Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project.

BACKGROUND: Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers. PATIENTS AND METHODS: Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm2. We investigated two markers of tumour proliferation: the Ki-67 index and phospho-histone H3 (PHH3) protein expression, quantified by pathologists and automatically via deep learning. Additionally, an unsupervised deep learning algorithm was trained to uncover previously unnoticed morphological features with diagnostic value. RESULTS: The accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value. CONCLUSIONS: This study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.

The In vitro Evaluation of the effect of xyliwhite, probiotic, and the conventional toothpastes on the enamel roughness and microhardness.

AIM: The aim of this study was to evaluate the effect of fluoride, Xylitol, Probiotic, and Whitening toothpastes on the permanent teeth enamel roughness and microhardness. MATERIALS AND METHODS: One hundred and twenty teeth were randomly divided into 2 groups, each group having 60 samples. G1: The group in which enamel roughness was examined (n = 60). G2: The group in which enamel microhardness was examined (n = 60). Then, these groups were randomly divided into 4 groups among themselves (n = 15). Each group was brushed using four different toothpastes for 1 week with a battery-powered toothbrush in the morning and evening for 2 min. Vicker's hardness tester was used to measure the changes in microhardness, and the profilometer was used to measure the changes in surface roughness. RESULTS: No statistically significant differences were found on surface roughness and microhardness values measured after tooth brushing process in group brushed with Colgate MaxFresh toothpaste (P > 0.01). Statistically significant decrease was observed on Vicker's hardness values measured after tooth brushing process in groups brushed with Ipana White Power Carbonate toothpaste, Xyliwhite Toothpaste Gel, and Periobiotic Probiotic Toothpaste (P < 0.01). Statistically significant increase was observed on surface roughness values in groups brushed with Ipana White Power Carbonate toothpaste, Xyliwhite Toothpaste Gel, Periobiotic Probiotic Toothpaste (P < 0.01). CONCLUSIONS: As a result, Colgate MaxFresh abrasive-free toothpaste with fluoride has no effect on permanent tooth enamel surface roughness and microhardness. Xyliwhite, Periobiotic, and Ipana White Power Carbonate-containing abrasive toothpastes led to changes negatively on permanent tooth enamel surface roughness and microhardness.

Antimicrobial Effect of Toothpastes Containing Fluoride, Xylitol, or Xylitol-Probiotic on Salivary Streptococcus mutans and Lactobacillus in Children.

AIM: This in vivo study was designed to compare the antimicrobial effect of toothpastes containing fluoride, xylitol, or xylitol-probiotic on Streptococcus mutans and Lactobacillus in 13-15-year-old children. MATERIALS AND METHODS: The study consisted of 60 pediatric patients who were randomly divided into three groups of 20 each. Group 1 recieved fluoride toothpaste (Colgate Max Fresh), group 2 used xylitol toothpaste (Xyliwhite), and group 3 used xylitol-probiotic toothpaste (PerioBiotic). Participants were asked to use the allocated dentifrice two times a day for 6 weeks. We performed tests on the saliva samples at the beginning of the study and after 6 weeks' duration following the use of toothpaste. The Statistical Package for the Social Sciences version 15 software and chi-square test were used for data analysis. RESULTS: PerioBiotic toothpaste and Colgate Max Fresh toothpaste showed significant reduction in the number of participants who, prior to commencing the study, were diagnosed with a high number of cariogenic bacteria. On the contrary, no significant changes were observed with respect to the number of participants with a very high number of S. mutans and Lactobacillus on Xyliwhite toothpaste group. CONCLUSION: In the light of the data obtained in this in-vivo study, a new innovational aspect has been reached in the use of probiotics to ensure the balance between bacterial flora in the oral cavity. In daily routine, the administration of probiotics to children is difficult. The toothpaste can be used as a vehicle to transport probiotics to children's mouth.

Outcomes of moderate sedation in paediatric dental patients.

BACKGROUND: The aim of this study was to evaluate the outcomes of moderate sedation with nitrous oxide/oxygen (N(2) O/O(2)) alone or combined with different dosages and administration routes of midazolam in uncooperative paediatric dental patients using the Bispectral Index System (BIS). METHODS: This one-year clinical study examined first-visit moderate sedation performed in 240 healthy children aged 4-6 years. Subjects were randomly divided into four groups according to drug, route and dosage, as follows: Group 1 - 0.20 mg/kg midazolam (40 mg/ml) delivered intranasally; Group 2 - 0.75 mg/kg midazolam (15 mg/3 ml) delivered orally; Group 3 - 0.50 mg/kg midazolam (15 mg/3 ml) delivered orally. All children in these three groups also received inhalation sedation with 50%-50% N(2) O/O(2), whereas children in Group 4 received inhalation sedation with 50%-50% N(2) O/O(2) only. The outcome of sedation was evaluated as either 'successful', 'failed' or 'not accepted'. RESULTS: The highest success rate was found in Group 1 (0.20 mg/kg intranasally, 87%), followed by Group 2 (0.75 mg/kg orally, 79%). The overall mean success rate for all groups was 73%. CONCLUSIONS: Moderate sedation can be successfully used in the clinical management of paediatric dental patients, with both intranasal and oral sedation using midazolam in conjunction with nitrous oxide found to be effective methods.

Rosai Dorfman disease of the parotid and submandibular glands: salivary gland scintigraphy and oral findings in two siblings.

Rosai-Dorfman disease (RDD) is an unusual clinical entity characterized by benign pseudolymphomatous proliferation with significant histiocytic infiltration. In the present paper, extranodal RDD of the major salivary glands causing salivary hypofunction and the results of salivary gland scintigraphy and ultrasound are presented in two siblings. Case 1: a 10-year-old boy with bilateral painless masses around the parotid and submandibular glands was referred. Ultrasound examination showed bilateral, well-defined, hypoechoic solid mass lesions within both parotid glands with minimal normal parenchyma in the upper poles. Both submandibular glands were markedly hypoechoic and heterogeneous. Mass lesions within the parotid glands appeared as cold lesions with regular contours on scintigraphy. Dynamic images showed normal uptake and normal response to secretion in the upper poles of the parotid glands, corresponding with ultrasonographically normal parenchyma. Both submandibular glands showed markedly diminished uptake and secretion. Case 2: a 9-year-old boy presented with mass lesions around the submandibular glands. Ultrasound examination showed normal parotid glands and markedly hypoechoic and heterogeneous submandibular glands. Salivary gland scintigraphy showed normal uptake and secretion of parotid glands with markedly diminished uptake and secretion in both submandibular glands. There were severe carious lesions in both patients due to salivary hypofunction. Treatments of the two patients' teeth were performed. Major salivary gland involvement of RDD is important for dentists as it may cause xerostomia and can mimic dental abscess. Functional evaluation of salivary glands with scintigraphy, besides radiological and pathological techniques, will help to explain whether salivary glands are affected or not and improve the diagnostic effectiveness.