Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Objective: This study aimed to evaluate the accuracy of predicting final adult height (FAH) in Korean girls with central precocious puberty (CPP) using artificial intelligence (AI)-derived bone age assessments integrated into the Bayley–Pinneau (BP) or Korean National Growth Chart (KGC) prediction models. Materials and Methods: This single-center, retrospective study included 122 Korean girls with CPP who received gonadotropinreleasing hormone agonist (GnRHa) treatment for at least two years between January 2000 and November 2022. We assessed bone age and predicted adult height at the initiation and completion of GnRHa treatment. We used three bone age assessment methods: human expert assessment based on the Greulich-Pyle (GP) atlas (Human-GP), AI-derived GP (AI-GP), and AI-weighted GP scoring (AI-GPw). We calculated predicted adult heights (PAHs) using both the BP and KGC models, generating 12 PAH estimates per patient (2 time points x 3 bone-age methods x 2 height-prediction models). We assessed prediction accuracy and agreement with FAH using linear regression analysis and Bland–Altman plots and performed multivariable analysis to identify significant predictors of FAH. Results: Human-GP, AI-GP, and AI-GPw demonstrated comparable overall performance in predicting FAH (R 2 : 0.470–0.646 and 0.691–0.822 for treatment initiation and completion, respectively). AI-GPw combined with BP yielded slightly better point estimates but showed no statistically significant differences. At both time points, the BP model demonstrated consistently narrower 95% limits of agreement (LoA) than the KGC model. Multivariable analysis identified AI-GPw-BP and height percentile score as significant predictors of FAH at both time points; mid-parental height was significant only at treatment initiation. Conclusion Human-GP, AI-GP, and AI-GPw demonstrated comparable accuracy in predicting FAH. The BP model demonstrated consistently narrower 95% LoA than did the KGC model. AI-GPw-BP was an independent predictor of FAH. These findings support the clinical utility of AI-derived bone age assessments for individualized FAH prediction in patients with CPP.

Background: TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. Methods: This study included patients aged ≥ 18 yrs who were diagnosed as having MDS(N = 1,244) or AML (N = 2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. Results: TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/ R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF > 50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Conclusions Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

Background: Primary Merkel cell carcinoma of the salivary gland is currently not listed in the World Health Organization classification. However, cases of Merkel cell type neuroendocrine carcinomas of the salivary gland with perinuclear cytokeratin 20 positivity have been intermittently reported. We here investigated the clinicopathologic features of additional cases. Methods: Data of four cases of Merkel cell type small cell neuroendocrine carcinoma of the salivary gland were retrieved. To confirm the tumors’ primary nature, clinical records and pathologic materials were reviewed. Optimal immunohistochemical staining was performed to support the diagnosis. Results: All tumors were located in the parotid gland. Possibilities of metastasis were excluded in all cases through a meticulous clinicopathological review. Tumor histology was consistent with the diagnosis of small cell neuroendocrine carcinoma. Tumors’ immunohistochemical phenotypes were consistent with Merkel cell carcinoma, including Merkel cell polyomavirus large T antigen positivity in two of the four cases. Conclusions Merkel cell carcinomas can originate in salivary glands and are partly associated with Merkel cell polyomavirus infection as in cutaneous Merkel cell carcinomas.

Purpose: Congenital hypothyroidism (CH) is a major preventable cause of intellectual disability, particularly in very low birth weight (VLBW) infants, who are at increased risk due to hypothalamic-pituitary-thyroid axis immaturity. Early differentiation between transient CH (TCH) and permanent CH (PCH) is crucial to optimize L-thyroxine (LT4) treatment duration. This study aimed to determine the incidence of PCH among Korean VLBW infants and to identify clinical factors that may aid in distinguishing TCH from PCH. Methods: This retrospective cohort study included VLBW infants diagnosed with CH and treated with LT4 at a single tertiary neonatal intensive care unit between 2011 and 2020. Infants requiring LT4 beyond 3 years were classified as PCH, while those who discontinued earlier were considered TCH. Clinical characteristics, neonatal morbidities, and thyroid-related parameters were compared between the groups. Results: Among 1,292 VLBW infants, 122 (9.4%) were diagnosed with CH. After excluding deaths and those lost to follow-up, 73 infants were included in the final analysis (TCH, n=50; PCH, n=23). The PCH group had a significantly higher mean gestational age and greater LT4 requirements at both 12 and 36 months of age. Major anomalies were more frequently observed in PCH infants, including congenital heart defects. In multivariate analysis, higher gestational age, the presence of major anomalies, screening thyroid-stimulating hormone (TSH) >10 μIU/mL, and higher LT4 dose at 36 months were significantly associated with PCH. Conclusion The incidence of PCH in Korean VLBW infants was relatively higher than that reported in previous studies studies. Screening TSH level and LT4 dose requirements may support individualized follow-up and help distinguish PCH from TCH.

Appendectomy as the standard treatment for acute appendicitis has been challenged by accumulating evidence supporting nonoperative management with antibiotics as a potential primary treatment. This review aimed to summarize the clinical outcomes and the optimal indications for nonoperative management of acute appendicitis in adults. Current evidence suggests that uncomplicated and complicated appendicitis have different pathophysiologies and should be treated differently. Nonoperative management for uncomplicated appendicitis was not inferior to appendectomy in terms of complications and length of stay, with less than a 30% failure rate at 1 year. The risk of perforation and postoperative complications did not increase even if nonoperative management failed. Complicated appendicitis with localized abscess or phlegmon could also be treated conservatively, with a success rate of more than 80%. An interval appendectomy following successful nonoperative management is recommended only for patients over the age of 40 years to exclude appendiceal malignancy. The presence of appendicoliths increased the risk of treatment failure and complications; thus, it may be an indication for appendectomy. Nonoperative management is a safe and feasible option for both uncomplicated and complicated appendicitis. Patients should be informed that nonoperative management may be a safe alternative to surgery, with the possibility of treatment failure.

Appendectomy as the standard treatment for acute appendicitis has been challenged by accumulating evidence supporting nonoperative management with antibiotics as a potential primary treatment. This review aimed to summarize the clinical outcomes and the optimal indications for nonoperative management of acute appendicitis in adults. Current evidence suggests that uncomplicated and complicated appendicitis have different pathophysiologies and should be treated differently. Nonoperative management for uncomplicated appendicitis was not inferior to appendectomy in terms of complications and length of stay, with less than a 30% failure rate at 1 year. The risk of perforation and postoperative complications did not increase even if nonoperative management failed. Complicated appendicitis with localized abscess or phlegmon could also be treated conservatively, with a success rate of more than 80%. An interval appendectomy following successful nonoperative management is recommended only for patients over the age of 40 years to exclude appendiceal malignancy. The presence of appendicoliths increased the risk of treatment failure and complications; thus, it may be an indication for appendectomy. Nonoperative management is a safe and feasible option for both uncomplicated and complicated appendicitis. Patients should be informed that nonoperative management may be a safe alternative to surgery, with the possibility of treatment failure.

Background/Aims: We previously reported that patients with moderate-to-severe ulcerative colitis (UC) often experience common mental disorders (CMDs) such as anxiety and depression, necessitating immediate psychological interventions within the first 4 weeks of diagnosis. In this 3-year follow-up study of the MOSAIK cohort in Korea, we examined the effects of CMDs at initial diagnosis on clinical outcomes and health-related quality of life (HRQoL). Methods: We examined differences in clinical outcomes (evaluated based on clinical response, relapse, hospitalization, and medication use) and HRQoL (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ] and Short Form 12 [SF-12]) according to Hospital Anxiety and Depression Scale (HADS) scores at diagnosis. Results: In a study involving 199 UC patients, 47.7% exhibited significant psychological distress (anxiety and/or depression) at diagnosis. Clinical follow-up showed no major differences in outcomes, including remission rates, response rates, or hospitalization rates, between patients with anxiety or depression at diagnosis and patients without anxiety or depression at diagnosis. The HRQoL at the end of follow-up was notably lower in those with baseline CMDs, particularly anxiety, across all domains of the IBDQ and SF-12. Linear mixed-effect models revealed that higher HADS scores, as well as higher Mayo scores, were independently associated with lower IBDQ scores and both summary domains of the SF-12. Additionally, regular attendance at follow-up visits during the study period was also related to improvements in HRQoL (all p<0.05). Conclusions While CMDs present at the time of UC diagnosis did not influence long-term clinical outcomes, they persistently impaired HRQoL. Our findings support the routine incorporation of psychological interventions into the long-term management of moderate-to-severe UC.

Appendectomy as the standard treatment for acute appendicitis has been challenged by accumulating evidence supporting nonoperative management with antibiotics as a potential primary treatment. This review aimed to summarize the clinical outcomes and the optimal indications for nonoperative management of acute appendicitis in adults. Current evidence suggests that uncomplicated and complicated appendicitis have different pathophysiologies and should be treated differently. Nonoperative management for uncomplicated appendicitis was not inferior to appendectomy in terms of complications and length of stay, with less than a 30% failure rate at 1 year. The risk of perforation and postoperative complications did not increase even if nonoperative management failed. Complicated appendicitis with localized abscess or phlegmon could also be treated conservatively, with a success rate of more than 80%. An interval appendectomy following successful nonoperative management is recommended only for patients over the age of 40 years to exclude appendiceal malignancy. The presence of appendicoliths increased the risk of treatment failure and complications; thus, it may be an indication for appendectomy. Nonoperative management is a safe and feasible option for both uncomplicated and complicated appendicitis. Patients should be informed that nonoperative management may be a safe alternative to surgery, with the possibility of treatment failure.

Appendectomy as the standard treatment for acute appendicitis has been challenged by accumulating evidence supporting nonoperative management with antibiotics as a potential primary treatment. This review aimed to summarize the clinical outcomes and the optimal indications for nonoperative management of acute appendicitis in adults. Current evidence suggests that uncomplicated and complicated appendicitis have different pathophysiologies and should be treated differently. Nonoperative management for uncomplicated appendicitis was not inferior to appendectomy in terms of complications and length of stay, with less than a 30% failure rate at 1 year. The risk of perforation and postoperative complications did not increase even if nonoperative management failed. Complicated appendicitis with localized abscess or phlegmon could also be treated conservatively, with a success rate of more than 80%. An interval appendectomy following successful nonoperative management is recommended only for patients over the age of 40 years to exclude appendiceal malignancy. The presence of appendicoliths increased the risk of treatment failure and complications; thus, it may be an indication for appendectomy. Nonoperative management is a safe and feasible option for both uncomplicated and complicated appendicitis. Patients should be informed that nonoperative management may be a safe alternative to surgery, with the possibility of treatment failure.