Cordotomy under general anesthesia for a pediatric palliative patient: illustrative case.

BACKGROUND: Computed tomography (CT)-guided cordotomy has been shown to be a safe and effective method for treating cancer pain in adults in a palliative care setting. Its effectiveness has been rarely reported in children. During cordotomy, patient feedback is considered essential. Unfortunately, in this report, the featured patient's age and demeanor precluded an awake cordotomy. The authors report the first case, to their knowledge, of percutaneous cordotomy with the patient under general anesthesia. OBSERVATIONS: An 11-year-old boy with osteosarcoma of the right pelvis presented with medically refractory unilateral nociceptive pain. The pain prevented ambulation, interfered with sleep, was the focus of his concern, and could not be relieved without sedation. A left percutaneous CT-guided cervical cordotomy while he was under general anesthesia was performed without complication and provided sufficient pain relief to allow ambulation and restorative sleep. Pain was no longer an issue for the patient and his family. LESSONS: CT-guided percutaneous cervical cordotomy can be accomplished in a pediatric patient under general anesthesia. The risks of cordotomy under general anesthesia without patient feedback must be weighed against the opportunity to improve palliative care. https://thejns.org/doi/abs/10.3171/CASE2427.

Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities.

An important host defence mechanism against pathogens is intracellular killing, which is achieved through phagocytosis, a cellular process for engulfing and neutralizing extracellular particles. Phagocytosis results in the formation of matured phagolysosomes, which are specialized compartments that provide a hostile environment and are considered the end point of the degradative pathway. However, all fungal pathogens studied to date have developed strategies to manipulate phagosomal function directly and also indirectly by redirecting phagosomes from the degradative pathway to a non-degradative pathway with the expulsion and even transfer of pathogens between cells. Here, using the major human fungal pathogens Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Histoplasma capsulatum as examples, we discuss the processes involved in host phagosome-fungal pathogen interactions, with a focus on fungal evasion strategies. We also discuss recent approaches to targeting intraphagosomal pathogens, including the redirection of phagosomes towards degradative pathways for fungal pathogen eradication.

Non-Motor Effects of Low-Frequency Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease: A Systematic Review.

INTRODUCTION: Deep brain stimulation of the subthalamic nucleus is an effective therapy for the motor symptoms of Parkinson's disease (PD). Typically, stimulation is applied at a high frequency (≥100 Hz) to alleviate motor symptoms. However, the effects on non-motor symptoms can be variable. Low-frequency oscillations are increasingly recognized as playing an important role in the non-motor functions of the subthalamic nucleus. Therefore, it has been hypothesized that low-frequency stimulation of the subthalamic nucleus (<100 Hz) may have a direct effect on these non-motor functions, thereby preferentially impacting non-motor symptoms of PD. Despite important therapeutic implications, the literature on this topic has not been summarized. METHOD: To understand the current state of the field, we performed a comprehensive systematic review of the literature assessing the non-motor effects of low-frequency stimulation of the subthalamic nucleus in PD. We performed a supplementary meta-analysis to assess the effects of low- versus high-frequency stimulation on verbal fluency outcomes. RESULTS: Our search returned 7,009 results, of which we screened 4,199 results. A total of 145 studies were further assessed for eligibility, and a total of 21 studies met our inclusion criteria, representing 297 patients. These studies were a mix of case reports and control trials. The four clinical outcomes measured were sleep, sensory perception, cognition, and mood. A supplementary meta-analysis of six studies investigating the impact of low-frequency stimulation on verbal fluency did not find any significant results when pooling across subgroups. CONCLUSION: LFS of the STN may have benefits on a range of cognitive and affective symptoms in PD. However, current studies in this space are heterogeneous, and the effect sizes are small. Factors that impact outcomes can be divided into stimulation and patient factors. Future work should consider the interactions between stimulation location and stimulation frequency as well as how these interact depending on the specific non-motor phenotype.

The Use of Augmented Reality as an Educational Tool in Minimally Invasive Transforaminal Lumbar Interbody Fusion.

BACKGROUND AND OBJECTIVES: One of the major challenges in training neurosurgical and orthopedic residents the technique for minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is the lack of visualization of surgical landmarks (pedicle, pars, lamina). This is due to the limited access to the bony spine through a tubular retractor, in addition to a smaller working corridor or patient-specific factors such as bony overgrowth, disk space collapse, and listhesis. These factors increase the possibility for surgical error and prolonged surgery time. With augmented reality (AR), relevant surgical anatomy can be projected directly into the user's field of view through the microscope. The purpose of this study was to assess the utility, accuracy, efficiency, and precision of AR-guided MIS-TLIF and to determine its impact in spine surgery training. METHODS: At 2 centers, 12 neurosurgical residents performed a one-level MIS-TLIF on a high-fidelity lumbar spine simulation model with and without AR projection into the microscope. For the MIS-TLIF procedures with AR, surgical landmarks were highlighted in different colors on preoperative image data. These landmarks were visualized in the spinal navigation application on the navigation monitor and in the microscope to confirm the relevant anatomy. Postprocedural surveys (National Aeronautics and Space Administration Task Load Index) were given to the residents. RESULTS: Twelve residents were included in this trial. AR-guided procedures had a consistent impact on resident anatomical orientation and workload experience. Procedures performed without AR had a significantly higher mental demand (P = .003) than with AR. Residents reported to a significantly higher rate that it was harder work for them to accomplish their level of performance without AR (P = .019). CONCLUSION: AR can bring a meaningful value in MIS teaching and training to confirm relevant anatomy in situations where the surgeon will have less direct visual access. AR used in surgical simulation can also speed the learning curve.

Unveiling the Role of Metal Ion Concentration versus Immune Sensitization in Orthodontic Patients-A Long-Term Prospective Evaluation.

Background: This longitudinal prospective study aimed to assess orthodontic patients' immune system response to metal ion release in saliva. Methods: Thirty adult patients (18-35 years) were equally divided into three groups: groups at the end (G1) and beginning (G2) of multibracket appliances (MBA) treatment and a non-treated control group (G3). Participants were evaluated at four timepoints within 21 days, with saliva samples being analyzed for metal ion concentrations and blood for the lymphocyte transformation test (LTT). Results: There were no significant differences between groups or timepoints for saliva. LTT analyses revealed hypersensitivity in one-third of all patients and 50% of G2 for nickel, with three developing sensitizations after MBA insertion. All nickel-sensitized patients exhibited varying elevated saliva nickel concentrations. The most nickel-sensitized patients had low ion saliva loads. In borderline nickel-sensitization cases, saliva ion concentrations were up to 20 times higher than the reference. Hypersensitivity to palladium, gold, and mercury was also observed. Conclusions: These findings indicate that increased MBA ion release was not inherently linked to the immune response (Type-IV sensitization), as reactions occurred even with ion levels below thresholds. This underlines the need for a comprehensive evaluation of the immune response to metal ion release in orthodontic patients.

Effect of surface treatment strategies on bond strength of additively and subtractively manufactured hybrid materials for permanent crowns.

OBJECTIVES: The purpose of this study is to evaluate the bond strength of different computer-aided design / computer-aided manufacturing (CAD/CAM) hybrid ceramic materials following different pretreatments. METHODS: A total of 306 CAD/CAM hybrid material specimens were manufactured, n = 102 for each material (VarseoSmile Crownplus [VSCP] by 3D-printing; Vita Enamic [VE] and Grandio Blocs [GB] by milling). Each material was randomly divided into six groups regarding different pretreatment strategies: control, silane, sandblasting (50 µm aluminum oxide particles), sandblasting + silane, etching (9% hydrofluorics acid), etching + silane. Subsequently, surface roughness (Ra) values, surface free energy (SFE) were measured. Each specimen was bonded with a dual-cured adhesive composite. Half of the specimens were subjected to thermocycling (5000 cycles, 5-55 °C). The shear bond strength (SBS) test was performed. Data were analyzed by using a two-way analysis of variance, independent t-test, and Mann-Whitney-U-test (α = 0.05). RESULTS: Material type (p = 0.001), pretreatment strategy (p < 0.001), and the interaction (p < 0.001) all had significant effects on Ra value. However, only etching on VSCP and VE surface increased SFE value significantly. Regarding SBS value, no significant difference was found among the three materials (p = 0.937), while the pretreatment strategy significantly influenced SBS (p < 0.05). Etching on VSCP specimens showed the lowest mean value among all groups, while sandblasting and silane result in higher SBS for all test materials. CONCLUSIONS: The bond strength of CAD/CAM hybrid ceramic materials for milling and 3D-printing was comparable. Sandblasting and silane coupling were suitable for both millable and printable materials, while hydrofluoric etching should not be recommended for CAD/CAM hybrid ceramic materials. CLINICAL RELEVANCE: Since comparable evidence between 3D-printable and millable CAD/CAM dental hybrid materials is scarce, the present study gives clear guidance for pretreatment planning on different materials.

The Effect of Build Angle and Artificial Aging on the Accuracy of SLA- and DLP-Printed Occlusal Devices.

The aim of this study is to investigate the influence of printing material, build angle, and artificial aging on the accuracy of SLA- and DLP-printed occlusal devices in comparison to each other and to subtractively manufactured devices. A total of 192 occlusal devices were manufactured by one SLA-printing and two DLP-printing methods in 5 different build angles as well as milling. The specimens were scanned and superimposed to their initial CAD data and each other to obtain trueness and precision data values. A second series of scans were performed after the specimens underwent an artificial aging simulation by thermocycling. Again, trueness and precision were investigated, and pre- and post-aging values were compared. A statistically significant influence was found for all main effects: manufacturing method, build angle, and thermocycling, confirmed by two-way ANOVA. Regarding trueness, overall tendency indicated that subtractively manufactured splints were more accurate than the 3D-printed, with mean deviation values around ±0.15 mm, followed by the DLP1 group, with ±0.25 mm at 0 degree build angle. Within the additive manufacturing methods, DLP splints had significantly higher trueness for all build angles compared to SLA, which had the highest mean deviation values, with ±0.32 mm being the truest to the original CAD file. Regarding precision, subtractive manufacturing showed better accuracy than additive manufacturing. The artificial aging demonstrated a significant influence on the dimensional accuracy of only SLA-printed splints.

Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis.

OBJECTIVES: B-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral B-cell development to identify the causes for the defect in B-cell reconstitution after RTX therapy. METHODS: We recruited 91 patients with AAV and performed deep phenotyping of the peripheral and bone marrow B-cell compartment by spectral flow and mass cytometry. B-cell development was studied by in vitro modelling and the role of BAFF receptor by quantitative PCR, western blot analysis and in vitro assays. RESULTS: Treatment-naïve patients with AAV showed low transitional B-cell numbers, suggesting impaired B-lymphopoiesis. We analysed bone marrow of treatment-naïve and RTX-treated patients with AAV and found reduced B-lymphoid precursors. In vitro modelling of B-lymphopoiesis from AAV haematopoietic stem cells showed intact, but slower and reduced immature B-cell development. In a subgroup of patients, after RTX treatment, the presence of transitional B cells did not translate in replenishment of naïve B cells, suggesting an impairment in peripheral B-cell maturation. We found low BAFF-receptor expression on B cells of RTX-treated patients with AAV, resulting in reduced survival in response to BAFF in vitro. CONCLUSIONS: Prolonged depletion of B cells in patients with AAV after RTX therapy indicates a B-cell defect that is unmasked by RTX treatment. Our data indicate that impaired bone marrow B-lymphopoiesis results in a delayed recovery of peripheral B cells that may be further aggravated by a survival defect of B cells. Our findings contribute to the understanding of AAV pathogenesis and may have clinical implications regarding RTX retreatment schedules and immunomonitoring after RTX therapy.

Microstructural investigation of hybrid CAD/CAM restorative dental materials by micro-CT and SEM.

OBJECTIVES: An increasing number of CAD/CAM (computer-aided design/computer-aided manufacturing) hybrid materials have been introduced to the dental market in recent years. In addition, CAD/CAM hybrid materials for additive manufacturing (AM) are becoming more attractive in digital dentistry. Studies on material microstructures using micro-computed tomography (µ-CT) combined with scanning electron microscopy (SEM) have only been available to a limited extent so far. METHODS: One CAD/CAM three-dimensional- (3D-) printable hybrid material (VarseoSmile Crown plus) and two CAD/CAM millable hybrid materials (Vita Enamic; Voco Grandio), as well as one direct composite material (Ceram.x duo), were included in the present study. Cylindrical samples with a diameter of 2 mm were produced from each material and investigated by means of synchrotron radiation µ-CT at a voxel size of 0.65 µm. Different samples from the same materials, obtained by cutting and polishing, were investigated by SEM. RESULTS: The 3D-printed hybrid material showed some agglomerations and a more irregular distribution of fillers, as well as a visible layered macrostructure and a few spherical pores due to the printing process. The CAD/CAM millable hybrid materials revealed a more homogenous distribution of ceramic particles. The direct composite material showed multiple air bubbles and microstructural irregularities based on manual processing. SIGNIFICANCE: The µ-CT and SEM analysis of the materials revealed different microstructures even though they belong to the same class of materials. It could be shown that µ-CT and SEM imaging are valuable tools to understand microstructure and related mechanical properties of materials.

Accuracy of the intaglio surface of 3D-printed hybrid resin-ceramic crowns, veneers and table-tops: An in vitro study.

OBJECTIVES: The present study aims to examine the influence of the build angle on the accuracy (trueness and precision) of 3D printed crowns, table-tops and veneers with a hybrid resin-ceramic material. METHODS: One crown, on table-top and one veneer were printed in five different build angles (0°, 30°, 45°, 60°, 90°) (n = 50) with the digital light processing (DLP) system (Varseo XS, Bego) using hybrid resin (Varseo Smile Crownplus A3, Bego). All printed restorations were scanned using the laboratory scanner (D2000, 3Shape) and matched onto the initial reference design in metrology software (Geomagic Control X, 3D Systems). The root mean square error (RMSE) was calculated between the scanned and reference data. The data was statistically analyzed using the Tukey multiple comparison test and Wilcoxon multiple comparison test. RESULTS: The crown group showed higher trueness at 30° (0.021 ± 0.002) and 45° (0.020 ± 0.002), and table-tops at 0° (0.015 ± 0.001) and 30° (0.014 ± 0.001) (p < 0.0001). Veneers demonstrated higher trueness at 30° (0.016 ± 0.002) (p < 0.0001). All three restoration types demonstrated the lowest trueness at a 90° build angle and portrayed deviations along the z axis. The veneer and table-top groups showed the lowest precision at 90° (veneers: 0.021 ± 0.008; table-tops: 0.013 ± 0.003). The crown group portrayed the lowest precision at 45° (0.017 ± 0.005) (p < 0.0001). CONCLUSION: The build angle of DLP-printed hybrid resin-ceramic restorations influences their accuracy. CLINICAL SIGNIFICANCE: Considering the build angle is important to achieve a better accuracy of 3D-printed resin-ceramic hybrid restorations. This may help predict or avoid the interference points between a restoration and a die and minimize the clinical adjustments.

Wear resistance and flexural properties of low force SLA- and DLP-printed splint materials in different printing orientations: An in vitro study.

OBJECTIVES: To investigate the influence of material and printing orientation on wear resistance and flexural properties of one low force SLA- and two DLP-printed splint materials and to compare these 3D-printed splints to a subtractively manufactured splint material. METHODS: Two DLP-printed (V-Print splint, LuxaPrint Ortho Plus) and one low force SLA-printed (Dental LT Clear) material, where specimens were printed in three printing orientations (0°, 45°, 90°), were investigated. In addition, one milled splint material (Zirlux Splint Transparent) was examined. A total of 160 specimens were produced for both test series. The two-body wear test was performed in a chewing simulator (80'000 cycles at 50 N with 5-55 °C thermocycling). Steatite balls were used as antagonists. The wear pattern was analyzed with a 3D digital microscope in terms of maximum vertical intrusion depth (mm) and total volume loss (mm³). The flexural properties were investigated by three-point bending in accordance with ISO 20795-1: 2013 (denture base polymers). The flexural strength (MPa) and the flexural modulus (MPa) were measured. Two-way ANOVA was performed to investigate the effects of the two independent variables material and printing orientation for the three 3D-printed materials. The comparison of the printing orientations within one material was carried out with one-way ANOVA with post-hoc Tukey tests. RESULTS: Two-way ANOVA revealed that wear and flexural properties are highly dependent on the 3D-printed material (p < 0.001). Across groups, a significant effect was observed for wear depth (p = 0.031) and wear volume (p = 0.044) with regard to printing orientation but this was not found for flexural strength (p = 0.080) and flexural modulus (p = 0.136). One-way ANOVA showed that both DLP-printed groups showed no significant differences within the printing orientations in terms of wear and flexural properties. Dental LT Clear showed that 90° oriented specimens had higher flexural strength than 0° oriented ones (p < 0.001) and 45° oriented specimens also showed higher values than 0° ones (p = 0.038). No significant differences were observed within the printing orientations for flexural modulus and wear behaviour within this group. T-tests showed that the milled splints exhibited statistically higher wear resistance and flexural properties compared to all three 3D-printed splint materials (p < 0.001) and that highly significant differences were found between the 3D-printed splint materials for both test series. CONCLUSION: Within the limitations of this in vitro study, it can be stated that wear behaviour and flexural properties are highly dependent on the 3D-printed material itself. Currently, milled splints exhibit higher wear resistance and flexural properties compared to 3D-printed splint materials. The printing orientation has a minor influence on the properties investigated. Nevertheless, two-way ANOVA also showed a significant influence of printing orientation in the wear test across groups and one-way ANOVA detected significant effects for SLA material in terms of flexural strength, with printing in 90° showing the highest flexural strength. Therefore, anisotropy was found in SLA material, but it can be limited with the employed printing parameters. Both DLP-printed materials showed no significant difference within the printing orientation.

Chronic endoplasmic reticulum stress in myotonic dystrophy type 2 promotes autoimmunity via mitochondrial DNA release.

Myotonic dystrophy type 2 (DM2) is a tetranucleotide CCTG repeat expansion disease associated with an increased prevalence of autoimmunity. Here, we identified an elevated type I interferon (IFN) signature in peripheral blood mononuclear cells and primary fibroblasts of DM2 patients as a trigger of chronic immune stimulation. Although RNA-repeat accumulation was prevalent in the cytosol of DM2-patient fibroblasts, type-I IFN release did not depend on innate RNA immune sensors but rather the DNA sensor cGAS and the prevalence of mitochondrial DNA (mtDNA) in the cytoplasm. Sublethal mtDNA release was promoted by a chronic activation of the ATF6 branch of the unfolded protein response (UPR) in reaction to RNA-repeat accumulation and non-AUG translated tetrapeptide expansion proteins. ATF6-dependent mtDNA release and resulting cGAS/STING activation could also be recapitulated in human THP-1 monocytes exposed to chronic endoplasmic reticulum (ER) stress. Altogether, our study demonstrates a novel mechanism by which large repeat expansions cause chronic endoplasmic reticulum stress and associated mtDNA leakage. This mtDNA is, in turn, sensed by the cGAS/STING pathway and induces a type-I IFN response predisposing to autoimmunity. Elucidating this pathway reveals new potential therapeutic targets for autoimmune disorders associated with repeat expansion diseases.

Antagonist enamel tooth wear produced by different dental ceramic systems: A systematic review and network meta-analysis of controlled clinical trials.

OBJECTIVES: The aim of this study was to evaluate the amount of enamel tooth wear induced by different antagonistic ceramic crown materials in the posterior area within a follow-up period up to 24 months in function. A network meta-analysis was performed to assess the effect of the materials on the mean vertical loss (MVL) of the antagonist enamel tooth surface. DATA: Main search terms used in combination: ceramic, dental materials, metal ceramic, tooth wear and dental enamel. SOURCES: An electronic search was conducted in PubMed/Medline, Embase, and Cochrane CENTRAL plus hand-searching. STUDY SELECTION: Eligibility criteria included clinical studies reporting on MVL on antagonist's tooth up to 24 months following the permanent crown placement. From a total of 5697 articles, 7 studies reporting on 261 crowns for 177 subjects with 3 ceramic materials (Lithium disilicate, metal-ceramic, monolithic zirconia) were included. Among all, metal-ceramic and zirconia caused significantly higher enamel tooth wear on antagonist teeth, representing 82.5 µm [54.4; 110.6]) and 40.1 µm [22.2; 58.0]) more MVL than natural teeth group. In contrast, lithium disilicate showed only 5.0 µm [-48.2; 58.1]) more MVL than occurs on opposing natural teeth. CONCLUSIONS: This systematic review demonstrated that prosthodontic ceramic materials produced significantly more antagonist enamel tooth wear than opposing natural enamel tooth wear, and ceramic material type was correlated to the degree of enamel tooth wear. Additional well-conducted, randomized controlled trials with homogeneous specimens are required due to inadequate sample size and number of the clinical studies included in the analyses. CLINICAL SIGNIFICANCE: The amount of wear caused by different restorative materials has a high influence on the antagonistic natural teeth and should therefore be evaluated intensively by the dentist.

Pharmacodynamic effects of molidustat on erythropoiesis in healthy cats.

BACKGROUND: Inhibition of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) stimulates erythropoiesis in rats, dogs, monkeys, and humans. HYPOTHESIS/OBJECTIVE: Determine if molidustat, a novel HIF-PH inhibitor, stimulates erythropoiesis in healthy cats. ANIMALS: Seventeen healthy adult laboratory cats. METHODS: Randomized, placebo-controlled study. Cats were treated PO once daily with suspensions of 0 (Group 1; n = 6), 5 (Group 2; n = 6), or 10 (Group 3; n = 5) mg/kg of molidustat. Effects on red blood cell parameters, reticulocyte indices and plasma erythropoietin (EPO) concentrations were evaluated. Molidustat treatment was stopped when hematocrit (HCT) exceeded 60%. RESULTS: Compared to placebo, a significant increase in mean HCT was evident starting on Day 14 (Group 2:54.4% vs 40.3%, P < .001, 95% confidence interval [CI] for the difference [8.95-19.28]; Group 3:61.2% vs 40.3%, P < .001, 95% CI [15.48-26.43]) and remained significantly higher for the entire treatment period. In molidustat-treated groups, HCT exceeded 60% on Day 21 (Group 2) and Day 14 (Group 3). Mean HCT in molidustat-treated cats returned to within the reference range (29%-45%) after Day 56 and was numerically comparable to placebo from Day 70 onwards. Red blood cell count and hemoglobin concentrations followed a similar pattern as HCT. Mean EPO concentrations significantly increased after molidustat administration on all assessment days. Molidustat treatments were well tolerated. CONCLUSIONS AND CLINICAL IMPORTANCE: Marked erythropoietic effects were identified after daily administration of molidustat to healthy cats and additional studies are warranted to evaluate the effects in anemic cats.

Mechanical properties of 3D-printed and milled composite resins for definitive restorations: An in vitro comparison of initial strength and fatigue behavior.

OBJECTIVE: To evaluate the flexural strength and fatigue behavior of a novel 3D-printed composite resin for definitive restorations. MATERIALS AND METHODS: Fifty disc-shaped specimens were manufactured from each of a nanohybrid composite resin (NHC), polymer-infiltrated ceramic network (PICN), and 3D-printed composite resin (3D) with CAD-CAM technology. Biaxial flexural strength (σin ) (n = 30 per group) and biaxial flexural fatigue strength (σff ) (n = 20 per group) were measured using piston-on-three-balls method, employing a staircase approach of 105 cycles. Weibull statistics, relative-strength degradation calculations, and fractography were performed. The results were analyzed with 1-way ANOVA and Games-Howell post hoc test (α = 0.05). RESULTS: Significant differences in σin and σff among the groups (p < 0.001) were detected. The NHC group provided the highest mean ± standard deviation σin and σff (237.3 ± 31.6 MPa and 141.3 ± 3.8 MPa), followed by the PICN (140.3 ± 12.9 MPa and 73.5 ± 9.9 MPa) and the 3D (83.6 ± 18.5 MPa and 37.4 ± 23.8 MPa) groups. The 3D group exhibited significantly lower Weibull modulus (m = 4.7) and up to 15% higher relative strength degradation with areas of nonhomogeneous microstructure as possible fracture origins. CONCLUSIONS: The 3D-printed composite resin exhibited the lowest mechanical properties, where areas of nonhomogeneous microstructure developed during the mixing procedure served as potential fracture origins. CLINICAL SIGNIFICANCE: The clinical indications of the investigated novel 3D-printed composite resin should be limited to long-term provisional restorations. A cautious procedure for mixing the components is crucial before the 3D-printing process, since nonhomogeneous areas developed during the mixing could act as fracture origins.

Segmentation of process-related contaminations on two-piece abutments using pixel-based machine learning: a new quantification approach?

PURPOSE: A reference method for quantifying contaminations on two-piece abutments manufactured using CAD/CAM has not yet been established. In the present in vitro study, a pixel--based machine learning (ML) method for detecting contamination on customized two-piece abutments was investigated and embedded in a semiautomated quantification pipeline. MATERIALS AND METHODS: Forty-nine CAD/CAM zirconia abutments were fabricated and bonded to a prefabricated titanium base. All samples were analyzed for contamination by scanning electron microscopy (SEM) imaging followed by pixel--based ML and thresholding (SW) for contamination detection; quantification was performed in the postprocessing pipeline. Wilcoxon signed-rank test and Bland-Altmann plot were applied to compare both methods. The contaminated area fraction was recorded as a percentage. RESULTS: There was no statistically significant difference between the percentages of contamination areas (median = 0.004) measured with ML (median = 0.008) and with SW (median = 0.012), asymptotic Wilcoxon test: P = 0.22. The Bland-Altmann plot demonstrated a mean difference of -0.006% (95% confidence interval [CI] from -0.011% to 0.0001%) with increased values from a contamination area fraction of > 0.03% for ML. CONCLUSION: Both segmentation methods showed comparable results in evaluating surface cleanliness; pixel-based ML is a promising assessment tool for detecting external contaminations on zirconia abutments. Further studies are required to investigate the clinical performance of this tool.

Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I/IIa MULTIVIR-01 study.

Introduction: Allogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population. Methods: We report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a newly developed T cell product with specificity for CMV and EBV derived from the allogeneic stem cell grafts used for transplantation. The study aimed at prevention and preemptive treatment of both viruses in patients after allogeneic stem cell transplantation targeting first infusion on day +30. Primary endpoints were acute transfusion reaction and acute-graft versus-host-disease after infusion of activated T cells. Results: Thirty-three patients were screened and 9 patients were treated with a total of 25 doses of the T cell product. We show that central manufacturing can be achieved successfully under study conditions and the product can be applied without major side effects. Overall survival, transplant related mortality, cumulative incidence of graft versus host disease and number of severe adverse events were not different between treatment and control groups. Expansion of CMV/EBV specific T cells was observed in a fraction of patients, but overall there was no difference in virus reactivation. Discussion: Our study results indicate peptide stimulated epitope specific T cells derived from stem cell grafts can be administered safely for prevention and preemptive treatment of reactivation without evidence for induction of acute graft versus host disease. Clinical trial registration: https://clinicaltrials.gov, identifier NCT02227641.

Survival and complications of 3D-printed, non-invasive restorations for prosthetic rehabilitations: A 12-month preliminary observational study.

AIM: The adjustment and transfer of a stable occlusion can be a major challenge in prosthetic rehabilitations. The aim of this study was to assess a non-invasive treatment option for complex prosthetic rehabilitations and occlusal analyses using 3D-printed restorations clinically. MATERIALS AND METHODS: Eleven patients received a partial or complete rehabilitation with the aid of 3D-printed restorations (n=171). After 12 months of clinical service, all restorations were analyzed using the United States Public Health Service (USPHS) criteria. RESULTS: The 12-month clinical data revealed that 3D-printed restorations showed a survival rate of 84.4%. Complications occurred mostly regarding the anatomical form (7%) or marginal integrity (6AC%) and were consequently rated "Charlie" or "Delta." Color stability and color match of 3D-printed restorations were rated "Alpha" in 83% and 73%, respectively, of all restorations. Marginal inflammation was rated "Alpha" in 89% of all restorations. An excellent surface texture and no secondary caries or postoperative sensitivities (100%) were observed. CONCLUSIONS: 3D-printed restorations might be an alternative treatment option for initiating complex prosthetic rehabilitations. Technical complications rarely occurred. Biological complications did not occur at all. The color stability showed promising results after 12 months of clinical service. However, the results should be interpreted with caution. Long-term results with a high number of restorations should be awaited.

The Assessability of Approximal Secondary Caries of Non-Invasive 3D-Printed Veneers Depending on the Restoration Thickness-An In Vitro Study.

To date, no scientific data is available regarding the development and radiographic assessment of approximal caries development after the insertion of 3D-printed, non-invasive veneers of different restoration thicknesses. For the present study, non-invasive veneers were fabricated from two different materials for printing and milling (Vita Enamic and VarseoSmile Crown plus). Three different restoration thicknesses (0.5, 0.7, and 0.9 mm) were selected. After digital design, leaving the approximal space free, and manufacturing of the restorations, adhesive insertion followed. All specimens were placed in a demineralizing solution for 28 days. Subsequently, a radiological and fluorescent examination was performed. The present study showed statistically significant interactions for the day (p < 0.0001) and manufacturing method (p < 0.0001) but not for restoration thickness. Additive manufactured restorations showed less radiological caries progression compared to subtractive manufactured restorations after 21 and 28 days (0.7 and 0.9 mm restoration thickness) (p < 0.0001). DIAGNOdent proved that the restoration thickness affected the caries progression within the subtractive group (p < 0.0001). Radiographic and fluorescence examination showed equivalent results regarding approximal caries assessment. For additive manufacturing, less caries progression was shown without consideration of the restoration thickness.

Influence of exposure of customized dental implant abutments to different cleaning procedures: an in vitro study using AI-assisted SEM/EDS analysis.

PURPOSE: Dental implant abutments are defined as medical devices by their intended use. Surfaces of custom-made CAD/CAM two-piece abutments may become contaminated during the manufacturing process in the dental lab. Inadequate reprocessing prior to patient care may contribute to implant-associated complications. Risk-adapted hygiene management is required to meet the requirements for medical devices. METHODS: A total of 49 CAD/CAM-manufactured zirconia copings were bonded to prefabricated titanium bases. One group was bonded, polished, and cleaned separately in dental laboratories throughout Germany (LA). Another group was left untreated (NC). Five groups received the following hygiene regimen: three-stage ultrasonic cleaning (CP and FP), steam (SC), argon-oxygen plasma (PL), and simple ultrasonic cleaning (UD). Contaminants were detected using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) and segmented and quantified using interactive machine learning (ML) and thresholding (SW). The data were statistically analysed using non-parametric tests (Kruskal-Wallis test, Dunn's test). RESULTS: Significant differences in contamination levels with the different cleaning procedures were found (p ≤ 0.01). The FP-NC/LA groups showed the most significant difference in contamination levels for both measurement methods (ML, SW), followed by CP-LA/NC and UD-LA/NC for SW and CP-LA/NC and PL-LA/NC for ML (p ≤ 0.05). EDS revealed organic contamination in all specimens; traces of aluminum, silicon, and calcium were detected. CONCLUSIONS: Chemothermal cleaning methods based on ultrasound and argon-oxygen plasma effectively removed process-related contamination from zirconia surfaces. Machine learning is a promising assessment tool for quantifying and monitoring external contamination on zirconia abutments.