who presented to our institution with foot and/or ankle pain and who underwent 3-dimensional computed tomography. Initially, a radiographic review was undertaken of all computed tomography scans to determine the prevalence of peroneal tubercles in children. The peroneal tubercles were measured and then classified according to height. The children with tubercles 3 mm or greater in height (adult mean height) underwent a more detailed chart review to evaluate for the incidence of painful tubercles. During the study period, 2,689 children were seen for foot and ankle pain, and 367 underwent a computed tomography scan during their treatment course. Of these 367 patients, 57% had a measurable peroneal tubercle, and 162 (44%) met the criteria for chart review. Only 3 adolescents (1.9%) were found to have clinical symptoms and ultimately underwent surgical excision with successful relief of symptoms. Peroneal tubercle hypertrophy appears to exist in the pediatric population; however, in contrast to adults with associated peroneal tendinopathy and tears, the children in our series had isolated painful tubercles without significant tendinopathy. The clinical examination is important in the diagnosis, and treatment by excision appears to be successful. Although a relatively rare etiology of pain, it is important that treating physicians keep this pathologic process in the differential diagnosis, because conservative management might not reduce the pain in these children.

Radiographic outcomes of ring external fixation for malunion and nonunion.

Ring external fixators such as the Ilizarov external fixator (IEF) and Taylor Spatial Frame (TSF) have revolutionized management of limb deformity. This study examines radiographic outcomes for treatment of malunions and nonunions with secondary emphasis on comparing radiographic union rates of TSF and IEF. A retrospective chart and radiograph review was performed. Fifty-four patients were included. Most injuries were in the tibia (96%). Fifty patients (93%) achieved radiographic union, two patients required further fixation, and two patients elected to undergo amputation. The preoperative coronal deformity improved from a mean of 12° (range, 0°-41°) to within 3° anatomic. Sagittal deformity improved from a mean of 11° (range, 0°-49°) to within 5° anatomic with some patients intentionally left in recurvatum to accommodate plantarflexion contractures. Limb length discrepancies were corrected to within 1 cm. Twenty-five patients experienced complications (mostly superficial pin tract infections). No statistically significant differences in the radiographic outcomes of TSF compared to IEF were identified.

Loss-of-function in IRF2BPL is associated with neurological phenotypes

The Interferon Regulatory Factor 2 Binding Protein Like (IRF2BPL) gene encodes a member of the IRF2BP family of transcriptional regulators. Currently the biological function of this gene is obscure, and the gene has not been associated with a Mendelian disease. Here we describe seven individuals affected with neurological symptoms who carry damaging heterozygous variants in IRF2BPL. Five cases carrying nonsense variants in IRF2BPL resulting in a premature stop codon display severe neurodevelopmental regression, hypotonia, progressive ataxia, seizures, and a lack of coordination. Two additional individuals, both with missense variants, display global developmental delay and seizures and a relatively milder phenotype than those with nonsense alleles. The bioinformatics signature for IRF2BPL based on population genomics is consistent with a gene that is intolerant to variation. We show that the IRF2BPL ortholog in the fruit fly, called pits (protein interacting with Ttk69 and Sin3A), is broadly expressed including the nervous system. Complete loss of pits is lethal early in development, whereas partial knock-down with RNA interference in neurons leads to neurodegeneration, revealing requirement for this gene in proper neuronal function and maintenance. The nonsense variants in IRF2BPL identified in patients behave as severe loss-of-function alleles in this model organism, while ectopic expression of the missense variants leads to a range of phenotypes. Taken together, IRF2BPL and pits are required in the nervous system in humans and flies, and their loss leads to a range of neurological phenotypes in both species.

Pediatric Proximal Femur Fractures

Pediatric proximal femur fractures are rare injuries resulting from high-energy trauma. The Delbet classification is used when describing these injuries, and associates fracture type to the development of avascular necrosis. Historically, casting was utilized in the treatment of these injuries, but high complication rates following this approach have changed the treatment modality to early and anatomic fixation. Complications associated with these injuries including avascular necrosis, non-union, coxa-vara, and premature physeal fusion. Achieving anatomic reduction and performing internal fixation within 24 h from time of injury has become the standard of care in the treatment of pediatric proximal femur fractures.

Gradual Deformity Correction in Blount Disease.

BACKGROUND Blount disease is a disorder of the posteromedial proximal tibial physis which causes a progressive varus, procurvatum, and internal rotation deformity of the tibia. Untreated, it can cause significant limb malalignment. The goal of this study is to evaluate the results of correction of Blount disease using types of external fixation. METHODS We conducted a retrospective review of 41 patients (51 limbs) who underwent correction of Blount disease with an Ilizarov external fixator or a Taylor spatial frame (TSF) by a single surgeon. The medial proximal tibial angle (MPTA), mean axis deviation (MAD), posterior proximal tibial angle, and joint line congruence angle (JLCA) were measured on radiographs preoperatively, at frame removal and at final follow-up. RESULTS The average age at treatment was 9.6 years old, with a mean follow-up time of 34 months. Mean preoperative MPTA, MAD, and JLCA were significantly improved at the time of frame removal as well as at final follow-up with no significant changes in correction between the time of frame removal and final follow-up. There was no difference in MPTA and MAD in patients treated with an Ilizarov frame versus a TSF. MPTA, MAD, and JLCA all significantly improved regardless of the underlying diagnosis (infantile vs. adolescent Blount disease) or history of prior surgical intervention. The most common complication was superficial pin-site infection. CONCLUSIONS Both Iliazarov and TSF are viable treatment options for infantile and adolescent Blount disease, with the ability to significantly improve both the limb mechanical axis and the mechanical axis of the affected tibia. Correction can be attained regardless of whether patients have previously failed surgical intervention. LEVEL OF EVIDENCE Level III-retrospective comparative study.Background: Blount disease is a disorder of the posteromedial proximal tibial physis which causes a progressive varus, procurvatum, and internal rotation deformity of the tibia. Untreated, it can cause significant limb malalignment. The goal of this study is to evaluate the results of correction of Blount disease using types of external fixation. Methods: We conducted a retrospective review of 41 patients (51 limbs) who underwent correction of Blount disease with an Ilizarov external fixator or a Taylor spatial frame (TSF) by a single surgeon. The medial proximal tibial angle (MPTA), mean axis deviation (MAD), posterior proximal tibial angle, and joint line congruence angle (JLCA) were measured on radiographs preoperatively, at frame removal and at final follow-up. Results: The average age at treatment was 9.6 years old, with a mean follow-up time of 34 months. Mean preoperative MPTA, MAD, and JLCA were significantly improved at the time of frame removal as well as at final follow-up with no significant changes in correction between the time of frame removal and final follow-up. There was no difference in MPTA and MAD in patients treated with an Ilizarov frame versus a TSF. MPTA, MAD, and JLCA all significantly improved regardless of the underlying diagnosis (infantile vs. adolescent Blount disease) or history of prior surgical intervention. The most common complication was superficial pin-site infection. Conclusions: Both Iliazarov and TSF are viable treatment options for infantile and adolescent Blount disease, with the ability to significantly improve both the limb mechanical axis and the mechanical axis of the affected tibia. Correction can be attained regardless of whether patients have previously failed surgical intervention. Level of Evidence: Level III—retrospective comparative study.

Distant Harrington rod migration 35 years after implantation

Harrington rods have been successfully implanted in thousands of patients for the correction of scoliotic deformity since the 1950s. An exceedingly rare complication of Harrington rod placement is loosening with resultant migration. The authors present a 50-year-old woman who had a single Harrington rod placed when she was 15 years old. Thirty-five years later, she presented with acute sensory changes in her lower extremities. Imaging revealed rod failure and migration of the hardware distally, resulting in penetration of the wall of the rectum. Due to the unique anatomical position of the migrated hardware, sigmoidoscopy was used to directly visualize and remove the rod. The patient ultimately made a full recovery. Rod migration is an exceedingly rare complication that has been described only a few times since the introduction of Harrington rods over 60 years ago. The case herein is particularly unique given the extensive period of time that passed before migration (35 years) and the use of sigmoidoscopy for hardware removal.