Dimitrios Konstantonis

Extraction decision and identification of treatment predictors in Class I malocclusions

BackgroundThe extraction rate in orthodontics varies throughout the years. While the extraction decision is easily made or excluded in clear-cut cases, it still remains controversial what makes an orthodontist decide to extract in borderline cases. The aim of this retrospective study was to identify the percentage of extraction cases in a large group of Class I malocclusions and to clarify which variables contributed most to the extraction decision.MethodsThe sample consisted of 542 randomly selected records of Class I patients treated in a university graduate program and in five private orthodontic offices. Of these patients, 331 were female and 211 male. The mean age was 14.55 (standard deviation (SD) 5.36) for the non-extraction group and 14.52 (SD 4.86) for the extraction group. The extensive series of 32 linear and angular measurements derived from the cephalometric analysis and the dental casts, along with the variables of age and gender, fueled a stepwise discriminant analysis.ResultsThe percentage of the patients treated with four first premolar extractions was 26.8%. The results showed that the variables of lower crowding, lower lip to E-plane, upper crowding, and overjet accounted most for the decision to extract at a very significant level (Sig. 0.000). The discriminant analysis assigned a classification power of 83.9% to the predictive model (p < 0.0001). Fishers linear discriminant functions provided a mathematical model, according to which any case can be classified into the adequate treatment group.ConclusionsIn a large contemporary sample of 542 Class I patients, the extraction rate was 26.8%. The most important measurements when the orthodontist decides extractions in Class I cases are lower crowding, lower lip to E-plane, upper crowding, and overjet. In clinical orthodontic practice, the findings facilitate treatment by providing evidence-based treatment predictors for Class I malocclusions.

Senescent human periodontal ligament fibroblasts after replicative exhaustion or ionizing radiation have a decreased capacity towards osteoblastic differentiation

Loss of teeth increases with age or after genotoxic treatments, like head and neck radiotherapy, due to periodontium breakdown. Periodontal ligament fibroblasts represent the main cell type in this tissue and are crucial for the maintenance of homeodynamics and for its regeneration. Here, we have studied the characteristics of human periodontal ligament fibroblasts (hPDLF) that became senescent after replicative exhaustion or after exposure to ionizing radiation, as well as their ability for osteoblastic differentiation. We found that senescent hPDLF express classical markers of senescence, as well as a catabolic phenotype, as shown by the decrease in collagen type I and the increase of MMP-2 expression. In addition, we observed a considerably decreased expression of the major transcription factor for osteoblastic differentiation, i.e. Runx2, a down-regulation which was found to be p53-dependent. In accordance to the above, senescent cells have a significantly decreased alkaline phosphatase gene expression and activity, as well as a reduced ability for osteoblastic differentiation, as found by Alizarin Red staining. Interestingly, cells from both type of senescence express similar characteristics, implying analogous functions in vivo. In conclusion, senescent hPDLF express a catabolic phenotype and express a significantly decreased ability towards an osteoblastic differentiation, thus probably affecting tissue development and integrity.

The role of cellular senescence on the cyclic stretching-mediated activation of MAPK and ALP expression and activity in human periodontal ligament fibroblasts.

Mechanical loading is considered to be a major parameter of the periodontal ligament (PDL) remodeling and differentiation. However, the molecular mechanisms that translate these forces to cellular responses are not fully elucidated. Especially, although aging affects PDL homeostasis, the role of cellular senescence on the activation of signaling pathways in periodontal ligament fibroblasts (PDLF) in response to mechanical stimulation has not been studied yet. Here, we present evidence showing that cyclic mechanical stimulation activates ERK, JNK and p38 MAPK in young (early-passage) human PDLF, in a RhoK-dependent manner. This response was found to be independent of the substratum (i.e. fibronectin or collagen) on which these cells grow. Stretching up-regulates also c-fos, a classical cellular response to mechanical deformation. Inhibition of ERK and JNK reduces, while that of p38 enhances stress-mediated c-fos expression. In addition, cyclic stretching stimulates the expression and activity of alkaline phosphatase (ALP), an early marker of osteoblastic differentiation. We have recently shown that senescent human PDLF have a significantly decreased expression of ALP, linked to an inability towards osteoblastic differentiation. Here, we found that senescent PDLF are able to respond to cyclic mechanical stretching by activating ERK, JNK and p38 MAPK, with similar kinetics compared to young cells, and by up-regulating c-fos and ALP expression and activity. However, even after stimulation, ALP levels in senescent cells are still much lower compared to the basal levels of their young counterparts, suggesting that senescence impairs the differentiation of human PDLF when subjected to cyclic mechanical deformation.

Soft tissue changes following extraction vs. nonextraction orthodontic fixed appliance treatment: a systematic review and meta‐analysis

The aim of this systematic review was to assess the effect of systematic extraction protocols during orthodontic fixed appliance treatment on the soft tissue profile of human patients. Nine databases were searched until December 2016 for controlled clinical studies including premolar extraction or nonextraction treatment. After elimination of duplicate studies, data extraction, and risk-of-bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MD) or standardized mean differences (SMD) and their 95% CIs were performed, followed by subgroup, meta-regression, and sensitivity analyses. Extraction treatment was associated with increased lower lip retraction (24 studies; 1,456 patients; MD = 1.96 mm), upper lip retraction (21 studies; 1,149 patients; MD = 1.26 mm), nasolabial angle (21 studies; 1,089 patients; MD = 4.21°), soft-tissue profile convexity (six studies; 408 patients; MD = 1.24°), and profile pleasantness (three studies; 249 patients; SMD = 0.41). Patient age, extraction protocol, and amount of upper incisor retraction during treatment were significantly associated with the observed extraction effects, while the quality of evidence was very low in all cases due to risk of bias, baseline confounding, inconsistency, and imprecision. Although tooth extractions seem to affect patient profile, existing studies are heterogenous and no consistent predictions of profile response can be made.

A cross-sectional analysis of the prevalence of tooth agenesis and structural dental anomalies in association with cleft type in non-syndromic oral cleft patients

BackgroundThe aim of this study was to investigate the prevalence of tooth agenesis, microdontia, and tooth malformation among non-syndromic oral cleft patients and their potential association with cleft type and gender.MethodsIntraoral records and radiographs of 154 patients (97 males and 57 females) were examined. The variables assessed were tooth agenesis, microdontia, dental malformations, and cleft types. The statistics included chi-square and Fisher’s exact tests as well as logistic regression to assess any mutual effects of gender and cleft type on the dental variables.ResultsTooth agenesis occurred in 50% of the sample and microdontia in 18%. Non-statistically significant odds ratios for the association of gender and cleft type with tooth agenesis were obtained. Tooth agenesis was substantially higher at the unilateral right CL + P and the bilateral CL + P in quadrant 1 and at the unilateral left CL + P and bilateral CL + P in quadrant 2. It was also higher, at the isolated cleft palate (CP) in quadrants 3 and 4. These results were attributed to teeth 22 (31.8%) and 12 (21.6%) in the maxilla and to teeth 35 (6.1%) and 45 (5.4%) in the mandible. In unilateral CL + P patients, the cleft quadrant that presented tooth agenesis was associated with the side of the cleft.ConclusionsInterdisciplinary treatment of the oral cleft patients should take into consideration the high prevalence of tooth agenesis and their association with the different cleft types. The most frequently affected teeth by cleft are by far the upper lateral incisors. Results indicate that tooth agenesis appears to be a genetically controlled anomaly related to the orofacial cleft development through various genetic links and not caused by the cleft disruptive process.

University clinic and private practice treatment outcomes in Class I extraction and nonextraction patients: A comparative study with the American Board of Orthodontics Objective Grading System.

INTRODUCTION The aim of this study was to compare treatment outcomes in university vs private practice settings with Class I patients using the American Board of Orthodontics Objective Grading System. METHODS A parent sample of 580 Class I patients treated with and without extractions of 4 first premolars was subjected to discriminant analysis to identify a borderline spectrum of 66 patients regarding the extraction modality. Of these patients, 34 were treated in private orthodontic practices, and 32 were treated in a university graduate orthodontic clinic. The treatment outcomes were evaluated using the 8 variables of the American Board of Orthodontics Objective Grading System. RESULTS The total scores ranged from 10 to 47 (mean, 25.44; SD, 9.8) for the university group and from 14 to 45 (mean, 25.94; SD, 7.7) for the private practice group. The university group achieved better scores for the variables of buccolingual inclination (mean difference, 2.28; 95% confidence interval [CI], 0.59, 3.98; P = 0.01) and marginal ridges (mean difference, 1.32; 95% CI, 0.28, 2.36; P = 0.01), and the private practice group achieved a better score for the variable of root angulation (mean difference, -0.65; 95% CI, -1.26, -0.03; P = 0.04). However, no statistically intergroup differences were found between the total American Board of Orthodontics Objective Grading System scores (mean difference, -0.5; 95% CI, -3.82, 4.82; P = 0.82). CONCLUSIONS Patients can receive similar quality of orthodontic treatment in a private practice and a university clinic. The orthodontists in the private practices were more successful in angulating the roots properly, whereas the orthodontic residents accomplished better torque control of the posterior segments and better marginal ridges.

Vertical skeletal changes after extraction and non-extraction treatment in matched class I patients identified by a discriminant analysis: cephalometric appraisal and Procrustes superimposition

BackgroundIn the long-lasting debate of extraction versus non-extraction treatment, the impact of extractions on the skeletal vertical dimension remains rather unclear. The aim of this retrospective research study was to obtain a bias-free sample of morphologically similar borderline patients treated with or without extraction of the four first premolars and to retrospectively evaluate the vertical changes that occurred.MethodsA borderline sample of 83 patients, 41 treated with four first premolar extractions and 42 treated without, was obtained by means of discriminant analysis applied to a previously investigated parent sample of 542 class I patients. The pretreatment and posttreatment cephalometric radiographs were analyzed digitally, and seven measurements were assessed for vertical skeletal changes. Also, average tracings between the two treatment groups were evaluated using the Procrustes superimposition method.ResultsThe variables of SN to Go-Gn and Y-axis showed adjusted intergroup differences of − 0.91° and − 1.11° (P = 0.04). Comparing the mean intra-group differences of all the variables simultaneously, a significant difference was found between the two treatment groups (overall P value = 0.04). In the extraction group, only the gonial angle showed a significant decrease (P = 0.01) while the overall P value evaluating the intra-group differences between pre- and posttreatment was significant (overall P value < 0.01). In the non-extraction group, the variable of N-ANS/N-Me showed a significant decrease (P = 0.02) and the overall P value evaluating the intra-group differences between pre- and posttreatment was also significant (overall P value < 0.01). Differences in treatment duration were assessed using a log-normal model and showed that extraction treatment lasted significantly longer than non-extraction treatment (P < 0.01).ConclusionsThe borderline group of patients identified by the discriminant analysis exhibited similar morphological characteristics at treatment’s onset; therefore, the posttreatment changes could safely be attributed to the choice of extraction or non-extraction treatment and not to pre-existing differences. Treatment choice had an impact on the patients’ vertical skeletal dimensions. Patients treated with four first premolar extractions showed a slight decrease in the vertical skeletal measurements, whereas non-extraction patient treatment showed a slight increase. The treatment time was also significantly higher in the extraction group.

Angiopoietin-2 Levels as Predictors of Outcome in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome

Pulmonary endothelium dysfunction is a key characteristic of ARDS. The aim of this study was to investigate endothelium-derived markers, such as angiopoietin-2 (Ang-2) and endothelial cell-specific molecule-1 (endocan), at the vascular and alveolar compartments as outcome predictors in ARDS. Fifty-three consecutive ARDS patients were studied. The primary outcome was 28-day mortality. Secondary endpoints were days of unassisted ventilation and days with organ failure other than ARDS, during the 28-day study period. Nonsurvivors presented higher lung injury scores and epithelial lining fluid (ELF) Ang-2 levels compared to survivors, with no significant differences in plasma Ang-2, endocan, and protein C concentrations between the two groups. In logistic regression analysis, ELF Ang-2 levels > 705 pg/ml were the only independent variable for 28-day mortality among the previous four. Plasma endocan values > 13 ng/pg were the only parameter predictive against days of unassisted ventilation during the 28-day study period. Finally, lung injury score > 2.25 and ELF Ang-2 levels > 705 pg/ml were associated with increased number of days with organ failure, other than ARDS. Our findings suggest that Ang-2 levels are increased in the alveolar compartment of ARDS patients, and this may be associated both with increased mortality and organ failure besides lung.

A geometric morphometric evaluation of hard and soft tissue profile changes in borderline extraction versus non-extraction patients

OBJECTIVES To evaluate the hard tissue and facial profile changes in matched extraction and non-extraction Class I patients by the use of geometric morphometrics. SUBJECTS AND METHODS From a parent sample of 542 Class I patients, previously subjected to discriminant analysis, a subsample of 68 borderline cases was obtained, 34 treated with extraction and 34 without extraction of 4 first premolars. Geometric morphometric methods (Procrustes superimposition and Principal Component Analysis) were applied on cephalometric tracings to assess the validity of the discriminant analysis in successfully identifying a morphologically homogeneous group and to evaluate inter- and intra-group skeletal and facial profile shape changes. RESULTS No significant pre-treatment shape difference between the two groups was found, thus validating the discriminant analysis. The non-extraction group showed increase in hard tissue facial height (P < 0.001), with slight lower lip retrusion and upper lip protrusion (P = 0.027). The extraction group showed retraction of the hard tissue and facial profile outline (P < 0.001). Permutation tests for post-treatment inter-group differences resulted in P = 0.054 for the soft tissue outline and P = 0.078 for the hard tissue skeletal component. CONCLUSIONS The evidence indicates that borderline cases treated with four premolar extractions will exhibit lip retrusion compared to non-extraction treatment.

Chronic thromboembolic pulmonary hypertension (CTEPH) and coagulation defects: Before and after treatment

Background: Although CTEPH is a thromboembolic disorder, the effect of the coagulation process in the pathogenesis and progression of the disease has not been fully elucidated. Aims: To assess coagulation in CTEPH and to evaluate differences after the initiation of PH-specific treatment. Methods: We studied 20 CTEPH patients (not on anticoagulation therapy at the time of tests) and 20 controls. CTEPH patients were reevaluated 1 year after therapy initiation. We performed Platelet- Function Analyzer/PFA-100 testing, ADP and epinephrine/EPI induced Light Transmission Aggregometry/LTA, Thrombelastometry/ROTEM (na-TEM) and Endogenous Thrombin Potential/ETP essay. Results: Before treatment and when compared to controls, CTEPH patients presented prolonged PFA-100 closure times (174.8sec±27.3, p=0.003), lower EPI and ADP-LTA (43.9%±11.2, p Conclusions: Our data suggest that the observed coagulation defects in CTEPH persist even after PH treatment initiation. EPI-LTA was the only index displaying significant increase after treatment.