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Abstract Background Navigated endodontics is a cutting-edge technology becoming increasingly more accessible for dental practitioners. Therefore, it is necessary to clarify the ideal technical parameters of this procedure to prevent collateral damage of the surrounding tissues. There is a limited number of studies available in published scientific literature referencing the possible collateral thermal damage due to high-speed rotary instruments used in guided endodontic drilling. The aim of our study was to investigate the different drilling parameters and their effect upon the temperature elevations measured on the outer surface of teeth during guided endodontic drilling. Methods In our in vitro study, 72 teeth with presumably narrow root canals were prepared using a guided endodontic approach through a 3D-printed guide. Teeth were randomly allocated into six different test groups consisting of 12 teeth each, of which, four parameters affecting temperature change were investigated: (a) access cavity preparation prior to endodontic drilling, (b) drill speed, (c) cooling, and (d) cooling fluid temperature. Temperature changes were recorded using a contact thermocouple electrode connected to a digital thermometer. Results The highest temperature elevations (14.62 °C ± 0.60 at 800 rpm and 13.76 °C ± 1.24 at 1000 rpm) were recorded in the groups in which drilling was performed without prior access cavity preparation nor without a significant difference between the different drill speeds (p = 0.243). Access cavity preparation significantly decreased temperature elevations (p

Abstract Alterations in mTOR signalling molecules, including RICTOR amplification, have been previously described in many cancers, particularly associated with poor prognosis. In this study, RICTOR copy number variation (CNV) results of diagnostic next-generation sequencing (NGS) were analysed in 420 various human malignant tissues. RICTOR amplification was tested by Droplet Digital PCR (ddPCR) and validated using the “gold standard” fluorescence in situ hybridisation (FISH). Additionally, the consequences of Rictor protein expression were also studied by immunohistochemistry. RICTOR amplification was presumed in 37 cases with CNV ≥ 3 by NGS, among these, 16 cases (16/420; 3.8%) could be validated by FISH, however, ddPCR confirmed only 11 RICTOR-amplified cases with lower sensitivity. Based on these, neither NGS nor ddPCR could replace traditional FISH in proof of RICTOR amplification. However, NGS could be beneficial to highlight potential RICTOR-amplified cases. The obtained results of the 14 different tumour types with FISH-validated RICTOR amplification demonstrate the importance of RICTOR amplification in a broad spectrum of tumours. The newly described RICTOR-amplified entities could initiate further collaborative studies with larger cohorts to analyse the prevalence of RICTOR amplification in rare diseases. Finally, our and further work could help to improve and expand future therapeutic opportunities for mTOR-targeted therapies.

Abstract Background The purpose of this in vitro study was to compare the accuracy of implant placement in model surgeries according to the design of the drills (straight drills or step drills) used to finalize the implant bed during pilot-guided static computer-assisted implant surgery (sCAIS). Methods Model surgeries were carried out on resin models randomly assigned to three study groups. Virtual planning software (coDiagnostiX 10.6, Dental Wings, Montreal, Canada) was used to plan the implant positions. In Groups 1 and 2, pilot-guided sCAIS was performed. Straight drills were used in Group 1, and step drills were used in Group 2 to finalize the implant beds. In Group 3, fully guided sCAIS was performed using a universal fully guided kit (RealGUIDE Full Surgical Kit 3DIEMME, RealGUIDE, Cantù, Como, Italy). A total of 90 dental implants (Callus Pro, Callus Implant Solutions GmbH, Nuremberg, Germany) were placed (six implants per model, five models per study group). The primary outcome variables (angular deviation, coronal global deviation, and apical global deviation) were calculated for all implants based on the comparison of the preoperative surgical plan with the postoperative scans. Results Group 2 (coronal global deviation, 0.78 ± 0.29 mm; apical global deviation, 1.02 ± 0.56 mm) showed significantly lower values of both global deviation variables than Group 1 (coronal global deviation, 0.95 ± 0.20 mm; apical global deviation, 1.42 ± 0.49 mm). However, there was no significant difference in angular deviation between Groups 1 and 2 (7.56 ± 2.92° and 6.44 ± 2.84°). Group 3 produced significantly lower values of all three primary outcome variables (angular deviation, 2.36 ± 0.90°; coronal global deviation, 0.59 ± 0.28 mm; apical global deviation, 0.90 ± 0.29 mm) than Group 1 and significantly lower angular deviation and coronal global deviation values than Group 2. Conclusions The design of the drills used to finalize implant osteotomies during pilot-guided sCAIS influences dental implant placement accuracy. Using step drills instead of straight drills for final osteotomies decreases deviation from the surgical plan. The fully guided approach performed better than the pilot-guided sCAIS.

Abstract TP53 aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next‐generation sequencing (NGS)‐based studies have identified frequent low‐burden TP53 mutations with variant allele frequencies below 10%, but the clinical impact of these low‐burden TP53 mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of TP53 mutations using a sensitive, NGS‐based mutation analysis in a ‘real‐world’ cohort of 901 patients with CLL. In total, 225 TP53 mutations were identified in 17.5% (158/901) of the patients; 48% of these alterations represented high‐burden mutations, while 52% were low‐burden TP53 mutations. Low‐burden mutations as sole alterations were identified in 39% (62/158) of all mutated cases with 82% (51/62) of these being represented by a single low‐burden TP53 mutation. Patients harbouring low‐burden TP53 mutations had significantly lower time to first treatment compared to patients with wild‐type TP53. Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low‐burden TP53 mutations. By demonstrating that patients with sole low‐burden TP53 variants represent more than one‐third of patients with TP53 mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of TP53 variant reporting to below 10% in the routine diagnostic setting.

The need for sensitive monitoring of minimal/measurable residual disease (MRD) in multiple myeloma emerged as novel therapies led to deeper responses. Moreover, the potential benefits of blood-based analyses, the so-called liquid biopsy is prompting more and more studies to assess its feasibility. Considering these recent demands, we aimed to optimize a highly sensitive molecular system based on the rearranged immunoglobulin (Ig) genes to monitor MRD from peripheral blood. We analyzed a small group of myeloma patients with the high-risk t(4;14) translocation, using next-generation sequencing of Ig genes and droplet digital PCR of patient-specific Ig heavy chain (IgH) sequences. Moreover, well established monitoring methods such as multiparametric flow cytometry and RT-qPCR of the fusion transcript IgH::MMSET (IgH and multiple myeloma SET domain-containing protein) were utilized to evaluate the feasibility of these novel molecular tools. Serum measurements of M-protein and free light chains together with the clinical assessment by the treating physician served as routine clinical data. We found significant correlation between our molecular data and clinical parameters, using Spearman correlations. While the comparisons of the Ig-based methods and the other monitoring methods (flow cytometry, qPCR) were not statistically evaluable, we found common trends in their target detection. Regarding longitudinal disease monitoring, the applied methods yielded complementary information thus increasing the reliability of MRD evaluation. We also detected indications of early relapse before clinical signs, although this implication needs further verification in a larger patient cohort.

Objectives: The influence of energy drinks on dental materials are relatively under addressed. Our aim was to investigate the effect of energy drinks on dental materials used intraorally in young individuals. Commonly used preventive, restorative, and orthodontic materials were tested in vitro. Methods: The effect of two commercially available energy drinks (HELL, BURN) was investigated on different dental materials: machined, anodized Titanium (grade 5: Ti6Al4V) and composites (Grandio Seal, VOCO; Filtek Z250, 3M ESPE; Estelite SQ, TOKUYAMA). The roughness (Ra) and morphological changes were examined by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Results: AFM and SEM revealed significant differences in the Ra and morphology of the samples. AFM results for the machined and anodized titanium samples showed that the two energy drinks modified the surface roughness differently; BURN changed the roughness of machined samples significantly, while anodized discs were not altered significantly by the two energy drinks. In case of composite samples there was no significant difference for the Estelite SQ, relative low differences for the Filtek Z250 and significant changes in the morphology and surface roughness of Grandio Seal. Significance: On all tested materials, changes in the surface roughness and morphology were more or less detected, proving energy drinks do in fact have a harmful effect. It can be concluded that material erosion depends on the material composition and particle arrangement. Where the surface is characterized by a regular, uniform particle arrangement, energy drinks are less able to influence the roughness, while for samples where the surface is rich in aggregates, the material erodes the surface much more easily.

Objectives: Soft tissue integration of dental implants lags behind natural biological integration of teeth mainly because of non-optimal surface features. Peri-implant infections resulting in loss of supporting bone jeopardize the success of implants. Our aim was to compare an anodized surface design with a turned one for a more optimal surface. Methods: Morphological and chemical structures of turned and anodized Ti surfaces (grade 5: Ti6Al4V) discs were examined by scanning electron microscopy (SEM-EDS), energy dispersive X-ray spectroscopy (EDS), and atomic force microscopy (AFM). The hydrophilic or hydrophobic features of the surfaces were determined by dynamic contact angle measurement. Results: SEM and AFM revealed significant differences in the morphology and roughness (Ra) of the samples. Anodized discs presented a granular structure, while turned ones had circular grooves. The roughness was significantly higher for the anodized samples compared to the turned ones. XPS and EDS confirmed typical elements for both Ti6Al4V samples. Due to anodization, the amount of Ti (IV) had increased and Ti (III) had decreased in the thicker oxide layer. Anodized samples resulted in a more hydrophilic surface than the turned ones. Significance: The results suggest that the tested anodized samples present optimal surface characteristics to be used as abutment material for an optimal soft tissue integration.

Abstract Background Chairside systems are becoming more popular for fabricating full-ceramic single restorations, but there is very little knowledge about the effect of the entire workflow process on restoration fit. Therefore, this study aimed to compare the absolute marginal discrepancy (AMD) and the full internal fit (FULL) of all-ceramic crowns made by two chairside systems, Planmeca FIT and CEREC, with detailed and standard mill settings. Methods One upper molar was prepared for an all-ceramic crown in human cadaver maxilla. Full-arch scans were made by Emerald or Omnicam four times each. Twenty-four e.max crowns were designed and milled by the Planmill 30s or 40s or CEREC MCXL mills with either detailed or standard settings. The cadaver tooth was extracted, and each crown was fixed on it and scanned by a high-resolution microCT scanner. The AMD and FULL were measured digitally in mesio-distal and bucco-lingual 2D slices. The actual and predicted times of the milling were also registered. Results No differences were observed between detailed or standard settings in either system. The AMD was significantly higher with CEREC (132 ± 12 μm) than with either Planmill 30s (71 ± 6.9 μm) or 40s (78 ± 7.7 μm). In standard mode, the FULL was significantly higher with CEREC (224 ± 9.6 μm) than with either Planmill 30s (169 ± 8.1 μm) or 40s (178 ± 8.5 μm). There was no difference between actual and predicted time with the two Planmeca models, but with CEREC, the actual time was significantly higher than the predicted time. The 30s had significantly higher actual and predicted times compared to all other models. Across all models, the average milling time was 7.2 min less in standard mode than in detailed mode. Conclusions All fit parameters were in an acceptable range. No differences in fit between Planmeca models suggest no effect of spindle number on accuracy. The detailed setting has no improvement in the marginal or internal fit of the restoration, yet it increases milling time.

Background: COVID-19 is a serious and potentially deadly disease. Early diagnosis of infected individuals will play an important role in stopping its further escalation. The present gold standard for sampling is the nasopharyngeal swab method. However, several recent papers suggested that saliva-based testing is a promising alternative that could simplify and accelerate COVID-19 diagnosis.Objectives: Our aim was to conduct a meta-analysis on the reliability and consistency of SARS-CoV-2 viral RNA detection in saliva specimens.Methods: We have reported our meta-analysis according to the Cochrane Handbook. We searched the Cochrane Library, Embase, Pubmed, Scopus, Web of Science and clinical trial registries for eligible studies published between 1 January and 25 April 2020. The number of positive tests and the total number of tests conducted were collected as raw data. The proportion of positive tests in the pooled data were calculated by score confidence-interval estimation with the Freeman–Tukey transformation. Heterogeneity was assessed using the I2 measure and the χ2-test.Results: The systematic search revealed 96 records after removal of duplicates. Twenty-six records were included for qualitative analysis and 5 records for quantitative synthesis. We found 91% (CI 80–99%) sensitivity for saliva tests and 98% (CI 89–100%) sensitivity for nasopharyngeal swab (NPS) tests in previously confirmed COVID-19 patients, with moderate heterogeneity among the studies. Additionally, we identified 18 registered, ongoing clinical trials of saliva-based tests for detection of the virus.Conclusion: Saliva tests offer a promising alternative to NPS for COVID-19 diagnosis. However, further diagnostic accuracy studies are needed to improve their specificity and sensitivity.

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