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

Dorsal Subluxation of the Proximal Interphalangeal Joint After Volar Base Fracture of the Middle Phalanx

Background: Treatment decisions regarding volar base fractures of the middle phalanx depend on whether the proximal interphalangeal (PIP) joint is reduced. Our aim was to study the agreement among hand surgeons in determining whether the PIP joint fractures are subluxated and to study the factors associated with subluxation of these fractures. Methods: In this retrospective chart review, 413 volar base fractures of the middle phalanx were included. Demographic and injury-related factors were gathered from medical records and radiographs. Using a Web-based survey, interobserver agreement was determined among 105 hand surgeons on the assessment of PIP joint subluxation of a series of 26 cases. Using the cohort of 413 fractures, a threshold for percent articular involvement and relative fracture displacement that corresponds with subluxation of the PIP joint was analyzed. Results: We found moderate to substantial agreement between hand surgeons on subluxation (κ = 0.59, P <.0001) and an overall percent agreement of 85%. Percent articular involvement and relative fracture displacement were independently associated with subluxation of the PIP joint (P <.001). Percent articular involvement of 35% had a specificity of 90% and a negative predicting value (NPV) of 92% for joint subluxation. Relative fracture displacement of 35% had a specificity of 92% and an NPV of 94% for joint subluxation. Conclusions: Surgeons generally agree on whether a PIP joint is subluxated. Percent articular involvement and relative fragment displacement are objective measurements that can help characterize joint stability and assist with decision-making

A Threshold QuickDASH Score for Estimating a Diagnosis of Major Depression in Patients With Fingertip Injuries in the American and Dutch Population

Background: The aim was to determine the threshold Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score that estimates a diagnosis of major depression in patients with fingertip injuries in American and Dutch patients. Methods: In this observational cross-sectional study, 112 patients with a recent fingertip injury measured symptoms of depression with the Patient Health Questionnaire and upper extremity disability with the QuickDASH. Results: In the US cohort, 8 of 56 patients had an estimated diagnosis of major depression. A threshold value of QuickDASH of 50 showed a sensitivity of 88% and a specificity of 81%, with a negative predicting value (NPV) of 95% for an estimated diagnosis of major depression. In the Dutch cohort, 7 of 56 patients had an estimated diagnosis of major depression. The same threshold score of 50 had a sensitivity of 71%, a specificity of 63%, and an NPV of 94%. Conclusions: We have found a correlation between experienced loss of function and an estimated diagnosis of major depression in patients with a fingertip injury. Referral to the primary care physician for further evaluation of depression in these patients is advised

Giant Cell Tumors of the Upper Extremity: Predictors of Recurrence

PURPOSE: Giant cell tumors (GCT) of the distal radius are thought to be more aggressive than in other locations. Therefore, the aim of this study was to investigate factors associated with recurrence of GCTs in the upper extremity. METHODS: We retrospectively identified 82 patients who underwent primary surgical treatment for an upper extremity GCT. Tumors were located in the radius (n = 47), humerus (n = 17), ulna (n = 9), and hand (n = 9). Treatment consisted of either wide resection or amputation or intralesional resection with or without adjuvants. A multivariable logistic regression was performed including tumor grade, type of surgery, and tumor location, from which the percentage of contribution to the model of each variable was calculated. RESULTS: The recurrence rate after intralesional resection was 48%; after wide resection or amputation, it was 12%. Two patients developed a pulmonary metastasis (2.4%). In multivariable analysis, intralesional resection was independently associated with recurrence. Intralesional resection had a 77% contribution to predict recurrence and the distal radius location had a 16% contribution in the predictive model. CONCLUSIONS: As expected, intralesional resection was the strongest independent predictor of recurrence after surgical treatment for GCT. The distal radius location contributed to the prediction of giant cell tumor recurrence to a lesser extent. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV