Performance of ACR TI-RADS and the Bethesda System in Predicting Risk of Malignancy in Thyroid Nodules at a Large Children's Hospital and a Comprehensive Review of the Pediatric Literature.

While thyroid nodules are less common in children than in adults, they are more frequently malignant. However, pediatric data are scarce regarding the performance characteristics of imaging and cytopathology classification systems validated to predict the risk of malignancy (ROM) in adults and select those patients who require fine-needle aspiration (FNA) and possibly surgical resection. We retrospectively reviewed the electronic medical records of all patients 18 years of age or younger who underwent thyroid FNA at our institution from 1 July 2015 to 31 May 2022. Based on surgical follow-up from 74 of the 208 FNA cases, we determined the ROM for the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) ultrasound risk stratification system and The Bethesda System for Reporting Thyroid Cytopathology and added our results to those of pediatric cohorts from other institutions already published in the literature. We found the following ROMs for 1458 cases using ACR TI-RADS (TR): TR1. Benign: 2.2%, TR2. Not Suspicious: 9.3%, TR3. Mildly Suspicious: 16.6%, TR4. Moderately Suspicious: 27.0%, and TR5. Highly Suspicious 76.5%; and for 5911 cases using the Bethesda system: Bethesda I. Unsatisfactory: 16.8%, Bethesda II. Benign: 7.2%, Bethesda III: Atypia of Undetermined Significance: 29.6%, Bethesda IV. Follicular Neoplasm: 42.3%, Bethesda V. Suspicious for Malignancy: 90.8%, and Bethesda VI. Malignant: 98.8%. We conclude that ACR TI-RADS levels imply higher ROMs for the pediatric population than the corresponding suggested ROMs for adults, and, in order to avoid missing malignancies, we should consider modifying or altogether abandoning size cutoffs for recommending FNA in children and adolescents whose thyroid glands are smaller than those of adults. The Bethesda categories also imply higher ROMs for pediatric patients compared to adults.

High Prevalence of Gene Fusions and Copy Number Alterations in Pediatric Radiation Therapy-Induced Papillary and Follicular Thyroid Carcinomas.

Background: Childhood cancer survivors and bone marrow transplant recipients treated with radiation therapy (RT) are at increased risk for subsequent thyroid cancer. However, the genetic landscape of pediatric thyroid cancer, both primary and RT-induced, remains poorly defined, as pediatric papillary thyroid carcinoma (PTC) has been understudied compared with adults and data on pediatric follicular thyroid carcinoma (FTC) are virtually nonexistent. The objective of this study was to characterize and compare the molecular profiles of pediatric RT-induced PTC and FTC cases with primary pediatric thyroid cancers. Methods: A total of 41 differentiated thyroid carcinomas (11 RT cases and 30 primary cases) from 37 patients seen at Phoenix Children's Hospital between January 1, 2010 and December 31, 2019 were evaluated by targeted next-generation sequencing and/or BRAF immunohistochemistry. Results: Eighty-six percent (6/7) of RT-PTC harbored a gene fusion (GF) compared with 56% (14/25) of primary PTC; 14% (1/7) of RT-PTC had a single-nucleotide variant (SNV; specifically, a point mutation in the DICER1 gene) compared with 44% (11/25) of primary PTC (all of the latter had the BRAFV600E mutation). An exceedingly rare ROS1 fusion was identified in a child with RT-PTC. With respect to FTC, copy number alterations (CNAs) were seen in 75% (3/4) of RT cases compared with 40% (2/5) of primary cases. None of the RT-FTC had SNVs compared with 100% (5/5) of primary FTC. Conclusions: In children, the molecular profile of subsequent RT-induced thyroid cancers appears to differ from primary (sporadic and syndromic) cases, with a high prevalence of GFs in RT-PTC (similar to PTC occurring after the Chernobyl nuclear reactor accident) and CNAs in RT-FTC. A better understanding of the molecular mechanisms underlying these cancers may lead to more accurate diagnosis, prognosis, and treatment, as some of the genomic alterations are potentially targetable.

Use of Procalcitonin for Identification of Cobacterial Pneumonia in Pediatric Patients.

OBJECTIVE: To evaluate the utility of procalcitonin (PCT) in identifying cobacterial pneumonia in pediatric patients with known viral respiratory infection. METHODS: A retrospective cohort study was conducted in a stand-alone children's hospital during 2 time periods (period 1: October 1, 2014, to March 31, 2015; period 2: October 1, 2015, to March 31, 2016). Patients admitted with any upper respiratory tract infection were included. Exclusion criteria included any condition compromising lung function, age <30 days or >18 years, or lack of PCT (period 2). PCT values of <0.5 ng/mL were considered normal, whereas values of >1.5 ng/mL were used to identify cobacterial pneumonia. Receiver-operator characteristic curves were used with multiple logistic regression to evaluate patient variables. RESULTS: Of the 374 pediatric patients evaluated, 64% were classified as having viral pneumonia and 23% as having cobacterial pneumonia across both study time periods. Non-significant predictors of cobacterial pneumonia included temperature (p = 0.0795, p = 0.1466), WBC count (p = 0.8774, p = 0.6675), and C-reactive protein (p = 0.7115, p = 0.3835). Median initial PCT for patients with viral pneumonia was 0.14 ng/mL compared with 1.41 ng/mL in patients with cobacterial pneumonia; median second PCTs were 0.26 ng/mL (viral pneumonia) and 4.55 ng/mL (cobacterial pneumonia). Patients with an elevated PCT had 17.5 times (95% CI, 5.2, 59.1) greater odds of having a cobacterial pneumonia. CONCLUSIONS: PCT was found to be strongly associated with cobacterial pneumonia with an underlying viral etiology. Temperature, WBC, and C-reactive protein failed to be significant predictors in differentiating between viral and cobacterial pneumonia.

The role of nucleotides in the immune and gastrointestinal systems: potential clinical applications.

Nucleotides are low molecular weight biological molecules key to biochemical processes. Sources include de novo synthesis, recovery via salvage mechanisms, and dietary intakes. Although endogenous production serves as the main nucleotide source, evidence suggests that exogenous sources are essential to immune competence, intestinal development, and recovery. Dietary nucleotides serve a marked role in rapidly proliferating cells where they are necessary for optimal function. Accordingly, dietary nucleotides are deemed conditionally essential in the presence of various physiological stresses, including growth and development, recovery from injury, infection, and certain disease states. Clinical studies that evaluated nutrition formulations of nucleotides in combination with other specific nutrient substances demonstrated improved clinical outcomes in patients characterized as critically ill, injured, immune suppressed, or with chronic gastrointestinal conditions. However, conclusions regarding specific benefits of nucleotides are limited. Scientific substantiation of nucleotide supplementation in infant formula has been reported to improve the maturation and development of the intestinal tract as well as immune function. All medical nutrition products except for one immune-modulating formulation are devoid of nucleotides. In an effort to build on this, the current review presents the data to support potential clinical applications for nucleotides in enteral nutrition that may contribute to improved outcomes in physiologically stressed patients.

Effects of short-chain fructooligosaccharides on satiety responses in healthy men and women.

In view of a dramatic increase in the incidence of obesity, the present study examined the appetite effects of a functional fiber as a potential dietary intervention. Fiber may increase satiety. Satiety effects also may be linked to colonic fermentation. Short-chain fructooligosaccharide (scFOS) are fermentable fibers that can be added to foods to influence these actions. The primary objective of this study was to determine if scFOS affects satiety and hunger and has an additive effect on food intake. Using a double-blind crossover design, 20 healthy subjects were assigned to consume two separate doses of 0 g, 5 g, or 8 g of scFOS. The first dose was mixed into a hot cocoa beverage and served with a breakfast meal of a bagel and cream cheese. A beverage was used in the test meal due to the ease with which scFOS can be added to this medium. Satiety was assessed with visual analogue scales (VASs) at 0, 15, 30, 45, 60, 90, 120, 180, and 240 min. Ad libitum food intake was measured at a lunch meal provided at the test site at 240 min. Subjects then recorded their food intake over the remainder of the 24-h study day. The second dose of scFOS was consumed in the form of 3 solid, chocolate-flavored chews (51-67 total kcal) without additional food or drink, 2h prior to the subject's dinner meal. Breath hydrogen measures were collected prior to the breakfast test meal (0 min) and the ad libitum lunch (240 min). Gastrointestinal tolerance was evaluated over the course of the 24-h study day using VAS. All treatments were well tolerated. No differences in subjective satiety over the morning, or food intake at lunch, were found. Over the remainder of the day, the high dose of scFOS reduced food intake in women, but increased food intake in men, suggesting a gender difference in the longer-term response. Breath hydrogen, used as a marker of fermentation, increased in a dose-dependent manner. These results indicate that scFOS undergoes fermentation within 240 min; however, acceptable amounts of scFOS did not enhance acute satiety or hunger.