Disruption of memory B-cell trafficking by belimumab in patients with systemic lupus erythematosus.

OBJECTIVES: Autoreactive memory B cells contribute to chronic and progressive courses in autoimmune diseases like systemic lupus erythematosus (SLE). The efficacy of belimumab (BEL), the first approved biologic treatment for SLE and lupus nephritis (LN), is generally attributed to depletion of activated naïve B cells and inhibition of B cell activation. BEL's effect on memory B cells (MBCs) is currently unexplained. We performed an in-depth cellular and transcriptomic analysis of BEL's impact on the blood MBC compartment in patients with SLE. METHODS: A retrospective meta-analysis was conducted, pooling flow cytometry data from four randomized trials involving 1245 patients with SLE treated with intravenous BEL or placebo. Then, extensive MBC phenotyping was performed using high-sensitivity flow cytometry in patients with mild/moderate SLE and severe SLE/LN treated with subcutaneous BEL. Finally, transcriptomic characterization of surging MBCs was performed by single-cell RNA sequencing. RESULTS: In BEL-treated patients, a significant increase in circulating MBCs, in a broad range of MBC subsets, was established at week 2, gradually returning to baseline by week 52. The increase was most prominent in patients with higher SLE disease activity, serologically active patients, and patients aged ≤18 years. MBCs had a non-proliferating phenotype with a prominent decrease in activation status and downregulation of numerous migration genes. CONCLUSION: Upon BEL initiation, an increase of MBCs was firmly established. In the small cohort investigated, circulating MBCs were de-activated, non-proliferative, and demonstrated characteristics of disrupted lymphocyte trafficking, expanding on our understanding of the therapeutic mechanism of B cell-activating factor inhibition by BEL. TRIAL REGISTRATION: ClinicalTrials.gov NCT00071487, NCT00410384, NCT01632241, NCT01649765, NCT03312907, NCT03747159.

In vivo ageing of zirconia dental ceramics - Part II: Highly-translucent and rapid-sintered 3Y-TZP.

OBJECTIVE: 3Y-TZP ceramics with reduced alumina content have improved translucency and are used in monolithic dental restorations without porcelain-based veneers. The workflow can be further streamlined with rapid sintering. This study was designed to assess how these approaches affect ageing when the materials are exposed to the oral environment in vivo. METHODS: 43 discs were fabricated from 3Y-TZP powder with 0.05% Al2O3 and sintered with conventional or rapid regimens (1450 °C 2 h, 1530 °C 2 h, or 1530 °C 25 min). Their surfaces were polished or airborne-particle abraded with 50 µm Al2O3. The discs were incorporated in complete dentures of 16 volunteers and worn continuously for up to 48 months. Ageing changes on disc surfaces were monitored every 6 months by X-ray diffraction, scanning electron microscopy and atomic force microscopy. Data was statistically analysed with linear models. RESULTS: The amount of monoclinic phase on polished surfaces increased linearly, reaching up to 40% after 48 months in vivo. The ageing process observed for rapid sintering was 1.6 times faster compared to conventional sintering. A nano-scale increase in roughness with microcracking was also detected on polished surfaces. Airborne-particle abraded surfaces did not exhibit clear signs of ageing during the course of the study. SIGNIFICANCE: Highly-translucent 3Y-TZP ceramics are more susceptible to ageing than classic 3Y-TZP. After 4 years in vivo, the extent of degradation did not yet constitute grounds for clinical concern, but was more pronounced in materials prepared with rapid sintering.

In vivo aging of zirconia dental ceramics - Part I: Biomedical grade 3Y-TZP.

OBJECTIVE: In vivo aging of biomedical grade 3Y-TZP ceramics in the oral environment was assessed and compared to artificially accelerated in vitro hydrothermal aging extrapolations at 37°C. METHODS: 88 discs were pressed and sintered (1450-1500°C) from two commercial 3Y-TZP compositions containing 0.25% Al2O3 to generate finer- and coarser-grained specimens. As-sintered (AS) and airborne-particle abraded (APA; 50µm Al2O3) surfaces were investigated. In vivo aging was performed by incorporating specimens in lingual flanges of complete dentures of 12 edentulous volunteers who wore them continuously for up to 24 months. For comparison, in vitro hydrothermal aging at 134°C was also performed and analysed by XRD and (FIB)-SEM. Data was statistically analysed with linear regression models. RESULTS: Finer and coarser-grained specimens exhibited statistically insignificant differences in aging in vivo. The monoclinic fraction (Xm) on AS surfaces abruptly increased to ∼8% after 6 months. The aging process then proceeded with slower linear kinetics (∼0.24%/month). After 24 months, Xm reached ∼12%. The calculated maximum transformed layer was 0.385µm representing one layer of transformed grains. APA surfaces were highly aging resistant. The initial Xm of ∼4.0% linearly increased by 0.03%/month in vivo. In vitro aging exhibited an initial induction period, followed by linear aging kinetics. Coarser-grained AS surfaces aged significantly faster than fine-grained (2.41%/h compared to 2.16%/h). APA discs aged at a rate of 0.3%/h in vitro. Microcracking within a single grain and pull-out of grain clusters were observed on aged AS surfaces. SIGNIFICANCE: Biomedical grade 3Y-TZP was susceptible to in vivo aging. After 2 years in vivo, the aging kinetics were almost 3-times faster than the generally accepted in vitro-in vivo extrapolation.

Ageing kinetics and strength of airborne-particle abraded 3Y-TZP ceramics.

OBJECTIVE: The combined effects of alumina airborne-particle abrasion and prolonged in vitro ageing on the flexural strength of 3Y-TZP ceramic have been studied. The aim was to identify the different effects on the surface and subsurface regions that govern the performance of this popular bioceramic known for its susceptibility to low-temperature degradation (LTD). METHODS: As-sintered or airborne-particle abraded 3Y-TZP discs were subjected to ageing at 134°C for up to 480h. Biaxial flexural strength was measured and the relative amount of monoclinic phase determined using X-ray diffraction. The transformed zone depth (TZD) was observed on cross-sections with scanning electron microscopy coupled with a focused ion beam. Segmented linear regression was used to analyze the flexural strength and TZD as functions of the ageing time. RESULTS: A two-step linear ageing kinetics was detected in airborne-particle abraded specimens, reflecting the different microstructures through which the LTD proceeds into the bulk. A 10µm thick altered zone under the abraded surface was involved in both the surface strengthening and the increased ageing resistance. When the zone was annihilated by the LTD, the strength of the ceramic specimens and the speed of LTD returned to the values measured before abrasion. Even at prolonged ageing times, the strength of abraded groups was not lower than that of as-sintered groups. SIGNIFICANCE: Both the ageing kinetics and the flexural strength were prominently affected by airborne-particle abrasion, which altered the subsurface microstructure and phase composition. Airborne-particle abrasion was not harmful to the 3Y-TZP ceramics' stability.

Implant-prosthetic rehabilitation after radiation treatment in head and neck cancer patients: a case-series report of outcome.

BACKGROUND: Slovenia has a high burden of head and neck cancer. Patients are mostly treated with surgery followed by radiation therapy. Advanced surgical and prosthodontic techniques have expanded the rehabilitation options. The aim of the study was to review the outcome of implant-prosthetic treatment after radiation therapy. PATIENTS AND METHODS: Twenty irradiated head and neck cancer patients who received a removable implant-supported denture at the University Medical Centre Ljubljana were included in the study. Kaplan-Meier survival analysis, Cox proportional hazard models and logistic regression were used to assess the implant survival and success rate. RESULTS: Twenty patients had 100 implants inserted. The estimated implant survival rate was 96% after 1 year and 87% after 5 years. Failures were mostly observed before loading (91.2%). Implants inserted in the transplanted bone were significantly more likely to fail. Out of 89 implants supporting the dentures, 79 implants (88.7%) were successful, meaning that they were functionally loaded and exhibited no pain, radiolucency or progressive bone loss. Prosthetic treatment was significantly less successful in older patients. The attachment system and the number of implants did not have a statistically significant influence on the success rate. CONCLUSIONS: Implant-supported dentures have been shown to be a reliable treatment modality after head and neck cancer surgery and radiation therapy. Possible early failures should be communicated with the patients.

Complexity of the relationships between the sintering-temperature-dependent grain size, airborne-particle abrasion, ageing and strength of 3Y-TZP ceramics.

OBJECTIVES: This study was designed to explore the complex relationships between the sintering-temperature-dependent grain size, airborne-particle abrasion, ageing and strength of 3Y-TZP ceramics. METHODS: Biomedical grade 3Y-TZP powder was used to fabricate 180 discs. Half of them were sintered at 1400°C for 2h and half at 1500°C for 2h. A total of 18 groups of 10 were formed and subjected to the fully crossed experimental protocol of airborne-particle abrasion with Al2O3 at 2.5bar (no abrasion, 50µm, 110µm) and accelerated ageing at 134°C (no ageing, 12h, 48h). The relative amount of monoclinic phase was determined with XRD. The biaxial flexural strength was measured and statistically analyzed using the three-way ANOVA followed by predetermined contrasts and Tukey's HSD test (α=0.05). RESULTS: The low-temperature-sintered, fine-grained ceramic exhibited an excellent ageing resistance, while the high-temperature-sintered, coarse-grained ceramic experienced a higher surface strengthening and a substantially improved ageing resistance with respect to the airborne-particle abrasion. The overall performance of this material was superior. SIGNIFICANCE: Our results show that the sintering temperature has a minor effect on the flexural strength, but it plays a crucial role in the surface strengthening and the ageing behaviour of 3Y-TZP dental ceramics.

Oral health of the elderly living in residential homes in Slovenia.

OBJECTIVES: To evaluate oral health status of the elderly, living in eight randomly selected residential homes for senior citizens across the country. BACKGROUND: The percentage of the elderly is growing worldwide. With ageing, risks of various oral diseases, including dental caries and periodontal disease, are growing. METHODS: Altogether 296 elderly people (88 men, 208 women) of average age 79.89 ± 7.4 years were questioned about their medical condition and oral health practice and examined orally. Evaluation of clinical examination was carried out by DMFT, plaque index (Silness and Löe, 1964) and Community Periodontal Index of Treatment Need (CPITN). RESULTS: Of 296 participants, 106 (35.8%) were edentulous, 95 (32.1%) had one to nine teeth and 95 persons (32.1%) had 10 or more teeth. The average number of teeth in an individual was small: 6.76 ± 7.47. The average number of teeth with caries lesions was 3.59 ± 4.70, filled teeth 1.94 ± 3.63 and teeth without caries or fillings 1.19 ± 2.41. The average DMFT value was 30.75. In 69.5% of participants, dental plaque was visible with the naked eye. Of 171 subjects, in whom CPITN index was appraised, 81.9% would need oral hygiene education, 56.7% would need scaling and root planning and 21.6% would need periodontal surgical treatment. CONCLUSIONS: The results of this study indicate poor oral health of the elderly living in residential homes situated in different towns in Slovenia. It is of utmost importance to highlight the necessity of improving oral health care of this population.