Purpose: To investigate the clinical characteristics and genetic features of childhood-onset congenital combined pituitary hormone deficiency (cCPHD) in Korean patients. Methods: We retrospectively analyzed 444 patients diagnosed with childhood-onset CPHD at a tertiary center between 1994 and 2021. After excluding acquired case, 43 patients with cCPHD were enrolled. Anthropometric measurements, hormone evaluations, brain magnetic resonance imaging (MRI), extrapituitary phenotypes, and adult outcomes were analyzed. Genetic analyses were performed on 26 patients using a targeted gene panel or whole exome sequencing. Results: Mean age at diagnosis was 3.2 years, and 41.9% were diagnosed at less than 1 year old. Short stature was the most frequent (37.2%) initial presentation, and mean height z-score was -2.4. More than half (n=23, 53.5%) of patients had neonatal features suggestive of hypopituitarism; however, only 15 (65.2%) were diagnosed in infancy. Growth hormone deficiency (GHD) was prevalent in 42 (97.7%), and 33 (76.7%) had 3 or more hormone deficiencies. Extrapituitary phenotypes were identified in 31 (72.1%). Brain MRI abnormalities correlated with a higher number of hormone deficiencies (P for trend 0.049) and were present in 33 patients (80.5%). Adult GHD was diagnosed in all 17 investigated patients, and metabolic disturbances were noted in 10 (58.9%). Pathogenic variants in POU1F1, GLI2, HESX1, TBC1D32, and ROBO1 were found in 5 (19.2%). Conclusion Considering the high proportion of neonatal presentations, identification of the early neonatal features of hypopituitarism to manage pituitary and extrapituitary phenotypes is critical. The genetic etiology of cCPHD warrants further exploration.

Purpose: To investigate the clinical characteristics and genetic features of childhood-onset congenital combined pituitary hormone deficiency (cCPHD) in Korean patients. Methods: We retrospectively analyzed 444 patients diagnosed with childhood-onset CPHD at a tertiary center between 1994 and 2021. After excluding acquired case, 43 patients with cCPHD were enrolled. Anthropometric measurements, hormone evaluations, brain magnetic resonance imaging (MRI), extrapituitary phenotypes, and adult outcomes were analyzed. Genetic analyses were performed on 26 patients using a targeted gene panel or whole exome sequencing. Results: Mean age at diagnosis was 3.2 years, and 41.9% were diagnosed at less than 1 year old. Short stature was the most frequent (37.2%) initial presentation, and mean height z-score was -2.4. More than half (n=23, 53.5%) of patients had neonatal features suggestive of hypopituitarism; however, only 15 (65.2%) were diagnosed in infancy. Growth hormone deficiency (GHD) was prevalent in 42 (97.7%), and 33 (76.7%) had 3 or more hormone deficiencies. Extrapituitary phenotypes were identified in 31 (72.1%). Brain MRI abnormalities correlated with a higher number of hormone deficiencies (P for trend 0.049) and were present in 33 patients (80.5%). Adult GHD was diagnosed in all 17 investigated patients, and metabolic disturbances were noted in 10 (58.9%). Pathogenic variants in POU1F1, GLI2, HESX1, TBC1D32, and ROBO1 were found in 5 (19.2%). Conclusion Considering the high proportion of neonatal presentations, identification of the early neonatal features of hypopituitarism to manage pituitary and extrapituitary phenotypes is critical. The genetic etiology of cCPHD warrants further exploration.

Purpose: To investigate the clinical characteristics and genetic features of childhood-onset congenital combined pituitary hormone deficiency (cCPHD) in Korean patients. Methods: We retrospectively analyzed 444 patients diagnosed with childhood-onset CPHD at a tertiary center between 1994 and 2021. After excluding acquired case, 43 patients with cCPHD were enrolled. Anthropometric measurements, hormone evaluations, brain magnetic resonance imaging (MRI), extrapituitary phenotypes, and adult outcomes were analyzed. Genetic analyses were performed on 26 patients using a targeted gene panel or whole exome sequencing. Results: Mean age at diagnosis was 3.2 years, and 41.9% were diagnosed at less than 1 year old. Short stature was the most frequent (37.2%) initial presentation, and mean height z-score was -2.4. More than half (n=23, 53.5%) of patients had neonatal features suggestive of hypopituitarism; however, only 15 (65.2%) were diagnosed in infancy. Growth hormone deficiency (GHD) was prevalent in 42 (97.7%), and 33 (76.7%) had 3 or more hormone deficiencies. Extrapituitary phenotypes were identified in 31 (72.1%). Brain MRI abnormalities correlated with a higher number of hormone deficiencies (P for trend 0.049) and were present in 33 patients (80.5%). Adult GHD was diagnosed in all 17 investigated patients, and metabolic disturbances were noted in 10 (58.9%). Pathogenic variants in POU1F1, GLI2, HESX1, TBC1D32, and ROBO1 were found in 5 (19.2%). Conclusion Considering the high proportion of neonatal presentations, identification of the early neonatal features of hypopituitarism to manage pituitary and extrapituitary phenotypes is critical. The genetic etiology of cCPHD warrants further exploration.

β-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified solubleβ-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation.Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived β-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.

Objective: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). Materials and Methods: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm 2 was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive.The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). Results: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4–79.9), 90.8% (95% CI: 85.6–94.2), and 83.5% (95% CI: 78.6–87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8–97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9–89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1–79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52–0.63) before training and 0.68 (95% CI: 0.62–0.74) after training, with a difference of 0.11 (95% CI: 0.02–0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69–0.74) before training and 0.79 (95% CI: 0.76–0.80) after training (P = 0.002). Conclusion Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.

OBJECTIVES: This study investigated the reporting rates of adverse events following immunization (AEFIs) to the spontaneous reporting system (SRS) and its predictors among individuals with AEFIs after coronavirus disease 2019 (COVID-19) vaccination. METHODS: A cross-sectional, web-based survey was conducted from December 2, 2021 to December 20, 2021, recruiting participants >14 days after completion of a primary COVID-19 vaccination series. Reporting rates were calculated by dividing the number of participants who reported AEFIs to the SRS by the total number of participants who experienced AEFIs. We estimated adjusted odds ratios (aORs) using multivariate logistic regression to determine factors associated with spontaneous AEFIs reporting. RESULTS: Among 2,993 participants, 90.9% and 88.7% experienced AEFIs after the first and second vaccine doses, respectively (reporting rates, 11.6 and 12.7%). Furthermore, 3.3% and 4.2% suffered moderate to severe AEFIs, respectively (reporting rates, 50.5 and 50.0%). Spontaneous reporting was more prevalent in female (aOR, 1.54; 95% confidence interval [CI], 1.31 to 1.81); those with moderate to severe AEFIs (aOR, 5.47; 95% CI, 4.45 to 6.73), comorbidities (aOR, 1.31; 95% CI, 1.09 to 1.57), a history of severe allergic reactions (aOR, 2.02; 95% CI, 1.47 to 2.77); and those who had received mRNA-1273 (aOR, 1.25; 95% CI, 1.05 to 1.49) or ChAdOx1 (aOR, 1.62; 95% CI, 1.15 to 2.30) vaccines versus BNT162b2. Reporting was less likely in older individuals (aOR, 0.98; 95% CI, 0.98 to 0.99 per 1-year age increment). CONCLUSIONS Spontaneous reporting of AEFIs after COVID-19 vaccination was associated with younger age, female sex, moderate to severe AEFIs, comorbidities, history of allergic reactions, and vaccine type. AEFIs under-reporting should be considered when delivering information to the community and in public health decision-making.

Hypernatremia is a common electrolyte disorder in children and elderly people and has high short-term mortality. However, no high-quality studies have examined the correction rate of hypernatremia and the amount of fluid required for correction. Therefore, in this study, we will compare the efficacy and safety of rapid intermittent bolus (RIB) and slow continuous infusion (SCI) of electrolyte-free solution in hypernatremia treatment. Methods: This is a prospective, investigator-initiated, multicenter, open-label, randomized controlled study with two experimental groups. A total of 166 participants with severe hypernatremia will be enrolled and divided into two randomized groups; both the RIB and SCI groups will be managed with electrolyte-free water. We plan to infuse the same amount of fluid to both groups, for 1 hour in the RIB group and continuously in the SCI group. The primary outcome is a rapid decrease in serum sodium levels within 24 hours. The secondary outcomes will further compare the efficacy and safety of the two treatment protocols. Conclusion: This is the first randomized controlled trial to evaluate the efficacy and safety of RIB correction compared with SCI in adult patients with severe hypernatremia.