Fibrodysplasia Ossificans Progressiva: what have we achieved and where are we now? follow-up to the 2015 Lorentz Workshop

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the ACVR1 gene was identified as the causative mutation of FOP in 2006. After this, the pathophysiology of FOP has been further elucidated through the efforts of research groups worldwide. In 2015, a workshop was held to gather these groups and discuss the new challenges in FOP research. Here we present an overview and update on these topics

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Ineffable Cultures or Material Devices : What Valuation Studies can Learn from the Disappearance of Ensured Solidarity in a Health Care Market

Valuation studies addresses how values are made in valuation practices. A next —or rather previous—question becomes: what then makes valuation practices? Two oppositional replies are starting to dominate how that question can be answered: a more materially oriented focus on devices of valuation and a more sociologically inclined focus on ineffable valuation cultures. The debate between proponents of both approaches may easily turn into the kind of leapfrog debates that have dominated many previous discussions on whether culture or materiality would play a decisive role in driving history. This paper explores a less repetitive reply. It does so by analyzing the puzzling case of the demise of solidarity as a core value within the recent Dutch health care system of regulated competition. While “solidarity among the insured” was both a strong cultural value within the Dutch welfare-based health system, and a value that was built into market devices by health economists, within a fairly short time “fairness” became of lesser importance than “competition”. This makes us call for a more historical, relational, and dynamic understanding of the role of economists, market devices, and of culture in valuation studies.

Military civilian partnerships: International proposals for bridging the Walker Dip.

The Walker Dip refers to the cycle of the improvement of care for the battle injured soldier over the course of a conflict, followed by the decline in the skills needed to provide this care during peacetime, and the requisite need to relearn those skills during the next conflict. As the operational tempo of the conflicts in Afghanistan and Iraq has declined, concerns have arisen regarding whether US military surgeons are prepared to meet the demands of future conflicts. This problem is not unique to the US military, and allied nations have taken creative steps to address the Walker Dip in their own surgical communities. A panel entitled "Military and Civilian Trauma System Integration: Where Have We Come; Where Are We Going and What Can We Learn from Our International Partners" at the 2018 American Association for the Surgery of Trauma meeting brought together a cadre of civilian and military surgeons with experience in this area. The efforts described involved the creation of a new trauma training program in Doha, Qatar, the military civilian partnership in the Netherlands, and the steps taken to address the deficit of penetrating trauma in Sweden. This article focuses on the lessons that can be learned from our allied partners to assure readiness for deployment among military surgeons. LEVEL OF EVIDENCE: Economic and Value Based Evaluations, level V

Military civilian partnerships: International proposals for bridging the Walker Dip.

The Walker Dip refers to the cycle of the improvement of care for the battle injured soldier over the course of a conflict, followed by the decline in the skills needed to provide this care during peacetime, and the requisite need to relearn those skills during the next conflict. As the operational tempo of the conflicts in Afghanistan and Iraq has declined, concerns have arisen regarding whether US military surgeons are prepared to meet the demands of future conflicts. This problem is not unique to the US military, and allied nations have taken creative steps to address the Walker Dip in their own surgical communities. A panel entitled "Military and Civilian Trauma System Integration: Where Have We Come; Where Are We Going and What Can We Learn from Our International Partners" at the 2018 American Association for the Surgery of Trauma meeting brought together a cadre of civilian and military surgeons with experience in this area. The efforts described involved the creation of a new trauma training program in Doha, Qatar, the military civilian partnership in the Netherlands, and the steps taken to address the deficit of penetrating trauma in Sweden. This article focuses on the lessons that can be learned from our allied partners to assure readiness for deployment among military surgeons. LEVEL OF EVIDENCE: Economic and Value Based Evaluations, level V

IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption

Objective: Autoantibodies are detected in most patients with rheumatoid arthritis (RA) and can be of the IgM, IgG or IgA subclass. Correlations between IgA autoantibodies and more severe disease activity have been previously reported, but the functional role of IgA autoantibodies in the pathogenesis of RA is ill understood. In this study, we explored the effect of IgA immune complexes on osteoclast mediated bone resorption. Methods: Anti-citrullinated peptide antibody (ACPA) and anti-carbamylated protein (anti-CarP) antibody levels of the IgA and IgG isotype and rheumatoid factor (RF) IgA were determined in synovial fluid (SF) of RA patients. Monocytes, neutrophils, and osteoclasts were stimulated with precipitated immune complexes from SF of RA patients or IgA- and IgG-coated beads. Activation was determined by neutrophil extracellular trap (NET) release, cytokine secretion, and bone resorption. Results: NET formation by neutrophils was enhanced by SF immune complexes compared to immune complexes from healthy or RA serum. Monocytes stimulated with isolated SF immune complexes released IL-6 and IL-8, which correlated with the levels of ACPA IgA levels in SF. Osteoclasts cultured in the presence of supernatant of IgA-activated monocytes resorbed significantly more bone compared to osteoclasts that were cultured in supernatant of IgG-activated monocytes (p=0.0233). Osteoclasts expressed the Fc receptor for IgA (FcαRI; CD89) and Fc gamma receptors. IgA-activated osteoclasts however produced significantly increased levels of IL-6 (p<0.0001) and IL-8 (p=0.0007) compared to IgG-activated osteoclasts. Both IL-6 (p=0.03) and IL-8 (p=0.0054) significantly enhanced bone resorption by osteoclasts. Conclusion: IgA autoantibodies induce release of IL-6 and IL-8 by immune cells as well as osteoclasts, which enhances bone resorption by osteoclasts. We anticipate that this will result in more severe disease activity in RA patients. Targeting IgA-FcαRI interactions therefore represents a promising novel therapeutic strategy for RA patients with IgA autoantibodies

Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop

none35siFibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the ACVR1 gene was identified as the causative mutation of FOP in 2006. After this, the pathophysiology of FOP has been further elucidated through the efforts of research groups worldwide. In 2015, a workshop was held to gather these groups and discuss the new challenges in FOP research. Here we present an overview and update on these topics.opende Ruiter R.D.; Smilde B.J.; Pals G.; Bravenboer N.; Knaus P.; Schoenmaker T.; Botman E.; Sanchez-Duffhues G.; Pacifici M.; Pignolo R.J.; Shore E.M.; van Egmond M.; Van Oosterwyck H.; Kaplan F.S.; Hsiao E.C.; Yu P.B.; Bocciardi R.; De Cunto C.L.; Longo Ribeiro Delai P.; de Vries T.J.; Hilderbrandt S.; Jaspers R.T.; Keen R.; Koolwijk P.; Morhart R.; Netelenbos J.C.; Rustemeyer T.; Scott C.; Stockklausner C.; ten Dijke P.; Triffit J.; Ventura F.; Ravazzolo R.; Micha D.; Eekhoff E.M.W.de Ruiter, R. D.; Smilde, B. J.; Pals, G.; Bravenboer, N.; Knaus, P.; Schoenmaker, T.; Botman, E.; Sanchez-Duffhues, G.; Pacifici, M.; Pignolo, R. J.; Shore, E. M.; van Egmond, M.; Van Oosterwyck, H.; Kaplan, F. S.; Hsiao, E. C.; Yu, P. B.; Bocciardi, R.; De Cunto, C. L.; Longo Ribeiro Delai, P.; de Vries, T. J.; Hilderbrandt, S.; Jaspers, R. T.; Keen, R.; Koolwijk, P.; Morhart, R.; Netelenbos, J. C.; Rustemeyer, T.; Scott, C.; Stockklausner, C.; ten Dijke, P.; Triffit, J.; Ventura, F.; Ravazzolo, R.; Micha, D.; Eekhoff, E. M. W