The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

<p>Abstract</p> <p>Introduction</p> <p>While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM^®) to BCG in patients after transurethral resection (TURB) of BC.</p> <p>Materials and methods</p> <p>This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed.</p> <p>Results</p> <p>Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p < 0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p < 0.001).</p> <p>Discussion</p> <p>This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted.</p> <p>Trial registration</p> <p>The trial has been registered in the ISRCTN registry <url>http://isrctn.org</url> under the registration number ISRCTN35881130.</p

Fracture Toughness of Cold Sprayed Pure Metals

The study of fracture toughness of pure Al, Cu, Ni and Ti deposited by cold spray was performed in order to obtain a fundamental understanding of the damage process and quantify the material performance. Rectangular specimens cut from self-standing deposits with fatigue pre-cracks were tested in three-point bending. The KIC values were obtained from J-R curves following the ASTM E1820 standard. The stress–strain behavior of the tested material was obtained from supplementary four-point bending. The cold spray deposits exhibited significantly lower fracture toughness than the corresponding wrought materials. The reduction was more pronounced for coatings with limited ductility (Ti and Cu), where the fracture toughness reached less than 12% of the wrought counterpart only. The higher ductility coatings of Al and Ni possessed fracture toughness of 18–25% of the wrought reference materials. The performed fractographic analysis revealed inter-particular decohesion as the major failure mode

Tailoring cold spray additive manufacturing of steel 316 L for static and cyclic load-bearing applications

Thanks to the low working temperature, less product size limitations and one order of magnitude higher deposition rates compared to the established additive manufacturing techniques, more attention has been brought to the potential of cold spraying for additive manufacturing. As a process dealing with deformation of solid particles possibly leaving non-bonded interfaces and causing work hardening, any optimization should (i) adjust spray parameters to obtain high performance as-sprayed parts and (ii) tune ductility and internal stresses by post-treatments. The present study first deals with strategies to optimize spray parameters for fabrication of high performance steel 316 L deposits. Next, the performances of deposits are further adjusted by various heat treatments. The structural strength of the freestanding samples before and after the heat treatments is evaluated under static and cyclic axial loading and supported by fatigue crack growth rate analysis. The results highlight the feasibility of obtaining high quality steel 316 L deposits using N2 as process gas, rather than the costly He that is commonly suggested. This study demonstrates the potential of cold spraying to be used for deposition of freeform structural components with a static strength comparable to that of bulk and laser-based additive manufactured materials and a fatigue strength similar to that of bulk cast material

Measurement of mechanical and fatigue properties using unified, simple-geometry specimens: Cold spray additively manufactured pure metals

A methodology that allows joint determination of fundamental engineering properties of materials/components vital to their efficient design and a safe service lifetime operation is presented. Using a combination of recently developed techniques, a simultaneous assessment of mechanical properties, fatigue crack growth rates, as well as fracture toughness is described. All these are performed using unified-geometry samples that are simple and easy to produce. The mechanical properties are measured in tensile and compressive modes, while the combination of developed bending test methods (quasi-static four-point bending and fatigue bending) enables to cover the fatigue loading from very low loads corresponding to crack propagation threshold values up to the high loads corresponding to a static fracture of the fracture toughness test. To validate and complement the bending data, additional resonant ultrasonic measurements of the corresponding properties are carried out. The methodology is partially suitable for testing of cold sprayed deposits. Therefore, Al, Cu, Ni and Ti deposits are tested and compared to cold-rolled sheet reference samples. The results are quantified in the form of NASGRO equation, widely used in software for prediction of fatigue lives. Together, the obtained set of data may be readily used for modeling of the performance of cold sprayed parts. Finally, fractographic analysis of the failed specimens is presented to describe the mechanisms leading to failure. At low loads, the reference sheets and the cold sprayed deposits exhibit similar behavior, where the cracks grow in a trans-crystalline mode without any significant interaction with deposit particle boundaries. Contrary to this, the behavior changes at higher loads: the particle interfaces in the cold sprayed deposits become the weak point and the cracks grow at high rates by inter-particle decohesion, while the sheet materials generally fail by striation mechanism at much lower rates