Updates in hyponatremia and hypernatremia.

PURPOSE OF REVIEW: Hyponatremia and hypernatremia are commonly encountered electrolyte abnormalities that require timely and careful intervention, as they can be associated with significant morbidity and mortality. RECENT FINDINGS: This review article addresses the etiology, presentation, diagnosis, and management of both hyponatremia and hypernatremia, emphasizing the latest advancements and emerging trends in pediatric care. SUMMARY: A methodical approach is needed to accurately assess and treat hyponatremia and hypernatremia. Both conditions continue to rely on serum and urine testing, however newer tests such as copeptin and stimulated testing may hold promise to further refine testing in the future.

Implementation of genomic medicine for rare disease in a tertiary healthcare system: Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD).

BACKGROUND: In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. METHODS: Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. RESULTS: Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. CONCLUSION: Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

Association of vitamin D deficiency with COVID-19 infection severity: Systematic review and meta-analysis.

BACKGROUND: We sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID-19) infection. METHODS: Multiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID-19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission. RESULTS: Seventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50-4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40-7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48-3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25-0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut-offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends. CONCLUSIONS: Vitamin D deficiency is associated with greater severity of COVID-19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID-19.

Are Clinicians Aggressive Enough in Treating Diabetes-Related Hyperlipidemia in Youth?

PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of death in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). Subclinical atherosclerotic changes are noted in youth with diabetes; therefore, timely identification and management of modifiable cardiovascular risk factors including hyperlipidemia is crucial. We review the current guidelines for hyperlipidemia screening and treatment in youth with T1D and T2D. We discuss the efficacy of non-pharmacological strategies including dietary modifications, exercise, and glycemic control and pharmacological therapy. We summarize reported rates of treatment of diabetes-related hyperlipidemia in youth. RECENT FINDINGS: Hyperlipidemia is prevalent among youth with T1D and T2D. Vast majority of youth with diabetes-related hyperlipidemia do not receive lipid-lowering treatments. There are several factors that contribute to suboptimal management of hyperlipidemia in youth with diabetes including limited data on efficacy and safety of statins in youth with diabetes. We propose strategies to improve hyperlipidemia management including education of providers and patients, quality improvement methods, and electronic health record alerts. Additionally, further studies are warranted to examine the safety of statins in youth with diabetes, cost-benefit analysis to aggressive screening and treatment, and long-term effect for improving cardiovascular morbidity and mortality.

Risk of substance use disorders among adolescents and emerging adults with type 1 diabetes: A population-based cohort study.

BACKGROUND: Adolescents and emerging adults with chronic health conditions such as type 1 diabetes mellitus (T1D) are more likely to engage in high-risk behaviors. Previous studies regarding substance use in adolescents and emerging adults with T1D are mostly derived from cross-sectional studies utilizing self-administered questionnaires and are limited by lack of population-based comparison groups. In addition, despite the rising popularity of vaping, little is known about the incidence of vaping in adolescents and emerging adults with T1D. METHODS: We explored the incidence and prospective risk of substance use disorders (SUD) and vaping in adolescents and emerging adults with T1D compared to age and gender matched nondiabetic referents residing in Olmsted County, Rochester, MN. RESULTS: Risk of incident SUD was higher in those with T1D compared to matched referents with alcohol, marijuana, and smoked tobacco being most common substances. When stratified by gender, these differences remained significant in males, but not females. CONCLUSIONS: While further work is needed to delineate the causative relationships between T1D, mental health, and substance abuse, our findings confirm the critical need for substance use screening and mental health support for adolescents and emerging adults with T1D.

Diagnostic accuracy of the McGill thyroid nodule score in paediatric patients.

INTRODUCTION: Thyroid cancer is the most common paediatric endocrine cancer; accurate diagnosis and prompt management of paediatric thyroid nodules is critical. The McGill Thyroid Nodule Score (MTNS), based upon clinical, ultrasound (US) and cytology criteria, has recently been modified and studied in a pilot paediatric group with good results. We aim to describe the diagnostic accuracy of the paediatric modified MTNS (PMTNS) in a large paediatric cohort. METHODS: We utilized an established retrospective cohort between 1996 and 2015 of 99 patients ≤21 years old with 131 thyroid nodules. Two experienced paediatric radiologists, blinded to pathology and radiology reports, reviewed US features. We abstracted cytology, histology and laboratory results, assigning each nodule a PMTNS. PMTNS performance was compared to FNA and histology. RESULTS: Approximately 33% of nodules were malignant. The cohort was predominantly adolescent (mean age 15.4 ± 3.8 years). The average PMTNS for malignant and benign nodules, based on final histology, was 12.7 ± 4.3 and 1.7 ± 2.9, respectively. A PMTNS ≥8 resulted in a 93.2% sensitivity and 93.1% specificity for detecting malignancy, while a PMTNS ≥9 resulted in a 90.9% sensitivity and 96.6% specificity. However, Bethesda cytology category ≥4 independently had a 97.7% sensitivity and 94.0% specificity for detecting malignancy. The PMTNS had diminishing diagnostic accuracy in younger children compared with older children. CONCLUSION: Paediatric modified McGill Thyroid Nodule Score predicts malignancy, perhaps due to the score's emphasis on cytology results; however, the score is less accurate in younger patients. While cytology results remain reliable, further work is needed to develop a non-invasive scoring system to predict malignancy in children.

Cryptosporidium species and subtype analysis in diarrhoeic pre-weaned lambs and goat kids from north-western Spain.

Faecal specimens from diarrhoeic pre-weaned lambs (n = 171) and goat kids (n = 118) were collected in 37 sheep and 23 goat flocks, respectively, from NW Spain and microscopically examined for the presence of Cryptosporidium oocysts. Positive specimens were selected for molecular characterization. Presence of Cryptosporidium oocysts were significantly higher in specimens from goat kids (62.7%) than from lambs (31.6%). PCR products of the SSU rRNA locus were obtained for 108 isolates, and three Cryptosporidium species were identified. Cryptosporidium parvum was the most common species identified from both lambs (74.4%) and goat kids (93.8%). The remaining PCR products from lambs (25.6%) and goat kids (7.7%) were identified as Cryptosporidium Ubiquitum and Cryptosporidium xiaoi, respectively. Five C. parvum subtypes were identified; IIaA13G1R1, IIaA14G2R1, IIaA15G2R1 and IIaA16G3R1 were found in both host species, and IIdA17G1 was only detected in goat kids. Subtype IIaA15G2R1 was the most common and widely distributed. The present study provides the first description of subtypes IIaA13G1R1 in both small ruminant species, IIaA14G2R1 in sheep and IIaA16G3R1 in goats. Our results also reveal that diarrhoeic pre-weaned lambs and goat kids must be considered important reservoirs of Cryptosporidium species with zoonotic potential, such as C. parvum and C. ubiquitum.

Profound Hypoglycemia and High Anion Gap Metabolic Acidosis in a Pediatric Leukemic Patient Receiving 6-Mercaptopurine.

A 13-year-old male undergoing maintenance chemotherapy with methotrexate and 6-mercaptopurine (6MP), for very high-risk B-cell acute lymphoblastic leukemia (ALL), presented with vomiting due to severe hypoglycemia with metabolic acidosis. While his laboratory values were concerning for a critically ill child, the patient was relatively well appearing. Hypoglycemia is a rare but serious side effect of 6MP with an unexpectedly variable presentation; therefore, a high index of suspicion is needed for its prompt detection and treatment. This patient also had severe metabolic acidosis, likely secondary to hypoglycemia, creating a serious clinical picture despite a well-appearing child. This example of incongruity between laboratory tests and clinical appearance adds nuance to the existing literature. Moreover, although 6MP-associated hypoglycemia is rare, it may be more prevalent than the literature suggests, as symptoms of hypoglycemia-nausea, vomiting, and somnolence-mirror common chemotherapy side effects. 6MP-induced hypoglycemia can be ameliorated with the addition of allopurinol to shunt metabolism in favor of the production of therapeutic metabolites over hepatotoxic metabolites. Additionally, a morning administration of 6MP and frequent snacks may also help to prevent hypoglycemia. Overall, this case adds to the literature of unusual reactions to 6MP including hypoglycemia in an older child without traditional risk factors.

Vitamin D levels, insulin resistance, and cardiovascular risks in very young obese children.

OBJECTIVE: To examine the relationships of 25-hydroxyvitamin D (25-OHD) levels with the measures of insulin resistance and cardiovascular risk, and identify the clinical factors associated with low 25-OHD in young obese children. DESIGN AND METHODS: Data from 83 children ages 2-6 years seen for obesity care (clinic latitude 42°N) were analyzed. Insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] and cardiovascular risks were examined in relationship to 25-OHD levels using correlation statistics. χ2 and logistic regression models were applied to identify the factors associated with vitamin D deficiency (25-OHD levels <20 ng/mL) and insufficiency (<30 ng/mL). RESULTS: Children's mean age was mean 4.9 years and they were predominantly Hispanic. Mean body mass index (BMI) Z-score was 3.2 and mean HOMA-IR was 2.8. Mean 25-OHD was 30.9 ng/mL (6% <20 ng/mL and 46% 20-29 ng/mL). There were no significant correlations between 25-OHD and BMI (Spearman's ρ=-0.096, p=0.389), BMI Z-score (Spearman's ρ=0.104, p=0.350), HOMA-IR (Spearman's ρ=-0.144, p=0.269), total cholesterol (Spearman's ρ=-0.028, p=0.833), or triglycerides (Spearman's ρ=-0.026, p=0.846). Vitamin D deficiency was significantly associated with older age, lower milk intake, and testing in winter months. 25-OHD level <30 ng/mL was associated with older age, African-American and Hispanic race/ethnicity, and testing in winter months. All factors retained significance in a multivariate logistic regression model, with African-American (odds ratio=14.4) and Hispanic (odds ratio=7.2) race/ethnicity being the strongest predictors of 25-OHD levels <30 ng/mL. CONCLUSIONS: In these children, 25-OHD was not associated with insulin resistance or cardiovascular risks. Considering age, race/ethnicity, diet, and season may help identify young obese children needing vitamin D management.

Exogenous Insulin Antibody Syndrome in a Pediatric Patient: Successful Treatment with Mycophenolate Mofetil.

INTRODUCTION: Exogenous insulin antibody syndrome (EIAS) rarely occurs in type 1 diabetes and should be considered in those with blood glucose levels outside the target range requiring greater than 2 units/kg/day of insulin without obesity. We describe the novel treatment of this condition using mycophenolate mofetil monotherapy in a pediatric patient in the outpatient setting. CASE PRESENTATION: A 17-year-old Caucasian male with type 1 diabetes experienced an abrupt increase in insulin requirements from 1.7 to 3.3 units/kg/day. Total insulin level was 7 µIU/mL with free insulin of 4.8 µIU/mL (68% of the total insulin), suggesting the presence of insulin antibodies. Switching from insulin aspart to glulisine was unsuccessful as insulin requirements increased to 4.4 units/kg/day. Treatment with oral mycophenolate mofetil decreased insulin requirements to 1.4 units/kg/day after 7 months. Total and free insulin levels improved to 5.2 and 4.6 µIU/mL, respectively (free insulin was 88% of total insulin). No adverse effects were encountered. CONCLUSION: Mycophenolate mofetil monotherapy is successful in safely treating EIAS in a pediatric patient.

Oral Glucose Tolerance Testing Using Candy: A Sweet Solution to Improve Screening in Children with Cystic Fibrosis?

INTRODUCTION: Oral glucose tolerance testing is recommended for all children with CF older than 9 years, yet compliance remains poor across centers. METHODS: We performed a small pilot study assessing the glycemic curves and participant satisfaction in seven children and adolescents. RESULTS: We chose a dextrose-based candy (Nerds®) free of any fat, fiber, gelatin, or corn syrup and performed the candy OGTT 1-4 days following the standard oral dextrose solution OGTT. Glucose values at 120 min were similar between the candy and oral dextrose solution (p = 0.8986). CONCLUSIONS: Our small pilot suggests that a carefully selected candy alternative may result in similar glycemic OGTT when compared to the standard oral dextrose solution. However, some participants preferred the oral dextrose solution to candy due to having to consume a large volume in a short period of time. This may have significant implications as centers consider candy alternatives to increase OGTT adherence rates.

Adolescents with Type 2 Diabetes: Overcoming Barriers to Effective Weight Management.

The prevalence of type 2 diabetes (T2DM) among children and adolescents has remarkably increased in the last two decades, particularly among ethnic minorities. Management of T2DM is challenging in the adolescent population due to a constellation of factors, including biological, socioeconomic, cultural, and psychological barriers. Weight reduction is an essential component in management of T2DM as weight loss is associated with improvement in insulin sensitivity and glycemic status. A family centered and culturally appropriate approach offered by a multidisciplinary team is crucial to address the biological, psychosocial, cultural, and financial barriers to weight management in youth with T2DM. Lifestyle interventions and pharmacotherapy have shown modest efficacy in achieving weight reduction in adolescents with T2DM. Bariatric surgery is associated with excellent weight reduction and remission of T2DM in youth. Emerging therapies for weight reduction in youth include digital technologies, newer GLP-1 agonists and endoscopic procedures.

Patient Satisfaction Scores Impact Pediatrician Practice Patterns, Job Satisfaction, and Burnout.

Patient satisfaction (PS) surveying has become a commonly used measure of physician performance, but little is known about the impact on pediatricians. To investigate our hypothesis that PS surveys negatively impact pediatricians, we conducted a survey at an academic children's medical center. Of 155 eligible physicians, 115 responded (response rate 74%). Two-thirds (68%) did not find the PS score report useful and 88% did not feel that PS scores accurately reflect the physician's clinical ability. A third reported ordering tests, medications, or consultations due to pressure for higher PS scores. In addition, one-third agreed that PS surveys contribute to burnout and make it difficult to practice meaningful medicine. Overall, PS score reporting has a negative impact on pediatricians, especially those who are female, BIPOC (Black, Indigenous, and People of color), subspecialists, younger, and attended non-US medical schools. Further investigation into improved methods for providing feedback to pediatric physicians is warranted.

Copeptin levels in hospitalized infants and children with suspected vasopressin-dependent disorders: a case series.

OBJECTIVES: There have been recent advances assessing copeptin levels in adults with suspected disorders of vasopressin release. Very limited data exits on copeptin levels in children and infants, especially in a critically-ill hospitalized population where hyper- and hypo-natremia are very common. Our objective is to describe the institutional experience assessing copeptin levels in hospitalized infants and children with hyper- or hypo-natremia. METHODS: We performed a single-center retrospective case series of all infants, children, and adolescents who had an ultrasensitive plasma copeptin level obtained between 2019-2021. RESULTS: A total of 29 critically ill patients (6 infants) were identified with 38 % of patients having copeptin levels after neurosurgical procedures for tumors or trauma. Approximately 13/17 children with hypernatremia had central diabetes insipidus (central diabetes insipidus) to diagnose CDI, A copeptin level ≤ 4.9 pmol/L resulted in an 88 % sensitivity (95 % CI 47-99 %), and 66 % specificity (95 % CI 30-93 %). Amongst those with hyponatremia levels were more variable, 8/12 children had syndrome of inappropriate antidiuresis (SIAD) with copeptin levels ranging 4.7-72.6 pmol/L. CONCLUSIONS: While difficult to conclude due to multiple limitations, this case series highlights that typical copeptin cutoffs used to diagnose DI in adults in an ambulatory setting may also translate to a critically-ill pediatric population. Large prospective studies are needed to confirm this observation. In addition, postoperative copeptin levels could potentially be utilized as an additional marker to predict permanent from transient DI, but much larger studies are needed. Further work is needed to establish normative copeptin levels in infants and patients with SIAD.

Glucagon fill rates and cost among children and adolescents with type 1 diabetes in the United States, 2011-2021.

AIMS: To characterize glucagon fill rates and costs among youth with type 1 diabetes mellitus (T1DM). METHODS: Claims-based analysis of commercially-insured youth with T1DM included in OptumLabs® Data Warehouse between 2011 and 2021. Glucagon fill rates and costs were calculated overall and by formulation (injectable, intranasal, autoinjector, and pre-filled syringe). Sociodemographic and clinical factors associated with glucagon fills were examined using Cox regression. RESULTS: We identified 13,267 children with T1DM (76.4% non-Hispanic White). Over mean follow-up of 2.81 years (SD 2.62), 70.0% filled glucagon, with stable fill rates from 2011 to 2021. Intranasal glucagon had rapid uptake following initial approval, and it accounted for almost half (46.6%) of all glucagon fills by 2021. Family income was positively associated with glucagon fills in a stepwise fashion (HR 1.39 [95% CI 1.27-1.52] for annual household income ≥$200,000 vs. <$40,000), while Black race was negatively associated with fills (HR 0.83 [95% CI 0.76-0.91]) compared to White race). Annual mean out-of-pocket costs ranged from $21-$68 (IQR $29-$44). CONCLUSION: Roughly 30% of commercially-insured youth with T1DM may lack access to unexpired glucagon, with significant disparities among Black and low-income patients. Health systems, clinicians, schools, and caregivers should work together to ensure children have reliable access to this critical medication.