Hemostatic Management in an Infant With Neuroblastoma and Severe Hemophilia B With Extended Half-life Recombinant Factor IX Fusion Protein.

In the rare co-occurrence of childhood cancer and severe hemophilia, hemostatic management is of paramount therapeutic importance. We present the case of an 11-month-old boy with severe congenital hemophilia B, who was diagnosed with metastatic high-risk neuroblastoma. He consequently developed paraneoplastic coagulopathy with life-threatening tumor hemorrhage and intracranial hemorrhage, showing central nervous system relapse. Management consisted of factor IX replacement with extended half-life factor IX fusion protein, adjusted to bleeding risk. Additional interventions included factor XIII, fibrinogen, fresh frozen plasma, tranexamic acid, and platelet transfusions. The half-life of factor IX products was markedly reduced requiring close factor IX monitoring and adequate replacement. This intensified treatment allowed chemotherapy, autologous stem cell transplantation, and GD2 antibody immune therapy without bleeding or thrombosis.

Age dependent ultrasound B-mode findings of the elbow joint in healthy children and adolescents.

Due to maturation of joints, various changes take place, not only in the field of paediatric rheumatology but also in paediatric orthopaedics musculoskeletal ultrasound plays an important role in both the diagnosis and the follow-up of diseases in this field. To differentiate between physiological and pathological findings, the knowledge of reference values of joint structures is indispensable. The objective was to define B-mode ultrasound age- and sex-related reference values for the elbow joint in healthy children and adolescents during maturation. In a cross-sectional, multicentre ultrasound study we examined both sides of the elbow joints of 437 healthy children and adolescents (194 boys/243 girls) being between one and less than 18 years old. The children were classified into six equal age groups and divided according to their gender. We measured the distance between the outer margin of the joint capsule and the bone surface to define the bone-capsule distance (BCD), the thickness of the joint cartilage as well as the thickness of the joint capsule. The bone-capsule junction zone and the shape of the joint capsule were analysed qualitatively. The bone capsule distance and the capsule thickness increased with age. In contrast, the joint cartilage thickness decreased. In most cases the junction zone was peaked. The joint capsule showed mostly a concave shape. Intra- and interobserver reliabilities were good. We propose B-mode ultrasound age- and sex-related reference values for the elbow joint in a large number of healthy children and adolescents for the first time. By applying these standard values to the ultrasound examination of the elbow joint, it may be possible to achieve greater certainty in the diagnosis of pathological processes.

Correction to: Age dependent ultrasound B-mode findings of the elbow joint in healthy children and adolescents.

The Second author's name was incorrectly published in the original article. The correct name is Hartwig Wilhelm Lehmann.

Arthrosonographic Reference Values of the Shoulder Joint in Healthy Children and Adolescents: A Cross-Sectional Multicentre Ultrasound Study.

Background Defining of gray scale ultrasound standard reference values of the shoulder joint in childhood and adolescence during maturation. PATIENTS: We examined 445 healthy girls and boys between 1 year and 18 years of age. Method A cross-sectional multicentre grey-scale ultrasound study was performed to examine the shoulder joint on both sides. The children were divided according to their gender and were further classified into six age groups, which constituted three-year age ranges, to record anatomical development changes. We measured the capsule-bone distance (BCD) as a representation of the intracapsular cavity, as well as the thickness of the joint capsule and joint cartilage. Values were expressed in mean±standard deviation (SD) and minimum-maximum (min-max). The shape of the joint capsule and capsule-bone junction zone was qualitatively analysed. Results The joint cartilage thickness decreased with increasing age in all joints independently from sex and body side. However, the BCD and the capsule thickness increased with age. There was no intraarticular fluid visible. The joint capsule had a predominantly concave form, whereas the capsule-bone junction was mostly sharp. Discussion This study is the first describing age-related normal values of the intracapsular cavity, joint capsule and cartilage thickness as well as their respective shape in a large cohort of healthy children. Conclusion The findings could be helpful to differentiate between physiological and pathological joint conditions and thereby distinguishing age-related variations from alterations caused by inflammation.

Age-dependent arthrosonographic reference values of the hip joint in healthy children and adolescents - a cross-sectional multicenter ultrasound study.

BACKGROUND: Musculoskeletal US is a noninvasive imaging method for diagnosing and monitoring inflammatory rheumatic diseases. OBJECTIVES: To develop age- and gender-related arthrosonographic reference intervals for the hip joint of healthy children and adolescents. MATERIALS AND METHODS: In a cross-sectional US study, we examined both hip joints of 445 children and adolescents with an age range of 1 year to 18 years. We measured the distance between the bone surface and the outer margin of the joint capsule to define the bone-capsule distance, the joint capsule and cartilage thickness, and the capsule layer thickness. Reference values were calculated. The shape of the joint capsule and bone-capsule junction zone were analyzed qualitatively. An intraobserver analysis was performed. RESULTS: Bone-capsule distance, capsule thickness and the anterior capsule layer increase with age. In contrast, joint cartilage decreases. The posterior capsule layer exhibited constant thickness across all age groups. The difference between both body sides and gender was collectively less than 0.5 mm. The intraobserver variations were within the calculated reference intervals. The insertion of the capsule to the bone was mostly a peaked one. The capsule shape had a convex or straight configuration in a neutral position and a concave position during outward rotation. The intraobserver analysis revealed good to very good concordance. CONCLUSION: We propose age- and gender-related reference intervals for the bone-capsule distance, joint capsule and cartilage thickness of the hip.

Pediatric musculoskeletal ultrasound: age- and sex-related normal B-mode findings of the knee.

Musculoskeletal ultrasound (MSUS) is an important tool for evaluating disease activity, therapeutic progress, and remission status of rheumatic diseases in children. Knowledge of age-related normal findings is essential when interpreting pathological findings such as those seen in juvenile idiopathic arthritis. To evaluate normal findings of the knee joint, we recorded age-related stages of musculoskeletal development in the knee of 435 healthy children between 1 and 18 years of age using high-resolution B-mode MSUS. We determined approximate age- and sex-related norms for the suprapatellar recess size, ossified patella size, and distal femoral intercondylar cartilage thickness. In almost all age-groups, over 64 % of children had visible fluid accumulation in the suprapatellar recess. Significant correlations were found between chronological age and the suprapatellar recess size and ossified patella length (p < 0.05). An age-dependent decrease in intercondylar cartilage thickness of the distal femoral epiphysis was found in children between 10 and 18 years of age. High-resolution B-mode MSUS is an excellent tool for assessing joint and skeletal development in children. Our reference data can be used to discriminate better between normal physiological findings and pathological abnormalities.

Naturally occurring genetic variants of human caspase-1 differ considerably in structure and the ability to activate interleukin-1ß.

Caspase-1 (Interleukin-1 Converting Enzyme, ICE) is a proinflammatory enzyme that plays pivotal roles in innate immunity and many inflammatory conditions such as periodic fever syndromes and gout. Inflammation is often mediated by enzymatic activation of interleukin (IL)-1ß and IL-18. We detected seven naturally occurring human CASP1 variants with different effects on protein structure, expression, and enzymatic activity. Most mutations destabilized the caspase-1 dimer interface as revealed by crystal structure analysis and homology modeling followed by molecular dynamics simulations. All variants demonstrated decreased or absent enzymatic and IL-1ß releasing activity in vitro, in a cell transfection model, and as low as 25% of normal ex vivo in a whole blood assay of samples taken from subjects with variant CASP1, a subset of whom suffered from unclassified autoinflammation. We conclude that decreased enzymatic activity of caspase-1 is compatible with normal life and does not prevent moderate and severe autoinflammation.

Smart Medication ™, an Electronic Diary for Surveillance of Haemophilia Home Care and Optimization of Resource Distribution.

This report describes the technical features and potential advantages of the application of electronic haemophilia treatment diary smart medication ™ and an evaluation of real-life electronic treatment data collected from haemophilia patients. Since 2012, a total of 663 patients from 30 German haemophilia treatment centres (HTCs) have used the device. Data of nine HTCs were merged for real-life data analysis. Patients were divided into four subgroups according to above versus below mean values for annual factor consumption (AFC) and annual joint bleeds (AJB), respectively. The largest subgroup comprised patients with low mean AFC and AJB less than 2.25 (group A: 42%). Second largest was the group with low mean AJB but high AFC (group B: 32%), suggesting that resources could be saved in some patients. The group with low AFC but high AJB may need increased factor dosing (group D: 13%). Patients who showed a high mean AJB despite high AFC (group C: 13%) may require special medical attention, such as pharmacokinetic-adapted treatment modification or orthopaedic measures. Smart medication ™ enables the HTC to quickly identify patients in need of treatment changes and, thus, to plan individualized therapy modifications prior to patient visits. The growing pool of real-life data facilitates data analysis and may play an important role in the optimization of resource distribution.