Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. Methods: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled. Results: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. Conclusion These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Background: Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea. Methods: This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for β-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly. Results: A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The β-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072‒). Conclusion The detection rate of GD in probable high-risk patients in Korea was lower than expected.However, the role of hemato-oncologists is still important in the diagnosis of GD.

OBJECTIVES: This retrospective study was performed to evaluate the clinical impact of diabetes mellitus on the prognosis in secondary space infection. MATERIALS AND METHODS: Medical records, radiographic images, computed tomography, and microbial studies of 51 patients (25 diabetic patients and 26 non-diabetic patients) were reviewed. Patients were diagnosed as secondary fascial space infections with odontogenic origin and underwent treatment at Chonnam National University Hospital, in Department of Oral and Maxillofacial Surgery, from January 2007 to February 2009. RESULTS: Compared to patients without diabetes, patients with diabetes were presented with the following characteristics: older age (diabetic patients: 62.9 years, non-diabetic patients, 47.8 years), more spaces involved (diabetic patients, 60%; non-diabetic patients, 27.3%), more intense treatment, longer hospitalization (diabetic patients, 28.9 days; non-diabetic patients, 15.4 days), higher white blood cell and C-reactive protein values, higher incidence of complication (diabetic patients, 40%; non-diabetic patients, 7.7%), and distinctive main causative microorganisms. CONCLUSION: These results suggest that the prognosis of diabetic patients is poorer than that of non-diabetic patients in secondary space infections since they had greater incidence rates of involved spaces, abnormal hematologic findings, more complications, and additional procedures, such as tracheostomy.
Abscess ; Bacterial Infections ; C-Reactive Protein ; Cellulitis ; Diabetes Complications ; Diabetes Mellitus ; Hospitalization ; Humans ; Incidence ; Leukocytes ; Medical Records ; Prognosis ; Retrospective Studies ; Surgery, Oral ; Tracheostomy

BACKGROUND/AIMS: The apolipoprotein B/A-I ratio (ApoB/A-I) is a powerful clinical indicator of atherosclerosis. Although numerous reports have shown the effect of non-alcoholic fatty liver disease (NAFLD) on cardiovascular disease, few reports have examined the relationship between NAFLD and the ApoB/A-I ratio. The aim of the study was to determine the association between NAFLD and the ApoB/A-I ratio in prediabetic patients. METHODS: This cross-sectional study was performed with data obtained from 701 patients (mean age, 47.9+/-9.6 years) diagnosed with prediabetes. Serum lipid profiles including lipoprotein, apolipoprotein, and calculated ApoB/A-I ratio as well as metabolic syndrome parameters such as fasting glucose and insulin were measured in each subject. RESULTS: Among the 701 patients, 340 (48%) had NAFLD. The number of male patients was 490 (NAFLD+, 276; and NAFLD-, 214). The odds ratios for the prevalence of NAFLD increased according to the quartiles of the ApoB/A-I ratio (1.886, 2.245, and 2.587) (p<0.001). CONCLUSIONS: The prevalence of NAFLD correlated with high ApoB/A-I ratio, suggesting that NAFLD increases the risk for atherosclerosis progression in male prediabetic patients.
Apolipoprotein A-I ; Apolipoproteins ; Atherosclerosis ; Cardiovascular Diseases ; Cross-Sectional Studies ; Fasting ; Fatty Liver ; Glucose ; Humans ; Insulin ; Lipoproteins ; Male ; Odds Ratio ; Prediabetic State ; Prevalence

PURPOSE: Second-generation tyrosine kinase inhibitors (second TKIs) such as nilotinib and dasatinib control the activity of most ABL kinase domain mutations observed in patients with imatinib resistance. Although in vitro data show that both agents can inhibit all mutations except T315I, some discrepancies have been observed in a small subset of mutation clones. Cytogenetic clonal evolution is the important resistance mechanism of chronic myeloid leukemia (CML). Accordingly, we observed the clinical significance of coexisting with clonal evolution and BCR-ABL mutant in CML patients treated with second TKIs. MATERIALS AND METHODS: We monitored BCR-ABL transcript kinetics, interrelationship of clones expressing non-mutated and mutant transcripts and clonal aberrations within Philadelphia (Ph) positive and negative clones, respectively, in eight patients with CML receiving dasatinib or nilotinib for 3~41 months. RESULTS: Clinical responses were correlated with in vitro sensitivity of the BCR-ABL mutants to the second TKIs in four patients. Four patients showed resistance to the second TKIs as compared to in vitro observations; three of them developed chromosomal abnormalities in the Ph chromosome positive or negative metaphases. Another patient lost the original mutation but acquired a more resistant new mutation and became resistant to the second TKI. CONCLUSION: Cytogenetic clonal evolution is an independent poor prognostic factor in CML, which could explain the onset of mechanisms for second TKIs resistance to ABL kinase domain mutations. The results indicate that an additional evaluation of chromosomal abnormalities is warranted when BCR-ABL mutants are more resistant than indicated by in vitro data.
Benzamides ; Chromosome Aberrations ; Clonal Evolution ; Clone Cells ; Cytogenetics ; Dasatinib ; Humans ; Hydrogen-Ion Concentration ; Kinetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Metaphase ; Philadelphia ; Phosphotransferases ; Piperazines ; Protein-Tyrosine Kinases ; Pyrimidines ; Thiazoles ; Tyrosine ; Imatinib Mesylate

The Korean Society of Cardiac Rehabilitation (KSCR) have recommended standards for establishing cardiac rehabilitation programs in terms of facility, equipment and staff. This is the first time a statement concerning these types of standards has been issued in Korea, and presents the minimal requirements for establishing cardiac rehabilitation programs. Cardiac rehabilitation facilities should contain individual spaces for patient examination, exercise stress testing, monitoring exercise training, patient education, patient preparation, storing medical records, showers and lockers, toilets, and walking tracks. Essential equipment must include at least four sets of aerobic exercise equipment such as treadmills, bicycles, arm ergometers, step machines, and floor mats, and medical equipment such as exercise stress test for ECG with gas analysis, telemetry ECG monitoring systems, sphygmomanometers, stethoscopes, pulse oximeters, glucometers, portable oxygenators, and emergency carts with defibrillators. Hospital staff should include a medical director (a physician with a subspecialty in cardiac rehabilitation), exercise physiologist, nurse specializing in cardiac rehabilitation, exercise specialist, physical therapist, and clinical nutritionist. All should have an expertise in exercise science and be trained in basic life support or advanced cardiac life support. This statement is a recommendation by KSCR and cardiac rehabilitation council of regional cardiocerebrovascular center, and set forth the standards for facilities, equipment, and staff to set up or upgrade cardiac rehabilitation programs in Korea. These recommendations should be developed as a national standard for the establishment of cardiac rehabilitation programs, and adjusted for the current situation of the Korean medical industry through nationwide and long-term research.
Advanced Cardiac Life Support ; Allyl Compounds ; Arm ; Defibrillators ; Electrocardiography ; Emergencies ; Exercise ; Exercise Test ; Floors and Floorcoverings ; Humans ; Korea ; Medical Records ; Oxygen ; Oxygenators ; Patient Education as Topic ; Physical Therapists ; Physician Executives ; Specialization ; Sphygmomanometers ; Stethoscopes ; Sulfides ; Telemetry ; Track and Field ; Walking

A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (> or =500/microL) and platelets (> or =20,000/microL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cytarabine/*therapeutic use/toxicity ; Disease-Free Survival ; Female ; Granulocyte Colony-Stimulating Factor/*therapeutic use/toxicity ; Humans ; Idarubicin/therapeutic use ; Leukemia, Myeloid, Acute/*drug therapy/mortality ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Vidarabine/*analogs & derivatives/therapeutic use/toxicity

A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (> or =500/microL) and platelets (> or =20,000/microL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cytarabine/*therapeutic use/toxicity ; Disease-Free Survival ; Female ; Granulocyte Colony-Stimulating Factor/*therapeutic use/toxicity ; Humans ; Idarubicin/therapeutic use ; Leukemia, Myeloid, Acute/*drug therapy/mortality ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Vidarabine/*analogs & derivatives/therapeutic use/toxicity

The objective of the current study was to investigate the treatment outcomes for the use of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) chemotherapy in adult patients with hemophagocytic lymphohistiocytosis (HLH). Seventeen HLH patients older than 18 yr of age were treated with CHOP chemotherapy. A response evaluation was conducted for every two cycles of chemotherapy. With CHOP chemotherapy, complete response was achieved for 7/17 patients (41.2%), a partial response for 3/17 patients (17.6%), and the overall response rate was 58.8%. The median response duration (RD) was not reached and the 2-yr RD rate was 68.6%, with a median follow-up of 100 weeks. Median overall survival (OS) was 18 weeks (95% CI, 6-30 weeks) and the 2-yr OS rate was 43.9%. Reported grade 3 or 4 non-hematological toxicities were increased serum liver enzyme levels and stomatitis. Grade 3 or 4 hematological toxicities were leukopenia (50.8%), anemia (20%), and thrombocytopenia (33.9%). Neutropenic fever was observed in 21.6% of patients (14/65 cycles), and most of the cases were resolved with supportive care including treatment with broad-spectrum antibiotics. CHOP chemotherapy seems to be effective in adult HLH patients and the toxicities are manageable.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse ; Cyclophosphamide/administration & dosage/adverse effects ; Doxorubicin/administration & dosage/adverse effects ; Female ; Follow-Up Studies ; Humans ; L-Lactate Dehydrogenase/blood ; Lymphohistiocytosis, Hemophagocytic/*drug therapy ; Male ; Middle Aged ; Prednisone/administration & dosage/adverse effects ; Remission Induction ; Survival Rate ; Treatment Outcome ; Vincristine/administration & dosage/adverse effects

PURPOSE: This study was undertaken to investigate the effect of a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor, FR167653, on urinary albumin excretion and on the expression of slit diaphragm-associated proteins in diabetic rats. METHODS: Thirty-two Sprague-Dawley rats were injected with diluent [control (C), N=16] or streptozotocin intraperitoneally (DM, N=16). Eight rats from each group were treated with 5 mg/kg/day FR 167653 (C+FR, DM+FR) for 6 weeks. At the time of sacrifice, 24-hour urinary albumin excretion was determined by ELISA. Glomerular nephrin, P-cadherin, and ZO-1 mRNA and protein expression were determined by real-time PCR and Western blot, respectively, with sieved glomeruli. RESULTS: Urinary albumin excretion was significantly higher in DM compared to C rats, and this increase in albuminuria was significantly inhibited by the administration of FR167653 in DM rats. Glomerular phospho-p38 MAPK protein expression was significantly increased in DM rats compared to C rats, and FR167653 treatment significantly attenuated the increase in phospho-p38 MAPK expression in DM glomeruli. Nephrin mRNA and protein expression were higher in 6-week DM compared to C glomeruli, and these increases were significantly abrogated with FR167653 treatment in DM rats. In contrast, FR167653 had no effects on the decrease in P-cadherin expression and the increase in ZO-1 expression observed in DM glomeruli. CONCLUSION: These findings suggest that FR167653, a p38 MAPK inhibitor, reduce the amount of albuminuria in early diabetic nephropathy, and this anti-proteinuric effect seems to be related with the change of glomerular nephrin expression.
Albuminuria ; Animals ; Blotting, Western ; Cadherins ; Diabetic Nephropathies ; Enzyme-Linked Immunosorbent Assay ; Membrane Proteins ; p38 Mitogen-Activated Protein Kinases ; Protein Kinases ; Proteins ; Pyrazoles ; Pyridines ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Streptozocin