Brice Ilharreborde

New Real-Time PCR-Based Method for Kingella kingae DNA Detection: Application to Samples Collected from 89 Children with Acute Arthritis

ABSTRACT Inoculation of blood culture vials with joint fluid samples has revealed the important pathogenic role of Kingella kingae in pediatric arthritis. However, recent studies based on broad-range 16S ribosomal DNA PCR and real-time PCR without a probe suggest that conventional methods remain suboptimal. We developed a new real-time PCR method with a probe that is highly specific for K. kingae and applied it to joint fluid samples collected from 89 children with suspected arthritis admitted to our institution during a 2-year period. Real-time PCR was also applied to blood samples obtained before surgery and to joint drainage fluid samples obtained during several days after surgery. Thirty-six (40%) of the 89 cases of suspected septic arthritis had positive culture. Staphylococcus aureus was the main isolate (n = 19/36, 53%), followed by K. kingae (n = 7/36, 19%). Specific real-time PCR identified K. kingae in 24 of the 53 culture-negative cases. Thus, K. kingae was present in 31 (52%) of the 60 documented cases, making it the leading pathogen. Real-time PCR on all 15 blood DNA extracts from patients with K. kingae infection was negative, demonstrating that joint fluid positivity did not result from DNA circulating in blood. Real-time PCR amplification of drainage fluid samples showed that the pathogen could be detected for up to 6 days after antibiotic initiation. K. kingae real-time PCR applied to DNA extracted from joint fluid samples, but not from blood samples, markedly improved the etiological diagnosis of septic arthritis in children. Retrospective diagnosis is feasible for up to 6 days after treatment initiation.

Angle Measurement Reproducibility Using EOSThree-Dimensional Reconstructions in Adolescent Idiopathic Scoliosis Treated by Posterior Instrumentation

Study Design. A reproducibility study was conducted in preoperative and postoperative three-dimensional (3D) measurements for patients operated for adolescent idiopathic scoliosis (AIS). Objective. To assess the reliability of preoperative and postoperative 3D reconstructions using EOS in patients operated for AIS. Summary of Background Data. No prior reliability study of 3D measurements has been performed in the literature for severe scoliosis and for operated patients. Methods. This series included 24 patients (62° ± 11) operated for Lenke 1 or 2 AIS, using either all-pedicle screw constructs (group 1) or hybrid constructs, with universal clamps at thoracic levels (group 2). All patients underwent low-dose standing biplanar radiographs, pre- and postoperatively. Three operators performed the 3D reconstruction process two times preoperatively and two times postoperatively (total 288 reconstructions). Intraoperator repeatability and interoperator reproducibility were calculated and compared between groups. Results. The preoperative reproducibility was between 4° and 6.5° for parameters dedicated to scoliosis (Cobb and apical vertebral rotation), between 4° and 7° for kyphosis and lordosis values, and between 1° and 5° for pelvic measurements. The postoperative reproducibility was between 5° and 8° for values of kyphosis and lordosis, between 1° and 5.5° for pelvic parameters, and between 6.5° and 10.5° for the scoliotic parameters. The reproducibility of the scoliotic parameters was slightly better in the hybrid construct group, but the difference was not significant (P = 0.8). No difference was found between groups for the other parameters. Conclusion. 3D postoperative reconstructions are as reproducible as preoperative ones. The reproducibility is not influenced by the type of implant used for correction. Mean difference between operator was higher than previously reported for the apical rotation measurement, but this difference can be explained by the severity of the curves and the lower visibility of the anatomical landmarks due to the implants.

Bioactive glass as a bone substitute for spinal fusion in adolescent idiopathic scoliosis: a comparative study with iliac crest autograft.

Background: Iliac crest autograft is currently the gold standard material for spinal fusion. However, its use is limited by additional operative time, increased blood loss, and morbidity. Recently, a synthetic osteoconductive bone graft material composed of bioactive glass has been described, with high effectiveness in animal models. Its ability to achieve spinal fusion in human has never been reported. The aim of this study was to compare bioactive glass and iliac crest autograft as bone substitutes in the treatment thoracic adolescent idiopathic scoliosis (AIS). Methods: Eighty-eight consecutive patients underwent posterior spinal fusion for progressive thoracic AIS. There were 2 study groups based on the type of bone graft used: iliac crest autograft (n = 40) or bioglass (n = 48). A minimum 2-year follow-up was required. Medical data and radiographs were retrospectively analyzed and compared using unpaired t test and Mann-Whitney U test. Results: Mean follow-up was 40 months in the autograft group and 38 months in the bioglass group. In the autograft group, there were 2 infections (5%) and 3 mechanical failures (7.5%). One infection (2%) and 1 early mechanical failure (2%) occurred in the bioglass group. Loss of correction of the main thoracic curve between immediate postoperative and latest follow-up averaged 15.5% for autograft group and 11% for the bioglass group (P = 0.025).The mean (±SD) gain of frontal balance between immediate postoperative latest follow-up was 0.8 (±9.3) mm in the autograft group and 8.1 (±12) mm for the bioglass group (P = 0.005). Conclusions: Results of this retrospective study suggest that bioglass is as effective as iliac crest graft to achieve fusion and maintain correction in AIS. Less complications were seen in the bioactive glass group, but the difference did not reach statistical significance. Bioactive glass can be proposed in the treatment of AIS, avoiding the morbidity of iliac crest harvesting. However, clinical and radiological outcomes need to be confirmed at long-term follow-up. Level of Evidence: Level III

How to determine the upper level of instrumentation in Lenke types 1 and 2 adolescent idiopathic scoliosis: a prospective study of 132 patients.

The selection of fusion levels continues to be controversial in adolescent idiopathic scoliosis (AIS). The classifications of King and Lenke remain the most widely used, but recent studies have demonstrated their shortcomings, including poor interobserver reproducibility. We propose a method of preoperative planning that is independent of anatomical classifications, based on the anticipated effect of curve reduction. The objectives of this preoperative strategy are (1) to achieve satisfactory T1 tilt and shoulder balance and (2) to restore balance in the coronal and sagittal planes. The purpose of the present study was to evaluate the results of our strategy of deciding the proximal level of arthrodesis in Lenke types 1 and 2 AIS. Methods: We included 132 adolescents operated on for thoracic AIS by posterior instrumentation. The choice of the proximal fusion level was based on preoperative analysis of the rigidity of the proximal curvature, T1 tilt, and shoulder balance. The preoperative, postoperative, and last follow-up radiographs were digitized then analyzed using computer software. Radiological parameters were compared using paired t tests. Results: Average age at the time of surgery was 15.2 years (SD, 1.7 years). Mean follow-up was 30.2 months. The clavicle angle and T1 tilt were significantly improved in both Lenke types 1 and 2 curves. No correlation was found between T1 tilt and shoulder balance. At last follow-up, 89% of the patients satisfied all criteria for balance. Conclusions: The results of the present preoperative strategy, to which we adhered in 97% of cases, are encouraging and show that the systematic instrumentation of the entire proximal curvature is not justified in Lenke type 2 curves. However, long-term consequences of the residual T1 tilt need to be studied further. Level of evidence: therapeutic level IV.

TIEG-null mice display an osteopenic gender-specific phenotype

TGFbeta inducible early gene-1 (TIEG) was originally cloned from human osteoblasts (OB) and has been shown to play an important role in TGFbeta/Smad signaling, regulation of gene expression and OB growth and differentiation. To better understand the biological role of TIEG in the skeleton, we have generated congenic TIEG-null (TIEG(-/-)) mice in a pure C57BL/6 background. Through the use of DXA and pQCT analysis, we have demonstrated that the femurs and tibias of two-month-old female TIEG(-/-) mice display significant decreases in total bone mineral content, density, and area relative to wild-type (WT) littermates. However, no differences were observed for any of these bone parameters in male mice. Further characterization of the bone phenotype of female TIEG(-/-) mice involved mechanical 3-point bending tests, micro-CT, and histomorphometric analyses of bone. The 3-point bending tests revealed that the femurs of female TIEG(-/-) mice have reduced strength with increased flexibility compared to WT littermates. Micro-CT analysis of femurs of two-month-old female TIEG(-/-) mice revealed significant decreases in cortical bone parameters compared to WT littermates. Histomorphometric evaluation of the distal femur revealed that female TIEG(-/-) mice also display a 31% decrease in cancellous bone area, which is primarily due to a decrease in trabecular number. At the cellular level, female TIEG(-/-) mice exhibit a 42% reduction in bone formation rate which is almost entirely due to a reduction in double labeled perimeter. Differences in mineral apposition rate were not detected between WT and TIEG(-/-) mice. Taken together, these findings suggest that female TIEG(-/-) mice are osteopenic mainly due to a decrease in the total number of functional/mature OBs.

Comparison of clinical and biologic features of Kingella kingae and Staphylococcus aureus arthritis at initial evaluation.

We conducted a retrospective study comparing the presenting clinical and biologic features of 64 children who had septic arthritis caused by Kingella kingae with 26 children who had septic arthritis caused by Staphylococcus aureus. Children with K. kingae septic arthritis were significantly younger than those with S. aureus septic arthritis. Otherwise, there were no significant differences between the 2 groups with respect to fever, location, white blood cell count, synovial fluid cell count, C-reactive protein, or serum fibrinogen. However, the clinical course was significantly better for children with septic arthritis caused by K. kingae as evidenced by shorter hospitalization and fewer adverse events. Presumptive antibiotic therapy for septic arthritis in young infants should take into account both of these pathogens, even in case of mild presentation.

Hybrid Constructs for Tridimensional Correction of the Thoracic Spine in Adolescent Idiopathic Scoliosis: A Comparative Analysis of Universal Clamps Versus Hooks

Study Design. Retrospective study of prospectively collected data. Objective. Compare Universal Clamps (UCs) and hooks for the thoracic correction of adolescent idiopathic scoliosis (AIS). Summary of Background Data. In scoliosis surgery, sagittal correction is as important as frontal correction due to the risk of junctional kyphosis. Compared to all-screw constructs, hybrid constructs with lumbar pedicle screws and thoracic hooks or sublaminar wires have been shown to achieve similar coronal correction while providing superior postoperative thoracic kyphosis. The authors used a novel sublaminar thoracic implant, the UC with improvements over sublaminar wires. Hybrid constructs using thoracic UCs were compared to those with thoracic hooks. Methods. This series involved 150 patients treated for AIS with hybrid constructs. A total of 75 consecutive patients operated from 2001 to 2003, who had thoracic hooks with in situ contouring, distraction, and compression (Group 1), were compared to 75 consecutive patients operated from 2004 to 2006, who had thoracic UCs with posteromedial translation (Group 2). All had intraoperative somatosensory/motor-evoked potential monitoring and at least 2-years follow-up. Results. Except for follow-up (longer in Group 1), the 2 groups were similar before surgery. The UCs achieved better thoracic coronal correction (P < 0.001), Cincinnati index (P < 0.001), kyphosis (P = 0.02), and apical rotation (P < 0.001). In normokyphotic or hypokyphotic patients, the UC corrected thoracic kyphosis by 11.2° (55%) versus 0.4° (2%) achieved by hooks (P < 0.0001). These differences were stable at last follow-up. There were no intraoperative complications or changes in somatosensory/motor-evoked potentials. UC reduced operative time by 20% (60 minutes; P < 0.001) and blood loss by 23% (250 mL; P < 0.001). Conclusion. Although both of these hybrid constructs efficaciously corrected the coronal and axial deformities in AIS, the results of the UC technique were superior to those achieved with hooks in all 3 planes, especially the sagittal plane. Moreover, the UC technique is straightforward and safe, reducing both operative duration and blood loss.

Adjacent segment disease after instrumented fusion for idiopathic scoliosis: review of current trends and controversies.

Study Design A literature-based review. Objective To summarize the clinical and morphologic findings leading to diagnosis, the etiologic factors, and principles of management. To identify the strengths and limits of past studies. Summary of Background Data There are considerable controversies regarding etiologic factors, diagnosis, and management of adjacent segment disease in patients instrumented for idiopathic scoliosis. Methods Summarized is past literature and, to some extent, personal experience of the authors. Results Several factors participating to this complex pathophysiology are reported. The clinical presentation, occurring after symptom free interval, can vary, and modern morphologic investigations help for diagnosis. Management is often surgical and remains challenging. Conclusions Long-term consequences of spinal fusions are now major concerns, especially in young patients undergoing surgical correction for idiopathic scoliosis. Adjacent segment disease is defined by a combination of clinical symptoms and morphologic findings. Several etiologic factors have been reported, but need to be further studied to prevent and improve the surgical management of this complication.

Reliability of cervical lordosis and global sagittal spinal balance measurements in adolescent idiopathic scoliosis

Study designRadiological reproducibility study.PurposeTo assess intra and interobserver reliability of radiographic measurements for global sagittal balance parameters and sagittal spine curves, including cervical spine.Summary of background dataSagittal spine balance in adolescent idiopathic scoliosis (AIS) is a main issue and many studies have been reported, showing that coronal and sagittal deformities often involve sagittal cervical unbalance. Global sagittal balance aims to obtain a horizontal gaze and gravity line at top of hips when subject is in a static position, involving adjustment of each spine curvature in the sagittal plane. To our knowledge, no study did use a methodologically validated imaging analysis tool able to appreciate sagittal spine contours and distances in AIS and especially in the cervical region.MethodsLateral full-spine low-dose EOS radiographs were performed in 75 patients divided in three groups (control subjects, AIS, operated AIS). Three observers digitally analyzed twice each radiograph and 11 sagittal measures were collected for each image. Reliability was assessed calculating intraobserver Pearson’s r correlation coefficient, interobserver intra-class correlation coefficient (ICC) completed with a two-by-two Bland–Altman plot analysis.ResultsThis measurement method has shown excellent intra and interobserver reliability in all parameters, sagittal curvatures, pelvic parameters and global sagittal balance.ConclusionsThis study validated a simple and efficient tool in AIS sagittal contour analysis. It defined new relevant landmarks allowing to characterize cervical segmental curvatures and cervical involvement in global balance.

Unusually severe cases of Kingella kingae osteoarticular infections in children

Backgrounds: With the development of molecular biology and specific polymerase chain reaction, Kingella kingae has become the primary diagnosis of osteoarticular infections in young children. Clinical features of these osteoarticular infections are typically mild, and outcome is almost always favorable. We report a series of unusually severe cases of K. kingae osteoarticular infections. Methods: All patients with severe osteoarticular infections at presentation were reviewed retrospectively in 2 European pediatric centers. K. kingae was identified using real-time polymerase chain reaction in blood, fluid joint or osseous samples. Clinical, laboratory tests and radiographic data during hospitalization and follow-up were analyzed. Results: Ten children (mean age 21 ± 12 months) with severe osteoarticular infections caused by K. kingae were identified between 2008 and 2011. Diagnostic delay averaged 13.2 ± 8 days. Only 1 patient was febrile at admission, and 50% children had normal C-reactive protein values (⩽10 mg/dL) at presentation. Surgical treatment was performed in all cases. Intravenous antibiotic therapy by cephalosporins for an average of 8 ± 6 days was followed by oral treatment for 27 ± 6 days. Mean follow-up was 24.8 ± 9 months, and satisfactory outcomes were reported in all cases. Two patients (20%) developed a central epiphysiodesis of the proximal humerus during follow-up, but without significant clinical consequence for the moment. Conclusions: Because of their mild clinical features at onset, diagnosis of K. kingae osteoarticular infections can be delayed. Care should be taken for early detection and treatment of these infections because bony lytic lesions and potentially definitive growth cartilage damage can occur.