Stage IV renal cell carcinoma achieves pathologic complete response after two ipilimumab plus nivolumab courses despite severe immune-related adverse events: a case report.

BACKGROUND: Ipilimumab (Ipi) plus nivolumab (Nivo) is the recommended first-line treatment for renal cell carcinoma (RCC). This report describes a case where pancreatic metastases disappeared after only two courses of Ipi + Nivo therapy. The primary tumor was cured by surgery, and a pathological Complete Response (pCR) was observed despite multiple serious immune-related Adverse Events (irAEs). CASE PRESENTATION: A 54-year-old woman with RCC and pancreatic metastasis at stage IV, diagnosed with intermediate risk according to the International Metastatic RCC Database Consortium classification, underwent initiation of Ipi + Nivo therapy. On day 26, she developed hyperthyroidism accompanied by tachycardia, leading to the commencement of metoprolol tartrate treatment. Following the resolution of tachycardia, a second course of Ipi + Nivo therapy was administered on day 50. By day 70, the patient exhibited Grade 3 hepatic dysfunction, followed by the onset of hypothyroidism on day 75, necessitating treatment with steroids and levothyroxine. After positive treatment, a Grade 3 skin disorder emerged on day 87 while tapering steroids, prompting treatment with methylprednisolone (mPSL) pulse therapy. The skin disorder responded to steroids, allowing for tapering. However, on day 113, a recurrence of Grade 3 skin disorder occurred, necessitating another mPSL pulse. The patient responded well to treatment, exhibiting improvement in her condition. On day 131, she presented at the hospital with complaints of respiratory distress, prompting a Computed Tomography (CT) scan that revealed interstitial pneumonia. By day 272, subsequent CT imaging showed the disappearance of pancreatic metastasis and shrinkage of the primary tumor. On day 294, she underwent a laparoscopic left nephrectomy. Pathological analysis confirmed a pCR in the primary tumor, indicating successful eradication of RCC through surgical intervention. CONCLUSIONS: This case report presents a scenario where multiple severe irAEs appeared in a patient, yet metastases disappeared after only two courses of Ipi + Nivo therapy. The patient was ultimately cured by surgery and achieved a pCR. This case highlights that despite the occurrence of severe irAEs during RCC treatment with Ipi + Nivo therapy, they can be managed appropriately to maximize the therapeutic effects of checkpoint inhibitors.

Immune checkpoint inhibitor therapy and elevated levels of C-reactive protein associated with COVID-19 aggravation in patients with lung cancer.

BACKGROUND: COVID-19 has become a significant health threat and a primary healthcare concern among the most vulnerable patients with cancer. Patients with COVID-19 who have lung cancer are at great risk and need careful monitoring if they are affected. This study aimed to investigate the clinical characteristics of COVID-19-positive patients with lung cancer and the risks associated with anticancer medication. METHODS: This study was a single-center, retrospective cohort study. Patients with lung cancer who presented with COVID-19 during hospitalization were divided into two groups: those who presented with respiratory failure and those who did not. The patient's background, clinical laboratory values, and anticancer drugs used for therapy were investigated to identify risk factors for respiratory failure. RESULTS: Thirty-one patients were included in the study; 18 (58.1%) were in the respiratory failure group and 13 (41.9%) were in the group without respiratory failure. In the respiratory failure group, there was a significant difference in using immune checkpoint inhibitor (ICI) use within 90 days (p = 0.025) and the level of C-reactive protein (CRP) level (p = 0.017). The analysis of the operating characteristic of the receiver revealed a cutoff value of 2.75 mg/dL for CRP (area under the curve = 0.744, sensitivity 0.611, specificity 0.923). CONCLUSIONS: A history of ICI within 90 days and elevated CRP (≥ 2.75 mg/dL) levels are potential factors leading to respiratory failure in COVID-19-affected patients undergoing chemotherapy for lung cancer.

Incorporating Cobalt Nanoparticles in Nitrogen-Doped Mesoporous Carbon Spheres through Composite Micelle Assembly for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries have exhibited tremendous potential among the various secondary batteries benefitting from their large energy density, low expense, and enhanced security. However, the commercial use for Li-S batteries is immensely limited by the insulation of S, noticeable volume expansion from S to Li2S2/Li2S, and the undesired shuttle effect of lithium polysulfides (LiPs). Herein, a composite sulfur host has been prepared by in situ incorporations of cobalt nanoparticles (NPs) into nitrogen-doped mesoporous carbon spheres (Co/N-PCSs) through the composite micelle assembly strategy. The resultant functional Co/N-PCSs not only possess uniform spherical morphology with large open mesopores, high surface area, and pore volume but also have small Co NPs homogeneously inlaid into the pore walls of carbon frameworks. Both the experimental and theoretical calculation results demonstrate that the formed cobalt NPs can efficiently accelerate the lithium-ion diffusion reaction and greatly entrap the soluble intermediate LiPs. Benefiting from the well-designed structure, the Co/N-PCSs@S cathode with a S loading of 73.82 wt % delivers superior electrochemical performance, including long cycling stability (60% for the residual capacity at 1 A g-1 within 300 cycles) and excellent rate performance (∼512 mAh g-1 at 6 A g-1). This design strategy of implanting metal NPs in mesoporous carbon can be inspiring in energy storage applications.

A novel approach of fabricating monodispersed spherical MoSiBTiC particles for additive manufacturing.

It is very challenging to fabricate spherical refractory material powders for additive manufacturing (AM) because of their high melting points and complex compositions. In this study, a novel technique, freeze-dry pulsated orifice ejection method (FD-POEM), was developed to fabricate spherical MoSiBTiC particles without a melting process. Elemental nanopowders were dispersed in water to prepare a high-concentration slurry, which was subsequently extruded from an orifice by diaphragm vibration and frozen instantly in liquid nitrogen. After a freeze-drying process, spherical composite particles with arbitrary composition ratios were obtained. The FD-POEM particles had a narrow size range and uniform elemental distribution. Mesh structures were formed within the FD-POEM particles, which was attributed to the sublimation of ice crystals. Furthermore, owing to their spherical morphology, the FD-POEM particles had a low avalanche angle of 42.6°, exhibiting good flowability. Consequently, the combination of FD-POEM and additive manufacturing has great potential for developing complex refractory components used in industrial applications.

Effects of process parameters on the mechanical properties of additively manufactured Zr-1Mo alloy builds.

In order to solve the artifact problem in magnetic resonance images, a low magnetic Zr-1Mo(wt%) alloy with high mechanical performance was successfully fabricated by laser powder bed fusion (L-PBF) using gas-atomized Zr-1Mo alloy powder. The as-built Zr-1Mo alloy showed superior strength and elongation compared to the as-cast Zr-1Mo alloy due to grain refinement and the inexistence of large casting defects. The microstructure of L-PBF-processed Zr-1Mo alloy builds was not sensitive to process parameters. On the other hand, morphology and distribution of defects, interstitials concentration, and crystallographic orientation comprehensively influenced the mechanical properties of the builds. Increasing interstitials concentration caused by increasing energy density render to increasing strength. Large pores caused by balling effect lead to a severe decrease of both strength and ductility of builds using high energy density (over 70.3 J·mm-3) and high scanning speed (1050/1200 mm·s-1). On the contrary, spherical pores possessing several microns in size has much less effect on mechanical properties than the large-size pores. There are two kinds of texture({1 1 0}α texture and {1 1 0}α+{1 0 2}α bi-texture) were confirmed in this study. {1 1 0}α texture contributed to the slight increase of elongation with increasing energy density in low scanning speed case (600/750 mm·s-1) and the superior elongation of low scanning speed specimens compare to that of high scanning speed specimens in medium energy density range (about 48 J·mm-3). From the viewpoints of the ultimate tensile strength(UTS) and elongation, it was found that an energy density of 84.4 mm·s-1 with a scanning speed of 600 mm·s-1 is preferable for the L-PBF-processed Zr-1Mo alloy in this study. These experimental results may provide direct guidelines regarding the applicability of Zr-1Mo alloy fabricated by L-PBF for biomedical applications.

Torque property of titanium alloy cerebral aneurysm clips in a magnetic resonance scanner.

Titanium (Ti) alloys have been introduced in magnetic resonance (MR) safe implantable medical devices because the susceptibility of Ti is approximately 1/10 that of the Co-Cr-Ni alloy (Elgiloy), which was the previously preferred MR-safe material. The torque applied to metallic materials in an MR imaging (MRI) scanner is commonly believed to increase with the susceptibility of the material. However, a visual inspection showed that the torque applied to Ti alloy cerebral aneurysm clips is comparable with that in the case of those of Elgiloy. In this study, we measured the torque applied to the small test pieces of rods and aneurysm clips quantitatively in a 3-T MRI using an accurate self-developed torque measurement apparatus. The maximum torques of Ti alloy and Elgiloy rod test pieces were comparable as 1.1 and 1.2 µN·m, respectively. The values for Ti alloy aneurysm clips were distinctly higher than the values for those of Elgiloy. These contradictory results of a larger torque for smaller-susceptibility products could be explained by our new theory, which takes into account the crystal susceptibility anisotropy in addition to the conventional torque due to the shape anisotropy.

Ultrathin and Light-Weight Graphene Aerogel with Precisely Tunable Density for Highly Efficient Microwave Absorbing.

Graphene aerogel (GA) possessing good electrical conductivity and low weight has been widely considered as a promising candidate for high-performance microwave-absorbing (MA) materials. However, simultaneous realization of high reflection loss (RL), low thickness, and light weight remains very challenging for GA because of the trade-off between impedance match and attenuation ability. Herein, through use of (3-aminopropyl)triethoxysilane as a surface modifier and cross-linker, the GA materials with precisely controlled density are fabricated via a unique solvothermal protocol of zero-volume shrinkage. The density-controlled GA (4.5 mg·cm-3) exhibits a remarkable minimum RL (RLmin) of -50 dB at a thickness of 1.14 mm in the K-band, owing to the optimized dielectric properties. Moreover, even higher attenuation ability without sacrificed impedance match is obtained by incorporating magnetic Fe3O4@C microspheres into the density-controlled GA. Superior MA performance involving unprecedented RLmin of -54.0 dB and qualified bandwidth covering 80% of the K-band has been achieved in the superlight Fe3O4@C/GA composite at a thickness less than 1 mm, which is highly desirable for MA material applied in mobile devices.

Hierarchical Nanoporous Copper Architectures via 3D Printing Technique for Highly Efficient Catalysts.

Nanoporous metals represent a class of functional materials with unique bicontinuous open porous structural properties, making them ideal candidates for various catalyst applications. However, the pursuit of nanoporous properties, extremely small pores, and high surface area, results in the restriction of mass transport. Herein, a free-standing hierarchical nanoporous Cu material, prepared by a selective laser melting 3D printing technique and a one-step dealloying process, is presented as a highly efficient electrocatalyst for methanol oxidation. It is demonstrated that the digitally controlled hierarchical structure with macro- and nano-scaled pores can be utilized for promoting and directing mass transport as well as for the enhancement of catalytic properties. This work highlights a facile, low-cost, and alternative strategy for hierarchical nanoporous structure design that can be applied to binary, ternary, and quaternary metal alloys for various functional applications.

Effect of adding support structures for overhanging part on fatigue strength in selective laser melting.

Selective laser melting (SLM) technology was recently introduced to fabricate dental prostheses. However, the fatigue strength of clasps in removable partial dentures prepared by SLM still requires improvement. In this study, we attempted to improve the fatigue strength of clasps by adding support structures for overhanging parts, which can generally be manufactured at an angle to be self-supporting. The results show that the fatigue strength of the supported specimens was more than twice that of unsupported specimens. Electron back-scattered diffraction analysis revealed that the supported specimens exhibited lower kernel average misorientation values than the unsupported specimens, which suggested that the support structure reduced the residual strain during the SLM process and helped to prevent micro-cracks led by thermal distortion. In addition, the supported specimens cooled more rapidly, thereby forming a finer grain size compared to that of the unsupported specimens, which contributed to improving the fatigue strength. The results of this study suggest that the fatigue strength of overhanging parts can be improved by intentionally adding support structures.

Synthesis of n-type Mg2Si/CNT Thermoelectric Nanofibers.

Magnesium silicide (Mg2Si)/carbon nanotube (CNT) thermoelectric nanofibers for use as a flexible thermoelectric material were successfully synthesized through the combined processes of the sol-gel method, magnesiothermic reduction, and liquid-solid phase reaction. In the resulting product, each CNT was coated with Mg2Si which was an approximately 60-nm-thick single crystal. The synthesized Mg2Si-coated CNTs exhibited n-type thermoelectric behavior confirming that n-type thermoelectric composite nanofibers were successfully obtained.

Magnetic susceptibility, artifact volume in MRI, and tensile properties of swaged Zr-Ag composites for biomedical applications.

Zr-Ag composites were fabricated to decrease the magnetic susceptibility by compensating for the magnetic susceptibility of their components. The Zr-Ag composites with a different Zr-Ag ratio were swaged, and their magnetic susceptibility, artifact volume, and mechanical properties were evaluated by magnetic balance, three-dimensional (3-D) artifact rendering, and a tensile test, respectively. These properties were correlated with the volume fraction of Ag using the linear rule of mixture. We successfully obtained the swaged Zr-Ag composites up to the reduction ratio of 96% for Zr-4, 16, 36, 64Ag and 86% for Zr-81Ag. However, the volume fraction of Ag after swaging tended to be lower than that before swaging, especially for Ag-rich Zr-Ag composites. The magnetic susceptibility of the composites linearly decreased with the increasing volume fraction of Ag. No artifact could be estimated with the Ag volume fraction in the range from 93.7% to 95.4% in three conditions. Young's modulus, ultimate tensile strength (UTS), and 0.2% yield strength of Zr-Ag composites showed slightly lower values compared to the estimated values using a linear rule of mixture. The decrease in magnetic susceptibility of Zr and Ag by alloying or combining would contribute to the decrease of the Ag fraction, leading to the improvement of mechanical properties.

Titanium-Zirconium Binary Alloy as Dental Implant Material: Analysis of the Influence of Compositional Change on Mechanical Properties and In Vitro Biologic Response.

PURPOSE: To evaluate the mechanical properties and biologic response of single-phase Ti-Zr alloys cast in higher-purity casting conditions, with comprehensive compositions (from 10 to 90 mol% of Zr). MATERIALS AND METHODS: The mechanical properties and in vitro biologic response with proportional increase of Zr to Ti-Zr alloy composition were assessed. Tensile strength, surface hardness, and Young's modulus were examined. The in vitro cell response of the alloys was also tested with mouse osteoblast cells. RESULTS: Analyses of mechanical tests demonstrated improved strength and reduced Young's modulus on this binary alloy system. In vitro cell culture studies with osteogenic MCT3T-E1 cells exhibited the highest attachment rate with the largest and more mature cells on Ti10Zr, instead of commercially pure Ti, whereas a significantly lower cell attachment rate and delayed alkaline phosphatase-specific activity (ALP) differentiation were detected on Ti50Zr. CONCLUSION: The results revealed that the composition did have an impact on the in vitro biologic response. Ti-Zr alloys with 50-50 mol% composition had a decreased biologic response, although the mechanical properties improved. The overall highest strength was Ti with 30 mol% Zr without significant decrease of biologic response.

Fatigue strength of Co-Cr-Mo alloy clasps prepared by selective laser melting.

We aimed to investigate the fatigue strength of Co-Cr-Mo clasps for removable partial dentures prepared by selective laser melting (SLM). The Co-Cr-Mo alloy specimens for tensile tests (dumbbell specimens) and fatigue tests (clasp specimens) were prepared by SLM with varying angles between the building and longitudinal directions (i.e., 0° (TL0, FL0), 45° (TL45, FL45), and 90° (TL90, FL90)). The clasp specimens were subjected to cyclic deformations of 0.25mm and 0.50mm for 10(6) cycles. The SLM specimens showed no obvious mechanical anisotropy in tensile tests and exhibited significantly higher yield strength and ultimate tensile strength than the cast specimens under all conditions. In contrast, a high degree of anisotropy in fatigue performance associated with the build orientation was found. For specimens under the 0.50mm deflection, FL90 exhibited significantly longer fatigue life (205,418 cycles) than the cast specimens (112,770 cycles). In contrast, the fatigue lives of FL0 (28,484 cycles) and FL45 (43,465 cycles) were significantly shorter. The surface roughnesses of FL0 and FL45 were considerably higher than those of the cast specimens, whereas there were no significant differences between FL90 and the cast specimens. Electron backscatter diffraction (EBSD) analysis indicated the grains of FL0 showed preferential close to <001> orientation of the γ phase along the normal direction to the fracture surface. In contrast, the FL45 and FL90 grains showed no significant preferential orientation. Fatigue strength may therefore be affected by a number of factors, including surface roughness and crystal orientation. The SLM process is a promising candidate for preparing tough removable partial denture frameworks, as long as the appropriate build direction is adopted.

Fabrication of titanium alloy frameworks for complete dentures by selective laser melting.

STATEMENT OF PROBLEM: Casting difficulties have led to the limited use of titanium in dental prostheses. The selective laser melting system was recently developed to fabricate biomedical components from titanium alloys. However, the fabrication of a titanium alloy framework for a maxillary complete denture by selective laser melting has not yet been investigated. PURPOSE: The purpose of the study was to fabricate thin titanium alloy frameworks for a maxillary complete denture with a selective laser melting system and to evaluate their hardness and microstructure. MATERIAL AND METHODS: A cast of an edentulous maxilla was scanned with a dental 3-dimensional cone-beam computed tomography system, and standard triangulation language data were produced with the DICOM Viewer (Digital Imaging and Communications in Medicine). Two types of metal frameworks for complete dentures were designed with 3-dimensional computer-aided design software. Two titanium alloy frameworks, SLM-1 and SLM-2, were fabricated from these designs with the selective laser melting system. Plate-shaped specimens were cut from the central flat region of SLM-1, SLM-2, and as-cast Ti-6Al-4V (As-cast). Vickers hardness testing, optical microscopy, and x-ray diffraction measurements were performed. RESULTS: Thin titanium alloy frameworks for maxillary complete dentures could be fabricated by selective laser melting. The hardness values for SLM-1 and SLM-2 were higher than that for the as-cast specimen. Optical microscopy images of the SLM-1 and SLM-2 microstructure showed that the specimens did not exhibit pores, indicating that dense frameworks were successfully obtained with the selective laser melting process. In the x-ray diffraction patterns, only peaks associated with the α phase were observed for SLM-1 and SLM-2. In addition, the lattice parameters for SLM-1 and SLM-2 were slightly larger than those for the as-cast specimen. CONCLUSIONS: The mechanical properties and microstructure of the denture frameworks prepared by selective laser melting indicate that these dentures are appropriate for clinical use.

Correlation between cyclic fatigue and the bending properties of nickel titanium endodontic instruments.

The effects of cyclic fatigue on bending properties of NiTi endodontic instruments were investigated. Sixteen Profiles(®) were divided into two groups (A, and B). The sequence of cantilever bending test and cyclic fatigue test was alternated repeatedly until file separation occurred. In the cyclic fatigue test, the instrument curvature was 19° in group A and 38° in group B. Fractographic examination was performed to determine fracture patterns. In group A, there were significant differences between the bending load values measured before the cyclic fatigue test and the last cantilever bending test before instrument fracture at each deflection (p<0.05). Fractographic examination showed the specific patterns of cyclic fatigue fracture. The stress required to induce martensitic transformation might be reduced due to the softening behavior caused by the cyclic fatigue under the relaxation condition of the superelasticity range (group A). The SEM images were able to display specific patterns indicating cyclic fatigue fracture.

Endodontic instruments after torsional failure: nanoindentation test.

This study aimed to evaluate effects of torsional loading on the mechanical properties of endodontic instruments using the nanoindentation technique. ProFile (PF; size 30, taper 04; Dentsply Maillefer, Switzerland) and stainless steel (SS; size 30, taper 02; Mani, Japan) instruments were subjected to torsional test. Nanoindentation was then performed adjacent to the edge of fracture (edge) and at the cutting part beside the shank (shank). Hardness and elastic modulus were measured under 100-mN force on 100 locations at each region, and compared to those obtained from the same regions on new instruments. It showed that PF and SS instruments failed at 559 ± 67 and 596 ± 73 rotation degrees and mean maximum torque of 0.90 ± 0.07 and 0.99 ± 0.05 N-cm, respectively. Hardness and elastic modulus ranged 4.8-6.7 and 118-339 GPa in SS, and 2.7-3.2 and 52-81 GPa in PF. Significant differences between torsion-fractured and new instruments in hardness and elastic modulus were detected in the SS system used. While in PF system, the edge region after torsional fracture had significantly lower hardness and elastic modulus compared to new instruments. The local hardness and modulus of elasticity of endodontic instruments adjacent to the fracture edge are significantly reduced by torsional loading.

Three-dimensional quantification of susceptibility artifacts from various metals in magnetic resonance images.

Susceptibility artifacts generated in magnetic resonance (MR) images were quantitatively evaluated for various metals using a three-dimensional (3-D) artifact rendering to demonstrate the correlation between magnetic susceptibility and artifact volume. Ten metals (stainless steel, Co-Cr alloy, Nb, Ti, Zr, Mo, Al, Sn, Cu and Ag) were prepared, and their magnetic susceptibilities measured using a magnetic balance. Each metal was embedded in a Ni-doped agarose gel phantom and the MR images of the metal-containing phantoms were taken using 1.5 and 3.0 T MR scanners under both fast spin echo and gradient echo conditions. 3-D renderings of the artifacts were constructed from the images and the artifact volumes were calculated for each metal. The artifact volumes of metals decreased with decreasing magnetic susceptibility, with the exception of Ag. Although Sn possesses the lowest absolute magnetic susceptibility (1.8×10(-6)), the artifact volume from Cu (-7.8×10(-6)) was smaller than that of Sn. This is because the magnetic susceptibility of Cu was close to that of the agarose gel phantom (-7.3×10(-6)). Since the difference in magnetic susceptibility between the agarose and Sn is close to that between the agarose and Ag (-17.5×10(-6)), their artifact volumes were almost the same, although they formed artifacts that were reversed in all three dimensions.

Microstructures and mechanical properties of Co-29Cr-6Mo alloy fabricated by selective laser melting process for dental applications.

The selective laser melting (SLM) process was applied to a Co-29Cr-6Mo alloy, and its microstructure, mechanical properties, and metal elution were investigated to determine whether the fabrication process is suitable for dental applications. The microstructure was evaluated using scanning electron microscopy with energy-dispersed X-ray spectroscopy (SEM-EDS), X-ray diffractometry (XRD), and electron back-scattered diffraction pattern analysis. The mechanical properties were evaluated using a tensile test. Dense builds were obtained when the input energy of the laser scan was higher than 400 J mm⁻³, whereas porous builds were formed when the input energy was lower than 150 J mm⁻³. The microstructure obtained was unique with fine cellular dendrites in the elongated grains parallel to the building direction. The γ phase was dominant in the build and its preferential <001> orientation was confirmed along the building direction, which was clearly observed for the builds fabricated at lower input energy. Although the mechanical anisotropy was confirmed in the SLM builds due to the unique microstructure, the yield strength, UTS, and elongation were higher than those of the as-cast alloy and satisfied the type 5 criteria in ISO22764. Metal elution from the SLM build was smaller than that of the as-cast alloy, and thus, the SLM process for the Co-29Cr-6Mo alloy is a promising candidate for fabricating dental devices.

Effect of cold rolling on the magnetic susceptibility of Zr-14Nb alloy.

The magnetic susceptibility of cold-rolled Zr-14Nb was evaluated to apply a new metallic medical device used for magnetic resonance imaging (MRI). The magnetic susceptibility of cold-rolled Zr-14Nb decreased up to the reduction ratio of 30%, then gradually decreased up to the ratio of 90%. Transmission electron microscopic observation revealed the strain-induced formation of ω phase after cold rolling at the reduction ratio of 5%, indicating that the initial decrease in magnetic susceptibility was caused by the formation of the ω phase. The ω phase was saturated at the reduction ratio of 30%. The formation of the ω phase could be explained on the basis of the increase in the Young's modulus and Vickers hardness of cold-rolled Zr-14Nb. The effect of texture formation on these properties was not obvious in the cold-rolled Zr-14Nb. Because of the strain-induced formation of the ω phase, the magnetic susceptibility of Zr-14Nb can be reduced by cold rolling to as low as that of as-cast Zr-9Nb, which is one-third that of Ti and Ti alloys. Therefore, cold-workable Zr-14Nb with low magnetic susceptibility could be a promising alloy for medical devices under MRI.