Complications After Renal Mass Biopsy: Frequency, Nature, Timing, and Associated Characteristics.

BACKGROUND. Observation periods after renal mass biopsy (RMB) range from 1 hour to overnight hospitalization. Short observation may improve efficiency by allowing use of the same recovery bed and other resources for RMBs in additional patients. OBJECTIVE. The purpose of this study was to evaluate the frequency, timing, and nature of complications after RMB, as well as to identify characteristics associated with such complications. METHODS. This retrospective study included 576 patients (mean age, 64.9 years; 345 men, 231 women) who underwent percutaneous ultrasound- or CT-guided RMB at one of three hospitals, performed by 22 radiologists, between January 1, 2008, and June 1, 2020. The EHR was reviewed to identify postbiopsy complications, which were classified as bleeding-related or non-bleeding-related and as acute (< 24 hours), subacute (24 hours to 30 days), or delayed (> 30 days). Deviations from normal clinical management (analgesia, unplanned laboratory testing, or additional imaging) were identified. RESULTS. Acute and subacute complications occurred after 3.6% (21/576) and 0.7% (4/576) of RMBs, respectively. No delayed complication or patient death occurred. A total of 76.2% (16/21) of acute complications were bleeding-related. A deviation from normal clinical management occurred after 1.6% (9/551) of RMBs that had no associated postbiopsy complication. Among the 16 patients with bleeding-related acute complications, all experienced a deviation, with mean time to deviation of 56 ± 47 (SD) minutes (range, 10-162 minutes; ≤ 120 minutes in 13/16 patients). The five non-bleeding-related acute complications all presented at the time of RMB completion. The four subacute complications occurred from 28 hours to 18 days after RMB. Patients with, versus those without, a bleeding-related complication had a lower platelet count (mean, 197.7 vs 250.4 × 109/L, p = .01) and greater frequency of entirely endophytic renal masses (47.4% vs 19.6%, p = .01). CONCLUSION. Complications after RMB were uncommon and presented either within 3 hours after biopsy or more than 24 hours after biopsy. CLINICAL IMPACT. A 3-hour monitoring window after RMB before patient discharge (in the absence of deviation from normal clinical management and complemented by informing patients of the low risk of a subacute complication) may provide both safe patient management and appropriate resource utilization.

Correlation of resin viscosity and monomer conversion to filler particle size in dental composites.

OBJECTIVE: The viscosity of dental resin composites is important in their formulation and clinical use; it depends on the filler particle size and loading. We intend to study the viscosity and conversion of composites made of low dispersity spherical silica fillers. METHODS: Experimental dental resin composites were formulated using low dispersity spherical silica particles of graded sizes (75, 150, 500, 350, 500, 1000nm) at several loading levels with resins based on Bis-GMA and UDMA. Their rheological properties and double bond conversion were measured with a rheometer and differential scanning calorimeter, respectively. RESULTS: The complex viscosity of the unpolymerized pastes can be fit to an extended Krieger-Dougherty equation that includes an adjustment factor to account for filler particle surface area. This relationship is also extended to estimate the degree of conversion, where the calculated or experimental viscosity is used to predict the resulting conversion. SIGNIFICANCE: The enhanced understanding of the relationship of filler size, composite viscosity, and monomer conversion will allow improved accuracy in the prediction of the properties of dental resin composite formulations to obtain ideal viscosity for their clinical use and a high degree of conversion.

Evaluation of the filler packing structures in dental resin composites: From theory to practice.

OBJECTIVES: The aim of this study is to evaluate the packing properties of uniform silica particles and their mixture with secondary particles yielding maximally loaded dental composites. We intend to verify the difference between the idealized models (the close-packed structures and the random-packed structures) and the actual experimental results, in order to provide guidance for the preparation of dental composites. The influence of secondary particle size and the resin composition on the physical-mechanical properties and the rheological properties of the experimental dental composites was also investigated. METHODS: Silica particles (S-920, S-360, and S-195) with average diameters of 920, 360, and 195nm were synthesized via the Stöber process. Their morphology and size distribution were determined by field-emission scanning electron microscopy and laser particle sizer. A series of silica fillers, S-920, S-920+195, S-920+360, and S-920+360+195, were then formulated with two Bis-GMA/TEGDMA resins (weight ratios of 70:30 and 50:50). For these experimental dental composites, their maximum filler loadings were assessed and compared to the theory. The mechanical properties, degree of conversion, depth of cure, and polymerization shrinkage of these composites were then evaluated. Their rheological behaviors were measured with a rheometer. RESULTS: Unimodal S-920 had the maximally filler loading of 70.80wt% with the 5B5T resin, close to the theoretical estimation of the random loose packing (71.92wt%). The maximum loading of the S-920+360+195 filled composite was 72.92wt% for the same resin, compared to the theoretical estimation of 89.29wt% obtained for the close-packed structures. These findings indicate that random loose packing matches more closely to the real packing state for the filler formulations used. When maximally loaded, the composite with S-920+360+195 produced the best mechanical properties and the lowest polymerization shrinkage. The degree of conversion and depth of cure were higher with secondary particles added, and the viscosity of all unpolymerized pastes exhibited shear thinning behavior. SIGNIFICANCE: Theoretical estimations of filler packing structures provide a useful guidance in the design of multimodal filler formulations and the preparation of dental composites with higher filler loading, improved physical-mechanical properties.

Synthesis of wrinkled mesoporous silica and its reinforcing effect for dental resin composites.

OBJECTIVE: The aim of this work is to explore the reinforcing effect of wrinkled mesoporous silica (WMS), which should allow micromechanical resin matrix/filler interlocking in dental resin composites, and to investigate the effect of silica morphology, loading, and compositions on their mechanical properties. METHODS: WMS (average diameter of 496nm) was prepared through the self-assembly method and characterized by the use of the electron microscopy, dynamic light scattering, and the N2 adsorption-desorption measurements. The mechanical properties of resin composites containing silanized WMS and nonporous smaller silica were evaluated with a universal mechanical testing machine. Field-emission scanning electron microscopy was used to study the fracture morphology of dental composites. Resin composites including silanized silica particles (average diameter of 507nm) served as the control group. RESULTS: Higher filler loading of silanized WMS substantially improved the mechanical properties of the neat resin matrix, over the composites loaded with regular silanized silica particles similar in size. The impregnation of smaller secondary silica particles with diameters of 90 and 190nm, denoted respectively as Si90 and Si190, increased the filler loading of the bimodal WMS filler (WMS-Si90 or WMS-Si190) to 60wt%, and the corresponding composites exhibited better mechanical properties than the control fillers made with regular silica particles. Among all composites, the optimal WMS-Si190- filled composite (mass ratio WMS:Si190=10:90, total filler loading 60wt%) exhibited the best mechanical performance including flexural strength, flexural modulus, compressive strength and Vickers microhardness. SIGNIFICANCE: The incorporation of WMS and its mixed bimodal fillers with smaller silica particles led to the design and formulation of dental resin composites with superior mechanical properties.

Surface modification of quartz fibres for dental composites through a sol-gel process.

In this study, quartz fibres (QFs) surface modification using a sol-gel method was proposed and dental posts reinforced with modified QFs were produced. A silica sol (SS) was prepared using tetraethoxysilane (TEOS) and 3-methacryloxypropyltrimethoxysilane (γ-MPS) as precursors. The amount of γ-MPS in the sol-gel system was varied from 0 to 24wt.% with a constant molar ratio of TEOS, ethanol, deionized water, and HCl. Thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), and contact angle (CA) measurements were used to characterize the modified QFs, which confirmed that SS had successfully coated the surface of QFs. SEM images showed good interfacial bonding between the modified QFs and the resin matrix. The results of three-point bending tests of the fibre reinforced composite (FRC) posts showed that the QFs modified by SS with 12wt.% γ-MPS presented the best mechanical properties, demonstrating improvements of 108.3% and 89.6% for the flexural strength and flexural modulus, respectively, compared with untreated QFs. Furthermore, the sorption and solubility of the prepared dental posts were also studied by immersing the posts in artificial saliva (AS) for 4weeks, and yielded favourable results. This sol-gel surface modification method promises to resolve interfacial bonding issues of fibres with the resin matrix, and produce FRC posts with excellent properties.

Monodisperse silica-filled composite restoratives mechanical and light transmission properties.

OBJECTIVES: The aim of this study was to formulate resin-based composites using spherical silica particulate fillers with graded size (75, 150, 350, 500, and 1000nm), and to evaluate the influence of their size and loading on the mechanical and light transmission properties of the resulting material. METHODS: A series of five spherical silica fillers were synthesized, and then formulated with BisGMA/TEGDMA or UDMA/TEGDMA resins. These were then tested for maximum filler loading, flexural strength and modulus, as well as transparency and depth of cure. RESULTS: Low dispersity spherical silica particles of 75, 150, 350, 500, and 1000nm were synthesized. Maximum loading was 70wt% for the three largest particle, and decreased for the smaller sizes, where UDMA-based resins allowed slightly higher loading. When maximally loaded, the largest particle sizes produced the highest flexural properties. However, when using the same loading, all filler sized produced similar flexural strengths and moduli. The optical properties and depth of cure were increased as the filler size decreased. SIGNIFICANCE: While hybrid filler particles are the norm in commercial materials, by studying and understanding the influence of individual components on the material properties, we can finely tune the properties of the materials as desired.

Application of close-packed structures in dental resin composites.

OBJECTIVE: The inorganic filler particles in dental resin composites serve to improve their mechanical properties and reduce polymerization shrinkage during their use. Efforts have been made in academia and industry to increase the filler particle content, but, few studies examine the theoretical basis for the maximum particle loading. METHODS: This work evaluates the packing of spherical particles in a close-packed state for highly loaded composites. RESULTS: Calculations show that for low dispersity particles, the maximum amount of particles is 74.05vol%, regardless of the particle size. This can be further improved by using a mix of large and small particles or by the use of non-spherical particles. For representative spherical particles with a diameter of 1000nm, two types of secondary particles with respective sizes of 414nm (dI) and 225nm (dII) are selected. The results show that after embedding secondary particles I & II into primary spherical particles, the packing factor is increased to 81.19% for the close-packed structures, which shows an improvement of 9.64%, compared to the 74.05% obtained only with primary spherical particles. This packing factor is also higher than either structure with the embedded secondary particles I or II. SIGNIFICANCE: Examples of these mixtures with different spherical particle sizes are shown as a theoretical estimation, serving as a guideline for the design and formulation of new dental resin composites with better properties and improved performance.

Inorganic Fillers for Dental Resin Composites: Present and Future.

Dental resins represent an important family of biomaterials that have been evolving in response to the needs in biocompatibility and mechanical properties. They are composite materials consisting of mostly inorganic fillers and additives bound together with a polymer matrix. A large number of fillers in a variety of forms (spheroidal, fibrous, porous, etc.) along with other additives have been studied to enhance the performance of the composites. Silane derivatives are attached as coupling agents to the fillers to improve their interfacial properties. A review of the literature on dental composite fillers seems to suggest that each of the fillers tested presents its own strengths and weaknesses, and often combinations of these yield resin composites with the desired balance of properties. Additives such as nanotubes, whiskers, fibers, and nanoclusters have been shown to enhance the properties of these hybrid materials, and their use in small fractions may enhance the overall performance of the dental resin materials.

Expression of xCT and activity of system xc(-) are regulated by NRF2 in human breast cancer cells in response to oxidative stress.

Cancer cells adapt to high levels of oxidative stress in order to survive and proliferate by activating key transcription factors. One such master regulator, the redox sensitive transcription factor NF E2 Related Factor 2 (NRF2), controls the expression of cellular defense genes including those encoding intracellular redox-balancing proteins involved in glutathione (GSH) synthesis. Under basal conditions, Kelch-like ECH-associated protein 1 (KEAP1) targets NRF2 for ubiquitination. In response to oxidative stress, NRF2 dissociates from KEAP1, entering the nucleus and binding to the antioxidant response element (ARE) in the promoter of its target genes. Elevated reactive oxygen species (ROS) production may deplete GSH levels within cancer cells. System xc(-), an antiporter that exports glutamate while importing cystine to be converted into cysteine for GSH synthesis, is upregulated in cancer cells in response to oxidative stress. Here, we provided evidence that the expression of xCT, the light chain subunit of system xc(-), is regulated by NRF2 in representative human breast cancer cells. Hydrogen peroxide (H2O2) treatment increased nuclear translocation of NRF2, also increasing levels of xCT mRNA and protein and extracellular glutamate release. Overexpression of NRF2 up-regulated the activity of the xCT promoter, which contains a proximal ARE. In contrast, overexpression of KEAP1 repressed promoter activity and decreased xCT protein levels, while siRNA knockdown of KEAP1 up-regulated xCT protein levels and transporter activity. These results demonstrate the importance of the KEAP1/NRF2 pathway in balancing oxidative stress in breast cancer cells through system xc(-). We have previously shown that xCT is upregulated in various cancer cell lines under oxidative stress. In the current investigation, we focused on MCF-7 cells as a model for mechanistic studies.

Stereochemical modification of geminal dialkyl substituents on pantothenamides alters antimicrobial activity.

Pantothenamides are N-substituted pantothenate derivatives which are known to exert antimicrobial activity through interference with coenzyme A (CoA) biosynthesis or downstream CoA-utilizing proteins. A previous report has shown that replacement of the ProR methyl group of the benchmark N-pentylpantothenamide with an allyl group (R-anti configuration) yielded one of the most potent antibacterial pantothenamides reported so far (MIC of 3.2 µM for both sensitive and resistant Staphylococcus aureus). We describe herein a synthetic route for accessing the corresponding R-syn diastereomer using a key diastereoselective reduction with Baker's yeast, and report on the scope of this reaction for modified systems. Interestingly, whilst the R-anti diastereomer is the only one to show antibacterial activity, the R-syn isomer proved to be significantly more potent against the malaria parasite (IC50 of 2.4±0.2 µM). Our research underlines the striking influence that stereochemistry has on the biological activity of pantothenamides, and may find utility in the study of various CoA-utilizing systems.

Exploring structural motifs necessary for substrate binding in the active site of Escherichia coli pantothenate kinase.

The coenzyme A (CoA) biosynthetic enzymes have been used to produce various CoA analogues, including mechanistic probes of CoA-dependent enzymes such as those involved in fatty acid biosynthesis. These enzymes are also important for the activation of the pantothenamide class of antibacterial agents, and of a recently reported family of antibiotic resistance inhibitors. Herein we report a study on the selectivity of pantothenate kinase, the first and rate limiting step of CoA biosynthesis. A robust synthetic route was developed to allow rapid access to a small library of pantothenate analogs diversified at the ß-alanine moiety, the carboxylate or the geminal dimethyl group. All derivatives were tested as substrates of Escherichia coli pantothenate kinase (EcPanK). Four derivatives, all N-aromatic pantothenamides, proved to be equivalent to the benchmark N-pentylpantothenamide (N5-pan) as substrates of EcPanK, while two others, also with N-aromatic groups, were some of the best substrates reported for this enzyme. This collection of data provides insight for the future design of PanK substrates in the production of useful CoA analogues.