Is Internal Rotation Measurement of the Hip Useful for Ruling in Cam or Pincer Morphology in Asymptomatic Males? A Diagnostic Accuracy Study.

BACKGROUND Cam and pincer morphologies are associated with limited internal rotation. However, the routine clinical examination for hip rotation has limited reliability. A more standardized method of measuring hip rotation might increase test-retest and interobserver reliability and might be useful as a screening test to detect different hip morphologies without the need for imaging. We developed an examination chair to standardize the measurement of internal hip rotation, which improved interobserver reliability. However, the diagnostic test accuracy for this test is unknown. QUESTION/PURPOSE Is a standardized method of determining internal hip rotation using an examination chair useful in detecting cam and pincer morphology with MRI as a reference standard? METHODS A diagnostic test accuracy study was conducted in a sample of asymptomatic males. Using an examination chair with a standardized seated position, internal rotation was measured in 1080 men aged 18 to 21 years who had been conscripted for the Swiss army. The chair prevents compensatory movement by stabilizing the pelvis and the thighs with belts. The force to produce the internal rotation was standardized with a pulley system. Previous results showed that the measurements with the examination chair are similar to clinical assessment but with higher interobserver agreement. A random sample of 430 asymptomatic males was invited to undergo hip MRI. Of those, 244 White European males responded to the invitation and had a mean age of 20 ± 0.7 years and a mean internal rotation of the hip of 33° ± 8.5°. Using MRI as the reference standard, 69% (169 of 244) had a normal hip, 24% (59 of 244) a definite cam morphology (Grades 2 and 3), 3% (8 of 244) an increased acetabular depth, and 3% (8 of 244) a combination of both. One experienced radiologist graded cam morphology as follows: 0 = normal, 1 = mild, 2 = moderate, and 3 = severe. Pincer morphology was defined by increased acetabular depth (≤ 3 mm distance between the center of the femoral neck and the line connecting the anterior and posterior acetabular rims). The intraobserver agreement was substantial (weighted κ of 0.65). A receiver operating characteristic (ROC) curve was fitted, and sensitivity, specificity, and likelihood ratios were estimated for different internal rotation cutoffs. RESULTS For cam morphology, the area under the ROC curve was 0.75 (95% CI 0.67 to 0.82). Internal hip rotation of less than 20° yielded a positive likelihood ratio of 9.57 (sensitivity 0.13, specificity 0.99), and a value of 40° or more resulted in a negative likelihood ratio of 0.36 (sensitivity 0.93, specificity 0.20). The area under the curve for detecting the combination of cam and pincer morphologies was 0.87 (95% CI 0.74 to 1.0). A cutoff of 20° yielded a positive likelihood ratio of 9.03 (sensitivity 0.33, specificity 0.96). CONCLUSION This examination chair showed moderate-to-good diagnostic value to rule in hip cam morphology in White European males. However, at the extremes of the 95% confidence intervals, diagnostic performance would be poor. Nonetheless, we believe this test can contribute to identifying cam morphologies, and we hope that future, larger studies-ideally in more diverse patient populations-will seek to validate this to arrive at more precise estimates of the diagnostic performance of this test. LEVEL OF EVIDENCE Level III, diagnostic study

Endoscopic sinus surgery training courses: Benefit and problems – a multicenter evaluation

Introduction: Dissection courses are important for trainees and surgeons in mastering the skills required to perform endoscopic sinus surgery (ESS) which is a common surgery in otorhinolaryngology. Aim: To evaluate the benefits of ESS training courses and ways to improve training. Material and methods: In a prospective study using a structured questionnaire, participants of ESS courses in the United Kingdom, Malaysia, India and Thailand were asked on their experiences in these courses and suggestions on improving them. Results and discussion: The majority of the participants have experiences in performing ESS prior to joining the course. Infundibulotomy was considered the easiest dissection step in ESS while frontal sinus surgery was considered the most challenging by the majority of the participants. The motivation for most of the participants in joining the course is to improve their skills with almost all stating that their expectations of the course have been fulfilled with improvement of their surgical techniques, anatomical skills and on patient’s safety. Almost all the participants were satisfied with the course and would recommend attending it. Conclusions: ESS dissection courses are an integral part in the learning process of trainees in becoming a competent surgeon and for surgeons to improve their techniques. Continuous improvement should be made to ensure that the participants will benefit from attending the cours

Single platelet and megakaryocyte morpho-dynamics uncovered by multicolor reporter mouse strains in vitro and in vivo

Visualizing cell behavior and effector function on a single cell level has been crucial for understanding key aspects of mammalian biology. Due to their small size, large number and rapid recruitment into thrombi, there is a lack of data on fate and behavior of individual platelets in thrombosis and hemostasis. Here we report the use of platelet lineage restricted multi-color reporter mouse strains to delineate platelet function on a single cell level. We show that genetic labeling allows for single platelet and megakaryocyte tracking and morphological analysis in vivo and in vitro, while not affecting lineage functions. Using Credriven Confetti expression, we provide insights into temporal gene expression patterns as well as spatial clustering of megakaryocytes in the bone marrow. In the vasculature, shape analysis of activated platelets recruited to thrombi identifies ubiquitous filopodia formation with no evidence of lamellipodia formation. Single cell tracking in complex thrombi reveals prominent myosin-dependent motility of platelets and highlights thrombus formation as a highly dynamic process amenable to modification and intervention of the acto-myosin cytoskeleton. Platelet function assays combining flow cytrometry, as well as in vivo, ex vivo and in vitro imaging show unaltered platelet functions of multicolor reporter mice compared to WT controls. In conclusion, platelet lineage multicolor reporter mice prove useful in furthering our understanding of platelet and megakaryocyte biology on a single cell level

CHronic Rhinosinusitis Outcome MEasures (CHROME), developing a core outcome set for trials of interventions in chronic rhinosinusitis

Statement of Problem: Evaluating the effectiveness of treatments in chronic rhinosinusitis (CRS) have been limited by both a paucity of high quality randomised trials, and the heterogeneity of outcomes in those that have been reported. Core outcome sets (COS) are an agreed, standardized set of outcomes that should be measured and reported by future trials as a minimum and will facilitate future meta-analysis of trial results in systematic reviews (SRs). We set out to develop a core outcome set for interventions for adults with CRS. Method(s) of study: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders’ views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed 110 patients and healthcare practitioners to individually rate the outcomes in terms of importance, on a Likert scale. Main Results: After 2 rounds of the iterative Delphi process, the 54 initial outcomes were distilled down to a final core-outcome set of 15 items, over 4 domains. Principal Conclusions: The authors hope inclusion of these core outcomes in future trials will increase the value of research on interventions for CRS in adults. It was felt important to make recommendations regarding how these outcomes should be measured, although additional work is now required to further develop and revalidate existing outcome measures

Vascular surveillance by haptotactic blood platelets in inflammation and infection

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets

Rhinology future debates, an EUFOREA report

The first Rhinology Future Debates was held in Brussels in December 2016, organized by EUFOREA (European Forum for Research and Education in Allergy and Airways diseases). The purpose of these debates is to bring novel developments in the field of Rhinology to the attention of the medical, paramedical and patient community, in a highly credible and balanced context. For the first time in Rhinology, a peer to peer scientific exchange with key experts in the field of rhinology and key medical colleagues from leading industries let to a brainstorming and discussion event on a number of hot issues in Rhinology. Novel developments are presented by key experts from industry and/or key thought leaders in Rhinology, and then followed by a lively debate on the potential positioning of new developments in care pathways, the strengths and weaknesses of the novel development(s), and comparisons with existing and/or competing products, devices, and/or molecules. As all debates are recorded and distributed on-line with limited editing (www.rhinology-future.com), EUFOREA aims at maximizing the education of the target groups on novel developments, allowing a critical appraisal of the future and a more rapid implementation of promising novel tools, techniques and/or molecules in clinical practise in Europe. The next Rhinology Future debate will be held in Brussels in December 2017

Thrombocytopenia and splenic platelet-directed immune responses after IV ChAdOx1 nCov-19 administration

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are based on a range of novel platforms, with adenovirus-based approaches (like ChAdOx1 nCov-19) being one of them. Recently, a novel complication of SARS-CoV-2–targeted adenovirus vaccines has emerged: immune thrombocytopenia, either isolated, or accompanied by thrombosis (then termed VITT). This complication is characterized by low platelet counts, and in the case of VITT, also by platelet-activating platelet factor 4 antibodies reminiscent of heparin-induced thrombocytopenia, leading to a prothrombotic state with clot formation at unusual anatomic sites. Here, we detected antiplatelet antibodies targeting platelet glycoprotein receptors in 30% of patients with proven VITT (n = 27) and 42% of patients with isolated thrombocytopenia after ChAdOx1 nCov-19 vaccination (n = 26), indicating broad antiplatelet autoimmunity in these clinical entities. We use in vitro and in vivo models to characterize possible mechanisms of these platelet-targeted autoimmune responses leading to thrombocytopenia. We show that IV but not intramuscular injection of ChAdOx1 nCov-19 triggers platelet-adenovirus aggregate formation and platelet activation in mice. After IV injection, these aggregates are phagocytosed by macrophages in the spleen, and platelet remnants are found in the marginal zone and follicles. This is followed by a pronounced B-cell response with the emergence of circulating antibodies binding to platelets. Our work contributes to the understanding of platelet-associated complications after ChAdOx1 nCov-19 administration and highlights accidental IV injection as a potential mechanism of platelet-targeted autoimmunity. Hence, preventing IV injection when administering adenovirus-based vaccines could be a potential measure against platelet-associated pathologies after vaccination