Variability exists in the incidence of PSIs and HACs in patients with brain tumors based on insurance status. Controlling for both patient and hospital factors can explain these differences. The cause of these disparities should be studied prospectively to begin the process of improving quality metrics in vulnerable patient populations.
BackgroundDendritic cell (DC) vaccine efficacy is directly related to the efficiency of DC migration to the lymph node after delivery to the patient. We discovered that a naturally occurring metabolite, sarcosine, increases DC migration in human and murine cells resulting in significantly improved anti-tumor efficacy. We hypothesized that sarcosine induced cell migration was due to chemokine signaling.MethodsDCs were harvested from the bone marrow of wild type C57BL/6 mice and electroporated with tumor messenger RNA (mRNA). Human DCs were isolated from peripheral blood mononuclear cells (PBMCs). DCs were treated with 20 mM of sarcosine. Antigen specific T cells were isolated from transgenic mice and injected intravenously into tumor bearing mice. DC vaccines were delivered via intradermal injection. In vivo migration was evaluated by flow cytometry and immunofluorescence microscopy. Gene expression in RNA was investigated in DCs via RT-PCR and Nanostring.ResultsSarcosine significantly increased human and murine DC migration in vitro. In vivo sarcosine-treated DCs had significantly increased migration to both the lymph nodes and spleens after intradermal delivery in mice. Sarcosine-treated DC vaccines resulted in significantly improved tumor control in a B16F10-OVA tumor flank model and improved survival in an intracranial GL261-gp100 glioma model. Gene expression demonstrated an upregulation of CXCR2, CXCL3 and CXCL1 in sarcosine- treated DCs. Further metabolic analysis demonstrated the up-regulation of cyclooxygenase-1 and Pik3cg. Sarcosine induced migration was abrogated by adding the CXCR2 neutralizing antibody in both human and murine DCs. CXCR2 neutralizing antibody also removed the survival benefit of sarcosine-treated DCs in the tumor models.ConclusionSarcosine increases the migration of murine and human DCs via the CXC chemokine pathway. This platform can be utilized to improve existing DC vaccine strategies.
La enfermedad de Pott o espondilodiscitis tuberculosa representa menos del 1% de los casos de tuberculosis. Sin embargo, el curso clínico indolente de esta enfermedad hace que su diagnóstico sea generalmente tardío, causando con ello la destrucción de las estructuras vertebrales. La deformidad resultante de la columna vertebral requiere tratamiento quirúrgico, el cual es complejo y requiere una estancia hospitalaria prolongada. Se describe el caso de un paciente varón de 52 años que fue diagnosticado de espondilodiscitis lumbar luego de la correspondiente evaluación clínica y estudios imagenológicos sin mostrar respuesta al tratamiento antibiótico empírico. Un abordaje transforaminal percutáneo, técnica mínimamente invasiva, permitió el diagnóstico de espondilodiscitis tuberculosa y la mejoría sintomática del paciente.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.