Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

BACKGROUND: The survival of non-small cell lung cancer (NSCLC) patients with brain metastases is reported to be 3~6 months even with aggressive treatment. Some patients have very short survival after aggressive treatment and reliable prognostic scoring systems for patients with cancer have a strong correlation with outcome, often supporting decision making and treatment recommendations. METHODS: A total of one hundred twenty two NSCLC patients with brain metastases who received gamma knife radiosurgery (GKRS) were analyzed. Survival analysis was calculated in all patients for thirteen available prognostic factors and four prognostic scoring systems: score index for radiosurgery (SIR), recursive partitioning analysis (RPA), graded prognostic assessment (GPA), and basic score for brain metastases (BSBM). RESULTS: Age, Karnofsky performance status, largest brain lesion volume, systemic chemotherapy, primary tumor control, and medication of epidermal growth factor receptor tyrosine kinase inhibitor were statistically independent prognostic factors for survival. A multivariate model of SIR and RPA identified significant differences between each group of scores. We found that three-tiered indices such as SIR and RPA are more useful than four-tiered scoring systems (GPA and BSBM). CONCLUSION: There is little value of RPA class III (most unfavorable group) for the same results of 6-month and 1-year survival rate. Thus, SIR is the most useful index to sort out patients with poorer prognosis. Further prospective trials should be performed to develop a new molecular- and gene-based prognostic index model.
Brain ; Carcinoma, Non-Small-Cell Lung ; Decision Making ; Humans ; Karnofsky Performance Status ; Neoplasm Metastasis ; Outpatients ; Prognosis ; Protein-Tyrosine Kinases ; Radiosurgery ; Receptor, Epidermal Growth Factor ; Survival Rate

BACKGROUND: We evaluated the clinical outcomes and prognostic factors of patients requiring prolonged mechanical ventilation (PMV), defined as ventilator care for > or =21 days, who were admitted to the medical intensive care unit (ICU) of a university hospital in Korea. METHODS: During the study period, a total of 2,644 patients were admitted to the medical ICU, and 136 patients (5.1%) were enrolled between 2005 and 2010. RESULTS: The mean age of the patients was 61.3+/-14.5 years, and 94 (69.1%) were male. The ICU and six-month cumulative mortality rates were 45.6 and 58.8%, respectively. There were 96 patients with tracheostomy placement after admission and their mean period from admission to the day of tracheostomy was 21.3+/-8.4 days. Sixty-three patients (46.3%) were successfully weaned from ventilator care. Of the ICU survivors (n=74), 34 patients (45.9%) were transferred to other hospitals (not university hospitals). Two variables (thrombocytopenia [hazard ratio (HR), 1.964; 95% confidence interval (CI), 1.225~3.148; p=0.005] and the requirement for vasopressors [HR, 1.822; 95% CI, 1.111~2.986; p=0.017] on day 21) were found to be independent factors of survival on based on the Cox proportional hazard model. CONCLUSION: We found that patients requiring PMV had high six-month cumulative mortality rates, and that two clinical variables (measured on day 21), thrombocytopenia and requirement for vasopressors, may be associated with prognostic indicators.
Humans ; Critical Care ; Intensive Care Units ; Korea ; Male ; Respiration, Artificial ; Survivors ; Thrombocytopenia ; Tracheostomy ; Ventilators, Mechanical

BACKGROUND: Maspin (mammary serine protease inhibitor) is a member of the serpin superfamily. A few studies have examined the role of maspin in tumor suppression of non-small cell lung cancer (NSCLC); however, its role in the development and progression of NSCLC still remains controversial. We evaluated the immunohistochemical expression of maspin in order to elucidate its clinical significance in NSCLC. METHODS: We analyzed 145 patients with pathologically confirmed NSCLC, including 66 cases of squamous cell carcinomas (SCCs) and 79 cases of adenocarcinomas (ADCs). We performed a immuno-histochemical stain with maspin and PCNA (proliferating cell nuclear antigen) using tissue microarray blocks. RESULTS: There were 108 men and 37 women in the study population. The mean age of patients in the study was 63.7 years (range, 40.0~82.0; median, 65.0). The proportion of maspin expression was significantly higher in SCCs (52/66, 78.8%; p<0.01) than in ADCs (17/79, 21.5%; p<0.01). Maspin expression was not associated with PCNA (p=0.828), lymph node involvement (p=0.483), or tumor stage (p=0.216), but showed correlation with well-to-moderate tumor differentiation (p=0.012). There was no observed correlation between maspin expression and survival with NSCLC (p=0.218). CONCLUSION: The present study suggests that maspin expression was significantly higher in SCCs than in ADCs and was associated with low histological grade. However, maspin expression was not an independent factor to predict a prognosis in NSCLC.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Female ; Humans ; Lymph Nodes ; Male ; Prognosis ; Proliferating Cell Nuclear Antigen ; Serine Proteases ; Serpins

BACKGROUND/AIMS: Pandemic influenza A (H1N1) virus infection presents with variable severity. However, little is known about clinical predictors of disease severity. We studied the clinical predictors of severe pandemic H1N1 pneumonia and their correlation with radiological findings. METHODS: We reviewed medical and radiological records of adults with pandemic H1N1 pneumonia. After classification of patients into severe and non-severe groups, the following data were evaluated: demographic data, pneumonia severity index (PSI), CURB65, risk factors, time to first dose of antiviral medication, routine laboratory data, clinical outcome, and radiological characteristics. RESULTS: Of 37 patients with pandemic H1N1 pneumonia, 12 and 25 were assigned to the severe and non-severe groups, respectively. PSI score, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dyhydrogenase (LDH) levels were higher in the severe group than in the non-severe group (p = 0.035, 0.0003, 0.0023, and 0.0002, respectively). AST, ALT, and LDH levels were positively correlated with the radiological findings (p < 0.0001, 0.0003, and < 0.0001, respectively) and with the number of involved lobes (p = 0.663, 0.0134, and 0.0019, respectively). The most common finding on high resolution computed tomography (HRCT) scans was ground-glass attenuation with consolidation (n = 22, 60%), which had a predominantly patchy distribution (n = 31). CONCLUSIONS: We demonstrated a positive correlation between clinical findings, such as serum AST, ALT, and LDH levels, and radiological findings. A combination of clinical and HRCT indicators would be useful in predicting the clinical outcome of pandemic H1N1 pneumonia.
Adolescent ; Adult ; Aged ; Alanine Transaminase/blood ; Antiviral Agents/therapeutic use ; Aspartate Aminotransferases/blood ; Biological Markers/blood ; Chi-Square Distribution ; Clinical Enzyme Tests ; Female ; Humans ; Influenza A Virus, H1N1 Subtype/*pathogenicity ; Influenza, Human/*diagnosis/mortality/radiography/therapy/virology ; L-Lactate Dehydrogenase/blood ; Lung/*radiography/virology ; Male ; Middle Aged ; *Pandemics ; Pneumonia, Viral/*diagnosis/mortality/radiography/therapy/virology ; Predictive Value of Tests ; Prognosis ; Republic of Korea/epidemiology ; Respiration, Artificial ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Severity of Illness Index ; *Tomography, X-Ray Computed ; Young Adult

Next to lymphatic involvement, genitourinary tuberculosis is considered the second most common manifestation of extrapulmonary tuberculosis worldwide. However, testicular and spermatic cord involvement is uncommon. We report here on a case of testicular and spermatic cord tuberculosis that masqueraded as testicular cancer. A 25-year-old man was admitted to our hospital with painless right scrotal swelling for past 2 months. The abdominal CT scan showed a heterogenous testicular mass that was suspicious for being malignancy. He underwent right radical orchiectomy; testicular and spermatic cord tuberculosis was revealed on histopathological examination. This case highlights the importance of taking a thoughtful diagnostic approach for testicular and spermatic cord tuberculosis, including fine needle aspiration before performing surgical exploration.
Adult ; Biopsy, Fine-Needle ; Humans ; Spermatic Cord ; Testicular Neoplasms ; Tuberculosis ; Tuberculosis, Urogenital ; Urogenital Neoplasms

BACKGROUND: Bronchoalveolar lavage (BAL) is a useful technique to recover lower airway fluid and cells involved in many respiratory diseases. Miliary tuberculosis is potentially lethal, but the clinical manifestations are nonspecific and typical radiologic findings may not be seen until late in the course of disease. In addition, invasive procedures are often needed to confirm disease diagnosis. This study analyzed the cells and the T-lymphocyte subset in BAL fluid from patients with miliary tuberculosis to determine specific characteristics of BAL fluid that may help in the diagnosis of miliary tuberculosis, using a less invasive procedure. METHODS: On a retrospective basis, we enrolled 20 miliary tuberculosis patients; 12 patients were male and the mean patient age was 40.5+/-16.2 years. We analyzed differential cell counts of BAL fluid and the T-lymphocyte subset of BAL fluid. RESULTS: Total cells and lymphocytes were increased in number in the BAL fluid. The percentage of CD4+ T-lymphocytes and the CD4/CD8 ratio in BAL fluid were significantly decreased and the percentage of CD8+ T-lymphocytes was relatively higher. These findings were more prominent in patients infected with the human immunodeficiency virus (HIV). In the HIV-infected patients, the proportion of lymphocytes was significantly higher in BAL fluid than in peripheral blood. There were no significant differences between the BAL fluid and the peripheral blood T-lymphocytes subpopulation. CONCLUSION: BAL fluid in patients with miliary tuberculosis demonstrated lymphocytosis, a lower percentage of CD4+ T-lymphocytes, a higher percentage of CD8+ T-lymphocytes, and a decreased CD4/CD8 ratio. These findings were more significant in HIV-infected subjects.
Bronchoalveolar Lavage ; Bronchoalveolar Lavage Fluid ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Cell Count ; HIV ; Humans ; Lymphocyte Subsets ; Lymphocytes ; Lymphocytosis ; Male ; Retrospective Studies ; T-Lymphocyte Subsets ; T-Lymphocytes ; Tuberculosis, Miliary

BACKGROUND: Synergistic antitumor effects of the combined chemoimmunotherapy based on dendritic cells have been reported recently. The aim of this study is to search new applicability of gefitinib into the combination treatment through the confirmation of gefitinib effects on the monocyte derived dendritic cells (moDCs); most potent antigen presenting cell (APC). METHODS: Immature and mature monocyte-derived dendritic cell (im, mMoDC)s were generated from peripheral blood monocyte (PBMC) in Opti-MEM culture medium supplemented with IL-4, GM-CSF and cocktail, consisting of TNF-alpha (10 ng/mL), IL-1beta (10 ng/mL), IL-6 (1,000 U/mL) and PGE2 (1 micro/mL). Various concentrations of gefitinib also added on day 6 to see the influence on immature and mature MoDCs. Immunophenotyping of DCs under the gefitinib was performed by using monoclonal antibodies (CD14, CD80, CD83, CD86, HLA-ABC, HLA-DR). Supernatant IL-12 production and apoptosis of DCs was evaluated. And MLR assay with [3H]-thymidine uptake assay was done. RESULTS: Expression of CD83, MHC I were decreased in mMoDCs and MHC I was decreased in imMoDCs under gefitinib. IL-12 production from mMoDCs was decreased under 10 microM of gefitinib sinificantly. Differences of T cell proliferation capacity were not observed in each concentration of geftinib. CONCLUSION: In spite of decreased expressions of some dendritic cell surface molecules and IL-12 production under 10 microM of gefitinib, significant negative influences of gefitinib in antigen presenting capacity and T cell stimulation were not observed.
Antibodies, Monoclonal ; Apoptosis ; Cell Proliferation ; Dendritic Cells ; Dinoprostone ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunophenotyping ; Interleukin-12 ; Interleukin-4 ; Interleukin-6 ; Monocytes ; Quinazolines ; Tumor Necrosis Factor-alpha

Choriocarcinoma, a type of germ cell tumor, follows molar pregnancy and gestational events, including abortion and ectopic pregnancy, with significantly elevated serum human chorionic gonadotropin (HCG) levels. Choriocarcinoma is rare, but very aggressive. The most common sites of metastatic involvement are the lung, vagina, and pelvic organs. We report the case of a 54-year-old woman with choriocarcinoma metastatic to the lung, with significant elevation of the serum HCG (>1,000,000 mIU/mL). Chest computed tomography (CT) on admission revealed multiple centrilobular nodules. The pathological examination of the specimen revealed tumor cell emboli in the pulmonary artery.
Choriocarcinoma ; Chorionic Gonadotropin ; Female ; Humans ; Hydatidiform Mole ; Lung ; Middle Aged ; Neoplasms, Germ Cell and Embryonal ; Neoplastic Cells, Circulating ; Pregnancy ; Pregnancy, Ectopic ; Pulmonary Artery ; Thorax ; Vagina