Mutations Preventing Regulated Exon Skipping in MET Cause Osteofibrous Dysplasia.

The periosteum contributes to bone repair and maintenance of cortical bone mass. In contrast to the understanding of bone development within the epiphyseal growth plate, factors that regulate periosteal osteogenesis have not been studied as intensively. Osteofibrous dysplasia (OFD) is a congenital disorder of osteogenesis and is typically sporadic and characterized by radiolucent lesions affecting the cortical bone immediately under the periosteum of the tibia and fibula. We identified germline mutations in MET, encoding a receptor tyrosine kinase, that segregate with an autosomal-dominant form of OFD in three families and a mutation in a fourth affected subject from a simplex family and with bilateral disease. Mutations identified in all families with dominant inheritance and in the one simplex subject with bilateral disease abolished the splice inclusion of exon 14 in MET transcripts, which resulted in a MET receptor (MET(Δ14)) lacking a cytoplasmic juxtamembrane domain. Splice exclusion of this domain occurs during normal embryonic development, and forced induction of this exon-exclusion event retarded osteoblastic differentiation in vitro and inhibited bone-matrix mineralization. In an additional subject with unilateral OFD, we identified a somatic MET mutation, also affecting exon 14, that substituted a tyrosine residue critical for MET receptor turnover and, as in the case of the MET(Δ14) mutations, had a stabilizing effect on the mature protein. Taken together, these data show that aberrant MET regulation via the juxtamembrane domain subverts core MET receptor functions that regulate osteogenesis within cortical diaphyseal bone.

Pediatric calcaneal osteomyelitis.

BACKGROUND: Osteomyelitis continues to be a common problem amongst the pediatric population. Osteomyelitis of the calcaneus is an uncommon problem that still poses a problem to the treating physician. The purpose of this article is to retrospectively review a large series of pediatric patients with calcaneal osteomyelitis. We compare our experience with that in the literature to determine any factors that may aid earlier diagnosis and or improve treatment outcomes. METHODS: A 10-year retrospective review was performed of clinical records of all cases of pediatric calcaneal osteomyelitis managed at the 2 children's orthopaedic departments in the Auckland region. The Osteomyelitis Database was used to identify all cases between 1997 and 2007, at Starship Children's Hospital, and 1998 and 2008 at Middlemore's Kids First Hospital. RESULTS: Sixty patients fulfilled the inclusion criteria, and had a review of clinical notes and relevant investigations. The average duration of symptoms before presentation to hospital was 6.8 days. About 40% of patients had a recent episode of trauma. About 82% of patients could not bear weight on admission. Only 22% of patients had a temperature above 38°C. Erythrocyte sedimentation rate was elevated in 81% and the C-reactive protein was elevated in 77% of patients. About 27% of patients had positive blood cultures with Staphylococcus aureus being the most commonly cultured organism. X-rays, bone scans, and magnetic resonance imaging were all used to aid the diagnosis. About 20% of patients had surgery with an average of 1.3 surgeries for those who progressed to surgery. Treatment length was an average of 2 weeks 6 days of intravenous antibiotics followed by 3 weeks 2 days of oral treatment. There were no postsurgical complications and 10 readmissions: 3 for relapse, 3 for peripherally inserted central catheter line problems, and 4 for antibiotic-associated complications. CONCLUSIONS: Although sometimes more difficult to diagnose, calcaneal osteomyelitis can be diagnosed with an appropriate history, clinical examination, and investigations. Treatment with intravenous and oral antibiotics and surgical debridement if indicated can lead to a good clinical outcome with minimal complications.

Decompression alone vs. decompression plus fusion for claudication secondary to lumbar spinal stenosis.

BACKGROUND: Degenerative lumbar spinal stenosis is a common condition, predominantly affecting middle-aged and elderly people. This study focused on patients with neurogenic claudication secondary to lumbar stenosis without spondylolisthesis or deformity. PURPOSE: To determine whether the addition of fusion to decompression resulted in improved clinical outcomes at 3, 12, and 24 months postsurgery. STUDY DESIGN/SETTING: The Canadian Spine Outcomes and Research Network (CSORN) prospective database that includes pre- and postoperative data from tertiary care hospitals. PATIENT SAMPLE: The CSORN database was queried for consecutive spine surgery cases of degenerative lumbar stenosis receiving surgical decompression for neurogenic claudication or radiculopathy. Neurogenic claudication patients with baseline and 2-year follow-up data, from four sites, formed the study sample (n=306). The sample was categorized into two groups: (1) those that had decompression alone, and (2) those that underwent decompression plus fusion. OUTCOME MEASURES: Change in modified Oswestry Disability Index (ODI), numerical rating scale for back/leg pain, the EuroQol EQ5D, the SF-12 physical, and mental component scores. The primary outcome measure was the ODI at 2 years postoperative. METHODS: We conducted a multicenter, ambispective review of consecutive spine surgery patients enrolled between October 2012 and January 2018. RESULTS: Baseline characteristics were comparable between groups except for female sex and multilevel pathology (both with greater proportion in the decompression plus fusion group). The decompression plus fusion group had clinically meaningfully more operative time, blood loss, rate of perioperative complication, and length of hospital stay (p<.05). These differences were preserved following adjustment for baseline differences between the groups. Both decompression and decompression plus fusion had a large clinically meaningful impact on generic and disease-specific patient-reported outcome measures within 3 months of surgery which was maintained out to 24-month follow-up. At any follow-up time point, there was no statistical evidence of a difference in these effects favoring decompression plus fusion over decompression alone. CONCLUSIONS: The addition of fusion to decompression did not result in improved outcomes at 3-, 12-, or 24-month follow-up. The addition of fusion to decompression provides no advantage to decompression alone for the treatment of patients with neurogenic claudication secondary to lumbar stenosis without spondylolisthesis or deformity.

Is spinal surgery safe in octogenarians?

BACKGROUND: An ageing population and advances in medical management often requires spinal surgeons to increasingly operate on patients older than 80 years. The ability to predict complications and mortality rates would allow discrimination of which octogenarians are able to safely undergo spinal surgery. Therefore, the aims of this study were to determine whether comorbidities and extent of surgery were associated with complications in this age group, in addition to which comorbidity and physical status assessment scales were best associated with the development of complications following spinal surgery. METHODS: A retrospective cohort study was performed. Comorbidities and physical health status were analysed using the American Society of Anesthesiologists (ASA) physical illness rating, Charlson Comorbidity Index (CCI) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score. Complications and extent of operation were sourced from patient records. The association between comorbidities/extent of operation and complications was analysed using negative binomial regression analysis. RESULTS: A total of 54 patients were included in our study (22 elective and 32 emergency); 38 patients suffered at least one complication (14 elective and 24 emergency, including six deaths). Increased CIRS-G and CCI scores were associated with increased incidence of total complications in the elective cohort. Increased number of operated spinal levels was also associated with complications. CONCLUSION: Elective spinal surgery can be safely performed in well selected patients over 80 years of age. However, extent of surgery, CIRS-G and CCI scores were associated with increased complications from spinal surgery in octogenarians.