Annual Change in Fungal Concentrations and Allergic Sensitization Rates to Alternaria and Cladosporium in Korea During the Period 1998-2022.

PURPOSE: Atmospheric fungi are associated with respiratory allergies in humans, and some fungal spores can cause allergic diseases. Environmental and biological factors influence the concentrations of atmospheric spores. In this study, we evaluated the climate change-induced annual variations in fungal spore concentrations and allergic sensitization rates in the Seoul Metropolitan Area over a period of 25 years. METHODS: Fungal spores and pollen were obtained from Hanyang University Seoul and Guri Hospitals; they were identified and counted for 25 years (1998-2022). The study participants included patients who underwent tests for allergic diseases in both hospitals. Their allergenic sensitization rates were determined via allergic skin prick and serum tests, after which their sensitization rates to allergenic fungi and pollens were calculated. The daily climatic variables were obtained from the Korea Meteorological Administration. RESULTS: The total annual atmospheric fungal concentrations decreased in both areas during the period. Simultaneously, we recruited 21,394 patients with allergies (asthma, 1,550; allergic rhinitis, 5,983; and atopic dermatitis, 5,422) from Seoul and Guri Hospitals for allergenic fungal sensitization evaluations over the period. The allergenic fungal sensitization rates decreased annually in both areas over that time `+(Alternaria [3.5%] and Cladosporium [4.4%] in 1998; Alternaria [0.2%] and Cladosporium [0.2%] in 2022). In contrast, the annual pollen concentrations increased with the sensitization rates to pollen in children. CONCLUSIONS: The atmospheric fungal concentrations decreased annually, with allergic sensitization rate decreasing over the period of 25 years. Allergenic fungal sporulation could decrease with climate changes, such as desertification and drought. Extended monitoring periods and further large-scale studies are required to confirm the causality and to evaluate the impact of climate change.

Monthly versus daily administration of vitamin D3 in children: a retrospective propensity score-matched study.

Objectives: We aimed to evaluate the efficacy and safety of monthly vitamin D3 administration compared to a daily dosing regimen in healthy children with vitamin D deficiency. Methods: This retrospective study included vitamin D deficient (serum 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL) children with precocious puberty who received gonadotropin-releasing hormone agonist every 4 weeks between December 2019 and November 2022. We used propensity scores to 1:1 match daily (1,000 IU daily) and monthly (25,000 IU per 4 weeks) administration of vitamin D3 based on age, sex, body mass index Z-scores, season of blood collection, and baseline serum 25(OH)D concentrations. Results: Of 299 children, 192 were matched based on propensity scores (126 girls and 66 boys, 10.5 ± 1.4years). After a mean follow-up of 5.9 months (standard deviation [SD] 2.5 months), the monthly group showed a statistically significant increase in serum 25(OH)D concentrations (10.9 ± 5.3 vs. 8.2 ± 7.2 ng/mL; p = 0.018), higher corrected dose-response (12.3 ± 5.9 vs. 8.2 ± 7.2 ng/mL increase per 1,000 IU daily; p = 0.002), and a higher proportion of patients attaining 25(OH)D > 20 ng/mL (78.1% vs. 58.3%,; p=0.005) compared with the daily group. No cases of hypercalcemia were observed in either group. Conclusions: Monthly administration of vitamin D3 may be an effective and safe alternative to correct hypovitaminosis D in pediatric population, possibly attributed to enhanced compliance.

Rapid weight gain in early life is associated with central precocious puberty in girls, not in boys - a nationwide population-based study in Korea.

Objectives: This study aimed to investigate the effect of rapid weight gain (RWG) on the incidence of central precocious puberty (CPP) using nationwide population-based data. Methods: A total of 253,967 children (101,841 boys and 152,126 girls) who underwent regular health consultations under the National Health Insurance Service from 2007 to 2010 were followed up until the age of 10 years for boys and 9 years for girls. We calculated differences in the weight Z-scores from 4-6 months to 9-12 months (infancy) and from 9-12 months to 18-24 months or 30-36 months (toddlerhood) using the lambda-mu-sigma method. The population was subdivided into four groups: RWGinf/tod (infancy > + 0.67 standard deviation score [SDS], toddlerhood > 0 SDS), RWGinf (infancy > + 0.67 SDS, toddlerhood < 0 SDS), RWGtod (toddlerhood > + 0.67 SDS), and control (no RWG). The diagnosis of CPP was based on the diagnostic codes of the International Classification of Diseases 10th revision and the prescription of gonadotropin-releasing hormone agonists. The cumulative risk of CPP based on age was analyzed using Kaplan-Meier survival curves, and the association between the RWG groups and CPP was assessed using multivariate logistic regression analysis. Results: CPP was diagnosed in 268 boys and 9,225 girls. For the girls, the CPP-free probability was the highest in the control group, followed by the RWGtod, RWGinf, and RWGinf/tod groups (log-rank p < 0.001). However, the incidence of CPP did not vary significantly for the boys. Compared to the control group, the other groups had a higher risk of CPP in girls (RWGinf/tod: adjusted odds ratio [aOR] 1.35, 95%, confidence interval [95% CI] 1.13-1.62; RWGinf: aOR 1.25, 95% CI 1.13-1.38; and RWGtod: aOR 1.18, 95% CI 1.09-1.28). Conclusions: This nationwide population-based study demonstrated that any RWG from birth to 3 years of age contributed to an increased risk of CPP in girls but not in boys. Girls who experienced RWG during both infancy and toddlerhood had the highest risk of developing CPP. These findings suggest that early detection and appropriate management of excessive weight gain in early life may be important for preventing CPP in girls.

Risk factors of postoperative hypoparathyroidism after total thyroidectomy in pediatric patients with thyroid cancer.

PURPOSE: Hypoparathyroidism (hypoPTH) is the most common complication following thyroidectomy. We investigated the frequency and risk factors of hypoPTH after total thyroidectomy (TT) in pediatric patients with thyroid cancer. METHODS: This retrospective study included 98 patients younger than 20 years who were diagnosed with thyroid cancer after T T during 1990-2018 and followed for more than 2 years at Seoul National University Hospital. HypoPTH was defined as receiving active vitamin D (1-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol) after surgery. RESULTS: The study included 27 boys (27.6%) and 71 girls (72.4%). The mean age at diagnosis was 14.9±3.7 years. HypoPTH occurred in 43 patients (43.9%). Twenty-one patients (21.4%) discontinued active vitamin D less than 6 months after surgery, while 14 (14.3%) continued active vitamin D for more than 2 years. Tumor multifocality (odds ratio [OR], 3.7 vs. single tumor; P=0.013) and preoperative calcium level (OR, 0.2; P=0.028) were independent predictors of hypoPTH immediately after TT. In addition, age (OR, 0.8; P=0.011) and preoperative calcium level (OR, 0.04; P=0.014) significantly decreased the risk for persistent hypoPTH requiring active vitamin D for more than 2 years. CONCLUSION: HypoPTH occurred in 43.9% of pediatric thyroid cancer patients after TT in this study. Among them, one-third of patients continued active vitamin D medication for more than 2 years, which was predicted by young age and low preoperative calcium level.

Free, bioavailable 25-hydroxyvitamin D levels and their association with diabetic ketoacidosis in children with type 1 diabetes at diagnosis.

Background: Considering the roles of 25-hydroxyvitamin D (25OHD) in glucose homeostasis and immune modulation, vitamin D deficiency may be related to the development of type 1 diabetes (T1DM) and diabetic ketoacidosis (DKA). We evaluated the total, free, bioavailable 25OHD levels and vitamin D binding protein (VDBP) levels and genotypes between T1DM patients and controls. Methods: This retrospective, cross-sectional study included 84 children with T1DM (38 boys and 46 girls, 8.0 ± 3.6 years) and 1:1 age- and sex-matched healthy controls. A multiplex liquid chromatography-tandem mass spectrometry-based assay was used to simultaneously measure vitamin D metabolites. Results: Patients with T1DM had lower levels of total 25OHD (16.3 ± 5.1 vs. 19.9 ± 6.5 ng/mL, P< 0.001) and VDBP (146.0 ± 27.8 vs. 224.9 ± 36.1 µg/mL, P = 0.001), but higher free 25OHD (8.0 ± 2.5 vs. 6.5 ± 2.3 pg/mL, P< 0.001) than controls. Patients who presented with DKA had lower levels of 25OHD in the total (15.0 ± 4.6 vs. 17.6 ± 5.2 ng/mL, P = 0.020), free (7.5 ± 2.6 vs. 8.4 ± 2.4 pg/mL, P = 0.059), and bioavailable (2.3 ± 0.9 vs. 2.8 ± 0.8 ng/mL, P = 0.014) forms than those without DKA at the T1DM diagnosis. The lower the total, free, and bioavailable 25OHD levels at diagnosis, the lower the pH and HCO3-. The proportions of the VDBP genotypes did not differ between the patients and controls. Conclusion: Patients with T1DM had higher levels of free 25OHD than healthy children, despite lower levels of total 25OHD. However, patients with DKA exhibited lower levels of bioavailable 25OHD than those without DKA at the T1DM diagnosis. The lower the concentrations of free and bioavailable 25OHD, the more severe the acidosis at the initial T1DM presentation.

Case Report and Review of Literature: Autosomal Recessive Hypophosphatemic Rickets Type 2 Caused by a Pathogenic Variant in ENPP1 Gene.

Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hereditary rickets, which is characterized by defective bone mineralization and renal phosphate wasting due to a loss-of-function variant in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene. Although pathogenic variant of ENPP1 has been known to manifest other phenotypes including arterial calcification, hearing loss, ossification of posterior longitudinal ligament, or pseudoxanthoma elasticum, there have been few reports including systematic examination in individuals diagnosed with ARHR2 to date. Herein, we report a case of ARHR2 with a bi-allelic pathogenic variant of ENPP1, in which the patient presented with gait abnormalities with severe genu varum at 26 months of age. Targeted gene panel sequencing was performed to investigate the genetic cause of rickets, and a homozygous nonsense variant in ENPP1, c.783C>G (p.Tyr261*), was identified. The patient was treated with oral phosphate and active vitamin D supplements and underwent corrective osteotomy for varus deformity. His phenotype was limited to rickets. A periodic systematic evaluation is needed to identify any comorbidities in ARHR2 patients since ENPP1 variants may present phenotypes other than rickets and symptoms may evolve or change over time.

Temporal Trends for Diabetes Management and Glycemic Control Between 2010 and 2019 in Korean Children and Adolescents with Type 1 Diabetes.

Purpose: There is increasing use of modern devices in the management of patients with type 1 diabetes (T1D). We investigated temporal trends for diabetes management and outcomes in Korean pediatric T1D patients over 10 years. Methods: We retrospectively collected the data from 752 participants (boys: 311, 41.4%) diagnosed with T1D and aged ≤18 years, with ≥1 year of follow-up between 2010 and 2019 in any of the seven study hospitals in Korea. Results: Over the 10-year study period, use of continuous glucose monitoring (CGM) increased from 1.4% to 39.3%. From 2010 to 2019, there was an increased use of multiple daily insulin injections (MDI; 63.9%-77.0%, respectively) and continuous subcutaneous insulin infusion (CSII; 2.1%-14.0%, respectively), but decreased use of conventional insulin therapy (CIT, 33.9%-9.0%, respectively). Mean glycated hemoglobin (HbA1c) decreased from 8.56% to 8.01% (P < 0.001) and was lower in younger patients, boys, and CGM users (P < 0.001). MDI and CSII users had lower mean HbA1c levels than CIT users (P = 0.003). Regarding the acute complications of T1D, CGM use was associated with lower incidences of diabetic ketoacidosis (P = 0.015); CSII users were likely to experience less severe hypoglycemia (P = 0.008). Conclusions: The use of CSII and CGM increased ∼7- and 30-fold, respectively, over the 10-year study period. The glycemic control of pediatric T1D patients in Korea improved from 2010 to 2019, probably because of increased use of T1D technologies.