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Helle Mätzke Rasmussen,1,2 Kirsten Nordbye-Nielsen,3 Bjarne Møller-Madsen,3 Mette Johansen,4 Niels Ellitsgaard,5 Charlotte Reinhardt Pedersen,6 Gija Rackauskaite,7 Henriette Engberg,8,9 Niels Wisbech Pedersen2 1Department of Pediatrics, The Danish Cerebral Palsy Follow-up Program, Lillebaelt Hospital, Kolding, 2Department of Orthopedic Surgery and Traumatology, Institute of Clinical Research, Odense University Hospital, University of Southern Denmark, Odense, 3Department of Children's Orthopaedics, Aarhus University Hospital, Institute of Clinical Research, Aarhus University, Aarhus, 4Department of Pediatrics, Aalborg University Hospital, Aalborg, 5Department of Orthopedic Surgery, Hvidovre University Hospital, Hvidovre, 6Department of Pediatrics, North Zealand Hospital Hilleroed, Hilleroed, 7Department of Pediatrics, Aarhus University Hospital, Aarhus, 8Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, 9Centre for Clinical Epidemiology, Odense University Hospital, Odense, Denmark Aim of database: The Danish Cerebral Palsy Follow-up Program is a combined follow-up program and national clinical quality database that aims to monitor and improve the quality of health care for children with cerebral palsy (CP). Study population: The database includes children with CP aged 0–15 years and children with symptoms of CP aged 0–5 years. Main variables: In the follow-up program, the children are offered examinations throughout their childhood by orthopedic surgeons, physiotherapists, occupational therapists, and pediatricians. Examinations of gross and fine motor function, manual ability, muscle tone, passive range of motion, use of orthotics, and assistive devices are performed once a year; radiographic examination of the hips is planned based on the child's age and gross motor function; and the diagnosis is performed once before the age of 5 years. Six indicators were developed based on scientific literature and consensus in the steering committee, and their calculation is based on the following four main variables: radiographic examination of the hip, gross motor function, manual ability, and diagnosis. Descriptive data: The 2014 annual report includes results of the quality indicators in three of five regions in Denmark comprising 432 children with CP, corresponding to a coverage of 82% of the expected population. Conclusion: The Danish Cerebral Palsy Follow-up Program is currently under development as a national clinical quality database in Denmark. The database holds potential for research in prevalence, clinical characteristics of the population, and the effects of prevention and treatment. Keywords: cerebral palsy, clinical quality database, hip surveillance

Background: Radial neck fracture in children is infrequent but when not managed accurately can lead to complications. Different methods have been developed for the reduction and fixation of this fracture. The purpose of this retrospective study is to evaluate our results using the Métaizeau centromedullary technique. Materials and Method: Our series comprises 19 children with displaced radial neck fractures treated in our institution in the period 2004-2008. One patient was excluded because of a very complex fracture dislocation of the elbow (exclusion criteria). Two patients refused to participate in the follow-up leaving 16 who were treated with this technique. Patients were evaluated clinically and radiologically. For the clinical evaluation, we used the Métaizeau's classification. The subjective evaluation was done using the DASH score, and the Steele's classification was used for the evaluation of the radiological results. FINDING/RESULTS: We found good clinical and radiological outcomes. The mean DASH score was 3.06. Patients who had undergone open reduction had inferior outcome. Conclusion: Our results are comparable to other studies. This study confirms the Métaizeau technique as an excellent treatment option for displaced paediatric radial neck fractures. [ABSTRACT FROM AUTHOR]

Background: Kidney transplant recipients receive maintenance immunosuppressive therapy to avoid allograft rejection resulting in increased risk of infections and infection-related morbidity and mortality. Approximately 98% of adults are infected with varicella zoster virus, which upon reactivation causes herpes zoster. The incidence of herpes zoster is higher in kidney transplant recipients than in immunocompetent individuals, and kidney transplant recipients are at increased risk of severe herpes zoster-associated disease. Vaccination with adjuvanted recombinant glycoprotein E subunit herpes zoster vaccine (RZV) prevents herpes zoster in older adults with excellent efficacy (90%), and vaccination of kidney transplant candidates is recommended in Danish and international guidelines. However, the robustness and duration of immune responses after RZV vaccination, as well as the optimal timing of vaccination in relation to transplantation remain unanswered questions. Thus, the aim of this study is to characterize the immune response to RZV vaccination in kidney transplant candidates and recipients at different timepoints before and after transplantation., Methods: The Herpes Virus Infections in Kidney Transplant Patients (HINT) study is a prospective observational cohort study. The study will include kidney transplant candidates on the waiting list for transplantation (n = 375) and kidney transplant recipients transplanted since January 1, 2019 (n = 500) from all Danish kidney transplant centers who are offered a RZV vaccine as routine care. Participants are followed with repeated blood sampling until 12 months after inclusion. In the case of transplantation or herpes zoster disease, additional blood samples will be collected until 12 months after transplantation. The immune response will be characterized by immunophenotyping and functional characterization of varicella zoster virus-specific T cells, by detection of anti-glycoprotein E antibodies, and by measuring cytokine profiles., Discussion: The study will provide new knowledge on the immune response to RZV vaccination in kidney transplant candidates and recipients and the robustness and duration of the response, potentially enhancing preventive strategies against herpes zoster in a population at increased risk., Trial Registration: ClinicalTrials.gov (NCT05604911)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Fractures in the lower leg are common in children and are most often due to accidental falls. A significant part of the fractures involves the growth plates. This review describes a broad range of techniques for treatment ranging from immobilization in a cast to open reduction and fixation with K-wires, screws, or flexible intramedullary nails. Premature growth arrest is relatively common following the physeal fractures in proximal or distal tibia. We recommend early consultation with a tertiary care centre for guidance and planning of the best treatment.

A large variety of fluorescent molecules are used on a regular basis to tag major histocompatibility complex (MHC) multimers for detection of antigen-specific T cells. We have evaluated the way in which the choice of fluorescent label can impact the detection of MHC multimer binding T cells in an exploratory proficiency panel where detection of MHC multimer binding T cells was assessed across 16 different laboratories. We found that the staining index (SI) of the multimer reagent provided the best direct correlation with the value of a given fluorochrome for T cell detection studies. The SI is dependent on flow cytometer settings and chosen antibody panel; hence, the optimal fluorochrome selection may differ from lab to lab. Consequently, we describe a strategy to evaluate performance of the detection channels and optimize the SI for selected fluorescent molecules. This approach can easily be used to test and optimize fluorescence detection in relation to MHC multimer staining and in general, for antibody-based identification of rare cell populations. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry., (© 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.)

Aim: To test the hypothesis that improvements in gait and function following individualized interdisciplinary interventions consisting of physical therapy, orthotics, spasticity management, and orthopaedic surgery using instrumented gait analysis are superior to 'usual care' in children with cerebral palsy (CP)., Method: This was a prospective, single-blind, parallel-group, randomized controlled trial investigating the effectiveness of interventions based on the use of gait analysis. Primary outcome was gait (Gait Deviation Index) and secondary outcomes were walking and patient-reported outcome measures of function, disability, and health-related quality of life. Follow-ups were done at 26 weeks (questionnaires) and at the primary end point of 52 weeks (all outcomes)., Results: Sixty participants with CP (39 males, 21 females, mean age 6y 10mo, standard deviation 1y 3mo, range 5y-9y 1mo) in Gross Motor Function Classification System levels I or II, were randomized to interventions with or without gait analysis. No significant or clinically relevant between-group differences in change scores of the primary or secondary outcomes were found. The recommended categories of interventions were dominated by non-surgical interventions and were applied in 36% to 86% of the participants., Interpretation: Interventions using gait analysis were not superior to 'usual care' on gait, walking, or patient-reported outcomes in a sample of relatively young and independently walking children with CP not expected to need surgery., What This Paper Adds: Gait analysis in children with cerebral palsy in Gross Motor Function Classification System levels I or II recommends interdisciplinary interventions. Compliance to interventions recommended after gait analysis was low. No statistically significant advantages were identified for the intervention group versus the control group., (© 2019 Mac Keith Press.)

Narcolepsy Type 1 (NT1) is a neurological sleep disorder, characterized by the loss of hypocretin/orexin signaling in the brain. Genetic, epidemiological and experimental data support the hypothesis that NT1 is a T-cell-mediated autoimmune disease targeting the hypocretin producing neurons. While autoreactive CD4 +  T cells have been detected in patients, CD8 +  T cells have only been examined to a minor extent. Here we detect CD8 +  T cells specific toward narcolepsy-relevant peptides presented primarily by NT1-associated HLA types in the blood of 20 patients with NT1 as well as in 52 healthy controls, using peptide-MHC-I multimers labeled with DNA barcodes. In healthy controls carrying the disease-predisposing HLA-DQB1*06:02 allele, the frequency of autoreactive CD8 +  T cells was lower as compared with both NT1 patients and HLA-DQB1*06:02-negative healthy individuals. These findings suggest that a certain level of CD8 +  T-cell reactivity combined with HLA-DQB1*06:02 expression is important for NT1 development.

Background and purpose - Threshold values defining 3 categories of passive range of motion are used in the Cerebral Palsy follow-Up Program to guide clinical decisions. The aim of this study was to investigate the threshold values by testing the hypothesis that passive range of motion in ankle dorsiflexion is associated with gross motor function and that function differs between the groups of participants in each category. Patients and methods - We analyzed data from 60 ambulatory children (aged 5-9 years) with spastic cerebral palsy. Outcomes were passive range of motion in ankle dorsiflexion with flexed and extended knee and gross motor function (Gait Deviation Index, Gait Variable Score of the ankle, peak dorsiflexion during gait, 1-minute walk, Gross Motor Function Measure, the Pediatric Quality of Life Inventory Cerebral Palsy Module, and Pediatric Outcomes Data Collection Instrument). Results - Significant (p < 0.05) and moderate correlations were documented for range of motion versus Gait Variable Score of the ankle (r = -0.37 and r = -0.37) and range of motion versus peak dorsiflexion (r = 0.49 and r = 0.55). Differences between the groups formed by the categories were shown for Gait Variable Score of the ankle and peak dorsiflexion (p < 0.05). No other significant correlations or differences between the categories were observed. Interpretation - The results suggest that threshold values for ankle dorsiflexion used in the Cerebral Palsy follow-Up Program are of limited clinical value in assessing overall gross motor function, but may be used to identify deviations in ankle-specific gait function.

When using elastic stable intramedullary nailing in children's distal radius shaft fractures, the surgical approach can either be lateral or dorsal. The aim of this article was to carry out a systematic review of the literature comparing the two types of approaches in terms of complications. An electronic search of databases was performed. Titles of articles were screened, and abstracts and full text were read. Data were extracted in terms of demographics and complications. The dorsal approach had a 2.6% rate of extensor pollicis longus tendon rupture, whereas the lateral approach had a 2.9% rate of transient superficial radial nerve palsy and 0.3% rate of permanent damage. These complications should be considered when deciding between the two surgical approaches.

In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC) are infiltrated with tumor-reactive T cells that could be efficiently employed for adoptive transfer immunotherapy. TILs and autologous tumor cell lines (TCL) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared with those generated from metastatic melanoma. Immune recognition of autologous TCLs or fresh tumor digests was observed in CD8 + TILs from 82% of patients (18/22). Cytotoxicity assays confirmed the tumoricidal capacity of RCC-TILs. The overall expansion capacity of RCC-TILs was similar to MM-TILs. However, the magnitude, polyfunctionality, and ability to expand in classical expansion protocols of CD8 + T-cell responses was lower compared with MM-TILs. The RCC-TILs that did react to the tumor were functional, and antigen presentation and processing of RCC tumors was similar to MM-TILs. Direct recognition of tumors with cytokine-induced overexpression of human leukocyte antigen class II was observed from CD4 + T cells (6/12; 50%). Thus, TILs from primary RCC specimens could be isolated, expanded, and could recognize tumors. However, immune responses of expanded CD8 + RCC-TILs were typically weaker than MM-TILs and displayed a mono-/oligofunctional pattern. The ability to select, enrich, and expand tumor-reactive polyfunctional T cells may be critical in developing effective ACT with TILs for RCC. In summary, TILs isolated from primary RCC specimens could recognize tumors. However, their immune responses were weaker than MM-TILs and displayed a mono-/oligofunctional pattern. The ability to select and expand polyfunctional T cells may improve cell therapy for RCC. Cancer Immunol Res; 6(2); 222-35. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Slipped capital femoral epiphysis (SCFE) is a serious orthopaedic hip disease in the adolescent population. It has a prevalence of 10.8 per 100.000 children and usually occurs in children 9-16 years of age. Despite focus on delay of the diagnosis, no improvements have been made. An adolescent complaining of stress-related pain in the hip, groin, thigh or knee should be suspected of having SCFE, until an X-ray has excluded this diagnosis. Delayed diagnosis may have serious consequences in terms of further displacement of the femoral head and risk of increased avascular necrosis.

Background Children with leg length discrepancy often undergo repeat imaging. Therefore, every effort to reduce radiation dose is important. Using low dose preview images and noise reduction software rather than diagnostic images for length measurements might contribute to reducing dose. Purpose To compare leg length measurements performed on diagnostic images and low dose preview images both acquired using a low-dose bi-planar imaging system. Material and Methods Preview and diagnostic images from 22 patients were retrospectively collected (14 girls, 8 boys; mean age, 12.8 years; age range, 10-15 years). All images were anonymized and measured independently by two musculoskeletal radiologists. Three sets of measurements were performed on all images; the mechanical axis lines of the femur and the tibia as well as the anatomical line of the entire extremity. Statistical significance was tested with a paired t-test. Results No statistically significant difference was found between measurements performed on the preview and on the diagnostic image. The mean tibial length difference between the observers was -0.06 cm (95% confidence interval [CI], -0.12 to 0.01) and -0.08 cm (95% CI, -0.21 to 0.05), respectively; 0.10 cm (95% CI, 0.02-0.17) and 0.06 cm (95% CI, -0.02 to 0.14) for the femoral measurements and 0.12 cm (95% CI, -0.05 to 0.26) and 0.08 cm (95% CI, -0.02 to 0.19) for total leg length discrepancy. ICCs were >0.99 indicating excellent inter- and intra-rater reliability. Conclusion The data strongly imply that leg length measurements performed on preview images from a low-dose bi-planar imaging system are comparable to measurements performed on diagnostic images.

Manual analysis of flow cytometry data and subjective gate-border decisions taken by individuals continue to be a source of variation in the assessment of antigen-specific T cells when comparing data across laboratories, and also over time in individual labs. Therefore, strategies to provide automated analysis of major histocompatibility complex (MHC) multimer-binding T cells represent an attractive solution to decrease subjectivity and technical variation. The challenge of using an automated analysis approach is that MHC multimer-binding T cell populations are often rare and therefore difficult to detect. We used a highly heterogeneous dataset from a recent MHC multimer proficiency panel to assess if MHC multimer-binding CD8 + T cells could be analyzed with computational solutions currently available, and if such analyses would reduce the technical variation across different laboratories. We used three different methods, FLOw Clustering without K (FLOCK), Scalable Weighted Iterative Flow-clustering Technique (SWIFT), and ReFlow to analyze flow cytometry data files from 28 laboratories. Each laboratory screened for antigen-responsive T cell populations with frequency ranging from 0.01 to 1.5% of lymphocytes within samples from two donors. Experience from this analysis shows that all three programs can be used for the identification of high to intermediate frequency of MHC multimer-binding T cell populations, with results very similar to that of manual gating. For the less frequent populations (<0.1% of live, single lymphocytes), SWIFT outperformed the other tools. As used in this study, none of the algorithms offered a completely automated pipeline for identification of MHC multimer populations, as varying degrees of human interventions were needed to complete the analysis. In this study, we demonstrate the feasibility of using automated analysis pipelines for assessing and identifying even rare populations of antigen-responsive T cells and discuss the main properties, differences, and advantages of the different methods tested.

Background: Children with cerebral palsy (CP) often have an altered gait. Orthopaedic surgery, spasticity management, physical therapy and orthotics are used to improve the gait. Interventions are individually tailored and are planned on the basis of clinical examinations and standardised measurements to assess walking ('care as usual'). However, these measurements do not describe features in the gait that reflect underlying neuro-musculoskeletal impairments. This can be done with 3-dimensional instrumented gait analysis (IGA). The aim of this study is to test the hypothesis that improvements in gait following individually tailored interventions when IGA is used are superior to those following 'care as usual'., Methods/design: A prospective, single blind, randomised, parallel group study will be conducted. Children aged 5 to 8 years with spastic CP, classified at Gross Motor Function Classification System levels I or II, will be included. The interventions under investigation are: 1) individually tailored interdisciplinary interventions based on the use of IGA, and 2) 'care as usual'. The primary outcome is gait measured by the Gait Deviation Index. Secondary outcome measures are: walking performance (1-min walk test) and patient-reported outcomes of functional mobility (Pediatric Evaluation of Disability Inventory), health-related quality of life (The Pediatric Quality of Life Inventory Cerebral Palsy Module) and overall health, pain and participation (The Pediatric Outcome Data Collection Instrument). The primary endpoint for assessing the outcome of the two interventions will be 52 weeks after start of intervention. A follow up will also be performed at 26 weeks; however, exclusively for the patient-reported outcomes., Discussion: To our knowledge, this is the first randomised controlled trial comparing the effects of an individually tailored interdisciplinary intervention based on the use of IGA versus 'care as usual' in children with CP. Consequently, the study will provide novel evidence for the use of IGA., Trial Registration: ClinicalTrials.gov NCT02160457 . Registered June 2, 2014.

The Gait Deviation Index (GDI) and Gait Profile Score (GPS) are the most used summary measures of gait in children with cerebral palsy (CP). However, the reliability and agreement of these indices have not been investigated, limiting their clinimetric quality for research and clinical practice. The aim of this study was to investigate the intra-rater reliability and agreement of summary measures of gait (GDI; GPS; and the Gait Variable Score (GVS) derived from the GPS). The intra-rater reliability and agreement were investigated across two repeated sessions in 18 children aged 5-12 years diagnosed with spastic CP. No systematic bias was observed between the sessions and no heteroscedasticity was observed in Bland-Altman plots. For the GDI and GPS, excellent reliability with intraclass correlation coefficient (ICC) values of 0.8-0.9 was found, while the GVS was found to have fair to good reliability with ICCs of 0.4-0.7. The agreement for the GDI and the logarithmically transformed GPS, in terms of the standard error of measurement as a percentage of the grand mean (SEM%) varied from 4.1 to 6.7%, whilst the smallest detectable change in percent (SDC%) ranged from 11.3 to 18.5%. For the logarithmically transformed GVS, we found a fair to large variation in SEM% from 7 to 29% and in SDC% from 18 to 81%. The GDI and GPS demonstrated excellent reliability and acceptable agreement proving that they can both be used in research and clinical practice. However, the observed large variability for some of the GVS requires cautious consideration when selecting outcome measures., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with strong evidence of viral carcinogenesis. The association of MCC with the Merkel cell polyomavirus (MCPyV) may explain the explicit immunogenicity of MCC. Indeed, MCPyV-encoded proteins are likely targets for cytotoxic immune responses to MCC as they are both foreign to the host and necessary to maintain the oncogenic phenotype. However, to date only a single MCPyV-derived CD8 T-cell epitope has been described, thus impeding specific monitoring of T-cell responses to MCC., Method: To overcome this limitation, we scanned the MCPyV oncoprotein large T and small T antigens and the virus capsid protein VP1 for potential T-cell epitopes, and tested for MHC class I affinity. We confirmed the relevance of these epitopes using a high-throughput platform for T-cell enrichment and combinatorial encoding of MHC class I multimers., Results: In peripheral blood from 38 patients with MCC and 30 healthy donors, we identified 53 MCPyV-directed CD8 T-cell responses against 35 different peptide sequences. Strikingly, T-cell responses against oncoproteins were exclusively present in patients with MCC, but not in healthy donors. We further demonstrate both the processing and presentation of the oncoprotein-derived epitopes, as well as the lytic activity of oncoprotein-specific T cells toward MHC-matched MCC cells. Demonstrating the presence of oncoprotein-specific T cells among tumor-infiltrating lymphocytes further substantiated the relevance of the identified epitopes., Conclusion: These T-cell epitopes represent ideal targets for antigen-specific immune therapy of MCC, and enable tracking and characterization of MCPyV-specific immune responses., (©2014 AACR.)

Introduction: The aetiology of congenital clubfoot is unclear. Although studies on populations, families, and twins suggest a genetic component to the aetiology, other studies have identified environmental factors. The purpose of this study was to calculate heritability in order to determine to what extent genetic and/or environmental factors contribute to the aetiology of congenital clubfoot and to asses whether there was a change in the prevalence over time., Materials and Methods: The Odense based Danish Twin Registry is unique as it contains data on all the approximately 85,000 twin pairs born in Denmark over the last 140 years. All 46,418 twin individuals born from 1931 through 1982, who had earlier consented to contact, received a 17-page Omnibus questionnaire in the spring of 2002. Data were analysed with structural equation models to identify the best fitting aetiological model based on a balance of goodness-of-fit and parsimony and to estimate heritability., Results: We found an overall self-reported prevalence of congenital clubfoot of 0.0027 (95 % confidence interval 0.0022-0.0034). Fifty-five complete (both twins answered the question) twin pairs were identified representing 12 monozygotic, 22 same-sex dizygotic, 18 opposite-sex dizygotic, and 3 with unclassified zygosity. The model with only environmental factors (CE) was best fitting based on AIC, and the model with an additive genetic factor (ACE) came in second. Due to the small statistical power, we hypothesise that the model with both genetic and environmental effects (ACE) was the better model. Choosing the ACE-model we found a heritability of clubfoot of 30 %. Regression coefficient for age was -0.002 (-0.011 to 0.005), indicating that there has been no change in prevalence of clubfoot over the 50-year age span we examined., Discussion: We conclude that non-genetic factors must play a role, and a genetic factor might contribute, in the aetiology of congenital clubfoot.

Background: Skeletally immature patients diagnosed with adolescent idiopathic scoliosis (AIS) and a Cobb angle above 25degrees is usually treated with a brace. Standard protocols in many centers include hospitalisation for a few days for the purpose of brace adaptation and fitting. The aim of this study is to compare compliance and satisfaction in hospitalization and out patient clinic protocols, at the initiation phase of brace treatment., Materials and Methods: Twenty-four consecutive patients with AIS were initiated with the Providence night time only brace at our department between October 2008 and September 2009. The first twelve patients were admitted for a maximum of 3 days during the initiation phase of brace treatment. The following twelve patients were initiated in an outpatient clinic set-up. In this later group, patients and parents were informed about the possibility to be admitted to the hospital, at the initiation phase but all patients chose to be treated as out patient's protocol. All patients were evaluated by means of conventional x-ray and patients reported outcome measurements. The mean follow up was 6 months for the outpatient group (3-8) and 12 months for the hospitalisation group (9-14). Scoliosis Quality of Life Index (SQLI) was used together with the Odense Scoliosis questionnaire, which was developed for this study. Compliance was measured using the patients' own statements and the Landauer compliance scoring system., Findings/results: The two groups' matches regarding the age, Risser grad, Cobb angle and primary correction. There were no statistically significant differences between the two groups regarding the SQLI and the Odense Scoliosis questionnaire. The compliance was higher in the ambulatory group., Conclusion: Outpatient initiation of bracing in scoliosis seems to give the same correction but better compliance compared to initiation during hospitalization.

Aim: Patients with neuromuscular diseases such as cerebral palsy (CP) and meningomyelocele (MMC) are prone to develop fixed knee flexion contracture. Distal femoral extension osteotomy allows acute correction of the deformity, but it is an extensive surgical procedure, and the complication rate is rather high. Immobilization can prolong the rehabilitation period, and may even result in deteriorated walking ability. The aim of this retrospective study was to evaluate the results of using anterior hemiepiphysiodesis of the distal femur to treat fixed flexion contracture of the knee., Materials and Methods: We studied 21 patients in our department from 2003 to 2009. Mean age was 10 years (5-15). Twelve suffered from MMC, five from CP, two from arthrogryposis, one had an enzyme defect, and one had Down's syndrome. Thirteen patients had a bilateral and eight a unilateral procedure. None of the patients underwent any other procedures. Two staples or 8-plates were inserted using two parapatellar incisions. Nine were operated on with staples and 12 with 8-plates. The plates or staples were removed when the desired effect of full knee extension was achieved or the patient reached skeletal maturity., Results: Mean fixed flexion contracture was 20° (10°-40°). Staples or 8-plates were removed after a mean of 24 (6-42) months. Mean fixed flexion contracture at removal was 10° (0°-30°). Two complications were seen: one infection and one supracondylar fracture., Conclusion: Anterior distal femoral hemiepiphysiodesis using 8-plates or staples seems to be effective for correcting fixed knee flexion deformity in skeletally immature individuals. The complication rate is low (10 %). Our results are comparable to those of Kramer, Klatt, and Stevens. This procedure should be the primary treatment for fixed knee flexion contractures in neuromuscular patients with sufficient remaining growth.

Fluorescently labeled multimeric complexes of peptide-MHC, the molecular entities recognized by the T cell receptor, have become essential reagents for detection of antigen-specific CD8(+) T cells by flow cytometry. Here we present a method for high-throughput parallel detection of antigen-specific T cells by combinatorial encoding of MHC multimers. Peptide-MHC complexes are produced by UV-mediated MHC peptide exchange and multimerized in the form of streptavidin-fluorochrome conjugates. Eight different fluorochromes are used for the generation of MHC multimers and, by a two-dimensional combinatorial matrix, these eight fluorochromes are combined to generate 28 unique two-color codes. By the use of combinatorial encoding, a large number of different T cell populations can be detected in a single sample. The method can be used for T cell epitope mapping, and also for the monitoring of CD8(+) immune responses during cancer and infectious disease or after immunotherapy. One panel of 28 combinatorially encoded MHC multimers can be prepared in 4 h. Staining and detection takes a further 3 h.

Musculoskeletal infections in children present a challenge regarding diagnosis and treatment. Conventional radiographs guide the initial radiographic assessment. Additional imaging is often performed to improve the diagnosis of the abnormality. The modalities used are ultrasound, bone-scan, computed tomography or magnetic resonance imaging (MRI). On suspicion of multifocal musculoskeletal infections (MMI), MRI may save time and improve preoperative planning. We highly recommend the use of MRI for the preoperative assessment of children with MMI.

Background: Legg-Calvé-Perthes disease (LCPD) was described a century ago. In previous long-term reports of patients with LCPD, nonoperative treatment varied considerably. The likelihood of hip osteoarthritis (OA) developing in patients with LCPD and possible need for THA are not well defined., Questions/purposes: The purpose of the study was to determine whether nonoperatively treated patients with LCPD (1) had an increased prevalence of THA compared with gender- and age-matched control subjects, (2) if patients with Stulberg Classes III/IV/V femoral heads had an increased risk of THA compared with those with Classes I/II femoral heads. Given the limitation in the study, we (3) evaluated whether patients with LCPD were at risk for having radiographic hip OA more commonly than control subjects and (4) whether hips with Classes III/IV/V femoral heads had an increased prevalence of OA compared with hips with Classes I/II femoral heads., Patients and Methods: The study population consisted of 167 patients with LCPD treated with a Thomas splint. The control population consisted of gender- and age-matched control subjects who were participants in the Copenhagen City Heart Study: the Osteoarthritis Substudy. Radiographs at skeletal maturity were classified according to the classification system of Stulberg et al. Data from the Danish Hip Arthroplasty Register and the Registries of the National Board of Health were collected to obtain the number of patients with LCPD having THA. At a mean followup of 47 years later (range, 37-58 years), weightbearing pelvic radiographs were obtained. Radiographic OA was defined as a joint space width of 2.0 mm or less., Results: Thirteen percent of patients with LCPD had THAs compared with none in the control group. Seven percent of the patients with LCPD had OA compared with 1% in the control group. The prevalence of THA and OA was increased in hips with Classes III/IV/V femoral heads compared with hips with Classes I/II femoral heads., Conclusions: Patients with LCPD have an increased risk of having THA compared with a gender- and age-matched control group. Our data suggest that patients with LCPD have a greater risk of having radiographic OA develop than a gender- and age-matched control group. It seems that patients with Classes III/IV/V femoral heads have an increased risk of THA and OA compared with patients with Classes I/II femoral heads., Level of Evidence: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Objective: To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis., Methods: A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n=167) or saline (n=170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary efficacy parameter. LFI, pain on walking 50 m based on visual analogue scale (VAS pain 50 m), paracetamol consumption, patients' global assessment, Nottingham health profile, joint effusion and number of responders were secondary efficacy parameters. The efficacy parameters were analysed by intention to treat (ITT) and per protocol (PP). All adverse events (AE) were recorded as safety parameters., Results: Time to recurrence showed no significant treatment effect (ITT analysis, p=0.26). Change from baseline in LFI and VAS pain 50 m for the ITT population showed no treatment effect. Paracetamol consumption, patients' global assessment, responder rates and AE displayed no significant difference between treatment groups, analysed by both ITT and PP. Treatment compliance was 95% in the hyaluronan group and 99% in the placebo group. No safety problems were registered., Conclusion: In patients fulfilling the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity (LFI > or = 10), five intra-articular injections of hyaluronan did not improve pain, function, paracetamol consumption or other efficacy parameters 3, 6, 9 and 12 months after the treatment.

Post-traumatic cortical bone cyst is a rare occurrence in children. It is typically located in the distal radius, as a result of greenstick fracture. We report three cases referred to our fracture clinic as a tumour in bones. In one of our cases, the cystic lesion was noted following a displaced fracture in the femur, which is not previously published in the literature. The cyst-like lesion appeared as an oval radiolucency proximal to the previous fracture site on radiograph films. These lesions can cause concern for the on-call teams as they can mimic an infection or a tumour of the bone. We highlight the pathogenesis of the lesion with a review of the literature.

We report our experience with elastic stable intramedullary titanium nailing (ESIN) of femoral shaft fractures in children. From 1998 to 2001, we treated 31 children (20 boys), median age 6 (4-11) years, with ESIN for 29 closed and 2 grade I open femoral shaft fractures. We reviewed 30 children clinically after median 1.5 (1-3) years. Their median hospital stay was 6 (2-20) days. All fractures were radiographically united at a median of 7 (5-9) weeks. The nails were removed in 29 children after a median of 22 (6-38) weeks postoperatively. At follow-up, we found a leg-length discrepancy up to 1 cm in 6 children and 10 degrees of internal rotational deformity in 1 child. No angular deformity had occurred. Elastic stable intramedullary nailing seems to be a safe method for the treatment of femoral shaft fractures in children between 4 and 11 years of age.

The nutritional status was evaluated prospectively in 47 consecutive patients who were amputated for lower extremity ischemia. It was good in 13 patients, reduced in 18, and poor in 16. Malnourished patients had a higher frequency of impaired wound healing, and an increased risk of postoperative cardiopulmonary and septic complications; all 6 deaths occurred in these groups.

In a prospective study, we performed 18 core decompressions for Stage I primary osteonecrosis of the femoral head. Only 5 patients (six hips) seemed to have benefited from the intervention for more than 1 year.

Eleven children with simple bone cysts in the proximal humerus metaphysis were treated with intracavity infiltration of methylprednisolone acetate. Nine patients were treated once; the remainder required second injections. Five lesions resolved completely, while six healed sufficiently to eliminate the risk of pathologic fracture, and to permit physical activities without restrictions. Simple bone cysts can be treated satisfactorily with injection of methylprednisolone acetate, thus obviating surgery.

In 33 patients who had major amputation for ischemia of the lower extremity, skin blood flow and perfusion pressure were compared in terms of prediction of amputation level. Skin blood pressure was measured photoelectrically. Only the blood flow was known to the surgeon. The primary amputation was performed below the level of the knee in 15 patients, through-knee in 14, and above the knee in only 4 patients. Primary healing was achieved in 27 patients, 5 patients had delayed healing at the same level, and 1 patient was reamputated. The same amputation level was predicted in 24 patients (primary healing/secondary healing/failure = 20/3/1) and a different one in 9 patients. In 4 patients the perfusion pressure suggested a more proximal amputation (2/2/0) and in 5 patients a more distal amputation (all primary healing). There was no difference between the two methods in predicting wound healing.

We recorded intraosseous pO2 in 9 patients with Garden Stage I fractures of the femoral neck during aspiration of the hemarthrosis. An increase in pO2 indicating restoration of the blood flow was seen in 2 of the patients.

Serum alkaline phosphatase (SAP) was analyzed in 193 patients treated with total hip arthroplasty (THA) and correlated with the degree of heterotopic bone formation (HBF) one year after surgery. The influence of indomethacin on changes in SAP related to the development of heterotopic bone was studied. Ninety-eight patients received 25 mg of indomethacin three times daily for the first six postoperative weeks; the remaining 95 patients received a placebo treatment. No further anti-inflammatory drugs were allowed during the six weeks. SAP was measured preoperatively and six weeks and 12 weeks after surgery. No patients at risk for developing heterotopic bone after THA could be identified from the preoperative level of SAP. The level of SAP six weeks after THA gradually increased with the amount of HBF. A rise in SAP above 250 IU/liter 12 weeks after surgery was associated with the development of severe heterotopic bone in 13 of 17 patients. Indomethacin inhibited the development of heterotopic bone associated with a rise in SAP following THA. Future studies on HBF and SAP following THA should include information on patient use of anti-inflammatory drugs in the early postoperative period.

In order to delineate groups of patients suitable for treatment to prevent heterotopic bone formation (HBF) following total hip replacement, 99 patients were examined to evaluate predisposing factors. One year after surgery, HBF was found in 73% of the patients. A significantly increased frequency of HBF was found among men. There was no correlation between age, severity of osteoarthritis, size of osteophytes, or preoperative hip movement and HBF. Previous ipsilateral hip surgery did not increase the risk of HBF. Although not significant, all patients who developed heterotopic bone after previous ipsi- or contralateral hip surgery showed HBF of the same or even a higher grade after the present replacement.

We compared intraosseous pressure, partial pressure of oxygen and carbon dioxide, and histopathology in 10 hips with arthrosis and in seven hips with nontraumatic necrosis of the femoral head. Hypoxia of the subchondral bone was present in both conditions. In arthrosis the intraosseous pressure was normal, whereas intraosseous hypertension was present in necrosis. Partial pressure of carbon dioxide was normal in both conditions. Identical signs of subchondral medullary and trabecular necrosis were found in both conditions.

Four frequently referenced radiological methods for assessment of osteoarthrosis in hip joints are compared with respect to their interobserver variation. One hundred hip joints were rated by four observers. Each observer applied all four methods to all the radiographs. The results were analysed by a new statistical method, which allowed detailed assessment of the nature and extent of interobserver variation. Significant differences in terms of intraobserver disagreement were found, and Heripret's method was the best in this respect. All four methods showed a significant degree of systematic disagreement among the observers. This suggests that the interobserver variation might be reduced by confronting the observers with the results of the statistical analysis of their judgements.

The erythrocyte sedimentation rate (ESR) was analyzed in 176 patients treated with cemented total hip arthroplasty (THA) for primary osteoarthritis and correlated with the degree of heterotopic bone formation (HBF) one year after the THA. Ninety patients were treated with indomethacin in the first six postoperative weeks, and 86 patients had no antiinflammatory treatment during that same period. The ESR was measured with the Westergren method and estimated preoperatively and six and 12 weeks after THA. Patients treated with indomethacin had no or only Grade I HBF and no significant elevation in the six- and 12-week ESR. In the placebo group, 44 patients (51%) developed Grade II or Grade III HBF, and six weeks after THA, patients with Grade III HBF had a significant elevated ESR when compared with patients without or with Grade I HBF. Moreover, in patients not treated with indomethacin in the first six postoperative weeks, an ESR above 35 mm/hour 12 weeks after THA was found to be a reliable predictor for the development of severe HBF.

The influence of treatment with indomethacin in the first 6 postoperative weeks on the incidence of early loosening and radiolucencies following cemented total hip replacement were studied in 102 hips. Ninety-nine hips in 99 patients without postoperative antiinflammatory treatment served as control group. One year after surgery, two patients in the indomethacin group and five patients in the control group were suspected of having loosening of one or both prosthetic components. However, no patients had a revision. The lateral acetabular cement-bone interface most frequently showed a radiolucent line. Concerning the incidence of radiolucent lines in any acetabular or femoral cement-bone interface zone, no difference could be shown between the two groups. When evaluated 1 year after surgery, postoperative treatment with indomethacin does not increase the incidence of aseptic loosening or cement-bone interface radiolucencies in cemented total hip replacement.

We studied the effect of indomethacin on the prevention of formation of heterotopic bone after total hip replacement. In a randomized, double-blind clinical trial involving 201 patients, 102 patients received twenty-five milligrams of indomethacin three times daily for the first six postoperative weeks, and the other ninety-nine patients received a placebo. One year after the operation, eighty-nine of those who had received indomethacin had no sign of heterotopic ossification, and the remaining thirteen had a grade-I lesion. In the group that had received a placebo, twenty-seven had no heterotopic ossification; twenty-four, a grade-I lesion; thirty, a grade-II lesion; and eighteen, a grade-III lesion. Significantly fewer patients who had received indomethacin had formation of heterotopic bone compared with those who had been given a placebo (chi-square test, p less than 0.0005). Only patients who had grade-III formation of heterotopic bone had a significant reduction in movement of the hip.