Purpose: Rare diseases necessitate consistent access to specialized health services. In Korea, despite the growing socioeconomic burden, insufficient comprehensive research is available on patients with rare diseases and their families, particularly concerning factors influencing the length of time to diagnosis. The aim of this study was to thoroughly characterize rare pediatric diseases and explore factors impacting the diagnostic odyssey. Methods: The study enrolled patients under 15 years old seeking medical care at the Seoul National University Children’s Hospital Rare Disease Center between January 2022 and December 2023. Participating patients were required to have been diagnosed with one of the 1,248 rare diseases recognized in Korea. A 33-question survey was developed to assess clinical features of the patients, characteristics of their primary caregivers, and their perceptions of ongoing medical care. Results: The study included 101 patients and their families. Regarding perceived cognitive and motor functions, most families indicated moderate or severe limitations (cognitive, 62.4%; motor, 57.4%). Over half of the families (53.5%) reported discontinuing employment to provide patient care. Neurological symptoms represented the most common initial chief concern, with dermatologic symptoms and laboratory test abnormalities also noted. Three factors were associated with time to diagnosis: the number of hospitals visited, whether the districts of residence and diagnosis aligned, and the age at symptom onset. Conclusion The comprehensive characterization of patients with rare diseases and their families in Korea, along with the identification of factors impacting the diagnostic odyssey, provides key insights for the development of a tailored support system.

Background/Aims: This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. Methods: The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Results: Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Conclusions Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Biliary hamartomas are tumor-like malformations of the liver. Biliary hamartomas are a type of fibrocystic disorder originating from ductal plate malformation and are typically considered benign, but with the risk of malignant transformation. In this case report, we present a rare occurrence of intrahepatic cholangiocarcinoma (ICC) that developed from biliary hamartomas, along with a literature review. A 76-year-old man with a diagnosis of biliary hamartomas had a history of recurrent cholangitis for 12 years, necessitating cholecystectomy, ERCP, and repeated antibiotic treatments. During his last episode, imaging studies revealed a hypervascular infiltrative mass in the right posterior liver segment. A liver biopsy confirmed adenocarcinoma and subsequent surgical pathology revealed ICC originating from biliary hamartomas. Chronic inflammation in the bile duct associated with biliary hamartomas may serve as a potential trigger for malignant transformation, as observed in this case. Therefore, close surveillance is essential for patients with biliary hamartomas presenting with infectious complications.

PURPOSE: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. MATERIALS AND METHODS: Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. RESULTS: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). CONCLUSIONS: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.
Ascites ; Biomarkers ; Carcinoembryonic Antigen ; Carcinoma ; Cohort Studies ; Diagnosis ; Down-Regulation ; Exosomes ; Humans ; Liver ; MicroRNAs ; Prognosis ; RNA ; Stomach Neoplasms

BACKGROUND: Patients who survive an acute phase of stroke are at risk of falls and fractures afterwards. However, it is largely unknown how frequent fractures occur in the Asian stroke population. METHODS: Patients with acute (< 7 days) ischemic stroke who were hospitalized between January 2011 and November 2013 were identified from a prospective multicenter stroke registry in Korea, and were linked to the National Health Insurance Service claim database. The incidences of fractures were investigated during the first 4 years after index stroke. The cumulative incidence functions (CIFs) were estimated by the Gray's test for competing risk data. Fine and Gray model for competing risk data was applied for exploring risk factors of post-stroke fractures. RESULTS: Among a total of 11,522 patients, 1,616 fracture events were identified: 712 spine fractures, 397 hip fractures and 714 other fractures. The CIFs of any fractures were 2.63% at 6 months, 4.43% at 1 year, 8.09% at 2 years and 13.00% at 4 years. Those of spine/hip fractures were 1.11%/0.61%, 1.88%/1.03%, 3.28%/1.86% and 5.79%/3.15%, respectively. Age by a 10-year increment (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.17–1.30), women (HR, 1.74; 95% CI, 1.54–1.97), previous fracture (HR, 1.72; 95% CI, 1.54–1.92) and osteoporosis (HR, 1.44; 95% CI, 1.27–1.63) were independent risk factors of post-stroke fracture. CONCLUSION: The CIFs of fractures are about 8% at 2 years and 13% at 4 years after acute ischemic stroke in Korea. Older age, women, pre-stroke fracture and osteoporosis raised the risk of post-stroke fractures.
Accidental Falls ; Asian Continental Ancestry Group ; Epidemiology ; Female ; Hip Fractures ; Humans ; Incidence ; Korea ; National Health Programs ; Osteoporosis ; Prospective Studies ; Risk Factors ; Spine ; Stroke

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m² or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m² (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m² along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m². CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m² and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.
Anemia ; Antigens, Surface ; Bilirubin ; Case-Control Studies* ; Female ; Glomerular Filtration Rate ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Male ; Multivariate Analysis ; Prevalence ; Proteinuria ; Renal Insufficiency, Chronic*

BACKGROUND/AIMS: This study analyzed the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic solid masses in patients with or without chronic pancreatitis as well as the clinical parameters relevant to a malignancy when EUS-FNA was negative or inconclusive. METHODS: A total of 97 patients, who underwent EUS-FNA for solid pancreatic masses over 2 years at a single institution, were evaluated. All patients underwent EUS-FNA for 3-5 passes with 22 or 25 G needles without an on-site cytopathologist. The final diagnosis was obtained by surgery or compatible clinical outcomes for a more than 12 month follow-up. The diagnostic yields in the patients with or without chronic pancreatitis were compared and the histories and laboratory data relevant to pancreatic ductal adenocarcinoma (PDAC) or pseudo-tumor were analyzed. RESULTS: The final diagnoses were adenocarcinoma in 88 patients (90.7%) and inflammatory pseudo-tumor in 9 (9.3%). The results of EUS-FNA were adenocarcinoma (74), suspicious (7), atypical (5), negative (10), and inadequate specimen (1). The diagnostic accuracies were 76.9% and 91.6% in patients with or without chronic pancreatitis, respectively. Among the 23 cases with non-diagnostic results of EUS-FNA, PDAC was finally diagnosed in 5 out of 7 suspicious, 3 out of 5 atypical, and 5 out of 10 negative cytology cases. The clinical parameters related to a pseudo-tumor were a history of alcohol consumption and pancreatitis, and normal alkaline phosphatase levels. CONCLUSIONS: The diagnostic accuracy of pancreatic masses in the background of chronic pancreatitis was low. When EUS-FNA produced inconclusive results, the histories of alcohol consumption, pancreatitis, and serum levels of alkaline phosphatase are useful for making a final diagnosis.
Adenocarcinoma ; Alcohol Drinking ; Alkaline Phosphatase ; Biopsy, Fine-Needle* ; Diagnosis ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Endosonography ; Follow-Up Studies ; Humans ; Needles ; Pancreatic Ducts ; Pancreatic Neoplasms ; Pancreatitis ; Pancreatitis, Chronic

BACKGROUND/AIMS: Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. METHODS: We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. RESULTS: A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27–96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. CONCLUSIONS: A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection.
Anemia ; Dizziness ; Dyspepsia ; Female ; Fibrosis ; Genotype ; Headache ; Hepacivirus* ; Hepatitis C* ; Hepatitis C, Chronic ; Hepatitis* ; Humans ; Korea ; Retrospective Studies* ; Ribavirin* ; RNA ; Sofosbuvir*

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and brushing cytology are used worldwide to diagnose pancreatic and biliary malignant tumors. Liquid-based cytology (LBC) has been developed and it is currently used to overcome the limitations of conventional smears (CS). In this study, the authors aimed to compare the diagnostic value of the CellPrepPlus (CP; Biodyne) LBC method with CS in samples obtained using EUS-FNA and brushing cytology. METHODS: This study prospectively enrolled 75 patients with pancreatic or biliary lesions from June 2012 to October 2013. For cytological analyses, including inadequate specimens, benign and atypical were further classified into benign, and suspicious and malignant were subcategorized as malignant. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were evaluated. RESULTS: In the EUS-FNA based cytological analysis of pancreatic specimens, CP had a sensitivity of 60.7%; specificity, 100%; accuracy, 77.1%; PPV, 100%; and NPV, 64.5%. CS had a sensitivity of 85.7%; specificity, 100%; accuracy, 91.7%; PPV, 100%; and NPV, 83.3%. In the brushing cytology based analysis of biliary specimens, CP had sensitivity of 53.1%; specificity, 100%; accuracy, 54.5%; PPV, 100%; and NPV, 6.3%. CS had a sensitivity of 78.1%; specificity, 100%; accuracy, 78.8%; PPV, 100%; and NPV, 12.5%. CONCLUSIONS: Our study found that CP had a lower sensitivity because of low cellularity compared with CS. Therefore, CP (LBC) has a lower diagnostic accuracy for pancreatic EUS-FNA based and biliary brush cytology based analyses compared with CS.
Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Humans ; Methods ; Prospective Studies ; Sensitivity and Specificity

BACKGROUND/AIMS: The combination of daclatasvir (DCV) and asunaprevir (ASV) has demonstrated a high sustained virologic response at 12 weeks (SVR12) and a low rate of adverse events in previous clinical studies. The purpose of this study was to clarify the results of treatment and side effects in Korean patients with chronic hepatitis C virus (HCV) genotype Ib infection. METHODS: We retrospectively analyzed clinical data from chronic HCV genotype Ib patients treated with DCV+ASV from August 2015 to September 2016 at five hospitals in the Daejeon-Chungcheong area. RESULTS: A total of 152 patients were examined for resistance associated variants (RAVs). Among them, 15 (9.9%) were positive for Y93 and one (0.7%) was positive for L31. Of 126 patients treated with DCV+ASV, 83 patients completed treatment and 76 patients were included in safety and efficacy analysis. Five (6.6%) were positive for Y93 and 12 (15.8%) exhibited cirrhotic change. DCV+ASV was the first-line treatment for 58 (76.3%) patients. Eleven (14.5%) patients relapsed after previous treatment that included interferon and seven (9.2%) of these patients were found to be intolerant of interferon. Adverse events occurred in 10 (13.2%) patients and two patients stopped the medication because of severe itching and skin rash. SVR12 was 89.5% (68/76) in all patients and 91.5% (65/71) in RAV-negative patients. CONCLUSIONS: DCV+ASV showed good efficacy in patients with HCV Ib infection in Korea. Close monitoring is needed for severe adverse events and treatment failure, which were uncommon.
Exanthema ; Genotype* ; Hepatitis C, Chronic ; Humans ; Interferons ; Korea ; Nicardipine ; Pruritus ; Retrospective Studies* ; Treatment Failure