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Objectives: To describe radiologist's attitudes and perspectives on evidence-based medicine (EBM) and their practice. Design: Face-to-face semistructured interviews, thematic analysis. Setting: 24 institutions across six Australian states and New Zealand. Transcripts were imported into HyperRESEARCH software and thematically analysed. Participants: 25 radiologists. Results: Six themes were identified: legitimising decisions (validated justification, prioritising patient preferences, reinforcing protocols), optimising outcomes (ensuring patient safety, maximising efficiency), availability of access (requiring immediacy, inadequacy of evidence, time constraints, proximity of peer networks, grasping information dispersion), overriding pragmatism ( perceptibly applicability, preserving the art of medicine, technical demands), limited confidence (conceptual obscurity, reputation-based trust, demands constant practice, suspicion and cynicism), and competing powers (hierarchical conflict, prevailing commercial interests). Conclusions: Radiologists believe EBM can support clinical decision-making for optimal patient outcomes and service efficiency but feel limited in their capacities to assimilate and apply EBM in practice. Improving access to evidence, providing ongoing education and training supplemented with practical tools for appraising evidence; and developing evidence-based guidelines and protocols may enhance feasibility and promote the confidence and skills among radiologists in applying EBM in radiology practice for better patient care. [ABSTRACT FROM AUTHOR]

Objective: Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management of this important emerging disorder., Methods: Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans. We then undertook a detailed analysis of the clinical, histopathological and imaging features of these patients., Results: All patients had prenatal or early onset hypotonia and/or congenital contractures. None had ophthalmoplegia. Scoliosis and respiratory insufficiency typically developed early and progressed rapidly, whereas limb weakness was often slowly progressive, and usually did not prevent independent walking. Cardiac involvement was present in 46% of patients. Relatives of 2 patients had dilated cardiomyopathy. Creatine kinase levels were normal to moderately elevated. Increased fiber size variation, internalized nuclei and cores were common histopathological abnormalities. Cap-like regions, whorled or ring fibers, and mitochondrial accumulations were also observed. Muscle magnetic resonance imaging showed gluteal, hamstring and calf muscle involvement. Western blot analysis showed a near-normal sized titin protein in all samples. The presence of 2 mutations predicted to impact both N2BA and N2B cardiac isoforms appeared to be associated with greatest risk of cardiac involvement. One-third of patients had 1 mutation predicted to impact exons present in fetal skeletal muscle, but not included within the mature skeletal muscle isoform transcript. This strongly suggests developmental isoforms are involved in the pathogenesis of this congenital/early onset disorder., Interpretation: This detailed clinical reference dataset will greatly facilitate diagnostic confirmation and management of patients, and has provided important insights into disease pathogenesis. Ann Neurol 2018;83:1105-1124., (© 2018 American Neurological Association.)

This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase. Distinctive histopathology showed abundant internalized nuclei, myofibrillar disorganization, desmin-positive inclusions, and thickened Z-bands. PYROXD1 is a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins (FAD-binding) and catalyze pyridine-nucleotide-dependent (NAD/NADH) reduction of thiol residues in other proteins. Complementation experiments in yeast lacking glutathione reductase glr1 show that human PYROXD1 has reductase activity that is strongly impaired by the disease-associated missense mutations. Immunolocalization studies in human muscle and zebrafish myofibers demonstrate that PYROXD1 localizes to the nucleus and to striated sarcomeric compartments. Zebrafish with ryroxD1 knock-down recapitulate features of PYROXD1 myopathy with sarcomeric disorganization, myofibrillar aggregates, and marked swimming defect. We characterize variants in the oxidoreductase PYROXD1 as a cause of early-onset myopathy with distinctive histopathology and introduce altered redox regulation as a primary cause of congenital muscle disease., (Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objective: The objectives of this study were to determine whether the fibulotalocalcaneal (FTC) ligament of the ankle, described in anatomical literature, can be identified on magnetic resonance (MR) imaging studies., Methods: Magnetic resonance imaging was performed on 6 cadaver ankles, which were then sectioned axially. The posterolateral ankle was inspected on MR imaging and cadaver sections for ligamentous thickening corresponding to the components of the FTC ligament: main stem and talar and peroneocalcaneal laminae., Results: The entire FTC ligament or components of it were seen in 5 (83%) of 6 ankles. In 3 (50%) of 6, all 3 components were present. The main stem of the FTC ligament attached to the posteromedial aspect of the lateral malleolus and then divided inferiorly into 2 laminae: The talar lamina extended horizontally to the talus, and the peroneocalcaneal lamina descended vertically to the calcaneus., Conclusions: The FTC ligament is a sheetlike extrinsic ligament, which is in continuity with the deep posterior crural fascia of the ankle and is visible on MR imaging.

Objective: This study was performed to examine the normal MR arthrographic anatomy of the popliteomeniscal fascicles with specific reference to the number of popliteomeniscal fascicles, thickness and course of the fascicles, and presence of other posterior attachments from the medial aponeurosis of the popliteus musculotendinous region., Materials and Methods: Multiplanar 1.5-T MR arthrography of 10 cadaveric knees was performed using a quadrature knee coil. Specimens were frozen and sectioned in the sagittal (n = 4), axial (n = 3), and coronal (n = 3) planes. MR images and anatomic specimens were correlated by two musculoskeletal radiologists., Results: Three popliteomeniscal fascicles were identified on MR arthrography: anteroinferior and posterosuperior fascicles in all 10 knees and posteroinferior fascicles in four of the knees. The posterosuperior popliteomeniscal fascicle was uniform in thickness, and the anteroinferior popliteomeniscal fascicle was variable in thickness. The anteroinferior popliteomeniscal fascicle formed a conjoined fibular attachment with the popliteofibular ligament. A medial aponeurotic extension from the popliteus musculotendinous region gave rise to the posteroinferior popliteomeniscal fascicle, which extended upward and attached to the inferomedial aspect of the posterior horn of the lateral meniscus. Additional attachments from the medial aponeurosis of the popliteus musculotendinous region to the posterior cruciate ligament, posterior capsule, oblique popliteal ligament, and posterior meniscofemoral ligament of Wrisberg were seen., Conclusion: Three popliteomeniscal fascicles were identified on MR arthrographic images. The popliteus muscle-tendon unit forms robust attachments in the superior, inferior, medial, and lateral oblique aspects, highlighting its importance in posterolateral stability of the knee.