Consensus Statement by the American Association of Clinical Endocrinology (AACE) and the American Head and Neck Society Endocrine Surgery Section (AHNS) on Pediatric Benign and Malignant Thyroid Surgery.

OBJECTIVES: To provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children. METHODS: A literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.). RESULTS: Twenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus. CONCLUSION: Pediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.

Sleep in Parental Caregivers and Children With Type 1 Diabetes.

The purpose of this cross-sectional, descriptive, pilot study was to examine the correlations in sleep between caregivers (≥18 years) and young (6-12 years) children with type 1 diabetes. Sleep was measured in both parent and child over 7 days using actigraphy and a sleep diary. Parents completed questionnaires on sleep, stress, depressive symptoms, and demographics. Children completed pediatric anxiety and fatigue questionnaires, and A1C (Hemoglobin A1c) was documented at clinic. Descriptive statistics and Pearson correlations were used to analyze data. Parents (N = 18, mean age: 39.3 ± 5.4 years, 100% Caucasian, 83% mothers) and children (N = 18, mean age: 9.6 ± 2.4 years, diagnosed for mean 3.0 ± 2.4 years, 66% female, mean A1C: 7.5 ± 0.8%) were recruited. Strong to moderate correlations were found for several measures including sleep measures based on actigraphy: mean sleep duration (hours; 7.6 ± 0.7 for parents and 8.8 ± 0.8 for children; r = .638, p = .004), mean sleep efficiency (r = .823, p < .001), and mean daily wake after sleep onset (minutes; r = .530, p = .024).

Validity of the American College of Radiology Thyroid Imaging Reporting and Data System in Children.

OBJECTIVE: To assess the validity of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for evaluating thyroid nodules in children. METHODS: Patients aged <19 years with thyroid nodule(s) evaluated by ultrasound (US) from 2007-2018 at a tertiary children's hospital were included. Two radiologists scored de-identified thyroid US images using ACR TI-RADS (from 1, "benign" to 5, "highly suspicious"). The radiologists recorded size and rated vascularity for each nodule. Ultrasound findings were compared to pathology results (operative cases, n = 91) and clinical follow-up without disease progression (non-operative cases, n = 15). RESULTS: Thyroid images from 115 patients were reviewed. Nine patients were excluded due to the absence of an evaluable nodule. Forty-seven benign and 59 malignant nodules were included. Median age at ultrasound was 15 years (range 0.9-18 years). Twenty (18.9%) patients were male. There was moderate agreement between TI-RADS levels assigned by the two raters (kappa = 0.57, p < 0.001). When the raters' levels were averaged, >3 as the threshold for malignancy correctly categorized the greatest percentage of nodules (68.9%). Eleven (18.6%) malignant nodules received a TI-RADS level of 2 (n = 3) or 3 (n = 8). Sensitivity, specificity, and positive and negative predictive values were 81.4%, 53.2%, 68.6%, and 69.4%, respectively. Although not part of TI-RADS, vascularity was similar between benign and malignant nodules (p = 0.56). CONCLUSION: In a pediatric population, TI-RADS can help distinguish between benign and malignant nodules with comparable sensitivity and specificity to adults. However, the positive and negative predictive values suggest TI-RADS alone cannot eliminate the need for FNA. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2394-2401, 2023.

Unique Molecular Signatures Are Associated with Aggressive Histology in Pediatric Differentiated Thyroid Cancer.

Background: Molecular testing (MT) enhances the diagnostic accuracy of thyroid fine-needle aspiration biopsy, reducing the need for diagnostic lobectomy in adult patients with indeterminate nodules (Bethesda class III/IV). However, little is known about genetic alterations in pediatric thyroid carcinoma (TC). Our aim was to analyze MT results of pediatric differentiated TC (DTC) cases to determine associations with histological and clinical features. Methods: A retrospective review identified all patients (aged <19 years) diagnosed with DTC from 2001 to 2017 at the University of Pittsburgh Medical Center. Histology was rereviewed to confirm diagnosis and identify tissue for MT using next-generation sequencing (ThyroSeq, version 3, TSv3). Correlation with histological and clinical features was analyzed using regression analysis. Results: Of 71 patients with MT results, 62 (87%) patients had papillary TC. All patients were alive at a median follow-up of 6 years (range 18 days to 18 years). Genetic alterations were identified in 65 (92%) patients. These alterations were grouped as BRAF-like point mutations or fusions (39, 55%), RAS-like mutations or fusions (21, 30%), or copy number alterations (5, 7%). On multiple regression analysis accounting for patient sex and tumor size in patients with papillary TC, increased tumor stage (ß: 0.234, p < 0.001), multifocal disease (odds ratio [OR]: 3.60, p = 0.042), and lymph node metastases (OR: 6.13, p = 0.044) were associated with BRAF-like gene fusions. When considering individual mutations, ETV6/NTRK3 fusions were associated with increased tumor stage (ß: 2.07, p = 0.023) and BRAF-like point mutations were associated with increased likelihood of surgery for recurrence over time (hazard ratio: 19.5, p = 0.004). Conclusions: Among our cohort of pediatric TC patients who underwent comprehensive MT, >90% had an identifiable genetic alteration. Aggressive features were primarily associated with BRAF-like gene fusions. Preoperative MT results may be useful in guiding the extent of the initial operation in pediatric patients (aged <19 years) with TC.

Chronic Lymphocytic Thyroiditis and Aggressiveness of Pediatric Differentiated Thyroid Cancer.

OBJECTIVES/HYPOTHESIS: Hashimoto's Thyroiditis (HT) is a common cause of hypothyroidism. Among adults with differentiated thyroid cancer (DTC), HT appears to be associated with less severe disease burden. In the absence of information regarding HT and disease burden among children with DTC, we assessed the relationship between pediatric DTC severity and HT. STUDY DESIGN: Retrospective cohort. METHODS: Charts from 90 pediatric patients who underwent surgical removal of DTC from 2002 to 2017 at tertiary-care children's hospital were reviewed. Demographic, clinical, surgical, pathology, and outcome details were compared between patients with and without HT. Consistency among diagnostic modalities of HT was also evaluated. RESULTS: Median age at presentation was 16.0 years (range 4.2-18.9 years). Twenty-two patients were male (24%). Forty-five patients (50%) had HT based on presence of thyroid autoantibodies and/or surgical pathology findings and 45 patients did not have HT. Patients with HT had increased odds of microcalcifications (odds ratio [OR]: 3.01, P = .031) and decreased odds of palpable nodules (OR: 0.212, P = .024) and T2 lesions (vs. T1) (OR: 0.261, P = .015) compared with non-HT. No significant differences in demographics and the incidence of multifocality, extrathyroidal extension, lymphovascular invasion, lymph node or pulmonary metastases, disease recurrence, or radioactive iodine treatment were found between the two groups. Thyroglobulin/thyroid peroxidase autoantibodies and surgical pathology indicative of HT were concordant in 82.4% (κ = 0.635, P < .001). CONCLUSION: HT was present in 50% of children with DTC. Patients with DTC and HT presented with smaller tumors compared to non-HT patients. No significant differences in other markers of disease aggressiveness were found between the two groups. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1668-1674, 2022.

Trait Mindfulness and Mindfulness Practices in Adolescents with Type 1 Diabetes: Descriptive and Comparative Study.

INTRODUCTION: Study describes mindfulness (trait and practices) and compares levels of trait mindfulness (low/high) and practices (yes/no) on demographic, clinical characteristics, and diabetes-related outcomes among adolescents with type 1 diabetes (T1D). METHODS: Adolescents completed a survey on demographics, clinical data, trait mindfulness/practices, diabetes-specific stress, and diabetes self-management (DSM). Glycemic control (A1c) obtained from medical records. T and χ2 tests were applied for comparative analyses. RESULTS: 129 adolescents (12-18 years) reported moderately high levels of mindfulness (31 ± 8; range, 10-40). One-third (30%) reported having experience with mindfulness practices (formal, informal, and religious). Adolescents who reported higher levels of trait mindfulness had higher insulin pump usage (p =.005), less diabetes-specific stress (p <.001), greater DSM (p =.006), and less A1c (p =.013). Adolescents who reported more types of mindfulness practices had greater DSM scores. DISCUSSION: Adolescents with higher levels of trait mindfulness and with more types of mindfulness practices had better diabetes-related outcomes. Introducing mindfulness training tailored to adolescents with T1D should be examined.

Consensus statement by the American Association of Clinical Endocrinology (AACE) and the American Head and Neck Society Endocrine Surgery Section (AHNS-ES) on Pediatric Benign and Malignant Thyroid Surgery.

OBJECTIVES: To provide a clinical disease state review of recent relevant literature and to generate expert consensus statements regarding the breadth of pediatric thyroid cancer diagnosis and care, with an emphasis on thyroid surgery. To generate expert statements to educate pediatric practitioners on the state-of-the-art practices and the value of surgical experience in the management of this unusual and challenging disease in children. METHODS: A literature search was conducted and statements were constructed and subjected to a modified Delphi process to measure the consensus of the expert author panel. The wording of statements, voting tabulation, and statistical analysis were overseen by a Delphi expert (J.J.S.). RESULTS: Twenty-five consensus statements were created and subjected to a modified Delphi analysis to measure the strength of consensus of the expert author panel. All statements reached a level of consensus, and the majority of statements reached the highest level of consensus. CONCLUSION: Pediatric thyroid cancer has many unique nuances, such as bulky cervical adenopathy on presentation, an increased incidence of diffuse sclerosing variant, and a longer potential lifespan to endure potential complications from treatment. Complications can be a burden to parents and patients alike. We suggest that optimal outcomes and decreased morbidity will come from the use of advanced imaging, diagnostic testing, and neural monitoring of patients treated at high-volume centers by high-volume surgeons.

Mechanism of bactericidal activity of silver nitrate - a concentration dependent bi-functional molecule.

Silver nitrate imparts different functions on bacteria depending upon its concentration. At lower concentration it induced synthesis of nanoparticles, whereas at higher concentrations it induced cell death. Bacillus licheniformis was used as model system. The MIC was 5 mM, and it induced catalase production, apoptotic body formation and DNA fragmentation.

Estimation of time since death based on light microscopic, electron microscopic, and electrolyte analysis in the gingival tissue.

BACKGROUND: Estimation of time since death is an important parameter in forensic science. Although there are various methods available, precise estimation is still to be established. AIM: The present study aimed to evaluate the histological and ultrastructural changes in the gingival tissue along with the changes in electrolyte levels (sodium, potassium, calcium, and magnesium) among the three groups which included normal, 2, and 4 h since death. MATERIALS AND METHODS: For light microscopic examination and electrolyte analysis, five normal gingival tissue samples were collected from patient following impaction procedure and five gingival tissue samples were obtained from postmortem specimen at 2 and 4 h since death. Each sample was divided into two parts. The first part was fixed in 10% formalin solution for the light microscopic analysis, and microscopic changes were observed between the groups. The second part was snap frozen at -80°C, until measurement of electrolyte using inductively coupled plasma-optical emission spectrometer, and the values were compared among the groups using Kruskal-Wallis test. For electron microscopic examination 2 and 4 h postmortem, gingival tissue samples were collected from the same individual and immediately fixed in 2.5% buffered glutaraldehyde, and the ultrastructural changes were compared with the normal gingival tissue. RESULTS: The light microscopic changes were observed as early as 2 h since death, but there was no significant difference observed between 2 and 4 h postmortem samples whereas ultrastructurally significant difference in morphology was observed between 2 and 4 h postmortem gingival tissue. Our results can confirm histomorphological changes within 2 and 4 h since death.

Follicle-stimulating hormone (FSH) transiently blocks FSH receptor transcription by increasing inhibitor of deoxyribonucleic acid binding/differentiation-2 and decreasing upstream stimulatory factor expression in rat Sertoli cells.

FSH acts through the FSH receptor (FSHR) to modulate cell processes that are required to support developing spermatozoa. Within the testis, only Sertoli cells possess receptors for FSH and are the major targets for this regulator of spermatogenesis. FSH stimulation of Sertoli cells for 24-48 h is known to induce Fshr mRNA expression through an E-box motif (CACGTG) located 25 bp upstream of the transcription start site. In contrast, FSH stimulation for 8 h inhibits Fshr transcription. DNA-protein binding studies performed using nuclear extracts from Sertoli cells show that protein binding to the Fshr promoter E-box was reduced 68% after 6 h of FSH stimulation but increased 191% over basal levels after 48 h of stimulation. The proteins binding to the Fshr E-box were identified as upstream stimulatory factor (USF)-1 and -2. FSH stimulation transiently decreased USF1 levels and increased the expression of the inhibitor of DNA binding/differentiation (ID)-2 repressor protein with the same kinetics as the decreased USF/E-box interactions. Overexpression of ID2 resulted in a dose-dependent decrease in USF-driven Fshr promoter activity in the MSC-1 Sertoli cell line, and ID2 inhibited USF binding to the Fshr E-box. Together, these studies suggest that stimulation of Sertoli cells with FSH transiently decreases expression of the USF1 activator and induces accumulation of the ID2 repressor, to block USF binding to the Fshr promoter and delay activation of Fshr transcription. This FSH-regulated mechanism may explain the cyclical changes in Fshr expression that occurs in Sertoli cells in vivo.

Mechanism of bactericidal activity of Silver Nitrate: a concentration dependent bi-functional molecule

Silver nitrate imparts different functions on bacteria depending upon its concentration. At lower concentration it induced synthesis of nanoparticles, whereas at higher concentrations it induced cell death. Bacillus licheniformis was used as model system. The MIC was 5 mM, and it induced catalase production, apoptotic body formation and DNA fragmentation.

Stromal changes in apparently normal mucosa of smokers and pan chewers: a multi-parametric approach

Aim: To compare and contrast the various changes in the connective tissue among patients with the habits of smoking, pan chewing and controls by using fluorescence spectroscopy, histopathology and transmission electron microscopy. Method: Thirty subjects were categorized into three groups: pan chewers, smokers and controls without any oral lesions. Fluorescence spectroscopy was carried out using FLUOROMAX-2. Excitation spectroscopy was performed at 280 and 320nm respectively and Emission spectroscopy was performed at 340 and 390nm excitation. Subsequently, histopathological evaluation and transmission electron microscopy was done for biopsies taken from test groups and controls. Results: The mean, standard deviation and test of significance of mean values between different groups for intensity-380nm, intensity–420nm and intensity – 460nm at 320 nm excitations, showed that the Mean values in group I and group II were significantly higher than the mean value in group III with a p-value of less than 0.001. Considering the histopathological parameters, the pattern of the sub-epithelial connective tissue, the presence of chronic inflammatory cells and lysis of connective tissue was significant. The ultrastructural analysis revealed the presence of epithelioid, spindle or elongated and stellate shaped fibroblasts in the connective tissue. Conclusion: In this pilot study, we could find variations in emission characteristics of various amino acids which correlated with histopathology and electron microscopy. Our study suggests that there are connective tissue changes in oral mucosa among smokers and pan chewers, though it is apparently normal in clinical presentation. These initial connective tissue changes could determine the progression of altered mucosa to a pre-cancer or cancer, which is further related to other complex interactions. Elaborate studies are required to evaluate the significance of our hypothesis.