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.

Objective: Recent studies have detailed the genomic landscape of endometrial cancer (EC); however, no study has focused on genetic alterations in advanced EC. We performed genomic profiling of patients with advanced EC using targeted next-generation sequencing (NGS). Methods: Archival tissue samples from 21 patients diagnosed with stage III and IV EC were obtained and subjected to NGS. Our data and the cancer genome atlas dataset were combined, and somatic mutation patterns were analyzed and compared according to the stage and histological type. Additionally, survival effects of specific mutated genes were analyzed. Results: Somatic mutation patterns of 38 genes were identified in 263 EC samples, and the most commonly mutated genes were PTEN and PIK3CA. PTEN was the most common in endometrioid histology, while PPP2R1A was the most commonly mutated gene in serous histology. The mutation rates of PPP2R1A and TP53 were significantly higher in advanced EC sample than in stage I samples (22.5% vs. 4.3% [p<0.001] and 8.4% vs. 1.4% [p=0.021], respectively). Survival analysis of the total population and endometrioid subgroup revealed that patients with PPP2R1A mutations had significantly shorter survival than did those without mutations (p=0.005 and p<0.001, respectively). Conclusion PPP2R1A mutations might have a role in dismal prognosis of advanced EC.

Background: Occupational hazards in crop farms vary diversely based on different field operations as soil management, harvesting processes, pesticide, or fertilizer application. We aimed at evaluating the immunological status of crop farmers, as limited systematic investigations on immune alteration involved with crop farming have been reported yet. Methods: Immunological parameters including plasma immunoglobulin level, major peripheral immune cells distribution, and level of cytokine production from activated T cell were conducted. Nineteen grape orchard, 48 onion open-field, and 21 rose greenhouse farmers were participated. Results: Significantly low proportion of natural killer (NK) cell, a core cell for innate immunity, was revealed in the grape farmers (19.8 ± 3.3%) in comparison to the onion farmers (26.4 ± 3.1%) and the rose farmers (26.9 ± 2.5%), whereas cytotoxic T lymphocyte proportion was lower in the grape and the onion farmers than the rose farmers. The proportion of NKT cell, an immune cell implicated with allergic response, was significantly higher in the grape (2.3 ± 0.3%) and the onion (1.6 ± 0.8%) farmers compared with the rose farmers (1.0 ± 0.4%). A significantly decreased interferon-gamma:interleukin-13 ratio was observed from ex vivo stimulated peripheral blood mononuclear cells of grape farmers compared with the other two groups. The grape farmers revealed the lowest levels of plasma IgG1 and IgG4, and their plasma IgE level was not significantly different from that of the onion or the rose farmers. Conclusion Our finding suggests the high vulnerability of workplace-mediated allergic immunity in grape orchard farmers followed by open-field onion farmers and then the rose greenhouse farmers.

Dear Editor, Acute promyelocytic leukemia (APL) is a subtype of acute myelocytic leukemia, characterized by the chromosomal abnormality t(15:17) coding a PML/RAR alpha fusion protein that affects differentiation of the promyelocyte cell in bone marrow. All-trans retinoic acid (ATRA), a key treatment for APL, acts as a differentiating agent in combination with other induction chemotherapy. Differentiation syndrome (DS) is a complication in APL patients undergoing induction chemotherapy with ATRA or arsenic trioxide [1]. The pathophysiology of DS is not understood precisely; however, it appears to be associated with a large pool of leukemic blasts, massive tissue infiltration of cells, cytokine increase, and systemic capillary leak syndrome, clinically presenting as dyspnea, fever, peripheral edema, weight gain, pleural, pericardial effusion, and acute kidney injury [2,3]. We present the case of a 66-year-old woman experiencing visual discomfort after starting ATRA treatment. This case highlights that visual symptoms can arise earlier than other well-known life-threatening symptoms of DS. A 66-year-old female patient presented with a fourmonth history of headaches, nausea, and vomiting. Blood tests revealed pancytopenia, and bone marrow examination confirmed PML/RARA gene positive. She was diag-nosed with APL for the first time and was admitted to the Department of Hematology and Medical Oncology at Ewha Womans University Mokdong Hospital for induction chemotherapy, where she received cytarabine, idarubicin, and ATRA as her induction chemotherapy treatment. Five days after ATRA treatment, she was referred for visualdimness and peripheral blurred vision. Her medical history included hypertension and branched retinal vein occlusion in her left eye, which had been treated with intravitreal injections three times two years prior. Her corrected visual acuity was 20 / 40 in the right eye and 20 / 32 in the left eye. Anterior segment finding was normal except for mild nuclear sclerosis in both eyes. Funduscopic examination revealed multiple retinal hemorrhages on the posterior pole in both eyes and Roth’s spot appearance in the left eye. Spectral-domain optical coherence tomography showed subretinal fluid (SRF) in the macula area of the right eye (Fig. 1A). Two days after ocular symptoms appeared, systemic DS symptoms, such as fever, weight gain, and dyspnea appeared, and pulmonary edema was evident in her chest x-ray. As a DS treatment protocol, intravenous dexamethasone was administered for 12 days. Two weeks later after the diagnosis of DS, SRF in macula became more aggravated, with involvement of the fellow eye, while ocular symptoms persisted. Twenty days after DS diagnosis, bilateral serous retinal detachment (SRD) was observed.However, fluorescein angiography showed no significant abnormality, with the exception of a previous branch retinal vein occlusion lesion in her left eye (Fig. 1B); the anterior segment was not remarkable. Her symptoms continued for about 1 month under ATRA treatment and slowly regressed with visual recovery in parallel with discontinuing ATRA (Fig. 1C). Two days after discontinuing ATRA, minimal SRF remained on her right eye. Two weeks later, her corrected visual acuity was 20 / 20 in the right eye and 20 / 25 in the left eye. She achieved complete remission of SRD with improvement in visual symptoms (Fig. 1D). We report the case of DS with ocular manifestation as a first symptom. Ocular manifestation of DS has been reported several times in previous case reports, involving retinal hemorrhage, SRD with intraretinal fluid, choroidal effusion, pseudotumor cerebri, and optic disc edema [2,4,5]. SRD can also appear in ocular infection, inflammatory disease, retinal vascular disease, malignancy, and leukemic retinopathy. Therefore, differential diagnosis should be considered. However, in this patient, the ocular symptom had developed after using the differentiating agent, ATRA. Systemic symptom appeared later. Anterior segments and fluorescein angiography findings were unre-markable to consider other differential diagnoses. After ceasing ATRA, bilateral SRD on optical coherence tomography was regressed, and the patient’s symptom was also relieved.In conclusion, patients receiving ATRA treatment may first present with acute visual symptoms, followed by life-threatening complications such as fever, dyspnea, peripheral edema, and weight gain. Thus, careful observation of ocular symptoms in APL patients is of the utmost importance if the patient is undergoing ATRA treatment.

Semisulcospira libertina, a species of freshwater snail, is widespread in East Asia. It is important as a food source. Additionally, it is a vector of clonorchiasis, paragonimiasis, metagonimiasis, and other parasites. Although S. libertina has ecological, commercial, and clinical importance, its whole-genome has not been reported yet. Here, we revealed the genome of S. libertina through de novo assembly. We assembled the whole-genome of S. libertina and determined its transcriptome for the first time using Illumina NovaSeq 6000 platform. According to the k-mer analysis, the genome size of S. libertina was estimated to be 3.04 Gb. Using RepeatMasker, a total of 53.68% of repeats were identified in the genome assembly. Genome data of S. libertina reported in this study will be useful for identification and conservation of S. libertina in East Asia.

Background and Objectives: PET/CT is widely used to determine whether metastasis or recurrence will occur following initial treatment of thyroid cancer. However, there are not much research on diagnostic usefulness of preoperative PET/CT imaging for papillary thyroid cancer (PTC). We analyzed the correlation between the preoperative maximum standard uptake value (SUVmax) of PET/CT and prognostic factors of PTC to evaluate the diagnostic usefulness of PET/CT. Materials and Methods: Of the 133 patients who underwent surgery for PTC, 88 patients who had an increased uptake in thyroid mass in preoperative PET/CT were enrolled. They were divided into two groups according to B-RAF gene mutation, extrathyroidal extension (ETE), lymph node metastasis, and recurrence. The average of the SUVmax for each group was analyzed through multiple regression analysis. Correlation analysis were performed on changes in SUVmax according to the size of the thyroid tumor. Statistical analysis was performed to determine whether there were stage differences between the 47 patients who had no increased uptake in PET/CT and the others who had. Results: There were no statistical correlation between recurrence, the presence of central/lateral lymph node metastasis, ETE, stage and the SUVmax in PET/CT (p=0.513, p=0.8, p=0.73, p=0.01, p=0.9). There were statistical correlations between the size of tumor (p=0.001), the presence of the B-RAF mutation (p=0.024) and SUVmax. Statistical correlations between the presence of the hypermetabolic uptake and high stage were found by the chi-square test (p=0.012). Conclusion The size of tumor, B-RAF are major factors in determining prognosis of PTC. There is a possibility that there is a correlation between preoperative SUVmax and prognosis of PTC.

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.

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

OBJECTIVES: The purpose of this study was to investigate the distinctive features of bodily panic symptoms and the predisposing conditions in Korean patients with panic disorder. METHODS: This was a retrospective chart review study and the data were collected from twelve university-affiliated hospitals in Korea. The patients selected met the diagnostic criteria for panic disorder, were older than 20 years of age, and had initially visited a psychiatry department. The assessments included the chief complaints related to bodily panic symptoms, recent stressors, recent history of alcohol and sleep problems, and time to visit an outpatient clinic. RESULTS: A total of 814 participants were included in the study. The most commonly experienced symptoms were cardiovascular and respiratory symptoms, which were observed in 63.9% and 55.4% of participants, respectively. Just before the onset of a panic attack, 25.6% of participants experienced sleep-related problems. Episodic binge drinking was also frequently observed (13.2%) and was more prevalent in men than in women (22.6% vs. 4.9%, p<0.001). About 75% of participants experienced stressful life events just before panic onset. Work-related issues were more prevalent in men than in women (22.0% vs. 13.4%, p=0.001). Family-related issues (4.8% vs. 14.1%, p<0.001) and conflict with a spouse or partner (4.0% vs.11.7%, p<0.001) were more prominent in women than in men. CONCLUSION Our results suggest that cardiovascular symptoms are the most common bodily panic symptoms in Korean patients. Our results suggest that a substantial portion of the Korean patients experienced stressful life events, sleep problems, and/or episodic binge drinking just before the onset of panic disorder.

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*