Perinatal airway management in neonatal goiter: A healthcare cost and utilization project (HCUP) kids' inpatient database analysis.

INTRODUCTION: Fetal goiter is a rare congenital disorder that can present with life-threatening neonatal airway obstruction. Lifesaving and function-preserving airway management strategies are available, but routine delivery affords a limited window for intervention. Accordingly, fetal goiter is reported among the most common indications for ex-utero intrapartum treatment (EXIT). While EXIT prolongs the window for airway intervention to benefit the neonate, it elevates the risk to the pregnant person and requires extensive resources; therefore, data to guide ideal treatment selection are essential. This study aims to compare perinatal airway interventions between individuals with a birth hospitalization discharge diagnosis (BHDD) of goiter and the general population. MATERIALS AND METHODS: Individuals with and without BHDD of goiter were identified in the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database from 2000 to 2019. The frequency of airway interventions on day of life (DOL) 0 or 1 were compared using the Rao-Scott chi-square test. Additionally, gestational age, type of intervention, complications, mortality, birth weight, and length of stay were examined for the goiter cohort. RESULTS: Two-hundred eighty-seven weighted cases of goiter were identified in the study period. The population was 61 % male, 55 % White, and median birthweight was 3.3 kg. The median length of stay was 4.3 days, and average total charges were $42,332. Airway intervention on DOL 0 or 1 was performed in 16.9 % of individuals with goiter compared to 1.6 % in neonates without goiter (p < 0.001). Interventions in the goiter cohort included endotracheal intubation in 16 % of cases, laryngoscopy/bronchoscopy in 1-5% of cases, and tracheostomy in <1 % of cases. Fewer than 1 % of individuals undergoing intubation additionally had mass decompression/resection on DOL 0 or 1. No neonates received extracorporeal membrane oxygenation cannulation or cardiopulmonary resuscitation. Hypoxic encephalopathy occurred in <1 % of cases, among which endotracheal intubation was the only airway intervention performed. There were no mortalities among neonates with goiter. CONCLUSION: Individuals with BHDD of goiter receive significantly higher rates of perinatal airway intervention. In most cases, endoscopic interventions alone were sufficient to avoid hypoxic neurological complications. These findings contribute to data to aid in clinical counseling and empower patients to make informed decisions according to their values and treatment goals.

Rates of Detecting Thyroid Nodules Recommended for Biopsy with Ultrasound: Are All Indications Equal?

Background: The use of thyroid ultrasound increases yearly, adding to costs and overdetection of clinically irrelevant nodules. We investigated which indications most commonly prompt referral for thyroid ultrasound and the diagnostic utility by indication. Methods: We performed a retrospective observational cohort study of adults (≥18 years) undergoing an initial dedicated thyroid ultrasound between 2017 and 2019 at a tertiary academic center. Indicated reasons for referral were categorized into suspected palpable nodule (SPN), compressive symptoms (CS), metabolic symptoms (MS), screening due to high-risk factors, follow-up of incidental finding on other imaging, and combination of factors. Percentage of ultrasounds with an identifiable nodule and with a nodule recommended for biopsy was compared by indication. Separate logistic regression models were used to identify factors associated with finding any nodule and a biopsy-recommended nodule. Results: Among the 1739 patients included, the most common indication for thyroid ultrasound was SPN (40%), followed by incidental imaging (28%), CS (13%), combination (11%), MS (6%), and high-risk factors (2%). Overall, 62% of ultrasounds identified a nodule. Ultrasounds performed for incidental findings had the highest rate of nodule identification (94%), compared with 55%, 39%, and 43%, for SPN, CS, and MS, respectively (p < 0.05). Only 27% of ultrasounds identified a biopsy-recommended nodule. Nodules found incidentally had the highest rate of biopsy-recommended nodules at 55%. Rates of biopsy-recommended nodules for SPN, CS, and MS were 21%, 6%, and 10%, respectively. Logistic regression demonstrated that compared with patients referred for an SPN, those with incidental nodules were 10 times more likely to have a nodule found on ultrasound (odds ratio [OR] = 10.6 [CI 7.0-16.0]), while those referred for CS were half as likely to have a nodule (OR = 0.5 [CI 0.4-0.7]). Similar factors were associated with identification of biopsy-recommended nodules. Conclusions: Of all new dedicated thyroid ultrasounds, only a quarter find biopsy-recommended nodules, and nearly 40% do not identify a nodule at all. Notably, only 55% of ultrasounds done for SPN found a nodule. Ultrasound for CS and MS had the lowest rates of detecting nodules. Providing clear guidance on when to order thyroid ultrasounds can help reduce unnecessary health care utilization and potential overtreatment.

How We Do It: Otolaryngology Applicant Impressions of Virtual Meet and Greets at a Single Institution.

BACKGROUND: The COVID-19 pandemic altered residency recruitment in the 2021 application cycle. As a result, many programs adapted by creating virtual opportunities to connect with applicants such as clerkships, open houses, meet and greets, and interviews. Recent research has explored applicant impressions on virtual interviews and open houses, but none have assessed the utility of meet and greets, optimal structure, or desired topics to be addressed. METHODS: We hosted two virtual meet and greets for otolaryngology applicants and subsequently conducted a structured survey to assess the benefit, gather insight into desired topics, and determine how future sessions could be optimized. RESULTS: Twenty of 65 participants responded to the survey (31% response rate). The majority of participants learned about the event through social media (n = 15) or online resources such as OtoMatch or HeadMirror (n = 12). Desired topics to be addressed included faculty-resident relationships (85%), research (80%), the city of Madison (75%), breadth and depth of faculty (75%), and ability to train residents for future positions and fellowships (75%), among others. Overall, participants found the events helpful in conveying the culture and environment, exposure to faculty and residents, addressing questions, and providing insight into intangible aspects of the program. The main area of improvement identified was related to having breakout rooms, longer sessions, and varying the topics for breakout rooms. CONCLUSION: Virtual meet and greets facilitate outreach and provide opportunities for applicants to engage with residency programs and demonstrate interest. While initially implemented due to the COVID-19 pandemic, they will likely remain helpful in generating interest, reaching broader audiences, and possibly facilitating a successful match. It is critical to understand and incorporate the content that applicants wish to learn about at virtual meet and greets to best address questions, highlight key features, and demonstrate the intangible aspects of a residency program.

Codesign and Usability Testing of a Mobile Application to Support Family-Delivered Enteral Tube Care.

BACKGROUND: Enteral tubes are prevalent among children with medical complexity (CMC), and complications can lead to costly health care use. Our objective was to design and test the usability of a mobile application (app) to support family-delivered enteral tube care. METHODS: Human-centered design methods (affinity diagramming, persona development, and software development) were applied with family caregivers of CMC to develop a prototype. During 3 waves of usability testing with design refinement between waves, screen capture software collected user-app interactions and inductive content analysis of narrative feedback identified areas for design improvement. The National Aeronautics and Space Administration Task Load Index and the System Usability Scale quantified mental workload and ease of use. RESULTS: Design participants identified core app functions, including displaying care routines, reminders, tracking inventory and health data, caregiver communication, and troubleshooting. Usability testing participants were 80% non-Hispanic white, 28% lived in rural settings, and 20% had not completed high school. Median years providing enteral care was 2 (range 1-14). Design iterations improved app function, simplification, and user experience. The mean System Usability Scale score was 76, indicating above-average usability. National Aeronautics and Space Administration Task Load Index revealed low mental demand, frustration, and effort. All 14 participants reported that they would recommend the app, and that the app would help with organization, communication, and caregiver transitions. CONCLUSIONS: Using a human-centered codesign process, we created a highly usable mobile application to support enteral tube caregiving at home. Future work involves evaluating the feasibility of longitudinal use and effectiveness in improving self-efficacy and reduce device complications.

Growth of Listeria monocytogenes in a Model High-Moisture Cheese on the Basis of pH, Moisture, and Acid Type.

ABSTRACT: High-moisture, low-acid cheeses have been shown to support Listeria monocytogenes growth during refrigerated storage. Prior studies suggest that organic acids vary in their antilisterial activity and that cheeses of lower pH delay growth longer than those of higher pH; however, no standard pH value for Listeria control in cheese exists. The objective of this research was to create a predictive model to include the effects of acid type, pH, and moisture on the growth of L. monocytogenes in a model cheese system. Cream, micellar casein, water, lactose, salt, and acid (citric, lactic, acetic, or propionic) were combined in 32 formulations targeting 4 pH values (5.25, 5.50, 5.75, and 6.00) and two moisture levels (50 and 56%). Each was inoculated with 3 log CFU/g L. monocytogenes (five-strain mixture) after which 25-g samples were vacuum sealed and stored 8 weeks at 4°C. Triplicate samples were enumerated on modified Oxford agar weekly in duplicate trials. Model cheeses formulated with acetic and propionic acids inhibited growth (i.e., no observed increase in L. monocytogenes populations over 8 weeks) at pH ≤5.75, while those formulated with lactic acid inhibited growth at pH 5.25 only. In contrast, all model cheeses formulated with citric acid supported growth. Resulting growth curves were fitted for lag phase and growth rate before constructing models for each. The pH and acid type were found to significantly affect both growth parameters (P < 0.05), while moisture (50 to 56%) was not statistically significant in either model (P ≥ 0.05). The effects of acetic and propionic acid were not significantly different. In contrast, model cheeses made with citric acid had significantly shorter lag phases than the other acids tested, but growth rates after lag were statistically similar to model cheeses made with lactic acid. These data suggest propionic ∼ acetic > lactic > citric acids in antilisterial activity within the model cheese system developed and can be used in formulating safe high-moisture cheeses.

Thioredoxin overexpression in mitochondria showed minimum effects on aging and age-related diseases in male C57BL/6 mice.

Objective: In this study, the effects of overexpression of thioredoxin 2 (Trx2) on aging and age-related diseases were examined using Trx2 transgenic mice [Tg(TXN2]+/0]. Because our previous studies demonstrated that thioredoxin (Trx) overexpression in the cytosol (Trx1) did not extend maximum lifespan, this study was conducted to test if increased Trx2 expression in mitochondria shows beneficial effects on aging and age-related pathology. Methods: Trx2 transgenic mice were generated using a fragment of the human genome containing the TXN2 gene. Effects of Trx2 overexpression on survival, age-related pathology, oxidative stress, and redox-sensitive signaling pathways were examined in male Tg(TXN2)+/0 mice. Results: Trx2 levels were significantly higher (approximately 1.6- to 5-fold) in all of the tissues we examined in Tg(TXN2)+/0 mice compared to wild-type (WT) littermates, and the expression levels were maintained during aging (up to 22-24 months old). Trx2 overexpression did not alter the levels of Trx1, glutaredoxin, glutathione, or other major antioxidant enzymes. Overexpression of Trx2 was associated with reduced reactive oxygen species (ROS) production from mitochondria and lower isoprostane levels compared to WT mice. When we conducted the survival study, male Tg(TXN2)+/0 mice showed a slight extension (approximately 8-9%] of mean, median, and 10th percentile lifespans; however, the survival curve was not significantly different from WT mice. Cross-sectional pathological analysis (22-24 months old) showed that Tg(TXN2)+/0 mice had a slightly higher severity of lymphoma; however, tumor burden, disease burden, and severity of glomerulonephritis and inflammation were similar to WT mice. Trx2 overexpression was also associated with higher c-Jun and c-Fos levels; however, mTOR activity and levels of NFκB p65 and p50 were similar to WT littermates. Conclusions: Our findings suggest that the increased levels of Trx2 in mitochondria over the lifespan in Tg(TXN2)+/0 mice showed a slight life-extending effect, reduced ROS production from mitochondria and oxidative damage to lipids, but showed no significant effects on aging and age-related diseases.

Thioredoxin and aging: What have we learned from the survival studies?

Our laboratory has conducted the first systematic survival studies to examine the biological effects of the antioxidant protein thioredoxin (Trx) on aging and age-related pathology. Our studies with C57BL/6 mice overexpressing Trx1 [Tg(act-TRX1)+/0 and Tg(TXN)+/0) demonstrated a slight extension in early lifespan compared to wild-type (WT) mice; however, no significant effects were observed in the later part of life. Overexpression of Trx2 in male C57BL/6 mice [Tg(TXN2)+/0] demonstrated a slightly extended lifespan compared to WT mice. The pathology results from two lines of Trx1 transgenic mice showed a slightly higher incidence of age-related neoplastic diseases compared to WT mice, and a slight increase in the severity of lymphoma, a major neoplastic disease, was observed in Trx2 transgenic mice. Together these studies indicate that Trx overexpression in one compartment of the cell (cytosol or mitochondria alone) has marginal beneficial effects on lifespan. On the other hand, down-regulation of Trx in either the cytosol (Trx1KO) or mitochondria (Trx2KO) showed no significant changes in lifespan compared to WT mice, despite several changes in pathophysiology of these knockout mice. When we examined the synergetic effects of overexpressing Trx1 and Trx2, TXNTg x TXN2Tg mice showed a significantly shorter lifespan with accelerated cancer development compared to WT mice. These results suggest that synergetic effects of Trx overexpression in both the cytosol and mitochondria on aging are deleterious and the development of age-related cancer is accelerated. On the other hand, we have recently found that down-regulation of Trx in both the cytosol and mitochondria in Trx1KO x Trx2KO mice has beneficial effects on aging. The results generated from our lab along with our ongoing study using Trx1KO x Trx2KO mice could elucidate the key pathways (i.e., apoptosis and autophagy) that prevent accumulation of damaged cells and genomic instability leading to reduced cancer formation.

Lifespan differences in emotional contagion while watching emotion-eliciting videos.

Previous research has examined empathic concern by presenting toddlers with a sad stimulus and examining their emotional response, with the conclusion that toddlers display empathy. Yet, such research has failed to include basic control conditions involving some other aversive stimulus such as white noise. Nor has it compared toddlers to adults to examine potential development in empathy. In the present study, we showed toddlers and adults four video types: infant crying, infant laughing, infant babbling, and a neutral infant accompanied by white noise. We then coded happiness and sadness while viewing the videos, and created a difference score (happiness minus sadness), testing 52 toddlers and 61 adults. Whereas adults showed more sadness towards infant crying than any other stimulus, toddlers' response to crying and white noise was similar. Thus, the toddler response to crying was comparable to previous studies (slight sadness), but was no different to white noise and was significantly reduced relative to adults. As such, toddlers' response seemed to be better characterized as a reaction to an aversive stimulus rather than empathy.

Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice.

We examined the effects of continuous overexpression of thioredoxin (Trx) 1 on aging in Trx1 transgenic mice [Tg(TXN)+/0]. This study was conducted to test whether increased thioredoxin expression over the lifespan in mice would alter aging and age-related pathology because our previous study demonstrated that Tg(act-TXN)+/0 mice had no significant maximum life extension, possibly due to the use of actin as a promoter, which may have resulted in loss of Trx1 overexpression during aging. To test this hypothesis, we generated new Trx1 transgenic mice using a fragment of the human genome containing the TXN gene with an endogenous promoter to ensure continuous overexpression of Trx1 throughout the lifespan. Universal overexpression of Trx1 was observed, and Trx1 overexpression was maintained during aging (up to 22-24 months old) in the Tg(TXN)+/0 mice. The levels of Trx1 are significantly higher (approximately 4 to 31 fold) in all of the tissues examined in the Tg(TXN)+/0 mice compared to the wild-type (WT) littermates. The overexpression of Trx1 did not cause any changes in the levels of Trx2, glutaredoxin, glutathione, or other major antioxidant enzymes. The survival study demonstrated that male Tg(TXN)+/0 mice slightly extended the earlier part of the lifespan compared to WT littermates, but no significant life extension was observed over the lifespan. The cross-sectional pathological analysis (22-25 months old) showed that Tg(TXN)+/0 mice had a significantly higher severity of lymphoma and more tumor burden than WT mice, which was associated with the suppression of the apoptosis signal-regulating kinase 1 (ASK1) pathway. Our findings suggest that the increased levels of Trx1 over the lifespan in Tg(TXN)+/0 mice showed some beneficial effects (slight extension of lifespan) in the earlier part of life but had no significant effects on median or maximum lifespans, and increased Trx1 levels enhanced tumor development in old mice.

Thioredoxin overexpression in both the cytosol and mitochondria accelerates age-related disease and shortens lifespan in male C57BL/6 mice.

To investigate the role of increased levels of thioredoxin (Trx) in both the cytosol (Trx1) and mitochondria (Trx2) on aging, we have conducted a study to examine survival and age-related diseases using male mice overexpressing Trx1 and Trx2 (TXNTg × TXN2Tg). Our study demonstrated that the upregulation of Trx in both the cytosol and mitochondria in male TXNTg × TXN2Tg C57BL/6 mice resulted in a significantly shorter lifespan compared to wild-type (WT) mice. Cross-sectional pathology data showed a slightly higher incidence of neoplastic diseases in TXNTg × TXN2Tg mice than WT mice. The incidence of lymphoma, a major neoplastic disease in C57BL/6 mice, was slightly higher in TXNTg × TXN2Tg mice than in WT mice, and more importantly, the severity of lymphoma was significantly higher in TXNTg × TXN2Tg mice compared to WT mice. Furthermore, the total number of histopathological changes in the whole body (disease burden) was significantly higher in TXNTg × TXN2Tg mice compared to WT mice. Therefore, our study suggests that overexpression of Trx in both the cytosol and mitochondria resulted in deleterious effects on aging and accelerated the development of age-related diseases, especially cancer, in male C57BL/6 mice.