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Introduction: 3D printing has quickly found many applications in medicine. However, as with any new technology the regulatory landscape is struggling to stay abreast. Unclear legislation or lack of legislation has been suggested as being one hindrance for wide-scale adoption.Methods: A scoping review was performed in PubMed, Web of Science, SCOPUS and Westlaw International to identify articles dealing with legal issues in medical 3D printing.Results: Thirty-four articles fulfilling inclusion criteria were identified in medical/technical databases and fifteen in the legal database. The majority of articles dealt with the USA, while the EU was also prominently represented. Some common unresolved legal issues were identified, among them terminological confusion between custom-made and patient-matched devices, lack of specific legislation for patient-matched products, and the undefined legal role of CAD files both from a liability and from an intellectual property standpoint. Data protection was mentioned only in two papers and seems an underexplored topic.Conclusion: In this scoping review, several relevant articles and several common unresolved legal issues were identified including a need for terminological uniformity in medical 3D printing. The results of this work are planned to inform our own deeper legal analysis of these issues in the future.

BackgroundExtranodal extension (ENE) is an important adverse prognostic factor in oropharyngeal cancer (OPC) and is often employed in therapeutic decision making. Clinician-based determination of ENE from radiological imaging is a difficult task with high inter-observer variability. However, the role of clinical specialty on the determination of ENE has been unexplored.MethodsPre-therapy computed tomography (CT) images for 24 human papillomavirus-positive (HPV+) OPC patients were selected for the analysis; 6 scans were randomly chosen to be duplicated, resulting in a total of 30 scans of which 21 had pathologically-confirmed ENE. 34 expert clinician annotators, comprised of 11 radiologists, 12 surgeons, and 11 radiation oncologists separately evaluated the 30 CT scans for ENE and noted the presence or absence of specific radiographic criteria and confidence in their prediction. Discriminative performance was measured using accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and Brier score for each physician. Statistical comparisons of discriminative performance were calculated using Mann Whitney U tests. Significant radiographic factors in correct discrimination of ENE status were determined through a logistic regression analysis. Interobserver agreement was measured using Fleiss’ kappa.ResultsThe median accuracy for ENE discrimination across all specialties was 0.57. There were significant differences between radiologists and surgeons for Brier score (0.33 vs. 0.26), radiation oncologists and surgeons for sensitivity (0.48 vs. 0.69), and radiation oncologists and radiologists/surgeons for specificity (0.89 vs. 0.56). There were no significant differences between specialties for accuracy or AUC. Indistinct capsular contour, nodal necrosis, and nodal matting were significant factors in regression analysis. Fleiss’ kappa was less than 0.6 for all the radiographic criteria, regardless of specialty.ConclusionsDetection of ENE in HPV+OPC patients on CT imaging remains a difficult task with high variability, regardless of clinician specialty. Although some differences do exist between the specialists, they are often minimal. Further research in automated analysis of ENE from radiographic images is likely needed.

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10-11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of

Neutrophil-to-lymphocyte ratio (NLR) in peripheral blood samples has been associated with prognosis in several cancers, including head and neck cancer; but in oropharyngeal carcinomas its prognostic value, especially in relation to human papillomavirus (HPV) infection, has been little studied. This meta-analysis including studies on the prognostic value of NLR in oropharyngeal carcinoma shows that an elevated pretreatment NLR is associated with a worse prognosis in oropharyngeal cancer, regardless of the type of treatment performed, but this prognostic value appears to be specific to HPV-positive oropharyngeal carcinomas. NLR could be used as an affordable prognostic marker in this type of cancers.

INTRODUCTION: Post-paralytic facial synkinesis after facial nerve injury produces functional disabilities and mimetic deficits, but also cosmetic and non-motor psychosocial impairments for the patients. These patients typically have a high and continuous high motivation for rehabilitation. The aim is to inform the affected patients and their therapeutic professionals (otorhinolaryngologist - head and neck surgeons; oral-maxillofacial surgeons, plastic and reconstructive surgeons, neurosurgeons, neurologists, and mime therapists be it speech and language therapy- or physiotherapy-based) and to provide practical recommendations for diagnostics and a stepwise systematic treatment approach of facial synkinesis. METHODS: In the first phase, a systematic literature search on the topic in PubMed and ScienceDirect starting in 2008 resulted in 132 articles. These were the basis for the review and a comprehensive series of consensus statements on the most important diagnostic tests and treatment options. In the second phase, one consensus article circulated among the membership of the International Head and Neck Scientific Group until a final agreement was reached for all recommendations. RESULTS: Diagnostics should include a standardized assessment of the degree of synkinesis using validated clinician-graded instruments and synkinesis-specific patient-reported outcome measures. Treatments for facial synkinesis include facial training mainly based on facial biofeedback retraining, chemodenervation with botulinum toxin, selective neurectomy, myectomy, and any combination treatment of these options. CONCLUSION: A basic understanding of the pathomechanisms of synkinesis is essential to understand the treatment strategies. A standardized assessment of the synkinetic symptoms and the individual synkinesis pattern is needed. The first-line treatment is facial training, followed by botulinum toxin. Surgery is reserved for individual cases with unsatisfactory first-line treatment. ispartof: Frontiers In Neurology vol:13 ispartof: location:Switzerland status: published