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

High Mutation Frequency of the PIGA

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Fc gamma receptor IIa suppresses type I and III interferon production by human myeloid immune cells

Type I and type III interferons (IFNs) are fundamental for antiviral immunity, but prolonged expression is also detrimental to the host. Therefore, upon viral infection high levels of type I and III IFNs are followed by a strong and rapid decline. However, the mechanisms responsible for this suppression are still largely unknown. Here, we show that IgG opsonization of model viruses influenza and respiratory syncytial virus (RSV) strongly and selectively suppressed type I and III IFN production by various human antigen-presenting cells. This suppression was induced by selective inhibition of TLR, RIG-I-like receptor, and STING-dependent type I and III IFN gene transcription. Surprisingly, type I and III IFN suppression was mediated by Syk and PI3K independent inhibitory signaling via FcγRIIa, thereby identifying a novel non-canonical FcγRIIa pathway in myeloid cells. Together, these results indicate that IgG opsonization of viruses functions as a novel negative feedback mechanism in humans, which may play a role in the selective suppression of type I and III IFN responses during the late-phase of viral infections. In addition, activation of this pathway may be used as a tool to limit type I IFN-associated pathology

Dietary sodium restriction prevents vascular endothelial growth factor inhibitor-induced hypertension

Background: Vascular endothelial growth factor inhibitors (VEGFIs) are effective anticancer agents which often induce hypertension. VEGFI-induced hypertension is sodium-sensitive in animal studies. Therefore, the efficacy of dietary sodium restriction (DSR) to prevent VEGFI-induced hypertension in cancer patients was studied. Methods: Cancer patients with VEGFI-induced hypertension (day mean >135/85 mmHg or a rise in systolic and/or diastolic BP ≥ 20 mmHg) were treated with DSR (aiming at <4 g salt/day). The primary endpoint was the difference in daytime mean arterial blood pressure (MAP) increase between the treatment cycle with and without DSR. Results: During the first VEGFI treatment cycle without DSR, mean daytime MAP increased from 95 to 110 mmHg. During the subsequent treatment cycle with DSR, mean daytime MAP increased from 94 to 102 mmHg. Therefore, DSR attenuated the increase in mean daytime MAP by 7 mmHg (95% CI 1.3–12.0, P = 0.009). DSR prevented the rise in the endothelin-1/renin ratio that normally accompanies VEGFI-induced hypertension (P = 0.020) and prevented the onset of proteinuria: 0.15 (0.10–0.25) g/24 h with DSR versus 0.19 (0.11–0.32) g/24 h without DSR; P = 0.005. Discussion: DSR significantly attenuated VEGFI induced BP rise and proteinuria and thus is an effective non-pharmacological intervention

Dendritic Cell Subsets in Oral Mucosa of Allergic and Healthy Subjects

Immunohistochemistry was used to identify, enumerate, and describe the tissue distribution of Langerhans type (CD1a and CD207), myeloid (CD1c and CD141), and plasmacytoid (CD303 and CD304) dendritic cell subsets in oral mucosa of allergic and non-allergic individuals. Allergic individuals have more CD141+ myeloid cells in epithelium and more CD1a+ Langerhans cells in the lamina propria compared to healthy controls, but similar numbers for the other DC subtypes. Our data are the first to describe the presence of CD303+ plasmacytoid DCs in human oral mucosa and a dense intraepithelial network of CD141+ DCs. The number of Langerhans type DCs (CD1a and CD207) and myeloid DCs (CD1c), was higher in the oral mucosa than in the nasal mucosa of the same individual independent of the atopic statu