Real-world effectiveness of burosumab in children with X-linked hypophosphatemic rickets.

BACKGROUND: X-linked hypophosphatemic rickets (XLH) is the most common cause of inherited rickets. Historically, XLH was treated with oral phosphate and calcitriol (conventional treatment). Burosumab, a fibroblast growth factor 23 (FGF-23) monoclonal antibody, was approved by the United States Food and Drug Administration (FDA) in 2018 for XLH treatment. Nevertheless, conventional treatment of XLH continues to be recommended by some specialists due to lack of published experience with burosumab in the clinical setting. We compared laboratory and radiographic changes observed following transition from conventional therapy to burosumab in pediatric XLH patients as part of routine care. METHODS: This retrospective single-center study identified and retroactively studied twelve patients aged 1-18 years old with XLH previously treated with conventional therapy and transitioned to burosumab. Laboratory studies and radiographs were obtained routinely as standard of care during two treatment periods: (1) conventional therapy and (2) burosumab treatment. Laboratory values and radiologic rickets severity scores were compared between periods. RESULTS: All laboratory values demonstrated improvement following 1 month of burosumab treatment, findings which were sustained over the 2-year study period. Rickets severity scores and height z-scores also improved with burosumab. There were no serious adverse events with burosumab, and adverse events overall were very infrequent and mild. One patient developed an asymptomatic mild elevation of serum phosphate while taking burosumab resulting in a temporary pause in therapy. CONCLUSIONS: Safety and effectiveness of burosumab in treatment of XLH were demonstrated as burosumab yielded statistically significant improvement in laboratory and radiographic markers of rickets and height compared to conventional therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sagittal Plane Deformities in Children with SMA2 following Posterior Spinal Instrumentation.

This is a retrospective radiographic review to assess post-operative sagittal plane deformities in patients with Spinal Muscular Atrophy type 2 that had been treated with posterior spinal instrumentation. Thirty-two patients with a history of either spinal fusion (N = 20) or growing rods (N = 12) were identified with an average of 7.6 (2.1-16.6) years post-operative follow-up. Forty percent (13/32) of the patients were identified as having obvious "tucked chin" (N = 4), "tipped trunk" (N = 9), or both (N = 3). Sacral incidence was the only parameter that was statistically significant change between pre-operative or immediate post-operative measurements (66.9° vs. 55.2° p = 0.03). However, at final follow-up, the post-operative thoracic kyphosis had decreased over time in those that developed a subsequent sagittal deformity (24.2°) whereas it increased in those that did not (44.7°, p = 0.008). This decrease in thoracic kyphosis throughout the instrumented levels, resulted in a greater lordotic imbalance (30.4° vs. 5.6°, p = 0.001) throughout the instrumented levels in the group that developed the subsequent cervical or pelvic sagittal deformities. In conclusion, sagittal plane deformities commonly develop outside the instrumented levels in children with SMA type 2 following posterior spinal instrumentation and may be the result of lordotic imbalance that occurs through continued anterior growth following posterior instrumentation.

Is prophylactic formal fusion with implant revision necessary in non-ambulatory children with spinal muscular atrophy and growing rods who are no longer lengthened?

STUDY DESIGN: Single center, retrospective chart review. OBJECTIVES: To determine if routine posterior spinal fusion (PSF) is unnecessary in non-ambulatory growing rod graduates with SMA. Most non-ambulatory children with SMA develop early-onset scoliosis (EOS). Posterior growing rods (GR) have been shown safe and effective in managing spinal deformities in these children. The best management of these children, once graduated from their GR, is currently unknown. In this study, we report the clinical results of managing these children without routine definitive fusion following a course of GR treatment. METHODS: A single-center, retrospective chart and radiographic review was performed on children with SMA treated with posterior distraction GR, with a two-year minimum follow-up since final lengthening. Electronic medical records and radiographs were reviewed for demographic variables, Cobb measurements, implant revisions, occult radiographic implant failure, symptomatic failure, and/or conversion to PSF. RESULT: 12 patients (2 type 1, 9 type 2, 1 type 1/2) met inclusion criteria. Mean age at growing rod insertion was 6.2 years of age (range 4.1-8.2) and age at final lengthening 10.3 years of age (range 9.3-11.9). The mean time between last lengthening and latest clinical or radiographic review was 5.5 (range 2.1-9.0) years. Average mean pre, post, final Cobb angles were 71°, 27° (p < 0.001), 25°. Following final lengthening, only one patient required hardware revision and conversion to definitive fusion in attempts to alleviate chronic hip pain, which was unsuccessful. One additional patient was found to have an occult rod failure that has not required treatment. CONCLUSION: While limited by sample size, this single-center cohort of non-ambulatory SMA patients with EOS treated with similar constructs suggests that routine, definitive fusion in SMA GR graduates may be unnecessary. LEVEL OF EVIDENCE: Level IV.

Pediatric cholangiopathies: diseases of the gallbladder and biliary tract.

Pediatric gallbladder and bile duct disease encompasses a broad spectrum of processes, from congenital to developmental to neoplastic. We describe normal pediatric biliary anatomy and summarize the most common pathologic entities, with a focus on non-invasive imaging techniques and findings. Ultrasound is the first-line imaging modality in children with suspected biliary pathology based on its widespread availability, cost effectiveness, and lack of ionizing radiation. MRI and MRCP are often used for further evaluation in cases of diagnostic uncertainty and for surgical planning.

Pediatric Gastrojejunostomy Tube Replacement: Effects of Communication on the Need for After-Hours Procedures.

OBJECTIVES: The aim of the study was to determine whether embedding into the radiology report a patient-specific plan in the event of gastrojejunostomy (GJ) tube dysfunction reduces the need for after-hours utilization of pediatric interventional radiology resources for the replacement of GJ tubes. MATERIALS AND METHODS: This is a Health Insurance Portability and Accountability Act compliant, institutional review board-approved retrospective repeated cross-sectional study of patients requiring after-hours (5 PM-7 AM) or weekend (Saturday and Sunday) GJ tube replacement at a dedicated children's hospital, before and after the inclusion of a patient-specific plan in the radiology report as part of the electronic medical record. RESULTS: During a 6-month period before the inclusion of a patient-specific plan, there were 242 total GJ tube changes performed by the pediatric interventional radiology service under image guidance. Twenty-six (10.7%) of these procedures were performed outside of standard operating hours at the request of the emergency department (ED) (6/26), inpatient service (8/26), or patient/caregiver (12/26). Of the 8 inpatients, 3 were admitted from the ED for the sole purpose of tube replacement. Data were again collected for 6 months following inclusion of a patient-specific plan during the same seasonal period of the following year. During this period, 240 total image-guided changes were performed. Fifteen (6.2%) were performed outside of standard operating hours at the request of the ED (2/15), inpatient service (4/15), or patient/caregiver (9/15). No patients were admitted for GJ tube replacement procedures following implementation of the enhanced reporting policy. These data indicate a trend toward reduced after-hours resource utilization for GJ tube replacement requests by the ED (23.1%-13.3%), inpatient service (30.8%-26.7%), and all patients (14.7%-11%). Fewer after-hours GJ tube changes reduced cost by proportionately reducing hourly compensation for interventional radiology nurses and technicians. CONCLUSIONS: Our single-center data suggest that the inclusion of patient-specific recommendations at the end of each radiology GJ tube procedure note, generated in collaboration with the feeding service or primary medical provider, reduces off-hour resource utilization in patients who could otherwise have their tubes replaced during standard operating hours with image guidance. Avoidance of tube-related admissions is likely the greatest source of cost savings, followed by lower radiology technical support costs. Cost savings related to improved ED workflow and reduced patient/family anxiety are difficult to quantify, but likely significant. Future studies should be designed to quantify these savings and to assess the effect of this intervention on patient/caregiver satisfaction.

Imaging assessment of patellar instability and its treatment in children and adolescents.

Transient patellar dislocation is a common entity in children and adolescents, characterized by lateral dislocation of the patella, usually with spontaneous reduction. Many predisposing conditions have been described, including trochlear dysplasia, excessive lateral patellar tilt, patella alta and lateralization of the tibial tuberosity. Associated injuries are bone bruises of the patella and lateral femoral condyle, tears of the medial retinaculum that include the medial patellofemoral ligament (MPFL), tears of the vastus medialis obliquus muscle, injuries of articular cartilage, and intra-articular bodies. Children who are refractory to conservative management, have a large cartilage defect, or are at substantial risk for recurrent dislocations are candidates for surgical procedures to prevent future dislocations. Procedures can include MPFL repair or reconstruction, tibial tubercle repositioning and lateral retinacular release. The purpose of this review is to illustrate the imaging findings of transient patellar dislocation in the acute setting, the normal imaging appearance after surgical intervention, and post-surgical complications.

Supply/Demand in Radiology: A Historical Perspective and Comparison to other Labor Markets.

RATIONALE AND OBJECTIVES: There has been attention on the job market recently and on radiology's supply/demand calculus. Supply is influenced by the number of trained radiologists, while demand is driven by demographics and technological innovation. We analyze the supply of radiologists historically and compare to other labor markets-medical and non-medical, domestic and foreign. MATERIALS AND METHODS: We review National Resident Matching Program data in radiology and several other specialties from 1991 to 2015. We also review surveys, physician recruitment data, and peer-reviewed commentaries on medical specialty job markets. Trends are compared across specialties. The regulation of American medical training is compared to that in the United Kingdom and to a nonmedical labor market, unionized theatrical stage employees. RESULTS: Radiology residency positions have increased since 1998 despite a downturn in the job market. This expansion coincides with a decreasing percentage of positions filled by domestic graduates. A similar trend has been seen in pathology, a notoriously oversupplied specialty. Conversely, other specialties have maintained their proportion of domestic graduates by way of limited supply or implicit demand. CONCLUSIONS: The radiology job market is currently oversupplied, primarily a result of increasing residency positions despite indicators of decreasing demand. The percentage of residency positions filled by domestic graduates has decreased during the same period, suggesting that medical student interest is responsive to the market. Other specialties, particularly pathology, demonstrate the dangers of chronic oversupply. We advocate a reduction of radiology residency positions such that supply closely approximates demand without exceeding it. Additional measures may be taken, if necessary, to restore market equilibrium in the event of a mild undersupply.

Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck.

BACKGROUND: Cumulative evidence implicates the epidermal growth factor receptor (EGFR) as an important therapeutic target in head and neck squamous cell carcinoma (HNSCC). The basis for the lack of correlation between EGFR expression in the HNSCC tumor and clinical responses to EGFR inhibitors is incompletely understood. Although a variety of mechanisms likely contribute to the effectiveness of EGFR blockade, this review focuses on the biologic implications of known EGFR variations and the role of the immune system in mediating clinical responses to EGFR inhibitors. METHODS: A Medline review of articles published in the last 10 years (1999-present) on EGFR in HNSCC was performed in combination with preliminary data from our laboratories. RESULTS: Studies published to date suggest no association between the expression of EGFR on HNSCC tumors and clinical responses to EGFR inhibitors. Several mechanisms have been proposed to mediate clinical response to EGFR inhibitors in HNSCC. Cumulative results from our laboratories support the role of several mechanisms, including cellular immune activation and mutated EGFR variants, in contributing to the discrepancy between level of EGFR expression and clinical response to EGFR inhibitors. CONCLUSION: The efficacy of EGFR targeted therapies may be mediated, at least in part, by the immune system and the presence of the truncated EGFR variant, EGFRvIII, among other factors. Criteria to identify the subset of patients likely to be responsive to EGFR targeted therapies are needed.