The Korean Academy of Asthma, Allergy, and Clinical Immunology task force report aims to provide new protocols for methacholine challenge test (MCT). Although new devices have different delivery system compared to old ones, previous protocols are still used, which cannot guarantee adequate diagnoses of asthma. Another important issue is the recent recommendation in European Respiratory Society (ERS) technical standard guideline to use a delivered methacholine dose that causes a 20% decrease in forced expiratory volume in 1 second (FEV1) (PD 20). Although the previous protocol based on the methacholine concentration causing a 20% decrease in FEV1 (PC 20) has been used globally, several studies have reported that PD 20 is more reliable and applicable for new protocols of MCT. Indeed, a tidal breathing inhalation protocol using a breath-actuated or continuous nebulizer is recommended. Herein, we recommend 3 protocols for the MCT using new devices and provide a brief summary of the change in strategy based on the updated ERS guideline.

Background: In South Korea, there have been few nationwide epidemiologic studies about premalignant actinic keratosis (AK), squamous cell carcinoma in situ (Bowen’s disease), nonmelanoma skin cancer (NMSC), malignant melanoma of the skin (MM), Kaposi’s sarcoma (KS), connective and soft tissue cancers, or mycosis fungoides (MF). Objective: Using a nationwide population-based study, we attempted to measure the incidence and the prevalence of the above-mentioned tumors in South Korea. Methods: The database we used included all claims in the Korean National Health Insurance program and the Korean Medical Aid program from 2008 to 2016. The International Classification of Diseases, 10th revision (ICD-10) was used to record diagnoses in this database. This data included AK, Bowen’s disease, NMSC, MM, KS, connective and soft tissue cancers, and MF. Results: The age-standardized incidence and prevalence rate of AK, Bowen’s disease, NMSC, MM, KS, connective and soft tissue cancers, as well as MF increased during the periods we investigated. The incidence and prevalence rate of AK and NMSC have increased two- to three-fold. In the case of Bowen’s disease, MM, KS, connective and soft tissue cancers, or MF, we observed no significant tendency in age-standardized incidence or prevalence. Conclusion We confirmed that the age-standardized incidence and prevalence rates of NMSC and AK tended to increase. These results might contribute to developing preventive and therapeutic strategies for skin cancers and may become a source for further studies.

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

BACKGROUND/AIMS: Entecavir is a potent nucleoside analogue with high efficacy and barrier for resistance. We aimed to investigate the long-term efficacy and viral resistance rate of entecavir and explore the factors associated with virologic response, including quantitative hepatitis B surface antigen (qHBsAg) levels. METHODS: One thousand and nine treatment-naïve chronic hepatitis B (CHB) patients were evaluated for cumulative rates of virologic response, biochemical response, and entecavir mutations. The role of baseline qHBsAg for virologic response was assessed in 271 patients with qHBsAg prior to entecavir treatment. RESULTS: The median duration of entecavir treatment was 26.5 months. The cumulative rate of virologic response at years 1, 3, and 5 were 79.0%, 95.6%, and 99.4%, respectively. The cumulative rate of entecavir resistance was 1.0% and 2.1% in years 3 and 5. Multivariate analysis identified baseline hepatitis B e antigen (HBeAg) negative status (p < 0.001) and lower hepatitis B virus (HBV) DNA (p < 0.001) as predictors of virologic response. Lower qHBsAg was an independent predictor of virologic response in patients with baseline qHBsAg. There were no serious adverse events during treatment. CONCLUSIONS: Long-term entecavir treatment of nucleos(t)ide-naïve CHB patients was associated with an excellent virologic response and a low rate of entecavir-resistant mutations at 5 years. Baseline HBV DNA load, qHBsAg levels, and HBeAg status were predictors of virologic response during entecavir treatment.
DNA ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens* ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Multivariate Analysis

No abstract available.
Skin* ; Tacrolimus* ; Wounds and Injuries*

BACKGROUND/AIMS: The aim of this study was to evaluate the relationship between controlled attenuation parameter (CAP) and hepatic steatosis, as assessed by ultrasound (US) in patients with alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). METHODS: Patients with either ALD or NAFLD who were diagnosed with fatty liver with US and whose CAP scores were measured, were retrospectively enrolled in this study. The degree of hepatic steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). RESULTS: A total of 186 patients were included: 106 with NAFLD and 80 with ALD. Regarding hepatic steatosis, the CAP score was significantly correlated with US (ρ=0.580, p<0.001), and there was no significant difference between the NAFLD and ALD groups (ρ=0.569, p<0.001; ρ=0.519, p<0.001; p=0.635). Using CAP, area under receiver operating characteristic curves for ≥S2 and ≥S3 steatosis were excellent (0.789 and 0.843, respectively). For sensitivity ≥90%, CAP cutoffs for the detection of ≥S2 and ≥S3 steastosis were separated with a gap of approximately 35 dB/m in all patients and in each of the NAFLD and ALD groups. CONCLUSIONS: The CAP score is well correlated with hepatic steatosis, as assessed by US, in both ALD and NAFLD.
Adult ; Aged ; Fatty Liver, Alcoholic/classification/*diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/classification/*diagnostic imaging ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity ; Severity of Illness Index ; Ultrasonography/methods/*statistics & numerical data

A 51-year-old male patient with chronic hepatitis B was referred to our hospital due to a 1-cm liver nodule on ultrasonography. Alpha-fetoprotein (AFP) was slightly elevated. The nodule showed prolonged enhancement on dynamic liver magnetic resonance imaging and appeared as a hyperintensity on both diffusion-weighted and T2-weighted imaging. The nodule was followed up because it was small and typical findings of hepatocellular carcinoma (HCC) were not observed in the dynamic imaging investigations. However, liver contrast-enhanced ultrasonography performed 1 month later showed enhancement during the arterial phase and definite washout during the delayed phase. Also, AFP had increased to over 200 ng/mL even though AST and ALT were decreased after administering an antiviral agent. He was presumptively diagnosed as HCC and underwent liver segmentectomy. Microscopy findings of the specimen indicated bile duct adenoma. After resection, the follow-up AFP had decreased to within the normal range. This patient represents a case of bile duct adenoma with AFP elevation mimicking HCC on contrast-enhanced ultrasonography.
Bile Duct Neoplasms/*complications/*diagnosis/pathology ; *Bile Ducts, Intrahepatic ; Hepatitis B, Chronic/*complications/*diagnosis/pathology ; Humans ; Liver/pathology/ultrasonography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed ; alpha-Fetoproteins/*metabolism

BACKGROUND/AIMS: The role of radiofrequency ablation (RFA) remains uncertain in patients with viable hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). METHODS: A total of 101 patients (April 2007 to August 2010) underwent RFA for residual or recurrent HCC after TACE. We analyzed their long-term outcomes and predictive factors. RESULTS: The overall survival rates after RFA were 93.1%, 65.4%, and 61.0% at 1, 3, and 5 years, respectively. Predictive factors for favorable overall survival were Child-Pugh class A (hazard ratio [HR], 3.45; p=0.001), serum alpha-fetoprotein (AFP) level <20 ng/mL (HR, 2.90; p=0.02), and recurrent tumors after the last TACE (HR, 3.14; p=0.007). The cumulative recurrence-free survival rate after RFA at 6 months was 50.1%. Predictive factors for early recurrence (within 6 months) were serum AFP level > or =20 ng/mL (HR, 3.02; p<0.001), tumor size > or =30 mm at RFA (HR, 2.90; p=0.005), and nonresponse to the last TACE (HR, 2.13; p=0.013). CONCLUSIONS: Patients with recurrent or residual HCC who undergo prior TACE show a favorable overall survival, although their tumors seem to recur early and frequently. While good liver function, a low serum AFP level, and recurrent tumors were independent predictive factors for a favorable overall survival, poor response to TACE, a high serum AFP level, and large tumors are associated with early recurrence.
Aged ; Carcinoma, Hepatocellular/*mortality/*therapy ; *Catheter Ablation ; Chemoembolization, Therapeutic/mortality ; Combined Modality Therapy/mortality ; Female ; Humans ; Liver Neoplasms/*mortality/*therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local/mortality ; Survival Rate ; Treatment Outcome ; alpha-Fetoproteins/analysis

BACKGROUND/AIMS: This study investigated the expression of nuclear factor kappaB (NF-kappaB) and the chemokine receptor (CXCR4) in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. METHODS: Seventy patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and immunohistochemistry was performed to determine the expression of NF-kappaB (IkappaB kinase alpha, p50, and p100/p52) and CXCR4. To classify DLBCL cases as germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 was used in this study. The expression was divided into two groups according to the intensity score (negative, 0 or 1+; positive, 2+ or 3+). RESULTS: The median age of the patients was 66 years (range, 17 to 87), and 58.6% were male. Twenty-seven patients (38.6%) had stage III or IV disease at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their International Prognostic Indexs (IPIs). The overall incidence of bone marrow involvement was 5.7%. Rates of positive NF-kappaB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-kappaB expression was associated with CXCR4 expression (p = 0.002), and 56 patients (80.0%) showed coexpression. However, the expression of NF-kappaB or CXCR4 was not associated with overall survival and EFS. On multivariate analysis that included age, gender, performance status, stage, and the IPI, no significant association between the grade of NF-kappaB or CXCR4 expression and survival was observed. CONCLUSIONS: The current study suggests that the tissue expression of NF-kappaB and CXCR4 may not be an independent prognostic marker in DLBCL patients treated with R-CHOP.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chi-Square Distribution ; Cyclophosphamide/administration & dosage ; Disease Progression ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse/chemistry/*drug therapy/mortality/pathology ; Male ; Middle Aged ; Multivariate Analysis ; NF-kappa B/*analysis ; Neoplasm Staging ; Predictive Value of Tests ; Prednisone/administration & dosage ; Proportional Hazards Models ; Receptors, CXCR4/*analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Markers, Biological/*analysis ; Vincristine/administration & dosage ; Young Adult

High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate analysis showed that the independent predictive risk factors for diabetes were hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR, 1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease.
Causality ; Comorbidity ; Diabetes Complications/diagnosis/epidemiology/physiopathology ; Elastic Modulus ; Elasticity Imaging Techniques/methods/statistics & numerical data ; End Stage Liver Disease/*epidemiology/physiopathology/*ultrasonography ; Fatty Liver/*epidemiology/physiopathology/*ultrasonography ; Female ; Humans ; Image Interpretation, Computer-Assisted/methods ; Incidence ; Liver/physiopathology/ultrasonography ; Liver Cirrhosis/*epidemiology/physiopathology/*ultrasonography ; Male ; Middle Aged ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity