Radiographic evaluation of a bone substitute material in alveolar ridge preservation for maxillary removable immediate dentures: A randomized controlled trial.

STATEMENT OF PROBLEM: Maxillary bone resorption after multiple extractions can jeopardize the success of an immediate denture, but whether bone volume preservation techniques are effective is unclear. PURPOSE: The purpose of this randomized controlled trial was to evaluate the efficacy of socket grafting with a xenogenic bone substitute in participants receiving maxillary immediate removable complete dentures in terms of bone volume preservation (height and width of the bone ridge). MATERIAL AND METHODS: The study was a single-blinded, randomized controlled clinical trial with 2 balanced parallel arms. Thirty-six participants who had Kennedy Class I edentulous posterior areas bilaterally for at least 3 months and required maxillary immediate removable complete dentures were enrolled. Duplicates of the removable complete denture were made and converted into radiographic and surgical guides. Participants allocated to the test group received deproteinized bovine bone mineral blended with 10% porcine collagen (DBBM-C) in the extraction sockets, and participants in the control group received no grafting material. With a radiographic guide in place, cone beam computed tomography scans were made 10 days after tooth extraction, when the immediate removable complete denture was delivered (D10, baseline), after 3 months (D90), and after 1 year (D365). The scans were superimposed, and measurements were made on the cross-sectional plane of each extraction site. The influence of various prognosis factors associated with bone volume preservation, including the location of tooth extraction, smoking habits, periodontal disease, and operator team, were analyzed. RESULTS: Of 36 participants, 3 were lost to follow-up. The mean ±standard deviation loss of height of the buccal crest was 1.2 ±1.8 mm in the control group and 0.3 ±1.2 mm in the test group after 3 months of healing (P<.001) and 2.1 ±2.0 mm in the control group and 0.7 ±1.4 mm in the test group after 1 year of follow-up (P<.001). Mean ±standard deviation horizontal ridge width change was 1.3 ±1.4 mm in the control group and 0.5 ±0.8 mm in the test group after 3 months (P<.001) and 2.2 ±1.4 mm in the control group and 0.9 ±1.1 mm in the test group after 1 year of follow-up (P<.001). None of the other prognostic factors had a significant effect at either time period. CONCLUSIONS: Grafting DBBM-C into the extraction socket after removing anterior teeth for immediate removable denture therapy resulted in significantly less vertical buccal crest and horizontal ridge resorption as compared with spontaneous socket healing after 1 year of follow-up. This procedure may be useful for preserving bone, especially when a fixed implant-supported prosthesis is planned.

Foxp3+ T cells induce perforin-dependent dendritic cell death in tumor-draining lymph nodes.

Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established ovalbumin (OVA)-expressing MCA101 tumors required both the adoptive transfer of OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, Foxp3(+) T cell neutralization induced a marked arrest in the migration of OTI T cells, increased numbers of dendritic cells (DCs), and enhanced OTI T cell priming. Using an in vitro cytotoxic assay and two-photon live microscopy after adoptive transfer of DCs, we demonstrated that Foxp3(+) T cells induced the death of DCs in tumor-draining lymph nodes, but not in the absence of tumor. DC death correlated with Foxp3(+) T cell-DC contacts, and it was tumor-antigen and perforin dependent. We conclude that Foxp3(+) T cell-dependent DC death in tumor-draining lymph nodes limits the onset of CD8(+) T cell responses.

European survey on criteria of aesthetics for periodontal evaluation: The ESCAPE study.

OBJECTIVE: The ESCAPE multicentre survey was designed to (a) compare the agreement of three relevant aesthetic scoring systems among different centres, and (b) evaluate the reproducibility of each question of the questionnaires. MATERIALS AND METHODS: EFP centres (n = 14) were involved in an e-survey. Forty-two participants (28 teachers, 14 postgraduate students) were asked to score the one-year aesthetic outcomes of photographs using the Before-After Scoring System (BASS), the Pink Esthetic Score (PES) and the Root coverage Esthetic Score (RES). Mean values of kappa statistics performed on each question were provided to resume global agreement of each method. RESULTS: Between teachers, a difference of kappa ≥ 0.41 (p = .01) was found for BASS (75%) and PES (57%). Similarly, RES (84%) and PES (57%) were different (p < .001). No difference was found between BASS (75%) and RES (84%). No difference was found between students, whatever the scoring system. Questions of each scoring system showed differences in their reproducibility. CONCLUSIONS: The outcomes of this study indicate that BASS and RES scoring systems are reproducible tools to evaluate aesthetic after root coverage therapies between different centres. Among the various variables, lack of scar, degree of root coverage, colour match and gingival margin that follows the CEJ show the best reliability.

Importance of pre-analytical steps for transcriptome and RT-qPCR analyses in the context of the phase II randomised multicentre trial REMAGUS02 of neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Identification of predictive markers of response to treatment is a major objective in breast cancer. A major problem in clinical sampling is the variability of RNA templates, requiring accurate management of tumour material and subsequent analyses for future translation in clinical practice. Our aim was to establish the feasibility and reliability of high throughput RNA analysis in a prospective trial. METHODS: This study was conducted on RNA from initial biopsies, in a prospective trial of neoadjuvant chemotherapy in 327 patients with inoperable breast cancer. Four independent centres included patients and samples. Human U133 GeneChips plus 2.0 arrays for transcriptome analysis and quantitative RT-qPCR of 45 target genes and 6 reference genes were analysed on total RNA. RESULTS: Thirty seven samples were excluded because i) they contained less than 30% malignant cells, or ii) they provided RNA Integrity Number (RIN) of poor quality. Among the 290 remaining cases, taking into account strict quality control criteria initially defined to ensure good quality of sampling, 78% and 82% samples were eligible for transcriptome and RT-qPCR analyses, respectively. For RT-qPCR, efficiency was corrected by using standard curves for each gene and each plate. It was greater than 90% for all genes. Clustering analysis highlighted relevant breast cancer phenotypes for both techniques (ER+, PR+, HER2+, triple negative). Interestingly, clustering on trancriptome data also demonstrated a "centre effect", probably due to the sampling or extraction methods used in on of the centres. Conversely, the calibration of RT-qPCR analysis led to the centre effect withdrawing, allowing multicentre analysis of gene transcripts with high accuracy. CONCLUSIONS: Our data showed that strict quality criteria for RNA integrity assessment and well calibrated and standardized RT-qPCR allows multicentre analysis of genes transcripts with high accuracy in the clinical context. More stringent criteria are needed for transcriptome analysis for clinical applications.

Power estimation of tests in log-linear non-uniform association models for ordinal agreement.

BACKGROUND: Log-linear association models have been extensively used to investigate the pattern of agreement between ordinal ratings. In 2007, log-linear non-uniform association models were introduced to estimate, from a cross-classification of two independent raters using an ordinal scale, varying degrees of distinguishability between distant and adjacent categories of the scale. METHODS: In this paper, a simple method based on simulations was proposed to estimate the power of non-uniform association models to detect heterogeneities across distinguishabilities between adjacent categories of an ordinal scale, illustrating some possible scale defects. RESULTS: Different scenarios of distinguishability patterns were investigated, as well as different scenarios of marginal heterogeneity within rater. For sample size of N = 50, the probabilities of detecting heterogeneities within the tables are lower than .80, whatever the number of categories. In additition, even for large samples, marginal heterogeneities within raters led to a decrease in power estimates. CONCLUSION: This paper provided some issues about how many objects had to be classified by two independent observers (or by the same observer at two different times) to be able to detect a given scale structure defect. Our results also highlighted the importance of marginal homogeneity within raters, to ensure optimal power when using non-uniform association models.

A comparison of methods of aesthetic assessment in root coverage procedures.

AIM: To evaluate the reliability of professional qualitative scoring methods used in evaluating aesthetic results after root coverage therapy and to evaluate the relationship between subjective and objective measurements. MATERIAL AND METHODS: A review panel of seven professional and non-professional, trained and untrained observers used photographic records to assess the overall cosmetic results of 162 root coverage surgical procedures in 133 patients (mean follow-up 17.51+/-17.37 months). Two different methods were used. In the before-after panel scoring system, observers evaluated the difference between preoperative and postoperative views, whereas in the random panel scoring system, observers rated each photograph independently. RESULTS: For both methods, intrarater agreement ranged from substantial to almost perfect for the periodontists. The best interrater agreement was found for trained periodontists using the five-point ordinal scale of the before-after panel scoring system (kappa=0.68). Neither root coverage percentage nor gingival augmentation was correlated to cosmetic assessment. CONCLUSIONS: The before-after scoring system is an acceptable and reliable method for professional cosmetic assessment of root coverage therapy. The overall cosmetic evaluation does not appear to be related to the percentage of root coverage.

High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients.

A high percentage of uveal melanoma patients develop metastatic tumors predominantly in the liver. We studied the molecular profiles derived from gene expression microarrays and comparative genomic hybridization microarrays, to identify genes associated with metastasis in this aggressive cancer. We compared 28 uveal melanomas from patients who developed liver metastases within three years of enucleation with 35 tumors from patients without metastases or who developed metastases more than 3 years after enucleation. Protein tyrosine phosphatase type IV A member 3 (PTP4A3/PRL3), was identified as a strong predictor of metastasis occurrence. We demonstrated that the differential expression of this gene, which maps to 8q24.3, was not merely a consequence of 8q chromosome overrepresentation. PTP4A3 overexpression in uveal melanoma cell lines significantly increased cell migration and invasiveness in vivo, suggesting a direct role for this protein in metastasis. Our findings suggest that PTP4A3 or its cellular substrates could constitute attractive therapeutic targets to treat metastatic uveal melanomas.

Relationship between sponsorship and failure rate of dental implants: a systematic approach.

BACKGROUND: The number of dental implant treatments increases annually. Dental implants are manufactured by competing companies. Systematic reviews and meta-analysis have shown a clear association between pharmaceutical industry funding of clinical trials and pro-industry results. So far, the impact of industry sponsorship on the outcomes and conclusions of dental implant clinical trials has never been explored. The aim of the present study was to examine financial sponsorship of dental implant trials, and to evaluate whether research funding sources may affect the annual failure rate. METHODS AND FINDINGS: A systematic approach was used to identify systematic reviews published between January 1993 and December 2008 that specifically deal with the length of survival of dental implants. Primary articles were extracted from these reviews. The failure rate of the dental implants included in the trials was calculated. Data on publication year, Impact Factor, prosthetic design, periodontal status reporting, number of dental implants included in the trials, methodological quality of the studies, presence of a statistical advisor, and financial sponsorship were extracted by two independent reviewers (kappa = 0.90; CI(95%) [0.77-1.00]). Univariate quasi-Poisson regression models and multivariate analysis were used to identify variables that were significantly associated with failure rates. Five systematic reviews were identified from which 41 analyzable trials were extracted. The mean annual failure rate estimate was 1.09%.(CI(95%) [0.84-1.42]). The funding source was not reported in 63% of the trials (26/41). Sixty-six percent of the trials were considered as having a risk of bias (27/41). Given study age, both industry associated (OR = 0.21; CI(95%) [0.12-0.38]) and unknown funding source trials (OR = 0.33; (CI(95%) [0.21-0.51]) had a lower annual failure rates compared with non-industry associated trials. A conflict of interest statement was disclosed in 2 trials. CONCLUSIONS: When controlling for other factors, the probability of annual failure for industry associated trials is significantly lower compared with non-industry associated trials. This bias may have significant implications on tooth extraction decision making, research on tooth preservation, and governmental health care policies.

Quality assessment of ordinal scale reproducibility: log-linear models provided useful information on scale structure.

OBJECTIVE: In health research, ordinal scales are extensively used. Reproducibility of ratings using these scales is important to assess their quality. This study aimed to compare two methods analyzing reproducibility: weighted Kappa statistic and log-linear models. STUDY DESIGN AND SETTING: Contributions of each method to the reproducibility assessment of ratings using ordinal scales were compared using intra- and interobserver data chosen in three different fields: Crow's feet scale in dermatology, dysplasia scale in oncology, updated Sydney scale in gastroenterology. RESULTS: Both methods provided an agreement level. In addition, log-linear models allowed evaluation of the structure of agreement. For the Crow's feet scale, both methods gave equivalent high agreement levels. For the dysplasia scale, log-linear models highlighted scale defects and Kappa statistic showed a moderate agreement. For the updated Sydney scale, log-linear models underlined a null distinguishability between two adjacent categories, whereas Kappa statistic gave a high global agreement level. CONCLUSION: Methods that can investigate level and structure of agreement between ordinal ratings are valuable tools, since they may highlight heterogeneities within the scales structure and suggest modifications to improve their reproducibility.

Log-linear non-uniform association models for agreement between two ratings on an ordinal scale.

In agreement studies, when objects are rated independently by two raters (or twice by the same rater), an association between their ratings on two categories arises, reflecting the distinguishability of these two categories for these raters. When ratings are performed on an ordinal scale, this association between ratings on two categories increases when the distance between these categories increases on the ordinal scale. Goodman's log-linear models derived for the analysis of agreement between two raters on an ordinal scale assume that distinguishabilities between adjacent categories are either constant, or a priori fixed. Log-non-linear models that allow variations of the distinguishabilities between adjacent categories along the scale, may lead to difficulties in parameter estimation. This paper describes a new class of log-linear non-uniform association models. These models extend the log-linear uniform association model by allowing variations of distinguishability between adjacent categories (along the scale). These new models are used to analyse ordinal agreement between dermatologists when assessing the severity of different cutaneous signs of ageing on women faces.