Nosology and classification of genetic skeletal disorders: 2010 revision.

Genetic disorders involving the skeletal system arise through disturbances in the complex processes of skeletal development, growth and homeostasis and remain a diagnostic challenge because of their variety. The Nosology and Classification of Genetic Skeletal Disorders provides an overview of recognized diagnostic entities and groups them by clinical and radiographic features and molecular pathogenesis. The aim is to provide the Genetics, Pediatrics and Radiology community with a list of recognized genetic skeletal disorders that can be of help in the diagnosis of individual cases, in the delineation of novel disorders, and in building bridges between clinicians and scientists interested in skeletal biology. In the 2010 revision, 456 conditions were included and placed in 40 groups defined by molecular, biochemical, and/or radiographic criteria. Of these conditions, 316 were associated with mutations in one or more of 226 different genes, ranging from common, recurrent mutations to "private" found in single families or individuals. Thus, the Nosology is a hybrid between a list of clinically defined disorders, waiting for molecular clarification, and an annotated database documenting the phenotypic spectrum produced by mutations in a given gene. The Nosology should be useful for the diagnosis of patients with genetic skeletal diseases, particularly in view of the information flood expected with the novel sequencing technologies; in the delineation of clinical entities and novel disorders, by providing an overview of established nosologic entities; and for scientists looking for the clinical correlates of genes, proteins and pathways involved in skeletal biology. © 2011 Wiley-Liss, Inc.

Need of reduced and harmonized bureaucracy in multi-centre clinical research - a case-report from a Swiss trial

Introduction We launched an investigator-initiated study(ISRCTN31181395) to evaluate the potential benefit of pharmacokinetic-guided dosage individualization of imatinib for leukaemia patients followed in public and private sectors. Following approval by the research ethics committee (REC) of the coordinating centre, recruitment throughout Switzerland necessitated to submit the protocol to 11 cantonal RECs.Materials and Methods We analysed requirements and evaluation procedures of the 12 RECs with associated costs.Results 1-18 copies of the dossier, in total 4300 printed pages, were required (printing/posting costs: ~300 CHF) to meet initial requirements. Meeting frequencies of RECs ranged between 2 weeks and 2 months, time from submission to first feedback took 2-75 days. Study approval was obtained from a chairman, a subor the full committee, the evaluation work being invoiced by 0-1000 CHF (median: 750 CHF, total: 9200 CHF). While 5 RECs gave immediate approval, the other 6 rose in total 38 queries before study release, mainly related to wording in the patient information, leading to 7 different final versions approved. Submission tasks employed an investigator half-time over about 6 months.Conclusion While the necessity of clinical research evaluation by independent RECs is undisputed, there is a need of further harmonization and cooperation in evaluation procedures. Current administrative burden is indeed complex, time-consuming and costly. A harmonized electronic application form, preferably compatible with other regulatory bodies and European countries, could increase transparency, improve communication, and encourage academic multi-centre clinical research in Switzerland.

Proposal of a new classification for optimising outcome assessment following partial cricotracheal resections in severe pediatric subglottic stenosis.

OBJECTIVE: Creation of a patent subglottic airway after partial cricotracheal resection (PCTR) may not always result in successful decannulation due to associated parameters such as co-morbidity and/or glottic involvement. We classified patients after incorporating these additional parameters into the original Myer-Cotton classification to assess whether this could better predict the outcome measures after PCTR. METHODS: One hundred children with Myer-Cotton grade III or IV subglottic stenosis who underwent PCTR between 1978 and 2008 were identified from a prospectively collected database. The patients were classified into four groups based on the association of co-morbidity and/or glottic involvement. Delay in decannulation, revision open surgery and rates of decannulation were the outcome measures compared between the groups. RESULTS: There were 68 children with Myer-Cotton grade III and 32 children with grade IV stenosis. Based on the new classification, there were 36 children with isolated SGS, 31 with associated co-morbidity, 19 with associated glottic involvement and 14 children with both co-morbidity and glottic involvement. A trend towards less optimal results was noticed with the association of co-morbidity and/or glottic involvement. Statistical significance was reached for maximum decannulation failure in the group with both co-morbidity and glottic involvement. Delayed decannulation significantly correlated in the group with associated glottic involvement. CONCLUSION: This new classification is relatively simple and aimed at providing more accurate and uniform prognostic information to both patients and surgeons when dealing with the whole spectrum of severe SGS.

Documentation of fracture severity with the AO classification of pediatric long-bone fractures.

BACKGROUND: The AO comprehensive pediatric longbone fracture classification system describes the localization and morphology of fractures, and considers severity in 3 categories: (1) simple, (2) wedge, and (3) complex. We evaluated the reliability and accuracy of surgeons in using this rating system. MATERIAL AND METHODS: In a first validation phase, 5 experienced pediatric (orthopedic) surgeons reviewed radiographs of 267 prospectively collected pediatric fractures (agreement study A). In a second study (B), 70 surgeons of various levels of experience in 15 clinics classified 275 fractures via internet. Simple fractures comprised about 90%, 99% and 100% of diaphyseal (D), metaphyseal (M), and epiphyseal (E) fractures, respectively. RESULTS: Kappa coefficients for severity coding in D fractures were 0.82 and 0.51 in studies A and B, respectively. The median accuracy of surgeons in classifying simple fractures was above 97% in both studies but was lower, 85% (46-100), for wedge or complex D fractures. INTERPRETATION: While reliability and accuracy estimates were satisfactory as a whole, the ratings of some individual surgeons were inadequate. Our findings suggest that the classification of fracture severity in children should be done in only two categories that distinguish between simple and wedge/complex fractures.

NanoImpactNet - building a multi-stakeholder dialogue on the health and environmental impact of nanomaterials

NanoImpactNet (NIN) is a multidisciplinary European Commission funded network on the environmental, health and safety (EHS) impact of nanomaterials. The 24 founding scientific institutes are leading European research groups active in the fields of nanosafety, nanorisk assessment and nanotoxicology. This 4-year project is the new focal point for information exchange within the research community. Contact with other stakeholders is vital and their needs are being surveyed. NIN is communicating with 100s of stakeholders: businesses; internet platforms; industry associations; regulators; policy makers; national ministries; international agencies; standard-setting bodies and NGOs concerned by labour rights, EHS or animal welfare. To improve this communication, internet research, a questionnaire distributed via partners and targeted phone calls were used to identify stakeholders' interests and needs. Knowledge gaps and the necessity for further data mentioned by representatives of all stakeholder groups in the targeted phone calls concerned: • the potential toxic and safety hazards of nanomaterials throughout their lifecycles; • the fate and persistence of nanoparticles in humans, animals and the environment; • the associated risks of nanoparticle exposure; • greater participation in: the preparation of nomenclature, standards, methodologies, protocols and benchmarks; • the development of best practice guidelines; • voluntary schemes on responsibility; • databases of materials, research topics and themes, but also of expertise. These findings suggested that stakeholders and NIN researchers share very similar knowledge needs, and that open communication and free movement of knowledge will benefit both researchers and industry. Subsequently a workshop was organised by NIN focused on building a sustainable multi-stakeholder dialogue. Specific questions were asked to different stakeholder groups to encourage discussions and open communication. 1. What information do stakeholders need from researchers and why? The discussions about this question confirmed the needs identified in the targeted phone calls. 2. How to communicate information? While it was agreed that reporting should be enhanced, commercial confidentiality and economic competition were identified as major obstacles. It was recognised that expertise was needed in the areas of commercial law and economics for a wellinformed treatment of this communication issue. 3. Can engineered nanomaterials be used safely? The idea that nanomaterials are probably safe because some of them have been produced 'for a long time', was questioned, since many materials in common use have been proved to be unsafe. The question of safety is also about whether the public has confidence. New legislation like REACH could help with this issue. Hazards do not materialise if exposure can be avoided or at least significantly reduced. Thus, there is a need for information on what can be regarded as acceptable levels of exposure. Finally, it was noted that there is no such thing as a perfectly safe material but only boundaries. At this moment we do not know where these boundaries lie. The matter of labelling of products containing nanomaterials was raised, as in the public mind safety and labelling are connected. This may need to be addressed since the issue of nanomaterials in food, drink and food packaging may be the first safety issue to attract public and media attention, and this may have an impact on 'nanotechnology as a whole. 4. Do we need more or other regulation? Any decision making process should accommodate the changing level of uncertainty. To address the uncertainties, adaptations of frameworks such as REACH may be indicated for nanomaterials. Regulation is often needed even if voluntary measures are welcome because it mitigates the effects of competition between industries. Data cannot be collected on voluntary bases for example. NIN will continue with an active stakeholder dialogue to further build on interdisciplinary relationships towards a healthy future with nanotechnology.

Management of a post-operative multi-resistant infectious spondylitis associated with a kyphotic deformity.

Anterior spinal infection (prevertebral abscess and/or discitis) after posterior instrumentation for vertebral fractures is a challenging complication, since a new implant may become necessary anteriorly, in a septic environment. Generally accepted management guidelines are yet to be established. The authors present a case of posterior instrumentation for fractures of T12 and L1, complicated after 9 months with an anterior infection (prevertebral abscess and discitis) with extended-spectrum beta-lactamase (ESBL) producing Escherichia coli (E. coli). This case is unique in that the multi-resistant organism was isolated only after the second stage of infection treatment, which consisted of anterior débridement and anterior implantation of titanium cages and rods. In this particular case, infection was controlled despite implantation of multiple cages, screws and rods, and fusion was achieved, by means of intravenous antibiotic treatment for 12 months. At the latest follow-up, 24 months post surgery, there was no evidence of infection. This problem case may be helpful for surgeons confronted with spinal deformities secondary to infections with multi-resistant organisms.

Classification and management of seeds in retinoblastoma. Ellsworth Lecture Ghent August 24th 2013.

Retinoblastoma has the unique capacity to accelerate its own intra-ocular propagation by adopting semi-solid or even liquid growth properties through seeding. Until recently, the presence of any degree of seeding was mostly incompatible with successful conservative management, due to the multiresistant nature of the seeds. Surprisingly, this well-recognized retinoblastoma behavior has not undergone any detailed description of seeding patterns and anatomic sites. In this paper, we describe the phenotypic variability of seeds across the four possible intraocular seeding compartments and classify them into three fundamental types: namely dust, spheres, and clouds. We also provide an overview of the different therapeutic strategies developed for seeding, with special attention to intravitreal chemotherapy as the treatment of choice for vitreous and retro-hyaloid seeding. Finally, we propose criteria to enable assessment of the response to treatment by reporting seed regression patterns, as well as a clinical grading system for the retinal toxicity observed following intravitreal melphalan.

Ascending aorta measurements as assessed by ECG-gated multi-detector computed tomography : a pilot study to etablish normative values for transcatheters therapies

Rapport de synthèse : Mesures de l'aorte ascendante par scanner synchronisé au rythme cardiaque: une étude pilote pour établir des valeurs normatives dans le cadre des futures thérapies par transcathéter. Objectif : L'objectif de cette étude est d'établir les valeurs morphométriques normatives de l'aorte ascendante à l'aide de l'angiographie par scanner synchronisé au rythme cardiaque, afin d'aider au développement des futurs traitements par transcathéter. Matériels et méthodes : Chez soixante-dix-sept patients (âgé de 22 à 83 ans, âge moyen: 54,7 ans), une angiographie par scanner synchronisé au rythme cardiaque a été réalisée pour évaluation des vaisseaux coronaires. Les examens ont été revus afin d'étudier l'anatomie de la chambre de chasse du ventricule gauche jusqu'au tronc brachio-céphalique droit. A l'aide de programmes de reconstructions multiplanaires et de segmentation automatique, différents diamètres et longueurs considérés comme importants pour les futurs traitements par transcathéter ont été mesurés. Les valeurs sont exprimées en moyennes, médianes, maximums, minimums, écart-types et en coefficients de variation. Les variations de diamètre de l'aorte ascendante durant le cycle cardiaque ont été aussi considérées. Résultats : Le diamètre moyen de la chambre de chasse du ventricule gauche était de 20.3+/-3.4 mm. Au niveau du sinus coronaire de l'aorte, il était de 34.2+/-4.1 mm et au niveau de la jonction sinotubulaire il était de 29.7+/-3.4 mm. Le diamètre moyen de l'aorte ascendante était de 32.7+/-3.8 mm. Le coefficient de variation de ces mesures variait de 12 à 17%. La distance moyenne entre l'insertion proximale des valvules aortiques et le départ du tronc brachio-céphalique droit était de 92.6+/-11.8 mm. La distance moyenne entre l'insertion proximale des valvules aortiques et l'origine de l'artère coronaire proximale était de 12.1+/-3.7 mm avec un coefficient de variation de 31%. La distance moyenne entre les deux ostia coronaires était de 7.2+/-3.1 mm avec un coefficient de variation de 43%. La longueur moyenne du petit arc de l'aorte ascendante entre l'artère coronaire gauche et le tronc brachio-céphalique droit était de 52.9+/-9.5 mm. La longueur moyenne de la continuité fibreuse entre la valve aortique et la valvule mitrale antérieure était de 14.6+/-3.3 mm avec un coefficient de variation de 23%. L'aire moyenne de la valve aortique était de 582.0+/-131.9 mm2. La variation du diamètre antéro-postérieur et transverse de l'aorte ascendante était respectivement de 8.4% et de 7.3%. Conclusion Il existe d'importantes variations inter-individuelles dans les mesures de l'aorte ascendante avec cependant des variations intra-individuelles faibles durant le cycle cardiaque. De ce fait, une approche personnalisée pour chaque patient est recommandée dans la confection des futures endoprothèses de l'aorte ascendante. Le scanner synchronisé au rythme cardiaque jouera un rôle prépondérant dans le bilan préthérapeutique. Abstract : The aim of this study was to provide an insight into normative values of the ascending aorta in regards to novel endovascular procedures using ECG-gated multi-detector CT angiography. Seventy-seven adult patients without ascending aortic abnormalities were evaluated. Measurements at relevant levels of the aortic root and ascending aorta were obtained. Diameter variations of the ascending aorta during cardiac cycle were also considered. Mean diameters (mm) were as follows: LV outflow tract 20.3+/-3.4, coronary sinus 34.2+/-4.1, sinotubular junction 29.7+-3.4 and mid ascending aorta 32.7+/-3.8 with coefficients of variation (CV) ranging from 12 to 17%. Mean distances (mm) were: from the plane passing through the proximal insertions of the aortic valve cusps to the right brachio-cephalic artery (BCA) 92.6111.8, from the plane passing through the proximal insertions of the aortic valve cusps to the proximal coronary ostium 12.1+/-3.7, and between both coronary ostia 7.2+/-3.1, minimal arc of the ascending aorta from left coronary ostium to right BCA 52.9 X9.5, and the fibrous continuity between the aortic valve and the anterior leaflet of the mitral valve 14.óf3.3, CV 13-43%. Mean aortic valve area was 582+-131.9 mm2. The variations of the antero-posterior and transverse diameters of the ascending aorta during the cardiac cycle were 8.4% and 7.3%, respectively. Results showed large inter-individual variations in diameters and distances but with limited intra-individual variations during the cardiac cycle. A personalized approach for planning endovascular devices must be considered.