Loeys-Dietz syndrome is a hereditary connective-tissue disorder first reported in 2005. It is caused by genetic defects in the transforming growth factor-beta (TGF-β) signaling pathway. TGF-β signaling plays an important role in connective-tissue development, differentiation, and homeostasis. Dysregulation of TGF-β signaling causes various defects in the skull, face, skeletal system, skin, and blood vessels. Symptoms of Loeys-Dietz syndrome include scoliosis, spider finger, joint laxity, club foot, hypertelorism, and cleft palate. In addition, aortic aneurysm, aortic dissection, bleeding tendency, delayed wound healing, allergic disease, and autoimmune disease have been reported. Here, we describe an 11-year-old male with type 1 diabetes mellitus who had frequent epistaxis and easy bruising from an early age, along with skin and joint hyperextension, atrophic scars, and long limbs. He was suspected of having a hereditary connective-tissue disorder and was diagnosed with Loeys-Dietz syndrome type 1 by next-generation sequencing. Similar to Marfan syndrome and Ehlers-Danlos syndrome, this disease has a high risk of aortic aneurysm and aortic dissection. In addition, because aortic dissection can occur at a young age, early diagnosis and periodic examination and treatment for cardiovascular diseases are necessary.

Purpose: Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. Materials and Methods: Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. Results: Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). Conclusion This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

The purpose of this study was to redesign a problem-based learning (PBL) curriculum and compare the differences between the previous and redesigned PBL based on the results of course satisfaction and student assessments. The PBL was redesigned using curriculum design guidelines (including revisions of curriculum objectives, learning components, learning environments, and assessment methods) that were developed based on previous studies and evaluation results. A comparative study was employed using course satisfaction surveys from the previous and redesigned curricula, and a total of 45 students participated. We also compared student assessment results from concept mapping, learning issue reports, modified essay questions, and reflection journals. We identified four key findings. First, we explored the possibility that the redesigned PBL could be implemented by student facilitators without professors as tutors. Second, the redesigned PBL fostered group dynamics that facilitated developing communication skills and collaborative learning through small-group discussions. Third, the new learning elements added in the redesigned PBL made a meaningful contribution to enhancing students’ clinical reasoning based on hypothetico-deductive reasoning. Fourth, concept maps in redesigned PBL contained more complex and various nodes and connections, and the levels of the nodes were more appropriate. The implications of this study can provide meaningful preliminary information for redesigning PBL curricula for medical students to develop their essential competencies through PBL.

Background/Aims: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most fatal complications of hematopoietic cell transplantation (HCT), and defibrotide is the only curative drug. We conducted this study to confirm the survival rate of VOD/SOS patients diagnosed in Korea and assess the efficacy of defibrotide. Methods: Patients diagnosed with VOD/SOS after allogenic HCT between 2003 and 2020 were enrolled. We investigated day +100 survival rates and associated risk factors in patients who satisfied the modified Seattle criteria within 50 days of HCT. Results: A total of 110 patients satisfied the modified Seattle criteria, of which 65.5% satisfied the Baltimore criteria. Thirty-seven patients were treated with defibrotide. The day +100 survival rate of the 110 patients was 65.3%. The survival rates in patients who did not meet the Baltimore criteria and in those who did were 86.8% and 53.7%, respectively (p = 0.001). The day +100 survival rate of patients treated with defibrotide was 50.5%. Among the patients receiving defibrotide, those whose creatinine levels were more than 1.2 times the baseline had a significantly lower survival rate at 26.7% (p = 0.014). On multivariate regression analysis, the hazard ratio of satisfaction of the Baltimore criteria was 4.54 (95% confidence interval [CI], 1.69 to 12.21; p = 0.003). In patients treated with defibrotide, the hazard ratio was 8.70 (95% CI, 2.26 to 33.45; p = 0.002), when creatinine was more than 1.2 times the baseline on administration. Conclusions The day +100 survival rate was significantly lower when the Baltimore criteria were satisfied, and when there was an increase in creatinine at the time of defibrotide administration.

One of the pathophysiologic mechanism of inherited thrombocytopenia is a defect in transcription factors that regulate the expression of multiple genes required for megakaryopoiesis. Runt-related transcription factor 1 (RUNX1) binds to its heterodimeric partner, core binding factor beta (CBFβ), and forms a core binding factor that regulates the expression of various target genes. The association between RUNX1 germline mutations and familial platelet disorder with associated myeloid malignancy was first reported in 1999. Although this disease has various phenotypes and penetration, the most common symptom is a bleeding tendency due to thrombocytopenia and platelet dysfunction. Myelodysplastic syndromes or acute myeloid leukemia may also develop in 35-40% of cases. We identified a heterozygous mutation in the RUNX1 gene using diagnostic exome sequencing in an adolescent with chronic thrombocytopenia.The patient will be followed continuously for hematologic malignancies that may develop in the future. This case illustrates the importance of diagnosing inherited thrombocytopenia to provide adequate follow-up for hematologic malignancies and reduce unnecessary treatment.

Background: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. Methods: We collected the data of a newly diagnosed pediatric HHA cohort (2007–2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997–2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. Results: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. Conclusion In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

No abstract available.
Latent Tuberculosis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

BACKGROUND: von Willebrand disease (VWD) is one of the most common inherited bleeding disorders. However, the number of patients who register to the Korea Hemophilia Foundation (KHF) is much lower than the expected prevalence rate and only few hospitals perform tests for diagnosis autonomously. Thus, we surveyed practical realities of VWD in Yeungnam region. METHODS: Patients with VWD (N=267) who were diagnosed at eleven university hospitals from March 1995 to March 2018 were enrolled in this study. We evaluated the medical records from each hospital retrospectively. RESULTS: Two hundred and twenty-eight children and 39 adults met the diagnostic criteria for VWD. Seventy-eight (57.4%) patients had the blood type O. Fifty-eight patients were definite type 1 (21.7%), 151 were possible type 1 (56.6%), and the others were type 2. Abnormal laboratory findings were the most common factor for the diagnosis in children. VWF mutations were detected in 17 patients. Patients with a family history showed age of diagnosis of 9 y, which is higher than in those with no family history (6 yr), and also showed a higher rate of significant bleeding (32.1% vs. 14.2%). VWF:RCo and VWF:Ag tests were performed in-hospital at only 1 of 11 hospitals. Twelve of 267 patients were enrolled at the KHF (4.5%). CONCLUSION: A high rate of out-sourcing studies may result in inaccurate diagnosis. The registration rate to the KHF is still lower than the prevalence rate. A comprehensive nationwide registration system is necessary in order to identify the actual prevalence rate and promote the diagnosis of VWD in Korea.
Adult ; Child ; Diagnosis ; Hemophilia A ; Hemorrhage ; Hospitals, University ; Humans ; Korea ; Medical Records ; Prevalence ; Retrospective Studies ; von Willebrand Diseases

BACKGROUND: Venous thromboembolism (VTE) is rare in pediatric patients compared to adults, but it's incidence is gradually increasing. The purpose of this study was to analyze the incidence, risk factors, and prognosis of pediatric patients with VTE in Korea. METHODS: Between January 2000 and July 2017, 249,312 medical records of the patients older than 1 year who were hospitalized in the department of pediatrics of 10 university hospitals in Yeungnam region were retrospectively reviewed. RESULTS: The overall incidence of VTE was 4.9 per 10,000 admissions. Of the total 123 patients, 80 (65.0%) were male and the median age was 10.8 years (range, 1.0–23.5 years). Magnetic resonance imaging was performed most frequently to confirm the diagnosis of VTE (43.1%). Thrombosis occurred in the cerebral vessels (46.3%), lower extremities (23.8%), pulmonary (19.5%), abdomen (9.8%), and upper extremities (4.1%). One hundred and six patients had underlying causes such as cancer (27.6%), infection (26.8%), intravenous catheter insertion (17.9%), and surgery (14.6%). Protein C was evaluated in 39 patients (31.7%), protein S in 40 (32.5%), antithrombin (AT) III in 52 (42.3%), and homocysteine in 21 (17.1%). Among them, one patient with a family history of AT III deficiency had SERPINC gene mutation. Seventy-seven patients (62.6%) started anticoagulation treatment. Most (52.0%) were treated for more than 90 days. CONCLUSION: Healthcare providers must be aware of the potential for VTE development in childhood. In the near future, a nationwide survey should be investigated to determine the incidence rate and the trends in VTE among Korean children.
Abdomen ; Adult ; Catheters ; Child ; Diagnosis ; Epidemiology ; Health Personnel ; Homocysteine ; Hospitals, University ; Humans ; Incidence ; Korea* ; Lower Extremity ; Magnetic Resonance Imaging ; Male ; Medical Records ; Pediatrics ; Prognosis ; Protein C ; Protein S ; Retrospective Studies ; Risk Factors ; Thrombosis ; Upper Extremity ; Venous Thromboembolism*

OBJECTIVES: Systemic antibiotic therapy with semisynthetic penicillinase-resistant penicillin or vancomycin and clindamycin are recommended for the treatment of staphylococcal scalded skin syndrome (SSSS). This study assessed the rate of antibiotic resistance of Staphylococcus aureus isolated from the anterior nares or skin of children diagnosed with SSSS. METHODS: A retrospective review of the medical records of 25 patients with SSSS between July 2010 and October 2014 was conducted. The clinical characteristics of patients were collected and the antibiotic susceptibility of S. aureus were analyzed using automated systems. RESULTS: The median age of the patients was 22 months (range: 2–95). Ninety-two percent of patients were less than 5 years of age. Nasal swab samples of all patients and skin swab samples of 17 patients were cultured to isolate S. aureus. Twenty-one (84%) of 25 patients were colonized with methicillin-resistant S. aureus (MRSA). The results of swab samples of the other four patients were no growth or isolation of bacteria other than S. aureus. Among 20 strains isolated from the anterior nares, 1 strain (5%) was methicillin-susceptible S. aureus. All 15 strains isolated from the skin were MRSA. All 21 strains isolated from anterior nares or skin were found to be resistant to clindamycin upon evaluation using automated systems. CONCLUSIONS: The rates of methicillin and clindamycin resistance in S. aureus colonized in children with SSSS were very high. Further studies evaluating proper antibiotic regimens and the effectiveness of systemic antibiotic therapy are needed.
Bacteria ; Child* ; Clindamycin ; Colon* ; Drug Resistance ; Drug Resistance, Microbial* ; Humans ; Medical Records ; Methicillin ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Penicillins ; Retrospective Studies ; Skin ; Staphylococcal Scalded Skin Syndrome* ; Staphylococcus aureus* ; Staphylococcus* ; Vancomycin