High BRAF variant allele frequencies are associated with distinct pathological features and responsiveness to target therapy in melanoma patients.

BACKGROUND: BRAF mutant melanoma patients are commonly treated with anti-BRAF therapeutic strategies. However, many factors, including the percentage of BRAF-mutated cells, may contribute to the great variability in patient outcomes. PATIENTS AND METHODS: The BRAF variant allele frequency (VAF; defined as the percentage of mutated alleles) of primary and secondary melanoma lesions, obtained from 327 patients with different disease stages, was assessed by pyrosequencing. The BRAF mutation rate and VAF were then correlated with melanoma pathological features and patients' clinical characteristics. Kaplan-Meier curves were used to study the correlations between BRAF VAF, overall survival (OS), and progression-free survival (PFS) in a subset of 62 patients treated by anti-BRAF/anti-MEK therapy after metastatic progression. RESULTS: A highly heterogeneous BRAF VAF was identified (3%-90%). Besides being correlated with age, a higher BRAF VAF level was related to moderate lymphocytic infiltration (P = 0.017), to melanoma thickness according to Clark levels, (level V versus III, P = 0.004; level V versus IV, P = 0.04), to lymph node metastases rather than cutaneous (P = 0.04) or visceral (P = 0.03) secondary lesions. In particular, a BRAF VAF >25% was significantly associated with a favorable outcome in patients treated with the combination of anti-BRAF/anti-MEK drug (OS P = 0.04; PFS P = 0.019), retaining a significant value as an independent factor for the OS and the PFS in the multivariate analysis (P = 0.014 and P = 0.003, respectively). CONCLUSION: These results definitively support the role of the BRAF VAF as a potential prognostic and predictive biomarker in melanoma patients in the context of BRAF inhibition.

Could different TMJ disc positions observed in MRI cause different sounds? Analysis on a group of subjects with ADD with reduction: a pilot study.

AIMS: Magnetic resonance imaging (MRI) is the method of choice for examining soft-tissue pathology of the temporomandibular joint (TMJ). MRI shows a high spatial resolution with accuracy for the identification of internal derangement. Tasaki developed a classification system for disc displacement in the TMJ, identifying eight different types of disc displacements in addition to the superior disc position. This study aims to test the ability of electrosonography (ESG) in discriminating different kinds of disc displacement according to the disc position criteria proposed, comparing the ESG results with those obtained by MRI. METHODOLOGY: Twenty-seven patients were selected from an initial group of 50 patients with articular disc displacement, selected by means of clinical examinations, according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and who had both MRI and ESG studies performed. For each patient and for each peak in ESG, both in the opening and closing movements, three different parts of the sound were analyzed. The frequency (Hz) and the mean amplitude (µV) of the sounds were calculated in the three analyzed windows. Afterwards, gathering the data for the Tasaki's classes and dividing opening and closing sounds, the number of peaks was calculated, as well as average and standard deviations for both the Hz and µV. RESULTS: The peak frequency shows significant differences between different disc positions during the first and second third of the opening phase and during the first third of the closing phase. The peak amplitude shows significant differences between different disc positions during all of the opening and closing phases. CONCLUSIONS: Although limited by sample size, the present study shows the presence of different sounds with different Hzs and µVs associated with different disc positions that were recorded with ESG.

Detection of sleep bruxism: comparison between an electromyographic and electrocardiographic portable holter and polysomnography.

Recent polysomnographic (PSG) studies showed that the sleep bruxism (SB) event is preceded by a sudden shift in autonomic cardiac activity. Therefore, heart rate could be the simplest-to-record parameter for use in addition to portable home EMG monitoring to improve the accuracy in automatic detection of SB events. The aim of the study was to compare the detection of SB episodes by combined surface electromyography and heart rate (HR) recorded by a compact portable device (Bruxoff(®) ), with the scoring of SB episodes by a PSG recording. Twenty-five subjects (14 'probable' bruxers and 11 non-bruxers) were selected for the study. Each subject underwent the Bruxoff and the PSG recordings during the same night. Rhythmic masseter muscle activities (RMMAs) were scored according to published criteria. Correlation coefficients and the Bland-Altman plots were calculated to measure the correlation and agreement between the two methods. Results showed a high correlation (Pearson's r = 0·95, P < 0·0001) and a high agreement (bias = 0·05) between Bruxoff and the PSG. Furthermore, the receiver operating characteristic curve analysis showed a high sensitivity and specificity of the portable device (92·3% and 91·6%, respectively) when the cut-off was set at 4 SB episodes per hour according to published criteria. The Bruxoff device showed a good diagnostic accuracy to differentiate RMMA from other oromotor activities. These findings are important in the light of the need for simple and reliable portable devices for the diagnosis of SB both in the clinical and research settings.

Deep bite: a case report with chewing pattern and electromyographic activity before and after therapy with function generating bite.

AIM: The purpose of this case report is the concurrent evaluation of the masticatory pattern and the electromyographic activity, recorded during mastication, before and after therapy of deep bite malocclusion. CASE REPORT: An 11-year-old boy, affected by deep bite (overbite = 5 mm) was treated by the use of a functional appliance (Function Generating Bite for Deep bite correction = FGB-D). Mandibular movements during mastication of a soft and a hard bolus were recorded both before and 10 months after correction of the malocclusion. Electromyographic activity (EMG) of the masseters and anterior temporalis muscles were recorded at the same time. Chewing cycles and EMG activity were recorded with the K7 I kinesiograph (Myotronics Inc., Seattle, WA-USA). Before therapy a higher EMG activity was recorded for both masseters and anterior temporalis muscles in comparison with the results after therapy. RESULTS: The results showed a great decrease of the EMG activity of masseter and anterior temporalis muscles. Moreover, the height and width of the chewing cycles in the frontal plane increased after therapy. CONCLUSION: The functional improvement showed after therapy with FGB-D showed that the functional appliance is able to correct the dental malocclusion and the masticatory function. The orthodontic treatment should consider not only the repositioning of teeth within the dental arches but also the effects on function, especially when the malocclusion involves the muscular and skeletal structures.

Diagnostic concordance between MRI and electrovibratography of the temporomandibular joint of subjects with disc displacement disorders.

OBJECTIVES: The aim of this study is to evaluate the diagnostic concordance of MRI and electrovibratography (EVG) of the temporomandibular joint (TMJ) in the diagnosis of articular disc displacement with reduction (ADDwR) and articular disc displacement without reduction (ADDw/oR). METHODS: 50 patients (12 males, 38 females; mean age 37.46 ± 15.64 years) with a hypothesis of disc displacement were selected. For each patient an MRI of the TMJ was performed. MRIs were evaluated sorting the 100 TMJs by kind of pathology (no pathology, ADDwR, ADDw/oR, and joint hypermobility). Afterwards, the patients had an EVG exam. The EVG exams were performed with vibration transducers over each TMJ, enabling simultaneous, bilateral recording of vibrations emanating from joint sounds during the opening and closing movements. The presence of a sound peak was compared with the MRI diagnosis of ADDwR, while a multipeak aspect was compared with ADDw/oR diagnosis using Cohen's kappa test. RESULTS: The presence of a peak-shaped track has high specificity for ADDwR (90.27%). The Cohen's kappa calculated for the ADDwR was 0.5615 (good-moderate). The presence of a multipeak-shaped track has low specificity (65.22%) and sensitivity (70.42%). The Cohen's kappa calculated for the ADDw/oR was 0.2992 (poor). CONCLUSIONS: The present study recommends the use of EVG to support the clinical diagnosis of a disc displacement with reduction when MRI is not available or when subjects cannot be investigated by MRI.

Reproducibility of surface EMG variables in isometric sub-maximal contractions of jaw elevator muscles.

The aims of this study were: (1) to develop and assess reproducibility of a new method for measuring masticatory force in the intercuspal position; (2) to test the reproducibility of surface EMG signal amplitude and spectral variables in constant force contractions of jaw elevator muscles and its dependency on inter-electrode distance. The study was performed on the masseter and temporalis anterior muscles of both sides of nine healthy volunteers. An intraoral compressive-force sensor was used to measure maximal voluntary contraction forces in the intercuspal position and to provide a visual feedback on sub-maximal forces to the subject. Three experimental sessions were performed in three days. In each session, three isometric contractions at 80% of the maximal force were sustained by the subjects for 30s. The intra-class correlation coefficient (ICC) of the maximal force measure was 71.9%. ICC of average rectified value and mean power spectral frequency of the EMG signal increased with inter-electrode distance, with values larger than 70% with 30 mm inter-electrode distance. It was concluded that surface EMG variables measured in isometric contractions of the jaw elevator muscles with the proposed force recording system show good reproducibility for clinical applications when a 30 mm inter-electrode distance is considered.

Treatment of mandibular class II furcation defects by the use of amelogenins and autologous bone. Two case reports.

The aim of this preliminary study was to evaluate the clinical effectiveness of the association of amelogenins and autologous bone graft in the management of mandibular class II furcation defects. This randomized case-controlled study was conducted on 2 patients who presented 2 contralateral mandibular buccal class II furcation lesions. One defect was treated by amelogenins and autologous bone graft (test site) and the other one by open flap debridement (control site). At baseline and at 12 months postoperatively, the full-mouth plaque score (FMPS) and the full-mouth bleeding score (FMBS), the probing depth (PD), the clinical attachment level (CAL) and the recession (REC) were recorded and a periapical radiograph of the selected area was taken. In addition, at 12 months a surgical re-entry was performed. Test sites had a greater horizontal PD reduction and radiographic bone filling compared to control sites. None of the treated sites achieved complete furcation closure. At the time of re-entry, furcations treated by amelogenins were partially filled by newly formed not soundable hard tissue, while furcations treated by conventional flap surgery were filled by epithelial and connective tissue. These findings suggest that the treatment of mandibular class II furcations by amelogenins and autologous bone graft may result in a significant clinical improvement. Further long-term studies conducted on a larger sample size are therefore needed to confirm our results.

Coronally advanced flap with or without enamel matrix derivative for root coverage: a 2-year study.

AIM: The purpose of this study was to assess the ability of enamel matrix derivative (EMD) to improve root coverage with a coronally advanced flap (CAF) during a 2-year follow-up. METHODS: Fifteen patients each with two single and similar bilateral Miller Class I or II gingival recessions (30 recessions) were selected. Each recession was randomly assigned to the test group (CAF+EMD) or the control group (CAF only). Clinical parameters recorded at baseline and at 6, 12 and 24 months were recession depth (R), recession width (WR), probing depth (PD), clinical attachment level (CAL) and keratinized tissue (KT). RESULTS: Reduction of R resulted in a significant CAL gain in both groups, whereas PD was not altered. In the test group, R decreased from 4.07 mm (SD+/-0.59) at baseline to 0.47 mm (SD+/-0.74) at 24 months, corresponding to a mean root coverage (MRC) of 90.67%, whereas in the control group R shrank from 4.13 mm (SD+/-0.74) at baseline to 0.60 mm (SD+/-0.83) at 24 months (MRC=86.67%). Complete root coverage was achieved at 24 months in 73.33% and 60% of the two groups. A significant KT increase was observed in both groups. CONCLUSIONS: Root coverage outcomes were similar in both groups and no statistically significant differences were found at all between them. Hence, the additional use of EMD to CAF is not justified for clinical benefits of root coverage, but as an attempt of achieving periodontal regeneration rather than repair.

Electromyographic evaluation of neuromuscular co-ordination during chewing in a subject with organic occlusion.

The neuromuscular co-ordination of the anterior masseter and temporal muscles during chewing has been studied. The subject analysed was 24 years old female with organic occlusion, molar and canine class 1, with 2 mm overbite and overjet, frontal disocclusion and canine protection, with no cranio-mandibular disorders. Masticatory cycles and electromyographic activity were recorded with a K6 I kinesiograph (Myotronics Inc., Seattle, WA, USA). The chewing cycles were recorded with a soft bolus and a hard bolus, on 3 consecutive days. Electromyographic analysis during masticatory cycles showed that electromyographic activity was higher in the masseter muscle homolateral to the chewing side than in the contralateral muscle, whereas the anterior temporal muscles achieved similar voltages. When chewing the hard bolus, versus the soft bolus, activity in the contralateral masseter muscle increased to a greater extent than in the homolateral masseter muscle. The results were analogous at all 3 recordings. When chewing, the subject showed good muscle co-ordination, which was constant over the 3 recordings made on 3 consecutive days. Increased activity of the contralateral masseter muscle when chewing the hard versus the soft bolus indicates the stomatognathic system's capability to adapt to load and its neuromuscular equilibrium.

Non-invasive assessment of motor unit anatomy in jaw-elevator muscles.

The estimation of fibre length in jaw-elevator muscles is important for modelling studies and clinical applications. The objective of this study was to identify, from multi-channel surface EMG recordings, the main innervation zone(s) of the superficial masseter and anterior temporalis muscles, and to estimate the fibre length of these muscles. Surface EMG signals were collected from 13 subjects with a 16-electrode linear array. The innervation zones of the masseter and anterior temporalis were identified and their variability intra- and inter-subject outlined. More than one main innervation zone location was identified in the masseter of all subjects and in the temporalis anterior of 12 subjects. Average estimated fibre lengths, for the right (left) side, were (mean+/-SD) 27.3+/-2.4 mm (27.0+/-1.7 mm) and 25.9+/-2.3 mm (26.6+/-1.6 mm), for the superficial masseter and temporalis anterior muscle, respectively. The range of innervation zone locations was up to approximately 50% of the fibre length, both within and between subjects. Fibre length estimates well matched with published data on cadavers. It was concluded that multi-channel surface EMG provides important and reliable information on the anatomy of single motor units in jaw-elevator muscles.

Treatment of wide, shallow, and predominantly 1-wall intrabony defects with a bioabsorbable membrane: a randomized controlled clinical trial.

BACKGROUND: The regenerative therapy of non-contained intrabony defects achieves better results when bioabsorbable membranes are combined with a filling material. The purpose of the present study was to analyze clinical and radiographic effectiveness of a space-making bioabsorbable membrane in the treatment of wide and shallow intrabony defects characterized by a relevant 1-wall component. METHODS: Eighteen pairs of angular bone defects were selected in 18 healthy, non-smoking patients (age range 30 to 66 years). Prior to the surgical phase, patients were enrolled in a strict periodontal program including oral hygiene instructions and scaling and root planing (presurgical full-mouth plaque score <10%). Using a split-mouth design, 18 sites were randomly assigned to receive guided tissue regeneration (GTR) using a bioabsorbable membrane (test group) and 18 to receive open flap debridement alone (control group). Clinical treatment outcome was evaluated 12 months postoperatively for changes in probing depth (PD), clinical attachment level (CAL), and position of gingival margin (REC) and radiographically for bone changes. RESULTS: Open flap debridement and GTR yielded statistically significant (P<0.0001) PD reduction (2.39+/- 0.92 mm and 3.44+/- 0.78 mm), CAL gain (1.50+/- 0.99 mm and 2.89 +/- 0.90 mm), increased REC (-0.89 +/- 0.58 mm and -0.56 +/- 0.92 mm) and bone fill (1.05+/- 0.94 mm and 2.13+/- 1.21 mm) when 12-month data were compared to baseline. The differences between test and control groups were statistically significant for all parameters (P<0.007) except for REC (P=0.25). CONCLUSION: The use of this bioabsorbable membrane would seem to be effective in the treatment of intrabony defects with unfavorable architecture without the use of filling materials.

Non-surgical periodontal therapy of cyclosporin A gingival overgrowth in organ transplant patients. Clinical results at 12 months.

AIM: The aim of the present study was to evaluate the clinical effects of non-surgical and supportive periodontal treatment on cyclosporin A-induced (CsA) gingival overgrowth (GO) in a group of transplant patients. METHODS: Thirty patients received etiological periodontal treatment and were placed in a -two-monthly recall program for 12 months. Plaque index, bleeding index, probing depth, degree of GO using the Seymour index (hypertrophy index, HI) and distance between the mucogingival junction and the base and the apex of each interdental papilla were recorded at baseline and repeated 12 months after treatment. RESULTS: At baseline, 22 patients had HI values >30% and were considered as ''responders''. A total of 376 gingival units (72.31%) in the anterior segments and 376 (54.97%) in the posterior ones presented GO with a mean HI value of 2.22 +/- 1.95 and 1.24 +/- 1.57, respectively. The etiological treatment resulted in a statistically significant improvement of all parameters assessed (P<0.0001). All patients had a decrease in the number of affected sites (mean HI values of 0.42 +/- 0.77 and 0.39 +/- 0.85 in the anterior and posterior segments) and none had HI values >30% and any gingival unit with score of 5 at the end of the observation period. CONCLUSIONS: Detailed instructions and intense motivation to oral home hygiene measures, inserted in an etiological treatment and a two-monthly maintenance therapy, appear to be effective in controlling the GO and in maintaining clinical improvements for prolonged time period.

Debridement and local application of tetracycline in the management of persistent periodontitis. Clinical and microbiological results after 12 months.

AIM: The purpose of this study was to evaluate the clinical and microbiological efficacy of local delivery of tetracycline in persistent periodontal lesions after topical therapy. METHODS: A total of 44 bilateral pockets 4-5 mm deep and bleeding on probing were selected in 11 non-smokers patients, 22 treated by scaling and root planing plus tetracycline fibres (test sites) and 22 with scaling and root planing alone (control sites) in a split-mouth design. Bleeding on probing, probing depth and clinical attachment level were recorded at baseline, 6 and 12 months postoperatively. The prevalence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus and Treponema denticola was monitored by PCR at baseline, fibres removal, 6 and 12 months following treatment. RESULTS: The improvements in clinical parameters were greater in the tetracycline than in the control group. The reduction of bleeding on probing scores was 86.4% and 40.9%, the decrease of probing depth was 2.25 mm and 1.19 mm and the gain of clinical attachment level was 2.04 mm and 0.64 mm for test and control groups, respectively, over the 12-month period. The adjunctive use of tetracycline consistently resulted in a lower percentages of sites with detectable levels of A. actinomycetemcomitans, P. intermedia and P. gingivalis, while no differences were detected between treatments in the prevalence of T. denticola and B. forsythus. The pathogens could be eliminated from 3 periodontal pockets by debridement alone and from 12 sites by tetracycline at 12 months. CONCLUSIONS: Tetracycline local delivery gave the greatest advantage in the long-term treatment of periodontal persistent lesions.

Perceptibility of condylar displacement through transcranial radiographs and split-cast technique on dry skull.

The authors compared the limit of perceptibility of transcranial radiographs and of the split-cast technique in detecting differences in condylar position. The study was carried out on two dried human skulls. The results indicated the split-cast method was superior to the radiographic method as it allowed differences in condylar position of 0.2 mm, both in sagittal and frontal plane, to be detected. The limit of perceptibility of transcranial radiographs for position differences in the sagittal plane was 0.6 mm for naked-eye examination and 0.2 mm when using the subtraction method. Differences in condylar position even as large as 0.6 mm in the frontal plane could not clearly be seen by naked-eye examination, and with the subtraction technique only if they were of at least 0.4 mm.

[AIDS and pedodontics: the real risk and its prevention]. / AIDS e pedodonzia: rischio reale e sua prevenzione.

The daily increase in carriers of the AIDS virus (150,000 is the latest estimate for Italy) means that the dentist must pay the utmost attention in selecting cases at risk and in defending himself from the possibility of contagion. Albeit to a lesser extent, the pedodontist is also involved in this problem. Here situations in which the risk of contagion is greatest because of the patient's social position or associated pathologies and the difficulty of the operation required are reported and some indications are offered to guide the pedodontist's professional behaviour.

[Professional, criminal and civil responsibility and the legal medical aspects of the performance of the dentist practicing local anesthesia and tooth extractions]. / Considerazioni sulla responsabilità professionale, penale, civile ed aspetti medico-legali sull'operato dell'odontostomatologo nella pratica dell'anestesia locale e delle estrazioni dentarie.

The paper affirms that the dentist can come up against severe complications while exercising his profession which expose him to charges outlined by the Penal and Civil Codes. The circumstances in which the operator's responsibility can be questioned during the use of local anesthesia and extraction are discussed.

[334 cases of salivary gland neoplasms seen at the Dentistry and Otorhinolaryngology Clinics of the University of Turin. II]. / Considerazioni su 334 casi di neoplasie di ghiandole salivari raccolti presso la Clinica Odontostomatologica e Otorinolaringoiatrica dell'Università di Torino. Parte II.

Three hundred and thirty-four cases of salivary gland neoplasms are reported which were diagnosed by the Departments of Dentistry and Otolaryngology of the University of Turin. Data referring to patients under observation during the same period are compared. It is stressed that in order to obtain a statistically valid comparison of salivary gland neoplasms, the source of and chronological period relating to the sample group must be taken into consideration given the different statistical clinical methods adopted over the years by the two departments in question. The present study completes earlier research carried out by the same authors using this data.

[Macroglossia. Considerations on a case load of 16 patients]. / Macroglossia. Considerazioni su una casistica di sedici pazienti.

The Authors have examined sixteen cases of macroglossia and after hinting at the various causes they dwell upon clinic and therapeutic problems presented by patients. From the analysis of individual cases it results that muscular idiopathic hypertrophy is the most recurrent cause of macroglossia. It is furthermore emphasized the relation between macroglossia and occlusal disharmony. The kinds of therapy used and compared are two: surgical and orthodontic.

[392 cases of neoplasms of the salivary glands seen at the Odontostomatologic and Otorhinolaryngologic Clinic of Turin University. I]. / Considerazioni su 392 casi di neoplasie di ghiandole salivari raccolte presso la Clinica Odontostomatologica e Otorinolaringoiatrica dell'Università di Torino. Parte I.

Three-hundred-ninety-two cases of salivary gland cancer observed at Turin University Dental and Ear, Nose and Throat Clinics have been examined. Statistical analysis of the age and sex of patients shows the importance of selecting the statistical population and of its origin for the purpose of reliable statistical study, examining the whole set and its structural breakdown in the two Clinics.