Tooth Wear Evaluation System (TWES) 2.0-Reliability of diagnosis with and without computer-assisted evaluation.

BACKGROUND: Tooth wear is a multifactorial process, leading to the loss of dental hard tissues. Therefore, it is important to detect the level of tooth wear at an early stage, so monitoring can be initiated. The Tooth Wear Evaluation System (TWES) enables such a multistage diagnosis of tooth wear. The further developed TWES 2.0 contains a complete taxonomy of tooth wear, but its reliability has not yet been validated. OBJECTIVES: The aim of the study was to examine in a randomised controlled trial (RCT) whether diagnoses made based on the TWES 2.0 are reproducible and whether this reproducibility is also achieved with computer-assisted diagnostics. METHODS: 44 dental students received extensive training in TWES 2.0 assessment and taxonomy. The students each evaluated at least 10 (of the present 14) anonymised patient cases using gypsum models and high-resolution intra-oral photographs according to TWES 2.0. One half initially evaluated on paper; the other half used dedicated software (CMDfact / CMDbrux). After half of the patient cases (5), the evaluation methods were switched (AB/BA crossover design). The diagnoses were then evaluated for agreement with the predefined sample solution. RESULTS: Evaluation of agreement with the sample solution according to Cohen's kappa indicated a value of 0.46 for manual (traditional) evaluation; and 0.44 for computer-assisted evaluation. Evaluation of agreement between examiners was 0.38 for manual and 0.48 for computer-assisted evaluation (Fleiss' kappa). CONCLUSION: The results of this study proved that the taxonomy of the TWES 2.0 has acceptable reliability and can thus be used by dentists. Accordingly, the system can be learned quickly even by untrained practitioners. Comparable results are achieved with computer-assisted evaluation.

Quality improvement of functional diagnostics in dentistry through computer-aided diagnosis: a randomized controlled trial.

Functional diagnostic examinations such as clinical functional analysis and manual structural analysis ('orthopedic tests') allow the dentist to establish a structured diagnosis. Previously, the process of correlating findings with the appropriate diagnoses was guided by human thought processes alone. The experimental diagnostic randomized controlled trial (RCT) in this study investigated whether computer-aided diagnosis (CADx) of temporomandibular disorders (TMD) offers quality advantages over traditional diagnosis (TRAD). SUBJECTS AND METHODS: Thirty-nine 5th-year dental students (examiners) at a university in Hamburg, Germany, received joint training in the diagnosis of TMD by clinical functional analysis and manual structural analysis ('orthopedic tests'). This study is based on anonymized data from 10 patients who were consecutively recruited at a specialized TMJ treatment center. The examiners were randomly allocated to two groups. Each examiner established a structured diagnosis through a traditional diagnostic method and by computer-aided diagnosis (CMDfact 4 functional diagnostics software) of five cases, each using the AB/BA crossover design. The diagnoses established by each individual examiner were then compared with the corresponding reference diagnoses (gold standard) and with those of the other examiners. RESULTS: Cohen's kappa coefficient analysis showed that median agreement with the reference diagnoses was significantly higher (P < 0.001) with computer assistance (median 0.692) than without it (0.553). Fleiss' kappa showed that the median interexaminer consistency of diagnoses was significantly higher (P < 0.001) with computer assistance (0.497) than with traditional diagnostic methods alone (0.271). Likewise, the number of false-positive and false-negative diagnoses was significantly lower with computer assistance (P < 0.001). CONCLUSIONS: This study determined that dentists who are less experienced and not specialized in dental functional diagnostics achieve a significantly better and more consistent diagnostic quality with computer assistance by means of the system used in this study. Therefore, it seems advisable to extend computer-aided diagnostics to further functional examination techniques (condylar position analysis and jaw motion analysis).

An open-label, prospective phase I/II study evaluating the immunogenicity and safety of a ras peptide vaccine plus GM-CSF in patients with non-small cell lung cancer.

Mutations of the ras gene have been reported in 20-40% of NSCLC patients. If present, they are critical for the malignant phenotype of these tumors. Therefore, targeting them by specific vaccination is a promising therapeutic approach. In a clinical trial we screened for ras mutations in patients with NSCLC. Patients with ras-positive tumors were immunized six times intradermally with a mixture of seven peptides representing the most common ras mutations. Objectives of the study were the feasibility, efficacy and safety of the vaccination. In addition, the induction of a specific immune reaction was investigated by DTH tests, and the induction of peptide-specific T cells was tested in ex vivo IFN-gamma-ELISPOT assays. Five of 18 patients had ras mutations at codon 12. Four of these patients, all with adenocarcinomas (stage I: n=3, stage IV: n=1) entered the study. The patient with stage IV disease withdrew prematurely after the third application because of disease progression associated with pulmonary embolism. Ras-specific T cells were not detected ex vivo. However, one patient developed a positive DTH reaction after the fifth vaccination that increased after the sixth vaccination. Our results are in line with earlier trials reporting ras mutations in 20-40% of NSCLC patients. Vaccination with mutated ras peptides is feasible and well tolerated. One patient revealed a positive DTH test. An ex vivo detectable T cell response was not induced in any of the patients.

Characterization of the interstitial lung and peripheral blood T cell receptor repertoire in cigarette smokers.

T lymphocytes modulate the pulmonary inflammatory response. The aim of this study was to evaluate the clonality within the interstitial lung and peripheral blood T cell receptor (TCR) repertoire in smokers. Interstitial T lymphocytes were isolated from surplus tissue of 16 patients (63 +/- 9 [+/- SD] yr old, 11 male) undergoing surgery due to lung cancer (n = 15) or emphysema. TCR clonality was assessed by PCR amplification followed by spectratyping. Nearly all TCR of interstitial lung lymphocytes showed oligoclonal bands (CD4(+) subset 13/16 patients, 81%; CD8(+) 100%) indicating a specific differentiation. Peripheral blood T lymphocytes (PBL) TCR (especially CD4(+)) had less oligoclonal bands (CD4(+) 31%, CD8(+) 88%). Likewise, more oligoclonal bands were seen in lung TCR (total of 168 bands; 37 CD4(+); 131 CD8(+)), compared with 59 bands in PBL TCR (13 CD4(+); 46 CD8(+)). Intraindividual comparison revealed a more prominent difference in TCR oligoclonality between lung and blood in CD8(+) T cells (median of difference lung minus blood 5; interquartile range 1-10; P = 0.002) compared with CD4(+) T cells (median 2, 0-3, P = 0.039). Thus, TCR oligoclonality is preferentially found in the CD8(+) T cell subset, most distinctive in the lung. These findings indicate a specific interstitial T cell differentiation in response to local stimuli.

c-kit expression in adenocarcinomas of the lung.

The tyrosine-kinase receptor c-kit (CD117) and its ligand stem cell factor are considered to be co-expressed in various solid tumors, including adenocarcinomas of the lung. The frequency of c-kit expression and its association with clinical parameters has not yet been evaluated in a larger population of lung adenocarcinomas. Therefore, tumor tissue of 95 consecutive patients with adenocarcinoma of the lung was stained using a polyclonal c-kit antibody. c-kit expression was correlated with relevant clinical parameters obtained by chart review. Positive c-kit expression in tumor tissue was observed in 61 of 95 patients (64%). Univariate analysis showed a significant effect of T (p = 0.003), N (p = 0.001) and M stage (p < 0.001) as well as of performance status (p = 0.001), surgical resection (p < 0.001), and LDH serum levels (p = 0.016) on survival. In contrast, c-kit protein expression was non- significant (p = 0.913). However, multivariate Cox regression with the influential parameters revealed a significant effect of c-kit expression on survival. Forward stepwise selection showed a 1.77-fold increased risk to die (hazard ratio, HR; 95% confidence interval, CI: 1.00-3.14, p = 0.047) for patients with c-kit-positive tumors. Similar data for c-kit expression were obtained by backward stepwise selection (HR: 1.78; 95% CI: 1.00-3.16; p = 0.044). In conclusion, the receptor tyrosine kinase c-kit is frequently expressed in adenocarcinomas of the lung and has a relevant effect on patient survival. The results of this study support clinical trials targeting the c-kit receptor with specific c-kit inhibitors (e.g. imatinib).