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.

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

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

BACKGROUND/AIMS: Carnitine and vitamin complex (Godex(R)) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients. METHODS: 130 treatment-naive patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months. RESULTS: Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-gamma secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment. CONCLUSIONS: ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.
Adult ; Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; Carnitine/*therapeutic use ; DNA, Viral/analysis ; Drug Therapy, Combination ; Enzyme-Linked Immunospot Assay ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy ; Humans ; Interferon-gamma/metabolism ; Male ; Middle Aged ; Mitochondria/physiology ; Treatment Outcome ; Vitamin B Complex/*therapeutic use

The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Cohort Studies ; Community-Acquired Infections/*mortality ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Pneumonia/*mortality ; Prospective Studies ; Republic of Korea ; *Severity of Illness Index ; Young Adult

Congenital melanocytic nevi (CMN) are benign pigmented lesions found in about 1% of all newborns or shortly after birth. Giant melanocytic nevi, with multifocal involvement, show significantly greater risk of developing malignant melanomas and neurocutaneous melanosis (NCM), particularly in a posterior axial location. NCM is a rare congenital disease characterized by multiple (> or =3) small nevi, or at least one large congenital melanocytic nevus in combination with cerebral and/or leptomeningeal melanin deposits or melanoma. Dandy-Walker malformation (DWM) consists of a cystic dilatation of the fourth ventricle, hypoplasia or aplasia of the cerebellar vermis, and enlarged posterior fossa with or without hydrocephalus. The association of DWM and NCM has rarely been reported in the literature. A 3 month-old girl presented with increased head circumference and multiple various sized black plaques on her whole body. She underwent a ventriculoperitoneal shunt operation when she was 2 months-old. A skin biopsy was taken from the largest and darkest plaque of the trunk and showed hyperpigmentation of the basal layer of the epidermis. The dermis contained nevus cells in nests and sheets throughout the dermis, but no cellular atypia was noted. Magnetic resonance image (MRI) of the brain revealed severe hydrocephalus with hypoplasia of cerebellar vermis and agenesis of cerebellar tonsil which are consistent with Dandy-Walker malformation. We recommended a spinal MRI for check up the presence of leptomeningeal melanosis, but could not evaluate the result because of her being adapted. Herein, we present a rare case of multiple congenital melanocytic nevi in association with DWM in a neonate.
Biopsy ; Brain ; Dandy-Walker Syndrome ; Dermis ; Dilatation ; Epidermis ; Fourth Ventricle ; Head ; Humans ; Hydrocephalus ; Hyperpigmentation ; Infant, Newborn ; Magnetic Resonance Spectroscopy ; Melanins ; Melanoma ; Melanosis ; Neurocutaneous Syndromes ; Nevus ; Nevus, Pigmented ; Palatine Tonsil ; Parturition ; Skin ; Ventriculoperitoneal Shunt

No abstract available.
Antiviral Agents/therapeutic use ; Ascites/diagnosis/prevention & control/therapy ; Cholagogues and Choleretics/therapeutic use ; Fatty Liver/diagnosis/diet therapy ; Fatty Liver, Alcoholic/diagnosis/drug therapy ; Hemorrhage/prevention & control/therapy ; Hepatic Encephalopathy/diagnosis/prevention & control/therapy ; Hepatitis B, Chronic/diagnosis/drug therapy ; Hepatitis C, Chronic/diagnosis/drug therapy ; Humans ; Liver Cirrhosis/*diagnosis/drug therapy/pathology/*therapy ; Liver Cirrhosis, Biliary/drug therapy ; Vasodilator Agents/therapeutic use