Profiling of Copy Number Alterations Using Low-Coverage Whole-Genome Sequencing Informs Differential Diagnosis and Prognosis in Primary Cutaneous Follicle Center Lymphoma.

Primary cutaneous follicle center lymphoma (PCFCL) has an excellent prognosis using local treatment, whereas nodal follicular lymphoma (nFL), occasionally presenting with cutaneous spread, often requires systemic therapy. Distinction of the 2 diseases based on histopathology alone might be challenging. Copy number alterations (CNAs) have scarcely been explored on a genome-wide scale in PCFCL; however, they might serve as potential biomarkers during differential diagnosis and risk stratification. Low-coverage whole-genome sequencing is a robust, high-throughput method for genome-wide copy number profiling. In this study, we analyzed 28 PCFCL samples from 20 patients and compared the copy number profiles with a cohort of diagnostic samples of 64 nFL patients. Although the copy number profile of PCFCL was similar to that of nFL, PCFCL lacked amplifications of 18q, with the frequency peaking at 18q21.33 in nFL cases involving the BCL2 locus (PCFCL: 5.0% vs nFL: 31.3%, P = .018, Fisher exact test). Development of distant cutaneous spread was significantly associated with higher genomic instability including the proportion of genome altered (0.02 vs 0.13, P = .033) and number of CNAs (2 vs 9 P = .017), as well as the enrichment of 2p22.2-p15 amplification involving REL and XPO1 (6.3% vs 60.0%, P = .005), 3q23-q24 amplification (0.0% vs 50.0%, P = .004), 6q16.1-q23.3 deletion (6.3% vs 50.0%, P = .018), and 9p21.3 deletion covering CDKN2A and CDKN2B loci (0.0% vs 40.0%, P = .014, all Fisher exact test) in PCFCL. Analysis of sequential tumor samples in 2 cases harboring an unfavorable clinical course pointed to the acquisition of 2p amplification in the earliest common progenitor underlining its pivotal role in malignant transformation. By performing genome-wide copy number profiling on the largest patient cohort to date, we identified distinctive CNA alterations conceivably facilitating the differential diagnosis of PCFCL and secondary cutaneous involvement of nFL and potentially aiding the risk stratification of patients with PCFCL in the future.

Effect of different parameters utilized for image guided endodontic root canal preparation on temperature changes: an in vitro study.

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 < 0.01) while drilling at 800 rpm (8.90 °C ± 0.50) produced significantly less heating of the root surface (p < 0.05) than drilling at 1000 rpm (10.09 °C ± 1.32). Cooling significantly decreased (p < 0.01) temperature elevations at a drill speed of 1000 rpm, and cooling liquid temperatures of 4-6 °C proved significantly (p < 0.01) more beneficial in decreasing temperature elevations (1.60 °C ± 1.17) than when compared with room temperature (21 °C) liquids (4.01 °C ± 0.22). CONCLUSIONS: Based on the results of our study, guided endodontic drilling at drill speeds not exceeding 1000 rpm following access cavity preparation, with constant cooling using a fluid cooler than room temperature, provides the best results in avoiding collateral thermal damage during navigated endodontic drilling of root canals.

Parallel testing of liquid biopsy (ctDNA) and tissue biopsy samples reveals a higher frequency of EZH2 mutations in follicular lymphoma.

BACKGROUND: Recent genomic studies revealed enhancer of zeste homolog 2 (EZH2) gain-of-function mutations, representing novel therapeutic targets in follicular lymphoma (FL) in around one quarter of patients. However, these analyses relied on single-site tissue biopsies and did not investigate the spatial heterogeneity and temporal dynamics of these alterations. OBJECTIVES: We aimed to perform a systematic analysis of EZH2 mutations using paired tissue (tumor biopsies [TB]) and liquid biopsies (LB) collected prior to treatment within the framework of a nationwide multicentric study. METHODS: Pretreatment LB and TB samples were collected from 123 patients. Among these, 114 had paired TB and LB, with 39 patients characterized with paired diagnostic and relapse samples available. The EZH2 mutation status and allele burden were assessed using an in-house-designed, highly sensitive multiplex droplet digital PCR assay. RESULTS: EZH2 mutation frequency was found to be 41.5% in the entire cohort. In patients with paired TB and LB samples, EZH2 mutations were identified in 37.8% of the patients with mutations exclusively found in 5.3% and 7.9% of TB and LB samples, respectively. EZH2 mutation status switch was documented in 35.9% of the patients with paired diagnostic and relapse samples. We also found that EZH2 wild-type clones may infiltrate the bone marrow more frequently compared to the EZH2 mutant ones. CONCLUSION: The in-depth spatio-temporal analysis identified EZH2 mutations in a considerably higher proportion of patients than previously reported. This expands the subset of FL patients who most likely would benefit from EZH2 inhibitor therapy.

High Tumor-Infiltrating Lymphocyte Count Is Associated with Distinct Gene Expression Profile and Longer Patient Survival in Advanced Ovarian Cancer.

Cancer-related immunity plays a significant role in the outcome of ovarian cancer, but the exact mechanisms are not fully explored. A retrospective, real-life observational study was conducted including 57 advanced ovarian cancer patients. Immunohistochemistry for CD4+, CD8+, and CD45+ was used for assessing tumor-infiltrating immune cells. Furthermore, an immune-related gene expression assay was performed on 12-10 samples from patients with less than and more than 1-year overall survival (OS), respectively. A higher number of CD4+ (p = 0.0028) and CD45+ (p = 0.0221) immune cells within the tumor microenvironment were associated with longer OS of patients. In a multivariate setting, higher CD4+ T cell infiltration predicted longer OS (p = 0.0392). Twenty-three differentially expressed genes-involved in antigen presentation, costimulatory signaling, matrix remodeling, metastasis formation, and myeloid cell activity-were found when comparing the prognostic groups. It was found that tumor-infiltrating immune cell counts are associated with peculiar gene expression patterns and bear prognostic information in ovarian cancer. SOX11 expression emerged and was validated as a predictive marker for OS.

Does implant drill design influence the accuracy of dental implant placement using static computer-assisted implant surgery? An in vitro study.

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.

Dissection of subclonal evolution by temporal mutation profiling in chronic lymphocytic leukemia patients treated with ibrutinib.

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance. To understand the landscape of genomic changes and the dynamics of subclonal architecture associated with ibrutinib treatment, an ultra-deep next-generation sequencing analysis of 30 recurrently mutated genes was performed on sequential samples of 20 patients, collected before and during single-agent ibrutinib treatment. Mutations in the SF3B1, MGAand BIRC3 genes were enriched during ibrutinib treatment, while aberrations in the BTK, PLCG2, RIPK1, NFKBIE and XPO1 genes were exclusively detected in posttreatment samples. Besides the canonical mutations, four novel BTK mutations and three previously unreported PLCG2 variants were identified. BTK and PLCG2 mutations were backtracked in five patients using digital droplet PCR and were detectable on average 10.5 months before clinical relapse. With a median follow-up time of 36.5 months, 7/9 patients harboring BTK mutations showed disease progression based on clinical and/or laboratory features. In conclusion, subclonal heterogeneity, dynamic clonal selection and various patterns of clonal variegation were identified with novel resistance-associated BTK mutations in individual patients treated with ibrutinib.

Marginal and internal fit of full ceramic crowns milled using CADCAM systems on cadaver full arch scans.

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.

[Classical and modern methods for the assessment of skeletal maturation and pubertal growth spurt]. / Klasszikus és modern vizsgálómódszerek a csontérettségi kor és a pubertáskori növekedési csúcs meghatározására.

The assessment of skeletal age is of utmost importance not only in the field of anthropology, forensic medicine, pediatrics, endocrinology but also in orthodontics and jaw orthopedics. Bone age refers to the individual's biological development which can differ within a relatively wide range for the same chronological age. Therefore, accurate assessment of skeletal maturity and pubertal growth plays an important role in establishing a diagnosis for certain diseases. In addition, it is essential for proper timing and success of treatments in many cases. Currently, there are many methods available to determine skeletal age and pubertal growth spurt. During growth, bones undergo significant changes, the sequence of which is strongly determined. These changes can be measured by various methods including radiological examinations. More specifically, these classical methods are often based on the radiological evaluation of morphological changes in the hand bones and cervical vertebrae. Methods based on dental development also exist to assess the biologic maturity of an individual. However, thanks to three-dimensional imaging techniques and molecular diagnostic methods, even more accurate tests can be performed to determine biological maturity. These modern methods rely on the information obtained from the cone-beam computer tomograph records and on the measurements of biomarkers present in different circulatory or other body fluids. The purpose of this summary is to provide an overview of the various classical and modern methods for the assessment of skeletal age that could aid us in many fields of science. Orv Hetil. 2018; 159(35): 1423-1432.

[Performance indicators of maxillofacial surgery inpatient departments]. / Az arc-, állcsont-szájsebészeti aktív fekvobetegosztályok teljesítménymutatói.

INTRODUCTION: In Hungary, the number and structure of the maxillofacial surgery departments underwent significant changes in recent decades. AIM: The aim of our study was to present the actual performance indicators of maxillofacial inpatient departments and based on the available data to compare the departments. METHOD: The study was based on the number of beds founded by the National Health Insurance Fund. Performance data were supplied by the National Health Insurance Fund Administration. The assessment included the following indicators: number of beds institutional breakdown by type, number of reimbursed cases, the weighted case number, hospital stay, bed occupancy rates and average length of stay. RESULTS: In the examined period 40% of active beds (65) were in university hospitals. The distribution of reimbursed cases was similar. The university hospitals showed higher weighted case number and case-mix index. The oral surgery departments' bed occupancy rate (45.75%) was below the national average. CONCLUSION: The indicators show significant differences among different departments in the examined period. Orv. Hetil., 2017, 158(12), 447-453.

[Reimbursement of public dental care in Germany, the United Kingdom, Hungary and Poland]. / A fogászati ellátás finanszírozása Németországban, az Egyesült Királyságban, Magyarországon és Lengyelországban.

INTRODUCTION: Dental treatments have the highest rate among medical interventions and their reimbursement is also significant. AIM: The aim of the study was to compare the outcome of the reformed healthcare system process on public dental services in four European countries. METHOD: Assessment base for the comparison of reimbursement of dental treatments and dental fee schedules provided by the health insurance funds were used. The following indicators were examined: the ratio of public dental services and the main oral health indicators. Among dental fee schedules, reimbursement of general dental activity, prevention, operative dentistry, endodontic and oral surgery were selected. RESULTS: The lowest value of population to active dentist ratio was found in Germany (population to active dentist ratio: 1247) and the highest in Hungary (population to active dentist ratio: 2020). Oral health indicators showed significant differences between the West-European and East-European countries. On the other hand, the ratio of completely edentulous people at the age of 65yrs did not show great variations. Reimbursement of public dental treatments indicated significantly higher value in Germany and the United Kingdom compared to the other countries. CONCLUSIONS: Reimbursement of public dental services varies considerably in the selected European countries.

Complex analysis of multiple single nucleotide polymorphisms as putative risk factors of tooth agenesis in the Hungarian population.

OBJECTIVES: The role was studied of multiple single nucleotide polymorphisms in tooth agenesis in the Hungarian population using a complex approach. METHODS: Eight SNPs, PAX9 -912 C/T, PAX9 -1031 A/G, MSX1 3755 A/G, FGFR1 T/C rs881301, IRF6 T/C rs764093, AXIN2-8150 A/G, AXIN2-8434 A/G and AXIN2-30224 C/T, were studied in 192 hypodontia and 17 oligodontia cases and in 260 healthy volunteers. Case-control analysis was performed to test both allelic and genotypic associations as well as associations at the level of haplotypes. Multivariate exploratory Bayesian network-based multi-level analysis of relevance (BN-BMLA) as well as logistic regression analysis were performed. RESULTS: Conventional statistics showed that PAX9 SNP -912 C/T and the MSX1 SNP changed the incidence of hypodontia, although after Bonferroni correction for multiple hypothesis testing, the effects were only borderline tendencies. Using a statistical analysis better suited for handling multiple hypotheses, the BN-BMLA, PAX9 SNPs clearly showed a synergistic effect. This was confirmed by other multivariate analyses and it remained significant after corrections for multiple hypothesis testing (p < 0.0025). The PAX9-1031-A-PAX9-912-T haplotype was the most relevant combination causing hypodontia. Interaction was weaker between PAX9 and MSX1, while other SNPs had no joint effect on hypodontia. CONCLUSION: This complex analysis shows the important role of PAX9 and MSX1 SNPs and of their interactions in tooth agenesis, while IRF6, FGFR1 and AXIN2 SNPs had no detectable role in the Hungarian population. These results also reveal that risk factors in hypodontia need to be identified in various populations, since there is considerable variability among them.

Low-burden TP53 mutations represent frequent genetic events in CLL with an increased risk for treatment initiation.

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.

TRPS1 expression in cytokeratin 5 expressing triple negative breast cancers, its value as a marker of breast origin.

The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization of the tumour as triple negative breast carcinoma (TNBC). The majority of TNBCs are aggressive tumours with common metastases and decreased expression of markers that could help in identifying the metastatic lesion as of mammary origin. Breast markers, such as gross cystic disease fluid protein-15 (GCDPF-15), GATA binding protein 3 (GATA3), mammaglobin (MGB) and SOX10, are not uniquely specific to BC. Our aim was to evaluate trichorhinophalangeal syndrome type 1 (TRPS1) protein as a breast marker in a series of cytokeratin-5-expressing TNBC, mostly corresponding to basal-like TNBCs, previously characterized for the expression of other breast markers. One hundred seventeen TNBCs in tissue microarrays were immunostained for TRPS1. The cut-off for positivity was ≥ 10%. The reproducibility of this classification was also assessed. TRPS1 positivity was detected in 92/117 (79%) cases, and this exceeded the expression of previously tested markers like SOX10 82 (70%), GATA3 11 (9%), MGB 10 (9%) and GCDFP-15 7 (6%). Of the 25 TRPS1-negative cases, 11 were positive with SOX10, whereas 5 to 6 dual negatives displayed positivity for the other makers. The evaluation showed substantial agreement. Of the five markers compared, TRPS1 seems the most sensitive marker for the mammary origin of CK5-expressing TNBCs. Cases that are negative are most often labelled with SOX10, and the remainder may still demonstrate positivity for any of the 3 other markers. TRPS1 has a place in breast marker panels.

Associations Between Temporomandibular Pain and Biobehavioral Variables in Dental Students in Response to an External Stressor.

AIMS: To assess changes in temporomandibular disorder (TMD) pain and multiple biobehavioral variables relevant to TMDs in response to an external stressor. METHODS: Self-reported data using online DC/TMD questionnaires were collected from volunteer dentistry graduate students. Data collection was performed on two occasions: during a non-exam period of the semester and during the subsequent exam period. Changes in the proportion of students with pain, differences in pain grade, and severity of biobehavioral status were measured and compared over the two periods. The association between severity of non-exam-period biobehavioral status and pain presence was also tested to assess whether biobehavioral variables can predict pain occurrence or persistence. Chi-square test, Wilcoxon signed-rank test, ANOVA, and Kruskal-Wallis tests were used for data analysis. P < .05 was considered significant. RESULTS: Of the 213 enrolled students, 102 remained after data reduction. In the non-exam period, the proportion of individuals with pain was 24.5%; in the exam period, the proportion was 54.9%, and more students had a higher pain grade. The severity of all biobehavioral variables was higher in the exam period, but there was no association between changes in the presence of pain and changes in biobehavioral variables. Higher anxiety and parafunction levels were found in those who reported pain on both occasions. CONCLUSION: Exam periods initiate readily measurable changes in the psychologic status of many students, as well as alterations in their temporomandibular pain. Higher levels of anxiety and oral behaviors during non-exam periods seem to be predictors for persisting pain.

Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing.

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.

Liquid biopsy-based monitoring of residual disease in multiple myeloma by analysis of the rearranged immunoglobulin genes-A feasibility study.

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.

Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma.

Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217 alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequencing identified genetic lesions affecting ZNF217 in 33% of 157 PMBCL patients. Subsequent gene expression profiling (n = 120) revealed changes in cytokine and interferon signal transduction in ZNF217-aberrant PMBCL cases. In vitro, knockout of ZNF217 led to changes in chromatin accessibility interfering with binding motifs for crucial lymphoma-associated transcription factors. This led to disturbed expression of interferon-responsive and inflammation-associated genes, altered cell behavior, and aberrant differentiation. Mass spectrometry demonstrates that ZNF217 acts within a histone modifier complex containing LSD1, CoREST and HDAC and interferes with H3K4 methylation and H3K27 acetylation. Concluding, our data suggest non-catalytic activity of ZNF217, which directs histone modifier complex function and controls B cell differentiation-associated patterns of chromatin structure.

[Clinical importance and diagnosis of halitosis]. / A halitózis klinikai jelentosége és diagnosztikája.

The origin of halitosis comes from the Latin word "halitus" meaning 'breath, exhaled air', and in the Hungarian terminology it means bad and smelly breath. The human body emits a number of volatile molecules, which have a peculiar odour. Their presence is influenced by several factors, such as genetic, nutritional and psychological factors. Since bad breath belongs to taboo subjects, halitosis can often lead to social isolation. To determine the incidence of halitosis, an exact diagnosis is needed which sometimes predestinates the possible treatment as well. Investigators estimate the incidence about 50% in the whole population. The male/female ratio is the same and the incidence is growing with age. The diagnosis can be genuine halitosis, pseudo halitosis and halitophobia. We can divide the genuine type into physiological and pathophysiological subtypes. The cause of the halitosis usually can be found in the oral cavity. The volatile sulfur compounds (VSC) produced by some of the oral bacteria are responsible for its development. Only 10% of the causes are extraoral, mostly inflammation of airways or gastrointestinal disorders. The judgment of halitosis is based on three objective methods: the organoleptic, the sulphide monitoring and the gas cromatography methods. Since the origin of the halitosis is mainly the oral cavity, dentists should treat them. Beyond the dental treatments the enhancement of the oral hygiene, the continuous motivation and monitoring are also very important, such as the use of tongue cleansing and special anti-malodour rinses.

[Health insurance reimbursement of dental care in Hungary]. / A fogászati ellátás egészségbiztositási finanszírozása Magyarországon.

The aim of this study was to assess the annual health insurance reimbursement of dental health service in Hungary. The assessment base of the study was the annual reports of National Health Insurance Fund Administration (OEP). Only the data collected from the services in contractual relationship with the OEP and delivered in 2008 were evaluated. Dental care services are organised in different levels: general dental service, specialist dental care, special dental care on university level and inpatient departments. Our study covers primary, outpatient and hospital dental care. Dental care was supplied by 3.378 general and specialist dental care services at the end of 2008. For the hospital treatment of more serious cases 17 inpatient departments are available with 154 patient beds. Within the period of examination (2008) 23.6 million interventions were carried out in 7.6 million cases. The total health insurance reimbursement of dental care (including primary, outpatient and hospital care) was 24.92 billion HUF (88.82 million Euro) in 2008. The health insurance reimbursement of dental care in Hungary is approximately 2% of the total health insurance expenditures of the National Health Insurance Fund Administration (OEP). Within the period under investigation, the health insurance reimbursement of dental care did not change significantly.

[Retrospective study of direct composite restorations according to the USPHS criteria]. / Direkt kompozit restaurációk retrospektív vizsgálata USPHS kritériumrendszer alapján.

The purpose of this retrospective study was to evaluate and describe the occurrence of different deficiencies of composite restorations in molar and premolar teeth. Further aim was to investigate possible correlations between occurring malformations and the localization or size of the restorations. 240 class II composite restorations (in 85 patients) were involved in the study. Control examinations were carried out five years after restorations, according to the United States Public Health Services' criteria. Namely, anatomic form, marginal integrity, marginal stain, color stability, surface smoothness, and the presence of secondary caries or fractures of the restorations. The associations between variables were calculated by bivariate analyses using either Pearson chi-square or Fisher tests. P < 0.05 was considered significant. In 0.8% of the fillings, secondary caries and in 0.4% of the cases, fracture was found as a failure. The frequency of adjacent deficiencies were found as follows: color instability, 12.5%; marginal stain, 20.8%; anatomic deformity, 15.0%; failure of marginal integrity, 8.8%; and surface roughness, 2.5%. Color instability was significantly more frequent in premolar teeth, than in molars (P = 0.031). Color instability (P = 0.015), marginal stain (P < 0.001) and anatomic form malformation (P = 0.002) occurred more frequently in MOD restorations than in MO/OD fillings. Our results suggest that class II restorations are correct both functionally and esthetically in 98.8% of the cases, even after a 5-year-period.