Holoprosencephaly (HPE) is a rare congenital disorder characterized by the incomplete separation of the prosencephalon. The clinical spectrum of HPE depends on the subtypes observed on imaging, which includes lobar, semilobar, and alobar variants. Cyclopia, the most severe form of alobar HPE, is typically associated with early postnatal death within a few days. We report the case of a female infant was born at 38 weeks and 6 days of gestation, weighing 2,410 g, to a 39-year-old mother via vaginal delivery. She was the second baby of dichorionic-diamniotic twins. The neonate was born with multiple defects including facial anomalies such as cyclopia and arrhinia and was diagnosed with alobar HPE with cyclopia. This condition was suspected prenatally at 17 weeks of gestation and confirmed postnatally using brain magnetic resonance imaging. The cause of death in our patient was aspiration pneumonia with aggravated central apnea, and she survived for 8 months (240 days) with comfort care alone, without aggressive life support. This is the first report of an infant with alobar HPE, cyclopia, and arrhinia surviving for 240 days with only comfort care, marking the longest documented survival for this typically lethal condition without invasive interventions.

Background and Objectives: This study aimed to analyze the outcomes of Fontan surgery in the Republic of Korea, as there were only a few studies from Asian countries. Methods: The medical records of 1,732 patients who underwent Fontan surgery in 10 cardiac centers were reviewed. Results: Among them, 1,040 (58.8%) were men. The mean age at Fontan surgery was 4.3±4.2 years, and 395 (22.8%) patients presented with heterotaxy syndrome. According to the types of Fontan surgery, 157 patients underwent atriopulmonary (AP) type; 303, lateral tunnel (LT) type; and 1,266, extracardiac conduit (ECC) type. The overall survival rates were 91.7%, 87.1%, and 74.4% at 10, 20, and 30 years, respectively. The risk factors of early mortality were male, heterotaxy syndrome, AP-type Fontan surgery, high mean pulmonary artery pressure (mPAP) in pre-Fontan cardiac catheterization, and early Fontan surgery year. The risk factors of late mortality were heterotaxy syndrome, genetic disorder, significant atrioventricular valve regurgitation (AVVR) before Fontan surgery, high mPAP in pre-Fontan cardiac catheterization, and no fenestration. Conclusions In Asian population with a high incidence of heterotaxy syndrome, the heterotaxy syndrome was identified as the poor prognostic factors for Fontan surgery. The preoperative low mPAP and less AVVR are associated with better early and long-term outcomes of Fontan surgery.

Purpose: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response. Materials and Methods: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins. Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways. Conclusions These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.

Purpose: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette–Guérin (BCG) therapy. Materials and Methods: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. Results: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively;p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien– Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). Conclusions Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.