Background and Objectives: The recent developments in chronic thromboembolic pulmonary hypertension (CTEPH) are emphasizing the multidisciplinary team. We report on the changes in clinical practice following the development of a multidisciplinary team, based on our 7 years of experience. Methods: Multidisciplinary team was established in 2015 offering both balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) with technical upgrades by internal and external expertise. For operable cases, PEA was recommended as the primary treatment modality, followed by pulmonary angiography and right heart catheterization after 6 months to evaluate treatment effect and identify patients requiring further BPA. For patients with inoperable anatomy or high surgical risk, BPA was recommended as the initial treatment modality. Patient data and clinical outcomes were closely monitored. Results: The number of CTEPH treatments rapidly increased and postoperative survival improved after team development. Before the team, 38 patients were treated by PEA for 18 years; however, 125 patients were treated by PEA or BPA after the team for 7 years. The number of PEA performed was 64 and that of BPA 342 sessions. World Health Organization functional class I or II was achieved in 93% of patients. The patients treated with PEA was younger, male dominant, higher pulmonary artery pressure, and smaller cardiac index, than BPA-only patients. In-hospital death after PEA was only 1 case and none after BPA. Conclusions The balanced development of BPA and PEA through a multidisciplinary team approach proved synergistic in increasing the number of actively treated CTEPH patients and improving clinical outcomes.

Purpose: This study aimed to investigate the potential role of copine-1 (CPNE1), a calcium-dependent membrane-binding protein encoded by the CPNE1 gene, in colorectal cancer (CRC). Despite previous research on the involvement of copine family members in various solid tumors, the specific role of CPNE1 in CRC remains poorly understood. Methods: We conducted clinicopathological analysis and functional studies to explore the impact of CPNE1 in human CRC.We examined the expression levels of CPNE1 in CRC patients and correlated it with invasive depth, lymph node metastasis, distant metastasis, lymphatic invasion, and TNM stage. Additionally, we performed experiments to assess the functional consequences of CPNE1 knockdown in CRC cells, including proliferation, colony formation, migration, invasion, and the expression of key regulators involved in the cell cycle and epithelial-mesenchymal transition (EMT). Furthermore, we evaluated the effects of CPNE1 knockdown on tumor growth using a xenograft mouse model. Results: High expression of CPNE1 was significantly associated with advanced tumor features in CRC patients. CPNE1 knockdown in CRC cells led to impaired abilities in proliferation, colony formation, migration, and invasion. Furthermore, CPNE1 silencing resulted in the suppression of protein expression related to the cell cycle and EMT. In the xenograft mouse model, CPNE1 knockdown inhibited tumor growth. Conclusion CPNE1 plays a crucial role in promoting tumorigenesis and metastasis in human CRC. By regulating the cell cycle and EMT, CPNE1 influences critical cellular processes at the membrane-cytoplasm interface. These results provide valuable insights into the potential development of novel therapeutic strategies for CRC targeting CPNE1.

Background: Factors related to the development and severity of polycystic liver disease (PLD) have not been well established. We aimed to evaluate the genetic and epidemiologic risk factors of PLD in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: Adult patients with inherited cystic kidney disease were enrolled from May 2019 to May 2021. Demographic, clinical, and laboratory data were collected at the initial study visit. The severity of PLD was graded based on the height-adjusted total liver volume: < 1,000 mL/m (Gr1), 1,000–1,800 mL/m (Gr2), and > 1,800 mL/m (Gr3). Targeted exome sequencing was done by a gene panel including 89 ciliopathy-related genes. We searched out the relative factors to the presence and the severity of PLD using logistic regression analysis. Results: Of 602 patients with typical ADPKD, 461 (76.6%) patients had PLD. The patients with PLD showed female predominance and a higher frequency of other ADPKD-related complications. The genetic variants with truncating mutation of PKD1 (PKD1-proteintruncating [PT]) or PKD2 commonly affected the development and severity of PLD. An older age, female sex, and higher kidney volume with Mayo classification 1C-1E was significantly associated with the development of PLD, but not with the severity of PLD. On the other hand, higher body mass index, lower hemoglobin, and higher alkaline phosphatase (ALP) were the significant risk factors of severe PLD (≥ Gr2). Conclusion Hepatic involvement in ADPKD could be related to kidney manifestations and genetic variants including PKD1-PT or PKD2. Monitoring hemoglobin and ALP and evaluating the genetic variants might help predict severe PLD.

Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. Methods: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19–50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. Results: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, –0.642; p = 0.009). Conclusion: We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.

Identifying genetic mutations in individuals with inherited cystic kidney disease is necessary for precise treatment. We aimed to elucidate the genetic characteristics of cystic kidney disease in the Korean population. Methods: We conducted a 3-year prospective, multicenter cohort study at eight hospitals from May 2019 to May 2022. Patients with more than three renal cysts were enrolled and classified into two categories, typical autosomal dominant polycystic kidney disease (ADPKD) and atypical PKD. We identified the clinical characteristics and performed a genetic analysis using a targeted gene panel. Results: A total of 725 adult patients were included in the study, of which 560 (77.2%) were diagnosed with typical ADPKD and 165 (22.8%) had atypical PKD. Among the typical ADPKD cases, the Mayo imaging classification was as follows: 1A (55, 9.9%), 1B (149, 26.6%), 1C (198, 35.8%), 1D (90, 16.3%), and 1E (61, 11.0%). The atypical PKD cases were classified as bilateral cystic with bilateral atrophic (31, 37.3%), lopsided (27, 32.5%), unilateral (nine, 10.8%), segmental (eight, 9.6%), bilateral cystic with unilateral atrophic (seven, 8.4%), and asymmetric (one, 1.2%). Pathogenic variants were found in 64.3% of the patients using the ciliopathy-related targeted gene panel. The typical ADPKD group demonstrated a higher discovery rate (62.3%) than the atypical PKD group (41.8%). Conclusion: We present a nationwide genetic cohort’s baseline clinical and genetic characteristics for Korean cystic kidney disease.

Mayo imaging classification (MIC) is a useful biomarker to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). This study was performed to validate MIC in the prediction of renal outcome in a prospective Korean ADPKD cohort and evaluate clinical parameters associated with rapid disease progression. Methods: A total of 178 ADPKD patients were enrolled and prospectively observed for an average duration of 6.2 ± 1.9 years. Rapid progressor was defined as MIC 1C through 1E while slow progressor was defined as 1A through 1B. Renal composite outcome (doubling of serum creatinine, 50% decline of estimated glomerular filtration rate [eGFR], or initiation of renal replacement therapy) as well as the annual percent change of height-adjusted total kidney volume (mHTKV-α), and eGFR decline (mGFR-α) were compared between groups. Results: A total of 110 patients (61.8%) were classified as rapid progressors. These patients were younger and showed a higher proportion of male patients. Rapid progressor was an independent predictor for renal outcome (hazard ratio, 4.09; 95% confidence interval, 1.23–13.54; p = 0.02). The mGFR-α was greater in rapid progressors (–3.58 mL/min per year in 1C, –3.7 in 1D, and –4.52 in 1E) compared with that in slow progressors (–1.54 in 1A and –2.06 in 1B). The mHTKV-α was faster in rapid progressors (5.3% per year in 1C, 9.4% in 1D, and 11.7% in 1E) compared with that in slow progressors (1.2% in 1A and 3.8% in 1B). Conclusion: MIC is a good predictive tool to define rapid progressors in Korean ADPKD patients.

Objective: Mood disorder and borderline personality pathology (BPP) are frequently comorbid and relate to childhood trauma. We investigated the relationship between childhood trauma and BPP features in mood disorder patients versus controls. Methods: A total of 488 mood disorder patients, particularly major depressive disorder (MDD), bipolar I disorder (BD I), and bipolar II disorder (BD II), and 734 controls were included. We examined between-group BPP-related differences and correlated between BPP and childhood trauma using the Childhood Trauma Questionnaire-Short Form (CTQ) and the Personality Assessment Inventory–Borderline Features Scale. Results: BD II patients showed significantly higher BPP. Emotional abuse and neglect were prominently associated with BPP, while affective instability and negative relationships exhibited a stronger association with childhood trauma. We also found a positive relationship between childhood trauma and BPP in MDD, BD I, and BD II patients. Conclusion The findings of the present study imply that BPP features are more likely to be found in patients with BD II than BD I or MDD. Mood disorder patients with severe childhood trauma may have higher BPP features. Thus, further study of the relationship between childhood trauma and BPP features could improve the therapeutic approaches and help understand patients with mood disorders.

Childhood adrenocortical carcinoma (ACC) is a rare disease that is mostly linked to familial cancer syndrome. Although the prevalence of ACC is extremely low in children, it is clinically important to diagnose ACC early because age and tumor stage are closely related to prognosis. From this perspective, understanding the underlying genetics and possible symptoms of ACC is crucial in managing ACC with familial cancer syndromes. In this report, we present the case of a 3-year-old girl who initially presented with symptoms of precocious puberty and was later found to have ACC by imaging analysis. On genetic analysis, the patient was found to have a MEN1 gene mutation. MEN1 mutations are found in patients with multiple endocrine neoplasia type 1 (MEN1), usually precipitating multiple endocrine tumors, including pituitary adenoma, parathyroid hyperplasia, and adrenal tumors. Although MEN1 mutation is usually inherited in an autosomal dominant manner, neither of the patient’s parents had the same mutation, making hers a case of sporadic MEN1 mutation with initial presentation of ACC. The clinical course and further investigations of this patient are discussed in detail in this report.

Purpose: The aim of this study is to evaluate the effect of body mass index (BMI) on peak serum growth hormone (GH) level after GH stimulation test in children with short stature. Methods: Data were obtained from retrospective medical record reviews of those who visited the pediatric endocrine clinic at St. Vincent’s Hospital of Catholic University for short stature from January 2010 to June 2019. A total of 115 children (66 boys and 49 girls) whose height was less than the third percentile according to age and sex underwent GH stimulation testing. Results: Of the 115 subjects, 47 were diagnosed with GH deficiency (GHD) and 68 were diagnosed with idiopathic short stature (ISS). In patients with GHD, weight standard deviation score (SDS) (P<0.001) and BMI SDS (P≤0.001) were higher, and free thyroxine (T4) level (P=0.012) was lower than those in the ISS group. In total subjects, peak serum GH level after GH stimulation test showed negative correlations with weight SDS (r=-0.465, P<0.001), BMI SDS (r=-0.398, P<0.001), and thyroid stimulating hormone (r=-0.248, P=0.008) and a positive correlation with free T4 (r=0.326, P<0.001). In multiple regression analysis, BMI SDS (P=0.003) was negatively associated with peak serum GH level in GH stimulation testing after adjusting for age, sex, pubertal status, and type of pharmacological stimulus. Conclusion The BMI SDS influences peak serum GH level after GH stimulation testing. We should consider BMI factors when interpreting the results of GH stimulation testing.

Purpose: The aim of this study is to evaluate the effect of body mass index (BMI) on peak serum growth hormone (GH) level after GH stimulation test in children with short stature. Methods: Data were obtained from retrospective medical record reviews of those who visited the pediatric endocrine clinic at St. Vincent’s Hospital of Catholic University for short stature from January 2010 to June 2019. A total of 115 children (66 boys and 49 girls) whose height was less than the third percentile according to age and sex underwent GH stimulation testing. Results: Of the 115 subjects, 47 were diagnosed with GH deficiency (GHD) and 68 were diagnosed with idiopathic short stature (ISS). In patients with GHD, weight standard deviation score (SDS) (P<0.001) and BMI SDS (P≤0.001) were higher, and free thyroxine (T4) level (P=0.012) was lower than those in the ISS group. In total subjects, peak serum GH level after GH stimulation test showed negative correlations with weight SDS (r=-0.465, P<0.001), BMI SDS (r=-0.398, P<0.001), and thyroid stimulating hormone (r=-0.248, P=0.008) and a positive correlation with free T4 (r=0.326, P<0.001). In multiple regression analysis, BMI SDS (P=0.003) was negatively associated with peak serum GH level in GH stimulation testing after adjusting for age, sex, pubertal status, and type of pharmacological stimulus. Conclusion The BMI SDS influences peak serum GH level after GH stimulation testing. We should consider BMI factors when interpreting the results of GH stimulation testing.