Cirulating Sézary Cells in the Diagnosis of Sézary Syndrome (Quantitative and Morphometric Analyses)

Plastic-embedded circulating Sézary cells were examined in semithin and thin sections (assisted by the nuclear contour index-NCI). Eight cases of Sézary syndrome were analyzed as well as 11 controls (3 cases of widespread eczemas and 8 cases of erythroderma), 7 cases of mycosis fungoides, and 3 healthy individuals. Discriminating criteria between Sézary syndrome and benign diseases were sought: in addition to Sézary cells (NCI > 6.5) intermediate lymphocytes (5.0 < NCI ≤ 6.5) proved to be helpful. Cases with Sézary syndrome were clearly differentiated when the following 3 ultrastructural criteria were fulfilled: (1) Sézary cells (SC) > 9%; (2) intermediate lymphocytes (IL) > 20%; (3) the sum of SC and IL > 37%.A good correlation between thin and semithin sections was obtained (correlation coefficient for Sézary cells r = 0.82). Usually the values of SC were slightly higher on thin sections. The diagnosis of SS can be made on semithin sections when the ultrastructural criteria are fulfilled. In this way 8 of 12 samples of Sézary syndrome were correctly classified. Therefore, semithin sections (studied by light microscopy) are recommended as a routine method in the diagnosis of cases suspected of Sézary syndrome, whereas thin sections (studied by electron microscopy) appeared to be necessary in problem cases only

Dermatofibrosarcoma Protuberans: Altered Collagen Metabolism in Cell Culture

Dermatofibrosarcoma protuberans is a low-grade malignant tumor that grows invasively but rarely forms metastases. Its origin is still controversial. We characterized the synthesis of collagen in detail in cells which were obtained from dermatofibrosarcoma protuberans tumors by enzymatic tissue disintegration. Similar to fibroblasts, all tumor cell strains produced considerable amounts of collagen. However, the rate was reduced compared to normal skin fibroblasts. Cells grown from the tumors synthesized type I collagen, but no type III could be detected. After serial passaging the cultures started to produce type III collagen, which is probably due to a slow overgrowth by normal fibroblasts

Introducing a Specific Term to Present Caries Experience in Populations with Low Caries Prevalence: Specific Affected Caries Index (SaC)

Up to now, indices like the mean dmft/DMFT and the SiC (Significant Caries Index) have been used to depict caries experience in populations with high prevalence. With the caries decline, particularly for populations with low caries levels, these indices reach their statistical limits. This paper aims to introduce a specific term, the Specific affected Caries Index (SaC) for the risk groups in populations with low caries prevalence and to illustrate its use based on the consecutive German National Oral Health Survey (GNOHS) in children. In groups with a caries prevalence less than one-third of the population, many caries-free children (DMFT = 0) are included in the SiC (risk group), which calls for a new way of illustration. Mean caries experience (DMFT), caries prevalence, the SiC and SaC were portrayed for 12-year-olds in the GNOHS from 1994/95 to 2016. The SaC describes the mean caries experience (DMFT) in the group presenting caries experience (DMFT > 0). In 12-year-old 6th graders in Germany, the mean caries experience decreased from 2.4 (1994/95) to 0.4 DMFT (2016), with a recent prevalence of 21.2% (DMFT > 0, 2016). In 2016, the mean number of affected teeth in children with DMFT > 0 (SaC) was 2.1, while the SiC including 12% DMFT-free children in the risk group was 1.3. The SiC fails to reflect the caries severity in children in a population with low caries prevalence. Therefore, the newly introduced term Specific affected Caries Index (SaC) may be used to describe accurately caries experience in caries risk children in populations presenting low caries prevalence

Alternative caries management options for primary molars:2.5-yr outcomes of a randomised clinical trial

Less invasive caries management techniques for treating cavitated carious primary teeth, which involve the concept of caries control by managing the activity of the biofilm, are becoming common. This study aimed to compare the clinical efficacy (minor/major failures) and survival rates (successful cases without any failures) of 3 carious lesion treatment approaches, the Hall Technique (HT), non-restorative caries treatment (NRCT), and conventional restorations (CR), for the management of occlusoproximal caries lesions (ICDAS 3-5) in primary molars. Results at 2.5 years are presented. A total of 169 children (3- to 8-year-olds) were enrolled in this secondary care-based, 3-arm parallel-group, randomised controlled trial. Participants were allocated to: HT (n = 52; sealing caries with stainless-steel crowns without caries removal), NRCT (n = 52; opening up the cavity and applying fluoride varnish), CR (n = 65; control arm, complete caries removal and compomer restoration). Statistical analyses were: non-parametric Kruskal-Wallis analysis of variance, Mann-Whitney U test and Kaplan-Meier survival analyses. One hundred and forty-two participants (84%; HT = 40/52; NRCT = 44/52; CR = 58/65) had follow-up data of 1-33 months (mean = 26). Overall, 25 (HT = 2, NRCT = 9, CR = 14) of 142 participants (17.6%) presented with at least 1 minor failure (reversible pulpitis, caries progression, or secondary caries; p = 0.013, CI = 0.012-0.018; Mann-Whitney U test). Ten (HT = 1, NRCT = 4, CR = 5) of 142 participants (7.04%) experienced at least 1 major failure (irreversible pulpitis, abscess, unrestorable tooth; p = 0.043, CI = 0.034-0.045). Independent comparisons between 2 samples found that NRCT-CR had no statistically significant difference in failures (p > 0.05), but for CR-HT (p = 0.037, CI = 0.030-0.040) and for NRCT-HT (p = 0.011, CI = 0.010-0.016; Kruskal-Wallis test) significant differences were observed. Cumulative survival rates were HT = 92.5%, NRCT = 70.5%, and CR = 67.2% (p = 0.012). NRCT and CR outcomes were comparable. HT performed better than NRCT and CR for all outcomes. This study was funded by the Paediatric Dentistry Department, Greifswald University, Germany (Trial registration No. NCT01797458)

Cost-effectiveness of managing cavitated primary molar caries lesions:A randomized trial in Germany

The Hall Technique (HT), Non-Restorative Cavity Control (NRCC) and conventional carious tissue removal and restoration (CR) are strategies for managing cavitated caries lesions in primary molars. A randomized controlled three-arm parallel group trial in a university clinic in Germany was used to measure the cost-effectiveness of these strategies. 142 children (HT: 40; NRCC: 44; CR: 58) were followed over a mean 2.5 years. A German healthcare perspective was chosen. The primary outcome was estimated molar survival; secondary outcomes were not needing extraction, not having pain or needing endodontic treatment/extraction, or not needing any re-intervention at all. Initial, maintenance and endodontic/restorative/extraction re-treatment costs were derived from fee items of the statutory insurance. Cumulative cost-effectiveness and cost-effectiveness acceptability were estimated from bootstrapped samples. HT molars survived longer (estimated mean; 95% CI: 29.7; 26.6–30.5 months) than NRCC (25.3; 21.2–28.7 months) and CR molars (24.1; 22.0–26.2 months). HT was also less costly (66; 62–71 Euro) than NRCC (296; 274–318 Euro) and CR (83; 73–92 Euro). HT was more cost-effective than NRCC and CR in >96% of samples, and had acceptable cost-effectiveness regardless of a payer’s willingness-to-pay. This superior cost-effectiveness was confirmed for secondary health outcomes. Cost-advantages were even more pronounced when costs were calculated per year of tooth retention (mean annual costs were HT: 29, NRCC: 154, CR: 61 Euro). HT was more cost-effective than CR or NRCC for managing cavitated caries lesions in primary molars, yielding better dental health outcomes at lower costs. If choosing between these three strategies for managing cavitated caries lesions in primary molars, dentists should prefer HT over NRCC or CR. This would also save costs for the healthcare payer

Antibody Production in Murine Polymicrobial Sepsis—Kinetics and Key Players

Although antigen-specific priming of antibody responses is impaired during sepsis, there is nevertheless a strong increase in IgM and IgG serum concentrations. Using colon ascendens stent peritonitis (CASP), a mouse model of polymicrobial abdominal sepsis, we observed substantial increases in IgM as well as IgG of all subclasses, starting at day 3 and peaking 2 weeks after sepsis induction. The dominant source of antibody-secreting cells was by far the spleen, with a minor contribution of the mesenteric lymph nodes. Remarkably, sepsis induction in splenectomized mice did not change the dynamics of the serum IgM/IgG reaction, indicating that the marginal zone B cells, which almost exclusively reside in the spleen, are dispensable in such a setting. Hence, in systemic bacterial infection, the function of the spleen as dominant niche of antibody-producing cells can be compensated by extra-splenic B cell populations as well as other lymphoid organs. Depletion of CD4+ T cells did not affect the IgM response, while it impaired IgG generation of all subclasses with the exception of IgG3. Taken together, our data demonstrate that the robust class-switched antibody response in sepsis encompasses both T cell-dependent and -independent components

Učinak prevalencije i težine molarno-incizalne hipomineralizacije na kvalitetu života povezanu s oralnim zdravljem: sistematizirani pregled i metaanaliza

Objectives: The aim of this systematic review and meta-analysis is to assess the association between the MIH presence as well as the severity and OHRQoL in children. Material and methods: Relevant studies were identified in PubMed, Embase, Cochrane and Google Scholar. Studies involving MIH and OHRQoL in children were included. A methodological quality assessment of included studies was performed using the Newcastle-Ottawa Scale (NOS) and its adapted version for cross-sectional studies. Random effects models were used to estimate summary effect measures for the association between MIH presence (presence vs. absence) as well as severity (moderate/severe MIH vs. no MIH) and OHRQoL using generic inverse variance meta-analyses. Tests for heterogeneity, publication bias and sensitivity of results were also performed. Results: Out of 1696 identified publications 11 studies reporting on 5,017 children were included in the meta-analysis assessing the impact of MIH presence. There was no statistically significant association between the presence of MIH and lower OHRQoL in affected children (OR = 1.72, 95% CI = 0.99–2.98). Concerning MIH severity and its impact on OHRQoL, a sum of 6 studies were included in the meta-analysis involving a total of 2,595 children. There was a significant association between moderate/severe MIH and lower OHRQoL in affected children (OR = 3.43, 95% CI = 1.69–6.98). Conclusion: Moderate/Severe MIH has a significant and clinically relevant negative impact on OHRQoL, and it should therefore be addressed adequately. Future research should also consider the impact of a uniform MIH diagnosis and precise severity criteria.Svrha istraživanja: Cilj ovog sistematiziranog pregleda i metaanalize bio je procijeniti povezanost između MIH-a i OHRQoL-a u djece. Materijali i metode: Pronađena su relevantna istraživanja u bazama PubMed, Embase, Cochrane i Google Scholar. Uključena su istraživanja koja su obrađivala MIH i OHRQoL u djece. Metodološka procjena kvalitete tih istraživanja obavljena je s pomoću ljestvice Newcastle-Ottawa (NOS) i njezine prilagođene verzije za presječne studije. Za procjenu sažetih mjera učinka za povezanost između prisutnosti MIH-a (prisutnost prema odsutnosti) upotrijebljeni su modeli slučajnih učinaka, a za težinu (umjereni/teški MIH prema odsutnosti MIH-a) i OHRQoL upotrijebljena je generička metaanaliza inverzne varijance. Obavljeni su i testovi heterogenosti, pristranosti objave i osjetljivosti rezultata. Rezultati: Od 1696 identificiranih časopisa, u metaanalizu procjene utjecaja prisutnosti MIH-a uključeno je 11 istraživanja koja su izvještavala o 5017 djece. Nije bilo statistički značajne povezanosti između prisutnosti MIH-a i nižega OHRQoL-a u pogođene djece (OR = 1,72, 95 % IP = 0,99–2,98). Kad je riječ o težini MIH-a i njegova utjecaja na OHRQoL, zbroj od 6 istraživanja uključen je u metaanalizu koja obuhvaća ukupno 2595 djece. Postojala je značajna povezanost između umjerenoga/teškoga MIH-a i nižega OHRQoL-a u pogođene djece (OR = 3,43, 95 % IP = 1,69 – 6,98)

Regulatory T cells with additional COX-2 expression are independent negative prognosticators for vulvar cancer patients

Vulvar cancer incidence numbers have been steadily rising over the past decades. In particular, the number of young patients with vulvar cancer has recently increased. Therefore, the need to identify new prognostic factors and, in addition, therapeutic options for vulvar carcinoma is more apparent. The aim of this study was to analyze the influx of COX-2 positive tumor-infiltrating lymphocytes and monocytes and their influence on prognosis. Using subtyping by immunofluorescence, the majority of COX-2 expressing immune cells were identified as FOXP3-positive regulatory T cells. In addition, peri- and intra-tumoral macrophages in the same tumor tissue were detected simultaneously as M2-polarized macrophages. COX-2 positive immune cells were independent negative prognostic markers in long-term overall survival of patients with vulvar cancer. These results show an influence of immune cell infiltration for vulvar carcinoma patients. Immune cell infiltration and immune checkpoint expression may, therefore, become interesting targets for further research on new vulvar cancer treatment strategies

Lysine-specific histone demethylase 1A (LSD1) in cervical cancer

PURPOSE Demethylation of DNA through enzymes like LSD1 showed a crucial impact on different kind of cancers. Epigenetic modifications in cervical cancer are still not fully investigated nevertheless of high interest for a therapeutic use. METHODS Tumor samples of 250 cervical cancer patients were immunochemically stained and evaluated based on Immunoreactive Score. Results were statistically analyzed for clinical and pathological parameters. RESULTS Our patient collective showed a disadvantage for 10-year survival for patients with a strong expression of LSD1 in the cytoplasm of cervical cancer cells. The results of the correlational analysis further revealed a negative correlation of LSD1 to G-protein coupled estrogen receptor (GPER). CONCLUSIONS Epigenetic changes through enzymes like LSD1 may also be of interest for patients with cervical cancer. A combined therapy with other proteins relayed to cervical cancer like GPER might be of interest for future investigations

LDOC1 as negative prognostic marker for vulvar cancer patients

So far, studies about targeted therapies and predictive biomarkers for vulva carcinomas are rare. The leucine zipper downregulated in cancer 1 gene (LDOC1) has been identified in various carcinomas as a tumor-relevant protein influencing patients&rsquo; survival and prognosis. Due to the lack of information about LDOC1 and its exact functionality, this study focuses on the expression of LDOC1 in vulvar carcinoma cells and its surrounding immune cells as well as its correlation to clinicopathological characteristics and prognosis. Additionally, a possible regulation of LDOC1 in vulvar cancer cell lines via the NF-&kappa;B signaling pathway was analyzed. Vulvar carcinoma sections of 157 patients were immunohistochemically stained and examined regarding LDOC1 expression by using the immunoreactive score (IRS). To characterize LDOC1-positively stained immune cell subpopulations, immunofluorescence double staining was performed. The effect of the NF-&kappa;B inhibitor C-DIM 12 (3,3&prime;-[(4-chlorophenyl)methylene]bis[1 H-indole]) on vulvar cancer cell lines A431 and SW 954 was measured according to MTT and BrdU assays. Baseline expression levels of LDOC1 in the vulvar cancer cell lines A431 and SW 954 was analyzed by real-time PCR. LDOC1 was expressed by about 90% of the cancer cells in the cytoplasm and about half of the cells in the nucleus. Cytoplasmatic expression of LDOC1 was associated with decreased ten-year overall survival of the patient, whereas nuclear staining showed a negative association with disease-free survival. Infiltrating immune cells were mainly macrophages followed by regulatory T cells. Incubation with C-DIM 12 decreased the cell viability and proliferation of vulvar cancer cell line A431, but not of cell line SW 954. LDOC1 expression on mRNA level was twice as high in the cell line A431 compared to the cell line SW 954. Overexpression of LDOC1 was associated with unfavorable overall and disease-free survival. Tumor growth could be inhibited by C-DIM 12 in vitro if the expressed LDOC1 level was high enough