Frances A. Farley

Pain management in children with and without cognitive impairment following spine fusion surgery

Background: We compared pain assessment and management practices in children with and without cognitive impairment (CI) undergoing spine fusion surgery.

Denosumab treatment for fibrous dysplasia

Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)‐regulating protein, α‐subunit of the Gs stimulatory protein (Gsα). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF‐κB ligand (RANKL) is a cell‐surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD‐like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal‐related events from bone metastases. We present the case of a 9‐year‐old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross‐linked C‐telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD‐related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases.

Cosegregation of Open-angle Glaucoma and the Nail-Patella Syndrome

PURPOSE To evaluate two families ascertained only for the presence of glaucoma in which both nail-patella syndrome and glaucoma occur in several generations and to determine whether the two diseases are genetically related. METHODS Ophthalmologic examinations and orthopedic examinations were performed. DNA samples from family members were screened with a microsatellite repeat marker at the argininosuccinate synthetase (ASS) locus at 9q34, and linkage analysis was performed. RESULTS Six patients with open-angle glaucoma were found among 13 patients with nail-patella syndrome in family UM:47. Seven patients with glaucoma were found among 11 patients with nail-patella syndrome in family UM:65. In both families, all individuals with glaucoma also had nail-patella syndrome. Two-point linkage analysis resulted in a lod score of 2.98 at a recombination fraction of 0.00 for open-angle glaucoma and nail-patella syndrome. CONCLUSIONS Linkage results presented here provide strong evidence that the orthopedic and nail anomalies in these two families result from the same nail-patella syndrome locus that has been previously linked to markers at 9q34. These data provide indirect evidence for a possible glaucoma locus at 9q34 and do not allow us to distinguish whether the glaucoma is the result of the nail-patella syndrome mutation or whether there is a separate locus responsible for glaucoma in these families. These studies suggest a need for ophthalmologic examination of individuals with nail-patella syndrome.

Low-dose ketorolac improves analgesia and reduces morphine requirements following posterior spinal fusion in adolescents

PurposeTo determine if low-dose ketorolac would improve analgesia while minimizing unwanted side effects in adolescents following posterior spinal fusion (PSF).MethodsA prospective randomized double-blind placebo-controlled trial assessed the analgesic effects of low-dose ketorolac following PSF. Thirty-five adolescents aged 11–17 yr were randomly assigned to receive placebo or 0.5 mg·kg−1 ketorolac (maximum of 15 mg) six hourly postoperatively for 36 hr in conjunction with standard morphine patient controlled analgesia (PCA). Pain and sedation were assessed twice daily for the first three postoperative days (POD). The incidence of side effects related to both non-steroidal anti-inflammatory agents and opioids were recorded.ResultsAdolescents in the ketorolac group received an average dose of 0.2 mg·kg−1 (average exposure 1.2 mg·kg−1), had lower pain scores on POD one and two (P < 0.05) and consumed less morphine in the postanesthesia care unit and on POD two. There was no difference in the incidence of pruritus, nausea, vomiting or constipation, but patients in the ketorolac group tolerated activity better on POD one (P < 0.05). There were no differences between groups with regard to postoperative blood loss or transfusion requirements. Fourteen patients were followed for two years and the incidence of curve progression, hardware failure or back pain at final follow-up was not different.ConclusionLow-dose ketorolac in conjunction with morphine PGA improved the quality of analgesia and reduced morphine requirements following PSF compared to placebo without increasing the incidence of non-steroidal anti-inflammatory side effects.RésuméObjectifDéterminer si une faible dose de kétorolac améliore l’analgésie tout en réduisant les effets secondaires chez des adolescents qui ont subi une spondylodèse postérieure (SDP).MéthodeUn essai à double insu, randomisé et contrôlé contre placebo a permis d’évaluer les effets analgésiques d’une faible dose de kétorolac administrée après une SDR Trente-cinq adolescents de 11–17 ans ont été répartis de manière aléatoire et ont reçu, soit un placebo, soit 0,5 mg·kg−1 de kétorolac (maximum de 15 mg) toutes les six heures après l’opération et ce, pendant 36 h en conjonction avec de la morphine normale en analgésie autocontrôlée (AAC). La douleur et la sédation ont été évaluées deux fois par jour pour les trois premiers jours postopératoires (JPO). L’incidence d’effets secondaires reliés aux anti-inflammatoires non stéroïdiens (AINS) et aux opioïdes a été notée.RésultatsLes sujets qui ont eu du kétorolac ont reçu une dose moyenne de 0,2 mg·kg−1 (exposition moyenne de 1,2 mg·kg−1), ont présenté des scores de douleur plus faibles aux JPO un et deux (P < 0,05) et ont pris moins de morphine à la salle de réveil et au deuxième JPO. Lincidence de prurit, nausées, vomissements ou constipation était comparable dans les deux groupes, mais les mouvements étaient mieux tolérés avec le kétorolac au premier JPO (P < 0,05). La perte sanguine postopératoire et les besoins de transfusion ont été comparables. Quatorze patients ont été suivis pendant deux ans et l’incidence de la progression de la courbe, de la défaillance du matériel ou de la douleur au dos n’était pas différente au dernier examen de suivi.ConclusionUne faible dose de kétorolac, administrée avec de la morphine en AAC, améliore la qualité de l’analgésie et réduit les besoins de morphine à la suite d’un SDP, en comparaison avec un placebo, et sans augmenter l’incidence d’effets secondaires des AINS.

The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis

Study Design. A matched, case‐control study comparing melatonin production in female patients with and without adolescent idiopathic scoliosis. Objectives. To determine whether melatonin production is decreased in adolescent idiopathic scoliosis. Summary of Background Data. A central etiology for idiopathic scoliosis has never been established. Previous authors have produced experimental scoliosis in chickens after pinealectomy, preventable by administration of melatonin. They suggested that a defect in melatonin synthesis might be involved in the pathogenesis of human idiopathic scoliosis. Methods. Nine female adolescents with no medical problems, normal neurologic examinations, radiographic idiopathic scoliosis of 15‐40°, and Risser Stage I‐III were in the patient group. Eighteen healthy adolescent girls with no medical problems, a negative school screening, and no family history of scoliosis were control subjects. Patients and control subjects were matched for age, weight, Tanner stage, sleep duration, and light exposure by multiple linear regression. Nighttime and daytime urine samples were analyzed for melatonin by high‐performance liquid chromatography. Results. Although nighttime melatonin levels were significantly higher than daytime levels in all volunteers (P < 0.00002), there were no significant differences in nighttime (P > 0.63) or daytime (P > 0.78) melatonin levels between patients and control subjects, even after matching by multiple linear regression analysis. A statistical analysis demonstrated that if a melatonin deficiency of 25% or more did exist in patients with scoliosis compared with control subjects, the likelihood that it would have been detected in this study was more than 98%. Conclusion. Although melatonin deficiency may cause scoliosis in the chicken, this study suggests that it is not a mechanism in the pathogenesis of adolescent idiopathic scoliosis in humans.

Compression plating of pediatric femoral shaft fractures.

The authors conducted a retrospective review of 60 children under the age of 16 years with femoral shaft fractures treated with compression plate fixation. All patients were followed to hardware removal. The 100% union rate and low complication rate after compression plate fixation of pediatric femur fractures compared favorably to the literature of other treatment options. Compression plate fixation is a safe and effective treatment in children with both isolated femoral shaft fractures and those associated with multiple injuries.

Syringomyelia and scoliosis in children.

We reviewed 28 patients < 18 years of age with scoliosis and syringomyelia. Children with scoliosis and syringomyelia had an equal incidence of left- and right-sided curves with a normal sagittal alignment. Most were first seen at Risser 0 with significant curves, and curve progression occurred in half of the patients. Bracing was not effective in preventing curve progression. Neurologic signs, present in most children, stabilized after syrinx drainage. Neither the sex or age of the child, nor the type of curve, nor the drainage of the syrinx was predictive of curve progression.

Operative versus nonoperative treatment of midshaft clavicle fractures in adolescents.

Background Midshaft clavicle fractures in adolescents have traditionally been treated nonoperatively. Recent studies in the adult literature have shown a higher prevalence of symptomatic malunion, nonunion, and poor functional outcome after nonoperative treatment of displaced fractures. The purpose of this study was to compare operative versus nonoperative treatment of displaced clavicle fractures in adolescents. Materials and Methods Adolescents who sustained closed midshaft clavicle fractures between 2000 and 2008 were identified in our institutional trauma registry. Medical records were reviewed for patient demographics, injury characteristics, treatment, and outcomes. Results Forty-two consecutive patients (mean age 15.4 y) with 43 closed midshaft clavicle fractures were identified. Twenty-five patients were treated nonoperatively with a sling or figure-of-8 brace. Seventeen patients were treated operatively with acute plate fixation for fractures displaced more than 2 centimeters. The average shortening at injury was 12.5 mm in the nonoperative group and 27.5 mm in the operative group (P=0.003). The mean time to radiographic union for displaced fractures was 8.7 weeks in the nonoperative group and 7.4 weeks in the operative group (P=0.02). There were no nonunions in either group. All complications in the operative group were related to local hardware prominence. The mean time to return to activities was 16 weeks in the nonoperative group and 12 weeks in the operative group. Symptomatic malunion, with a mean fracture shortening of 26 mm, developed in 5 patients in the nonoperative group. Four of these patients elected corrective osteotomy with internal fixation and all went on to union with resolution of their symptoms. Conclusions Plate fixation of displaced midshaft clavicle fracture reliably restores length and alignment. It resulted in shorter time to union with low complication rates. Symptomatic malunion in adolescents may be more common than earlier thought after significantly displaced fractures. Corrective osteotomy with plate fixation can restore clavicle anatomy and eliminate symptoms associated with malunion. Level of Evidence Therapeutic level III.

Community-associated methicillin-resistant Staphylococcus aureus in acute musculoskeletal infection in children: a game changer.

Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a virulent pathogen responsible for an increasing number of invasive musculoskeletal infections in healthy children. The purpose of this study is to characterize the presentation, clinical course, treatment, complications, and long-term morbidity of CA-MRSA musculoskeletal infection in children. Methods A retrospective study of children with CA-MRSA musculoskeletal infections from 2 institutions was conducted. Results The study group included 27 patients. Clinical presentation involved an extremity in 23 of 27 patients. Twelve patients required admission to the intensive care unit. Four of these patients developed acute multisystem failure. Magnetic resonance imaging was obtained in 21 patients and was diagnostic in all. Seven patients developed deep venous thrombosis and septic pulmonary emboli. All patients required surgical intervention, and 16 of 27 required multiple debridements. Conclusions CA-MRSA is limb and life threatening. Prompt recognition and treatment are critical. Aggressive surgical drainage/debridement in addition to long-term antibiotics is required. There is significant potential for long-term morbidity despite aggressive management. Level of Evidence Level IV, retrospective case series.

Narrow window of bone age in children with slipped capital femoral epiphyses

Summary Pelvis radiographs of 30 children with slipped capital femoral epiphyses (SCFE) were reviewed by four readers to determine the skeletal age. The average chronologic age for girls was 12.1 ± 1.0 years and that for boys was 14.4 ± 1.3 years; the average pelvic bone age was 13.2 ± 0.6 for girls and 15.1 ± 0.6 years for boys. The chronologic age range was 98 months, and skeletal age range was only 50 months. Pelvis bone age was advanced in the youngest children, normal in most children, and mildly delayed in older children. We conclude that there is a uniform skeletal age or “narrow window” during which epiphyseal slipping occurs, regardless of the childs chronologic age.