Citations

Objective To evaluate the association of perioperative blood transfusion ( PBT ) with survival after nephrectomy. Patients and Methods We identified 2318 patients who underwent partial or radical nephrectomy at M ayo C linic between 1990 and 2006. PBT was defined as transfusion of allogenic red blood cells during surgery or postoperative hospitalisation. Survival was estimated using the K aplan– M eier method and compared with the log‐rank test. Cox proportional hazards regression models were used to evaluate the association of PBT with outcome. Results In all, 498 patients (21%) received a PBT . The median (interquartile range) number of units transfused was 3 (2, 5). Patients receiving a PBT were significantly older at surgery ( P < 0.001), more likely to be female ( P < 0.001), with more frequent symptomatic presentation ( P < 0.001), worse E astern C ooperative O ncology G roup performance status ( P < 0.001), and more frequent adverse pathological features, such as high nuclear grade ( P < 0.001), locally‐advanced tumour stage ( P < 0.001) and lymph node invasion ( P < 0.001). The median follow‐up was 9.1 years. Receipt of a PBT was associated with adverse 5‐year cancer‐specific (68% vs 92%; P < 0.001) and overall (56% vs 82%; P < 0.001) survival. On multivariate analyses, PBT remained associated with higher risk of death from any cause (hazard ratio [ HR ] 1.23; P = 0.02). Among patients who received a PBT , an increasing number of units transfused was independently associated with increased all‐cause mortality ( HR 1.08; P = 0.001). Conclusion PBT is associated with a significantly increased risk of mortality after nephrectomy. While external validation is needed, continued efforts to minimise the use of blood products in these patients are warranted.

ABSTRACTUnlike human malaria parasites that induce persistent infection, some rodent malaria parasites, likePlasmodium yoeliistrain 17XNL (Py17XNL), induce a transient (self-curing) malaria infection. Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells. In order to better understand the correspondence between murine malaria models and human malaria, and in particular the role of MHC (HLA) class II molecules, we studied the ability of humanized mice expressing human HLA class II molecules to clear Py17XNL infection. We showed that humanized mice expressing HLA-DR4 (DR0401) molecules and lacking mouse MHC class II molecules (EA0) have impaired production of specific antibodies to Py17XNL and cannot cure the infection. In contrast, mice expressing HLA-DR4 (DR0402), HLA-DQ6 (DQ0601), HLA-DQ8 (DQ0302), or HLA-DR3 (DR0301) molecules in an EA0background were able to elicit specific antibodies and self-cure the infection. In a series of experiments, we determined that the inability of humanized DR0401.EA0mice to elicit specific antibodies was due to expansion and activation of regulatory CD4+Foxp3+T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions. Treg depletion allowed the DR0401.EA0mice to elicit specific antibodies and self-cure the infection. Our results demonstrated a differential role of MHC (HLA) class II molecules in supporting antibody responses to Py17XNL malaria and revealed a new mechanism by which malaria parasites stimulate B cell-suppressogenic Tregs that prevent clearance of infection.

Shear wave dispersion ultrasound vibrometry (SDUV) has been introduced to use the dispersive nature of shear wave speed to locally estimate the material properties or tissue. Shear waves were created using a mechanical shaker and pulsed radiation force. Using the information from the phase one can estimate the shear velocity. A theoretical Voigt model allows us to find, at different frequencies (100–400 Hz), the viscosity and shear elasticity of the polymer gel dosimeter. The aim of this work was to perform the SDUV and mechanical vibrometry techniques to study the viscoelastic properties of absorbed dose phantoms. The experiments were performed using five phantoms of different absorbed doses varying 10 up to 50 Gy, while a nonirradiated phantom was kept as a control. The SDUV technique was performed using a pulsed radiation force to vibrate the gel provide by a confocal transducer with a focal depth of 70 mm, nominal frequency of 3 MHz. For the mechanical vibrometry and SDUV experiments, shear wave motion measurements were made with a commercial ultrasound machine with a research using a 10 MHz linear array transducer. The quantitative elasticity and viscosity results for these two experiments were compared.

This work introduces a new method based on acoustic radiation force and magnetic measurement for interrogating the mechanical properties of fluid and biological tissues. In this method, ultrasound radiation is used to exert a low-frequency (in kHz range) force on a rigid magnetized target immersed in a viscoelastic medium. In response, the target vibrates in a pattern determined by viscoelastic properties of medium. We report the relation between the magnetic field signal and the incident ultrasonic pressure field in terms of the mechanical parameters of the medium. Simulations were conducted to demonstrate a simple approach based on using amplitude-modulated ultrasound to generate a dynamic acoustic radiation force on a magnetic target. The magnetic field generated by vibration of this target is then obtained and used to estimate the radiation-force-induced displacement as a function of time. It was observed that the intensity of the dynamic component of the magnetic field caused by the acoustic excitation is high enough to be registered by a conventional magnetic sensor. This proposed methodology presents a powerful tool for evaluation of acoustic radiation force as well as the mechanical properties of soft material.