Cartilage thickness of the knee joint in juvenile idiopathic arthritis: comparative assessment by ultrasonography and magnetic resonance imaging.

OBJECTIVE: The functional disability experienced in juvenile idiopathic arthritis (JIA) is primarily caused by joint effusion, synovial membrane hypertrophy, and periarticular soft tissue edema, leading to the degeneration of the osteocartilaginous structures because of the inflammatory process in the synovium. The ability to visualize the inflammatory changes and hence the ensuing osteocartilaginous degeneration is, therefore, of great importance in pediatric rheumatology. Ultrasonography (US) has been validated as a tool for measuring cartilage thickness in healthy children and, previously, we have found good agreement with the measures obtained by magnetic resonance imaging (MRI). Our aim is to validate and compare US with MRI measurements of distal femoral cartilage thickness in the knee joint at the medial condyle, lateral condyle, and intercondylar spots in children with JIA, and to locate the best spot for imaging comparisons. METHODS: One knee from each of 23 children with oligoarticular JIA were investigated by both MRI and US. Outcome measures of imaging procedures were distal femoral cartilage thickness. RESULTS: We found a high level of agreement between MRI and US measurements of mean cartilage thickness, and Rho values between modalities were high (between 0.70 and 0.86, p < 0.05 for all). We found a thinner cartilage thickness at the medial condyle in comparison to the other investigated points. Evaluation of anatomical landmarks for optimal measurement of cartilage thickness was found to be the intercondylar spot, which was easier to locate in addition to a smaller variance around the mean for that anatomical measuring point. CONCLUSION: US measurements of distal femoral cartilage thickness are highly correlated to MRI measurements. The intercondylar notch of the distal femoral cartilage may be the best anatomical point for cartilage thickness measurements of the knee. US is a reliant and nonexpensive, non-invasive modality for visualization of childhood femoral cartilage.

Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group.

The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Patients aged 18-75 years were eligible. Thirty-nine patients aged 18-65 years and 27 patients aged 66-75 years were enrolled. The median age of the two age groups was 55 and 70 years, respectively. The overall response rate was 73.8% for the entire cohort: 69.9% in the younger and 80.8% in the elderly subgroup. With a median follow up of 22 months, the 2-year overall survival probability was 60.7% in patients aged 65 years or under and 55.6% in patients aged over 65 years (P=0.40). The estimated progression-free survival at two years was 33.1% (95%CI: 19.1%-47.9%) in patients aged under 65 years and 44.4% (95%CI: 25.6%-61.8%) in the elderly subgroup (P=0.74). Median duration of response was ten months in the younger subgroup, and not reached in the elderly patient subgroup (P=0.33). Four patients aged 64-75 years (6%) died from treatment-related complications. Survival in the two age groups was similar despite a de-escalation of induction treatment in patients aged over 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern, especially in the elderly patients, we conclude from these data that de-escalation of induction therapy in elderly primary central nervous system lymphoma patients followed by maintenance treatment seems to be a promising treatment strategy. (clinicaltrials.gov identifier:01458730).

Ten-year review of Danish children with chronic non-bacterial osteitis.

OBJECTIVES: To compare clinical characteristics of children with chronic non-infectious osteomyelitis (CNO) with either mono- or multifocal bone lesions, and to report potential advantages of using whole-body MRI. METHODS: A retrospective evaluation of 31 children (19 girls, 12 boys) diagnosed with CNO between 2001 and 2011. CNO was diagnosed as mono-, or multifocal inflammatory bone lesions (osteomyelitis, osteitis, osteosclerosis), duration of complaints more than 6 weeks and exclusion of infection and malignancy. Clinical and radiological data were registered. The definition of mono- or multifocality was based on the description of imaging results. RESULTS: Mean age at disease onset was 10.3 ± 2.6 years. Mean duration of active disease was 44.4 ± 25.6 months. Twenty-two (71.0%) had two or more bone lesions and 9 (29.0%) had one lesion. Of those with multifocal lesions six were initially detected as monofocal. The most frequent location of the bone lesions was in the metaphysis of the lower extremities. MRI/CT discovered most lesions compared to x-ray and scintigraphy. MRI was performed in 93.5% of which 25.8 % had a whole-body-MRI. Whole-body MRI revealed disclosure of several silent lesions. Extra-osseous involvement occurred in 64.5%. In the multifocal group 22.7 % had psoriasis and 13.6 % had pustulosis palmoplantaris but neither was seen in the monofocal group. All were treated with NSAIDs; 54.8% corticosteroids, 29.1 % methotrexate, 9.7 % pamidronate and 3.2 % infliximab. CONCLUSIONS: Monofocal CNO had comparable clinical and radiological characteristics to multifocal disease. We conclude that whole-body MRI is a relevant screening instrument for the diagnosis of CNO.

Efficacy of anti-IL-1 treatment in Majeed syndrome.

BACKGROUND AND OBJECTIVE: Majeed syndrome is an autosomal recessive disorder characterised by the triad of chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anaemia and a neutrophilic dermatosis that is caused by mutations in LPIN2. Long-term outcome is poor. This is the first report detailing the treatment of Majeed syndrome with biological agents and demonstrates clinical improvement with IL-1blockade. METHODS: We describe the clinical presentation, genetic analysis, cytokine profiles and response to biological therapy in two brothers with Majeed syndrome. RESULTS: Both boys were homozygous for a novel 2-base pair deletion in LPIN2 (c.1312_1313delCT; p.Leu438fs+16X), confirming the diagnosis. Their bone disease and anaemia were refractory to treatment with corticosteroids. Both siblings had elevated proinflammatory cytokines in their serum, including tumour necrosis factor α (TNF-α), however a trial of the TNF inhibitor etanercept resulted in no improvement. IL-1 inhibition with either a recombinant IL-1 receptor antagonist (anakinra) or an anti-IL-1ß antibody (canakinumab) resulted in dramatic clinical and laboratory improvement. CONCLUSIONS: The differential response to treatment with TNF-α or IL-1 blocking agents sheds light into disease pathogenesis; it supports the hypothesis that Majeed syndrome is an IL-1ß dependent autoinflammatory disorder, and further underscores the importance of IL-1 in sterile bone inflammation.

MRI and pathology in persistent postherniotomy pain.

BACKGROUND: Persistent postherniotomy pain impairs everyday life in 5% to 10% of patients. MRI can potentially be useful in the investigation of pathogenic mechanisms and guide surgeons in mesh removal and neurectomy. No study has investigated interobserver agreement or MRI-specific findings in persistent postherniotomy pain. STUDY DESIGN: Thirty-two patients with persistent postherniotomy pain > 1 year after uni- or bilateral groin hernia repair and 6 pain-free postherniotomy controls were MRI scanned, resulting in a total of 32 painful groins, 15 pain-free operated groins, and 29 pain-free unoperated groins scanned. Two blinded observers separately assessed groins using a predefined list of possible MRI pathology and anatomic landmarks. Primary outcomes included interobserver agreement assessed by calculating kappa-coefficients. Secondary outcomes included frequency of MRI pathology in painful groins versus unoperated and pain-free groins. RESULTS: Interobserver agreement was poor, ranging from kappa = 0.24 to 0.55 ("fair" to "moderate") except for "contrast enhancement in groin" (kappa = 0.69, substantial). Pathologic changes in the form of "contrast enhancement in groin," "edema," and "spermatic cord caliber increased" were significantly more often seen in painful versus unoperated groins (p < 0.02). No significant difference was seen when painful and pain-free operated groins were compared (p < 0.05). No pathologic finding was specific or seen in all painful groins. CONCLUSIONS: Interobserver agreement is low and MRI-assessed pathology unspecific for persistent postherniotomy pain. Additional studies are required on interobserver agreement for pathology before MRI can be recommended as guidance and indication for surgical treatment of persistent postherniotomy pain.

Optimisation of scoliosis examinations in children.

OBJECTIVE: To present results of optimising scoliosis examination by changing from a conventional film/grid (F/G) to air-gap technique using computed radiography (CR), and to evaluate different methods for estimating effective radiation doses. MATERIALS AND METHODS: Forty-nine children and adolescents were examined with an F/G technique, and 21 with air-gap and CR techniques. Entrance surface doses (ESD) were determined with lithium fluoride thermoluminescence dosimeters. For all patients, the effective radiation doses were determined using a hermaphrodite PCXMC computer program. For all F/G radiographs, the effective doses were also determined according to the NRPB-R279 report, and for 22 children (>9 years and/or >40 kg) also with the ODS-60 program, which allows separate gender calculations. Accumulated doses for 37 children examined more than once with F/G examinations were assessed. RESULTS: For F/G techniques, the ESDs for both frontal and lateral views varied with age and were significantly correlated to the patients' thickness. The calculated effective doses using the PCXMC program and the NRPB-R279 did not differ significantly for all frontal and lateral radiographs, respectively, but ODS-60 gave significantly higher values in female subjects. With air-gap and CR techniques, the mean effective doses were reduced by a factor over 10. The mean accumulated effective dose for 37 children with a mean of seven F/G examinations was 6.1 mSv, implying a risk of death of about 1:2,000 for boys and at least 1:1,000 for girls. CONCLUSIONS: Paediatric scoliosis radiography should be considered a specialised procedure, which has to be optimised using a non-grid technique.