Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

Background/Aims: To investigate epidemiologic characteristics, clinical and economic burdens, and factors associated with mortality in complicated skin and skin structure infection (cSSSI) patients in Korea. Methods: A retrospective, observational, nationwide study was conducted between April to July 2012 at 14 tertiary-hospitals in Korea. Eligible patients were hospitalized adults with community acquired cSSSI, who underwent surgical intervention and completed treatment between November 2009 and October 2011. Data on demography, clinical characteristics, outcomes and medical resource utilization were collected through medical record review. Direct medical costs were calculated by multiplying quantities of resources utilized by each unit price in Korea. Results: Of 473 patients enrolled, 449 patients (except 24 patients with no record on surgical intervention) were eligible for analysis. Microbiological testing was performed on 66.1% of patients and 8.2% had multiple pathogens. Among culture confirmed pathogens (n = 297 patients, 340 episodes), 76.2% were gram-positive (Staphylococcus aureus; 41.2%) and 23.8% were gram-negative. The median duration of hospital stay was 16 days. Among treated patients, 3.3% experienced recurrence and 4.2% died in-hospital. The mean direct medical costs amounted to $4,195/ person, with the greatest expenses for hospitalization and antibiotics. The in-hospital mortality and total medical costs were higher in combined antibiotics therapy than monotherapy (p < 0.05). Charlson’s comorbidity index ≥ 3, standardized early warning scoring ≥ 4, sub-fascia infections and combined initial therapy, were all found to be associated with higher mortality. Conclusions Korean patients with community-onset cSSSI suffer from considerable clinical and economic burden. Efforts should be made to reduce this burden through appropriate initial treatment.

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and theKorean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measlesmumps- rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and the Korean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measles-mumps-rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

BACKGROUND/AIMS: Barcelona Clinic Liver Cancer (BCLC) C stage demonstrates considerable heterogeneity because it includes patients with either symptomatic tumors (performance status [PS], 1–2) or with an invasive tumoral pattern reflected by the presence of vascular invasion (VI) or extrahepatic spread (EHS). This study aimed to derive a more relevant staging system by modification of the BCLC system considering the prognostic implication of PS. METHODS: A total of 7,501 subjects who were registered in the Korean multicenter hepatocellular carcinoma (HCC) registry database from 2008 to 2013 were analyzed. The relative goodness-of-fit between staging systems was compared using the Akaike information criterion (AIC) and integrated area under the curve (IAUC). Three modified BCLC (m-BCLC) systems (#1, #2, and #3) were devised by reducing the role of PS. RESULTS: As a result, the BCLC C stage, which includes patients with PS 1–2 without VI/EHS, was reassigned to stage 0, A, or B according to their tumor burden in the m-BCLC #2 model. This model was identified as the most explanatory and desirable model for HCC staging by demonstrating the smallest AIC (AIC=70,088.01) and the largest IAUC (IAUC=0.722), while the original BCLC showed the largest AIC (AIC=70,697.17) and the smallest IAUC (IAUC=0.705). The m-BCLC #2 stage C was further subclassified into C1, C2, C3, and C4 according to the Child-Pugh score, PS, presence of EHS, and tumor extent. The C1 to C4 subgroups showed significantly different overall survival distribution between groups (p<0.001). CONCLUSIONS: An accurate and relevant staging system for patients with HCC was derived though modification of the BCLC system based on PS.
Carcinoma, Hepatocellular ; Humans ; Liver Neoplasms ; Liver ; Population Characteristics ; Tumor Burden

BACKGROUND/AIMS: Phosphatase and tensin homolog (PTEN) is a known tumor suppressor gene that is downregulated in hepatocellular carcinoma (HCC). Here, we investigated the association between single nucleotide polymorphisms (SNPs) of PTEN and HCC development in patients with hepatitis B virus (HBV) infection. METHODS: Six SNPs of PTEN at positions rs1234221, rs1903860, rs1234220, rs1903858, rs2299941, and rs17431184 were analyzed in a development population (417 chronic HBV carriers without HCC and 281 chronic HBV carriers with HCC). PTEN rs1903858, rs1903860, and rs2299941 SNPs were further assessed for the development of HCC in a validation population of 200 patients with HBV-related liver cirrhosis. RESULTS: In the development population, PTEN rs1903860 C allele, rs1903858 G allele, and rs2299941 G allele were associated with a low risk of HCC. The haplotype A-T-A-A-A was associated with an increased risk of HCC (recessive model; odds ratio=2.277, 95% confidence interval [CI] =1.144-4.532, P=0.019). In the validation population, PTEN rs2299941 G allele was the only significant protective genetic polymorphism related to HCC development after adjustment for age and sex (hazard ratio=0.582, 95% CI =0.353–0.962, P=0.035). CONCLUSIONS: These findings suggest that genetic polymorphisms in PTEN may affect HCC development in patients with chronic HBV infection.
Alleles ; Carcinoma, Hepatocellular ; Genes, Tumor Suppressor ; Haplotypes ; Hepatitis B virus ; Hepatitis B ; Hepatitis ; Humans ; Liver Cirrhosis ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide

Severe hypercalcemia is rarely encountered in children, even though serum calcium concentrations above 15-16 mg/dL could be life-threatening. We present a patient having severe hypercalcemia and azotemia. A 14-year-old boy with no significant past medical history was referred to our hospital with hypercalcemia and azotemia. Laboratory and imaging studies excluded hyperparathyroidism and solid tumor. Other laboratory findings including a peripheral blood profile were unremarkable. His hypercalcemia was not improved with massive hydration, diuretics, or even hemodialysis, but noticeably reversed with administration of calcitonin. A bone marrow biopsy performed to rule out the possibility of hematological malignancy revealed acute lymphoblastic leukemia. His hypercalcemia and azotemia resolved shortly after initiation of induction chemotherapy. Results in this patient indicate that a hematological malignancy could present with severe hypercalcemia even though blast cells have not appeared in the peripheral blood. Therefore, extensive evaluation to determine the cause of hypercalcemia is necessary. Additionally, appropriate treatment, viz., hydration or administration of calcitonin is important to prevent complications of severe hypercalcemia, including renal failure and nephrocalcinosis.
Acute Kidney Injury* ; Adolescent ; Azotemia ; Biopsy ; Bone Marrow ; Calcitonin ; Calcium ; Child ; Diuretics ; Hematologic Neoplasms ; Humans ; Hypercalcemia* ; Hyperparathyroidism ; Induction Chemotherapy ; Leukemia ; Male ; Nephrocalcinosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Renal Dialysis ; Renal Insufficiency

BACKGROUND/AIMS: The first edition of the Korean treatment guidelines for chronic myelogenous leukemia (CML) was published in 2006. We intend to update those guidelines to include the use of next-generation tyrosine kinase inhibitors (TKIs). METHODS: New guidelines were developed in 2012 based on the results of a survey and a consensus meeting of various Korean experts, the reports of recent clinical studies, and updated guidelines from external study groups. RESULTS: An assessment of risk factors is strongly recommended before treating newly diagnosed chronic phase CML. Imatinib, dasatinib, and nilotinib are reimbursable in Korea as first-line treatments, and the patient's age, comorbidities, and possible adverse events should be considered in the choice of treatment. Molecular studies are recommended for assessing treatment efficacy instead of invasive cytogenetic response evaluations, and an early response is believed to correlate with a good prognosis. Second-line TKIs can be considered for patients who fail or are intolerant of first-line therapy, pending analysis of ABL tyrosine kinase mutation status. For treating advanced stages, a combination of TKIs with cytotoxic agents and hematopoietic cell transplantation is recommended. The adverse effects of TKI therapy can be managed via dose reduction and supportive care, or switching to an alternate TKI. CONCLUSIONS: The use of TKIs has improved the outcome of CML treatment. Treatment-free remission after discontinuing TKIs might be possible in select patients who achieve sufficient response, indicating that curative treatment for CML can be expected in the future.
Cell Transplantation ; Comorbidity ; Consensus ; Cytogenetics ; Cytotoxins ; Hematology* ; Humans ; Korea ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Prognosis ; Protein-Tyrosine Kinases ; Risk Factors ; Transplants ; Treatment Outcome ; Dasatinib ; Imatinib Mesylate

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.
Anti-Bacterial Agents/*administration & dosage ; Cell Survival/*drug effects ; Cephalosporins/administration & dosage ; Ciprofloxacin/administration & dosage ; Community-Acquired Infections/drug therapy/*microbiology ; Dose-Response Relationship, Drug ; Drug Combinations ; Drug Resistance, Bacterial/drug effects ; Escherichia coli/*drug effects ; Escherichia coli Infections/drug therapy/*microbiology ; Fosfomycin/administration & dosage ; Humans ; Nitrofurantoin/administration & dosage ; Penicillins/administration & dosage ; Republic of Korea ; Sulfadoxine/administration & dosage ; Treatment Outcome ; Trimethoprim/administration & dosage ; Urinary Tract Infections/diagnosis/*microbiology

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.
Anti-Bacterial Agents/*administration & dosage ; Cell Survival/*drug effects ; Cephalosporins/administration & dosage ; Ciprofloxacin/administration & dosage ; Community-Acquired Infections/drug therapy/*microbiology ; Dose-Response Relationship, Drug ; Drug Combinations ; Drug Resistance, Bacterial/drug effects ; Escherichia coli/*drug effects ; Escherichia coli Infections/drug therapy/*microbiology ; Fosfomycin/administration & dosage ; Humans ; Nitrofurantoin/administration & dosage ; Penicillins/administration & dosage ; Republic of Korea ; Sulfadoxine/administration & dosage ; Treatment Outcome ; Trimethoprim/administration & dosage ; Urinary Tract Infections/diagnosis/*microbiology