Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40

SGN-40 is a therapeutic antibody targeting CD40, which induces potent anti-lymphoma activities via direct apoptotic signalling cells and by cell-mediated cytotoxicity. Here we show antibody-dependent cellular phagocytosis (ADCP) by macrophages to contribute significantly to the therapeutic activities and that the antitumour effects of SGN-40 depend on Fc interactions

Allergen Uptake, Activation, and IL-23 Production by Pulmonary Myeloid DCs Drives Airway Hyperresponsiveness in Asthma-Susceptible Mice

Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs) are important mediators of allergic asthma, yet the precise signals which render endogenous DCs “pro-asthmatic”, and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J), or resistant (C3H) to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC) allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23), whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs) to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness

International lower limb collaborative (INTELLECT) study: a multicentre, international retrospective audit of lower extremity open fractures

Trauma remains a major cause of mortality and disability across the world1, with a higher burden in developing nations2. Open lower extremity injuries are devastating events from a physical3, mental health4, and socioeconomic5 standpoint. The potential sequelae, including risk of chronic infection and amputation, can lead to delayed recovery and major disability6. This international study aimed to describe global disparities, timely intervention, guideline-directed care, and economic aspects of open lower limb injuries

Treating open lower limb fractures successfully; thoughts and current practice on therapy and centralization in The Netherlands

Introduction: The British Orthopedic Association (BOA) and British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) updated the evidence-based guidelines for the treatment and care of open lower limb fractures (BOAST 4). Following this, a Dutch version has been developed. The main points are multidisciplinary care, planning, and treatment of these injuries. Early osteosynthesis (within 7–14 days) combined with soft-tissue coverage results in more efficient care and less complications. Aim: To study the variation in treatment and thoughts among trauma, orthopedic, and plastic surgeons. Materials and methods: In this cross-sectional study 94 surgeons (57 trauma, 23 plastic, and 14 orthopedic surgeons) working at 46 centers completed an online questionnaire, consisting of 5 demographic, 14 hospital-related, 8 BOAST 4-related, and 2 centralization-related questions. Results: There was a strong agreement among surgeons about the best moment for multidisciplinary consultation, which was before initial debridement, while in practice, this often does not occur. All surgeons agreed that the initial debridement should be performed immediately by any surgeon, but not solely by trainees. Plastic surgeons responded that the definitive stabilization and wound cover should not exceed 7 days, while half of the trauma and orthopedic surgeons agreed that it should not exceed 14 days. Finally, most surgeons agreed that Gustilo 3 fractures should be centralized. However, there was disagreement on the need for centralization of Gustilo 2 fractures. Discussion: Surgeons agree on better and earlier multidisciplinary treatment of open lower limb fractures and the centralization of Gustilo 3 fractures