BACKGROUND: Mast cell leukemia (MCL) is the most aggressive form of systemic mastocytosis disorders. Owing to its rarity, neither pathogenesis nor standard treatment is established for this orphan disease. Hence, we tried to treat a patient with MCL based on the exome and transcriptome sequencing results of the patient's own DNA and RNA. METHODS: First, tumor DNA and RNA were extracted from bone marrow at the time of diagnosis. Germline DNA was extracted from the patient's saliva 45 days after induction chemotherapy and used as a control. Then, we performed whole-exome sequencing (WES) using the DNA and whole transcriptome sequencing (WTS) using the RNA. Single nucleotide variants (SNVs) were called using MuTect and GATK. Samtools, FusionMap, and Gene Set Enrichment Analysis were utilized to analyze WTS results. RESULTS: WES and WTS results revealed mutation in KIT S476I. Fusion analysis was performed using WTS data, which suggested a possible RARα-B2M fusion. When RNA expression analysis was performed using WTS data, upregulation of PIK3/AKT pathway, downstream of KIT and mTOR, was observed. Based on our WES and WTS results, we first administered all-trans retinoic acid, then dasatinib, and finally, an mTOR inhibitor. CONCLUSION: We present a case of orphan disease where we used a targeted approach using WES and WTS data of the patient. Even though our treatment was not successful, use of our approach warrants further validation.
Bone Marrow ; Diagnosis ; DNA ; Exome ; Humans ; Precision Medicine ; Induction Chemotherapy ; Leukemia ; Leukemia, Mast-Cell* ; Mast Cells* ; Mastocytosis, Systemic ; Rare Diseases ; RNA ; Saliva ; Transcriptome ; Tretinoin ; Up-Regulation ; Dasatinib

Remission is a primary end point of in clinical practice and trials of treatments for rheumatoid arthritis (RA). The 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were developed to provide a consensus definition of remission. This study aimed to assess the concordance between the new remission criteria and the physician’s clinical judgment of remission and also to identify factors that affect the discordance between these two approaches. A total of 3,209 patients with RA were included from the KORean Observational Study Network for Arthritis (KORONA) database. The frequency of remission was evaluated based on each approach. The agreement between the results was estimated by Cohen's kappa (κ). Patients with remission according to the 2011 ACR/EULAR criteria (i.e. the Boolean criteria) and/or physician judgment (n = 855) were divided into three groups: concordant remission, the Boolean criteria only, and physician judgment only. Multinomial logistic regression analysis was used to identify factors responsible for the assignment of patients with remission to one of the discordant groups rather than the concordant group. The remission rates using the Boolean criteria and physician judgment were 10.5% and 19.9%, respectively. The agreement between two approaches for remission was low (κ = 0.226) and the concordant remission rate was only 5.5% (n = 177). Pain affected classification in both discordant groups, whereas fatigue was associated with remission only by physician clinical judgment. The Boolean criteria were more stringent than clinical judgment. Patient subjective symptoms such as pain and fatigue were associated with discordance between the two approaches.
Arthritis ; Arthritis, Rheumatoid* ; Classification ; Consensus ; Fatigue ; Humans ; Judgment* ; Logistic Models ; Observational Study ; Rheumatic Diseases

BACKGROUND: The purpose of this study was to determine the prognostic significance of chest computed tomographic (CT) parameters in acute submassive pulmonary embolism (PE). METHODS: Between January 2006 and December 2009, 268 consecutive patients with acute submassive PE that was confirmed by chest CT with pulmonary angiography in emergency room were studied. One experienced radiologist measured CT parameters and judged the presence of right ventricular dysfunction. CT parameters were analyzed to determine their ability to predict a major adverse event (MAE). RESULTS: There were 220 patients included and 61 (27.7%) had MAE. Left ventricular and right ventricular maximum minor axis (36.4+/-8.0 vs. 41.7+/-7.4, p<0.01; 45.7+/-9.4 vs. 41.5+/-7.6, p<0.01), superior vena cava diameter (19.2+/-3.4 vs. 18.0+/-3.4, p=0.02), azygos vein diameter (10.0+/-2.2 vs. 9.2+/-2.3, p=0.02), septal displacement (19 vs. 18, p<0.01) were significantly higher in MAE group than in no MAE group. Patients with MAE had high right ventricular/left ventricular dimension ratio (RV/LV ratio) compared to patients without MAE (1.34+/-0.48 vs. 1.03+/-0.28, p<0.01). The most useful cut-off value of RV/LV ratio for MAE was 1.3 and the area under the curve was 0.71 (0.62~0.79). CONCLUSION: RV/LV ratio on chest CT was a significant predictor of submassive PE related shock, intubation, in-hospital mortality, thrombolysis, thrombectomy within 30 days.
Angiography ; Axis, Cervical Vertebra ; Azygos Vein ; Displacement (Psychology) ; Emergencies ; Hospital Mortality ; Humans ; Intubation ; Prognosis ; Pulmonary Embolism ; Shock ; Thorax ; Thrombectomy ; Vena Cava, Superior ; Ventricular Dysfunction, Right

BACKGROUND: The purpose of this study was to determine the prognostic significance of chest computed tomographic (CT) parameters in acute submassive pulmonary embolism (PE). METHODS: Between January 2006 and December 2009, 268 consecutive patients with acute submassive PE that was confirmed by chest CT with pulmonary angiography in emergency room were studied. One experienced radiologist measured CT parameters and judged the presence of right ventricular dysfunction. CT parameters were analyzed to determine their ability to predict a major adverse event (MAE). RESULTS: There were 220 patients included and 61 (27.7%) had MAE. Left ventricular and right ventricular maximum minor axis (36.4+/-8.0 vs. 41.7+/-7.4, p<0.01; 45.7+/-9.4 vs. 41.5+/-7.6, p<0.01), superior vena cava diameter (19.2+/-3.4 vs. 18.0+/-3.4, p=0.02), azygos vein diameter (10.0+/-2.2 vs. 9.2+/-2.3, p=0.02), septal displacement (19 vs. 18, p<0.01) were significantly higher in MAE group than in no MAE group. Patients with MAE had high right ventricular/left ventricular dimension ratio (RV/LV ratio) compared to patients without MAE (1.34+/-0.48 vs. 1.03+/-0.28, p<0.01). The most useful cut-off value of RV/LV ratio for MAE was 1.3 and the area under the curve was 0.71 (0.62~0.79). CONCLUSION: RV/LV ratio on chest CT was a significant predictor of submassive PE related shock, intubation, in-hospital mortality, thrombolysis, thrombectomy within 30 days.
Angiography ; Axis, Cervical Vertebra ; Azygos Vein ; Displacement (Psychology) ; Emergencies ; Hospital Mortality ; Humans ; Intubation ; Prognosis ; Pulmonary Embolism ; Shock ; Thorax ; Thrombectomy ; Vena Cava, Superior ; Ventricular Dysfunction, Right

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder of unknown etiology. Inflammation may usually extend beyond the joints and involve other organs. Clinically detectable splenomegaly is present in 5~10% of RA. Methotrexate (MTX) is a structural analog of folic acid that inhibits the enzyme dihydrofolate reductase, so cellular proliferation is reduced. MTX has been proven to be effective in treating RA and is believed to be nononcogenic at low, weekly dose employed in the patients with RA. However, recently there has been increased concern about the oncogenic potential of MTX because of several case reports describing the occurrence of non-Hodgkin's Lymphoma (NHL) in the patients with RA treated with MTX. A 65-year-old woman with RA was treated with low dose MTX (i.e. 10 mg/week) for 3 years. Because of prolonged left upper abdominal pain and thrombocytopenia associated with huge splenomegaly, splenectomy was performed. Biopsy revealed splenic B-cell NHL. We report a case of RA with splenomegaly who developed B-cell NHL in spleen during low dose MTX therapy.
Abdominal Pain ; Aged ; Arthritis, Rheumatoid* ; B-Lymphocytes ; Biopsy ; Cell Proliferation ; Female ; Folic Acid ; Humans ; Inflammation ; Joints ; Lymphoma, Non-Hodgkin* ; Methotrexate ; Spleen ; Splenectomy ; Splenomegaly ; Tetrahydrofolate Dehydrogenase ; Thrombocytopenia

OBJECTIVE: The purpose of our study was to describe acute necrotizing encephalopathy in Korean infants and children, and we sought to evaluate the prognostic factors. MATERIALS AND METHODS: Acute necrotizing encephalopathy was diagnosed in 14 Korean infants and children. We retrospectively analyzed the neuroimaging findings including the follow-up changes. The clinical course of the disease was graded, and we evaluated prognostic factors including age, serum level of the aminotransferase, hemorrhage, and localized atrophy of the brain. RESULTS: This encephalopathy predominantly affected the bilateral thalami (n=14), pons (n=12), and midbrain (n=10) in a symmetrical pattern. Hemorrhage was observed in eight patients (57%). On the follow-up images (n=12), the brain lesions were reduced in extent for all patients, and generalized atrophy was seen in six patients. Localized tissue loss was observed in five patients and a complete resolution occurred for one patient. All the patients survived and two recovered completely; mild (n=6) to severe (n=6) neurological deficits persisted in the remaining 12 patients. The significant prognostic factors identified in this study were the presence of hemorrhage (p = 0.009) and localized atrophy (p = 0.015). CONCLUSION: Acute necrotizing encephalopathy in Korean patients showed the characteristic patterns of the post-infectious encephalopathy as described in the literature. The high survival rate and the relatively favorable clinical course observed for the present study suggest a more diverse spectrum of disease severity than was previously described. The presence of hemorrhage and localized tissue loss on MR images may suggest a poor prognosis.
Brain/pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Korea ; Leukoencephalitis, Acute Hemorrhagic/complications/*pathology ; *Magnetic Resonance Imaging ; Male ; Prognosis ; Retrospective Studies

PURPOSE: This paper is proposing an improved CT-free registration method which may provide us an accurate and reliable placement of acetabular cup without CT/MRI images. DESIGN AND METHODS: The proposed method employs a T-bar shaped gauge placed on the anatomical landmarks of the pelvis for the registration. The T-bar shaped gauge has its own LED markers and the position of the gauge is obtained through OPTOTRAK3020 system. These landmark points are the anterior superior iliac spines and the symphysis pubis defining anterior pelvic plane. Two subjects were tested to compare the landmark based registration and the proposed T-bar based registration. RESULTS: The measurement deviations of the pelvic obliquity in the frontal plane, tilt in the sagittal plane, and rotation in the transverse plane were 2.08, 1.41, and 2.51 degrees respectively in the point based registration. The T-bar based registration produced 40% smaller deviations(p<0.05): the pelvic obliquity in the frontal plane, tilt in the sagittal plane, and rotation in the transverse plane were 0.84, 0.81, and 1.17 degrees respectively in the T-bar based registration. There was no outlier exceeding 5 degrees in measurement deviation by the T-bar based registration while the outliers were found by the landmark based registration. CONCLUSIONS: We found that T-bar based CT free registration method is more reliable and accurate than the landmark based registration for the acetabular cup navigation. Also, the new method produced more precise registration(p<0.05). We are expecting some offset error of the new registration method due to the skin thickness existing between the T-bar frame and the bony pelvic frame, which may be compensated if we may accumulate sufficient database of the offset.
Acetabulum ; Arthroplasty, Replacement, Hip* ; Pelvis ; Skin ; Spine

OBJECTIVES: Recently,tinea pedis has been reported to be a type of occupational dermatoses because of its high prevalence in specific working conditions.Although there is no doubt that the environment surrounding work places, the usual habits of workers etc are intimately related to this skin conditions, there is some controversy as to whether or not this condition is a real occupational illness and what is the exact cause of the high prevalence of this illness is. In this study, the prevalence of tinea pedis in workers from the shipbuilding industry was investigated andthe risk factors of this disease were evaluated. This study also aimed to verify whether or not tinea pedis is one of the occupational diseases. METHODS: The results of interviews, questionnaires and clinical findings from 1,419 workers who visited the occupational health center for an annual routine check for their health state were analyzed. RESULTS: Among the 1,419 workers, 778 workers (54.8%)had tinea pedis. By simple logistic regression analysis,the prevalence of tinea pedis was found to be affected by some variables, including the job category, the types of work,the kinds of footwear, whether or not they were using communal baths in the work places, and a family history of tinea pedis.In contrast, by multiple logistic regression analysis,only utilization of the communal baths in the work places and a family history of tinea pedis turned out to be statistically significant risk factors. CONCLUSIONS: In this study, the major factors contributing to the high prevalence of tinea pedis are the use of communal baths in the workplace and a positive family history. However, the wearing of safety shoes was not statistically significant. Therefore, tinea pedis could not be confirmed to be an occupational disease. On the basis of these results, a solution to the environmental hygiene of communal baths and the personal hygiene of individuals needs to be improved in order to prevent tinea pedis.
Baths ; Humans ; Hygiene ; Logistic Models ; Occupational Diseases ; Occupational Health ; Prevalence* ; Questionnaires ; Risk Factors* ; Shoes ; Skin ; Skin Diseases ; Tinea Pedis* ; Tinea* ; Workplace

OBJECTIVE: Maternal anemia is one of the most common hematologic disorders of the child-bearingmothers. However the role of maternal anemia in the etiology of preterm delivery and adverse pregnancyoutcomes remains a source of controversy. The aim of this study was to determine the effects of maternalanemia on the preterm birth and the adverse pregnancy outcomes. STUDY DESIGN: A total of 1,010 women aged 19~44 years, who admitted to our hospitalfor the delivery between December 1994 and October 1995, were recruited into a hospitalbaed case-control study design. 259 women complicated by maternal anemia(cases) werecompared with 751 women without maternal anemia(controls). Multiple logistic regressionanalyses were performed to control for the effects of other potentially confounding factors,including maternal age, body mass index, previous term delivery, previous preterm deliveryand previous abortion. In all logistic regression analyses odds ratio and 95% confidenceintervals were calculated. RESULTS: The prevalence of maternal anemia(hemoglobin<10g/dl) was 25.6%. Therewas a positive linear relationship between the prepartum hemoglobin concentration and thepostpartum concentration. There was no significant differences of the incidence of pretermbirth and the neonatal morbidity, such as poor Apgar scores, fetal distress, congenitalanomaly, birth trauma, admission to neonatal intensive care unit, resuscitation and sepsisbetween case and control groups. Small for gestational age and low birth weight were associatedwith an somewhat decreased risk of maternal anemia and large for gestational age, notmacrosomia, was associated with an 70% increased risk of maternal anemia at the time ofdelivery. Maternal anemia was associated with 6.5 fold increases in the risks of postpartumbleeding, 8.5 fold increases in the postpartum transfusion and 80% increases in the puerperalfever respectively. CONCLUSIONS: Maternal anemia was not associated with increased risks of preterm birthand the neonatal morbidty. However there was a significant relationship between maternalanemia and postpartum maternal morbidity, such as postpartum bleeding, postpartum transfusionand puerperal fever.
Abortion, Induced ; Anemia* ; Body Mass Index ; Case-Control Studies* ; Female ; Fetal Distress ; Fever ; Gestational Age ; Hemorrhage ; Humans ; Incidence ; Infant, Low Birth Weight ; Infant, Newborn ; Intensive Care, Neonatal ; Logistic Models ; Maternal Age ; Odds Ratio ; Parturition ; Postpartum Period ; Pregnancy ; Pregnancy Outcome* ; Pregnancy* ; Premature Birth* ; Prevalence ; Resuscitation

BACKGROUND: Atrial fibrillation is one of the most common cardiac arrhythmias which has been recieved relatively little attention until recently.Despite the variety of treatment modalities including drugs,surgery,catheter ablation and devices,the overall treatment of atrial fibrillation is not always satisfactory.Phalmacotherapy is still the most commonly used treatment through the unfavorable side effects of antiarrhythmic drugs are problematic.The purpose of this study is to compare the efficacy of class Ic antiarrhythmic drugs,propafenone versus flecainide. METHODS: We treated one hundred eighteen patients with atrial fibrillation by class Ic antiarrhythmic drugs,propafenone or flecainide with/without DC cardioversion to convert to and maintain the sinus rythm. We compared the clinical findings,drug efficacy,side sffects of drugs between two groups. RESULTS: 30 patients were treated by propafenne and 88 patients by flecainide.21 and 60 patients in each group were lone atrial fibrillation,14 and 49 patients were paroxysmal atrial fibrillation.Mean duration of drug administration were 360.9,339.4 days,respectively.The convesion rate to sinus rhythm by drugs was 25.0% in propafenone group and 30.7% in flecainide group(p=NS).The 300 days-manitenance rates of sinus rhythm after conversion by drugs or DC cardioversion were 63,3%,70.4%(p=NS)respectively. The side effects of drugs were dizziness,nausia and vomitting in both group and 1st degree AV block,transient sinus node dysfunction and decreased visual acuity in flecainde group.The drugs were discontinued in 11(37.7%) and 26(29.5%) patients in each group due to recurrence of atrial fibrillation or side effects of drugs. CONCLUSION: This study suggests that propafenone and flecainide are comparably effective in maintaining sinus rhythm in atrial fibrillation patients.Futher prospective and large study is required to confirm this findings.
Anti-Arrhythmia Agents ; Arrhythmias, Cardiac ; Atrial Fibrillation* ; Electric Countershock ; Flecainide* ; Humans ; Propafenone* ; Recurrence ; Sick Sinus Syndrome ; Visual Acuity