Yun Seong Kim

Prognostic value of volumetric parameters measured by F-18 FDG PET/CT in surgically resected non-small-cell lung cancer.

Objectives The aim of this study was to evaluate the usefulness of the tumor burden as characterized by the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by F-18 fluoro-2-deoxyglucose (F-18 FDG) PET-computed tomography (CT) in predicting recurrence-free survival (RFS) and overall survival (OS) in surgically resected non-small-cell lung cancer (NSCLC) patients. Methods We retrospectively reviewed 91 patients with pathologically documented stages I–IIIA NSCLC. MTV and TLG were obtained according to various thresholds of the standard uptake value (SUV) of primary tumor using preoperative F-18 FDG PET-CT. We used comparison receiver-operating characteristic curve analysis to test the statistical significance of the differences among the multiple volumetric parameters calculated by various SUV cutoff values. RFS and OS were evaluated with the Kaplan–Meier method and Cox regression analysis. Results On comparison receiver-operating characteristic curve analysis, no significant difference was found among the volumetric parameters calculated using various thresholds of SUV. Regardless of the thresholds, patients with smaller MTV and lower TLG showed longer RFS and OS. MTV and TLG measured by F-18 FDG PET-CT were found to have better predictive performance than SUVmax for recurrence and death. According to multivariate analyses, MTV2.5 was revealed as a significant prognostic factor for RFS. Tumor size over 3 cm was selected as a significant prognostic indicator of OS. Conclusion Volume-based parameters of F-18 FDG PET-CT may have a role in providing prognostic information in NSCLC patients who have received surgical treatment.

A prospective longitudinal study evaluating the usefulness of a T-cell-based assay for latent tuberculosis infection in kidney transplant recipients.

We evaluated whether ELISPOT assay can predict tuberculosis (TB) development in kidney‐transplantation (KT) recipients with a negative tuberculin skin test (TST). All adult patients admitted to a KT institute between June 2008 and December 2009 were enrolled; TB development after KT was observed between June 2008 and December 2010. Isoniazid (INH) was given to those patients with positive TST or clinical risk factors for latent TB infection (LTBI). ELISPOT assay was performed on all patients, and TB development after KT was observed by a researcher blinded to the results of ELISPOT. A total of 312 KT recipients including 242 (78%) living‐donor KT were enrolled. Of the 312 patients, 40 (13%) had positive TST or clinical risk factors for LTBI and received INH; none developed TB after KT. Of the remaining 272 patients, 4 (6%) of 71 with positive ELISPOT assay developed TB after KT, whereas none of the 201 patients with negative (n = 171) or indeterminate ELISPOTs (n = 30) developed TB after KT (rate difference between positive and negative/indeterminate ELISPOT, 3.3 per 100 person‐years [95% CI 1.4–5.1, p<0.001]). Positive ELISPOT results predict subsequent development of TB in KT recipients in whom LTBI cannot be detected by TST or who lack clinical risk factors for LTBI.

Triple-Combination Antiviral Drug for Pandemic H1N1 Influenza Virus Infection in Critically Ill Patients on Mechanical Ventilation

ABSTRACT A recent in vitro study showed that the three compounds of antiviral drugs with different mechanisms of action (amantadine, ribavirin, and oseltamivir) could result in synergistic antiviral activity against influenza virus. However, no clinical studies have evaluated the efficacy and safety of combination antiviral therapy in patients with severe influenza illness. A total of 245 adult patients who were critically ill with confirmed pandemic influenza A/H1N1 2009 (pH1N1) virus infection and were admitted to one of the intensive care units of 28 hospitals in Korea were reviewed. Patients who required ventilator support and received either triple-combination antiviral drug (TCAD) therapy or oseltamivir monotherapy were analyzed. A total of 127 patients were included in our analysis. Among them, 24 patients received TCAD therapy, and 103 patients received oseltamivir monotherapy. The 14-day mortality was 17% in the TCAD group and 35% in the oseltamivir group (P = 0.08), and the 90-day mortality was 46% in the TCAD group and 59% in the oseltamivir group (P = 0.23). None of the toxicities attributable to antiviral drugs occurred in either group of our study, including hemolytic anemia and hepatic toxicities related to the use of ribavirin. Logistic regression analysis indicated that the odds ratio for the association of TCAD with 90-day mortality was 0.58 (95% confidence interval, 0.24 to 1.42; P = 0.24). Although this study was retrospective and did not provide virologic outcomes, our results suggest that the treatment outcome of the triple combination of amantadine, ribavirin, and oseltamivir was comparable to that of oseltamivir monotherapy.

Trichinella spiralis: Infection reduces airway allergic inflammation in mice

In an effort to define the mechanism underlying the host immune downregulation inherent to Trichinella spiralis infection, we compared the levels of Th1, Th2, and regulatory cytokines and CD4(+)CD25(+) forkhead box P3 (FoxP3)(+) T (T(reg)) cell recruitment, as well as cellular pathology in the airway between T. spiralis infected and uninfected asthma-induced mice. After the induction of allergic airway inflammation, we noted influxes of inflammatory cells into the peribronchial tree. However, in the T. spiralis infection groups, cellular infiltration was minimal around the bronchial tree, with only a smattering of inflammatory cells. In the OVA-challenged group after T. spiralis infection, the numbers of macrophages and eosinophils in the bronchial alveolar lavage fluid were reduced by 23% and 52%, respectively, as compared to those of the OVA-challenged group. Airway hyperresponsiveness of OVA-challenged mice after T. spiralis infection was significantly suppressed as compared to the OVA-only challenged mice. The T. spiralis-infected mice exhibited a significant reduction in IL-5 concentrations relative to that noted in the OVA-challenged group (p<0.01). Nevertheless, the regulatory cytokines IL-10 and TGF-β levels were increased significantly as the result of T. spiralis infection, and we verified the recruitment of T(reg) cells in lung draining lymph nodes via T. spiralis infection. Therefore, T(reg) cells, which were recruited by T. spiralis infection, might ameliorate lung function and reduce allergic airway inflammation.

Efficacy of Oral Ribavirin in Hematologic Disease Patients with Paramyxovirus Infection: Analytic Strategy Using Propensity Scores

ABSTRACT Few antiviral agents are available for treating paramyxovirus infections, such as those involving respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV). We evaluated the effect of oral ribavirin on clinical outcomes of paramyxovirus infections in patients with hematological diseases. All adult patients with paramyxovirus were retrospectively reviewed over a 2-year period. Patients who received oral ribavirin were compared to those who received supportive care without ribavirin therapy. A propensity-matched case-control study and a logistic regression model with inverse probability of treatment weighting (IPTW) were performed to reduce the effect of selection bias in assignment for oral ribavirin therapy. A total of 145 patients, including 64 (44%) with PIV, 60 (41%) with RSV, and 21 (15%) with hMPV, were analyzed. Of these 145 patients, 114 (78%) received oral ribavirin and the remaining 31 (21%) constituted the nonribavirin group. Thirty-day mortality and underlying respiratory death rates were 31% (35/114) and 12% (14/114), respectively, for the oral ribavirin group versus 19% (6/31) and 16% (5/31), respectively, for the nonribavirin group (P = 0.21 and P = 0.56). In the case-control study, the 30-day mortality rate in the ribavirin group was 24% (5/21) versus 19% (4/21) in the nonribavirin group (P = 0.71). In addition, the logistic regression model with IPTW revealed no significant difference in 30-day mortality (adjusted hazard ratio of 1.3; 95% confidence interval [95% CI] of 0.3 to 5.8) between the two groups. Steroid use (adjusted odds ratio, 5.67; P = 0.01) and upper respiratory tract infection (adjusted odds ratio, 0.07; P = 0.001) was independently associated with mortality. Our data suggest that oral ribavirin therapy may not improve clinical outcomes in hematologic disease patients infected with paramyxovirus.

Treatment Outcome and Mortality among Patients with Multidrug-resistant Tuberculosis in Tuberculosis Hospitals of the Public Sector

This study was conducted to evaluate treatment outcome, mortality, and predictors of both in patients with multidrug-resistant tuberculosis (MDR-TB) at 3 TB referral hospitals in the public sector of Korea. We included MDR-TB patients treated at 3 TB referral hospitals in 2004 and reviewed retrospectively their medical records and mortality data. Of 202 MDR-TB patients, 75 (37.1%) had treatment success and 127 (62.9%) poor outcomes. Default rate was high (37.1%, 75/202), comprising 59.1% of poor outcomes. Male sex (adjusted odds ratio [aOR], 2.91; 95% confidence interval [CI], 1.13-7.49), positive smear at treatment initiation (aOR, 5.50; 95% CI, 1.22-24.90), and extensively drug-resistant TB (aOR, 10.72; 95% CI, 1.23-93.64) were independent predictors of poor outcome. The all-cause mortality rate was 31.2% (63/202) during the 3-4 yr after treatment initiation. In conclusion, the treatment outcomes of patients with MDR-TB at the 3 TB hospitals are poor, which may reflect the current status of MDR-TB in the public sector of Korea. A more comprehensive program against MDR-TB needs to be integrated into the National Tuberculosis Program of Korea.

Four Cases of a Cerebral Air Embolism Complicating a Percutaneous Transthoracic Needle Biopsy

A percutaneous transthoracic needle biopsy is a common procedure in the practice of pulmonology. An air embolism is a rare but potentially fatal complication of a percutaneous transthoracic needle biopsy. We report four cases of a cerebral air embolism that developed after a percutaneous transthoracic needle biopsy. Early diagnosis and the rapid application of hyperbaric oxygen therapy is the mainstay of therapy for an embolism. Prevention is the best course and it is essential that possible risk factors be avoided.

Phase I study of autologous dendritic cell tumor vaccine in patients with non-small cell lung cancer

BACKGROUND A dendritic cell vaccine has been developed as a novel strategy for generating antitumor immunity in the treatment of cancer. The purpose of this study was to assess the maximal tolerated dose, safety, and immunologic response of a new dendritic cell vaccine (DC-Vac) into which tumor lysate was loaded by electroporation and pulse in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Fifteen patients with inoperable stage III or IV NSCLC were assigned to cohorts that received 3, 6, or 12 × 10(6) DC-Vac intradermally 3 times at 2 week intervals. We also evaluated immunologic and tumor responses. RESULTS The maximum dose of DC-Vac (12 × 10(6)) was shown to be safe. In 5 of 9 patients, the vaccine resulted in increased interferon (IFN)-γ production by CD8+ cells after exposure to tumor lysate. Additionally, there were mixed responses which do fulfill progressive disease definition but demonstrate some clinical benefit in two patients. CONCLUSION The administration of tumor lysate-loaded autologous dendritic cells by electroporation and pulse was non-toxic and induced immunologic responses to tumor antigens. The two mixed tumor responses which were achieved may represent a potential benefit of this new DC-Vac.

Protease-activated receptor 2 is involved in Th2 responses against Trichinella spiralis infection.

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.

Low-dose heparin during extracorporeal membrane oxygenation treatment in adults

Dear Editor, Bleeding during extracorporeal membrane oxygenation (ECMO) is a potentially severe complication [1]. Excess anticoagulation may result in bleeding, unnecessary transfusions, and mortality [2]. Recent technological advances have reduced the amount of anticoagulation needed to prevent thrombosis [3]. We evaluated whether a lower target activated clotting time (ACT) during ECMO results in fewer hemorrhagic complications and a reduced need for blood products. The conventional (group C) and lower (group L) target groups comprised patients who received anticoagulation to maintain an ACT of 180–220 or 140–160 s, respectively, by continuous infusion of unfractionated heparin. Seventy-one patients were analyzed (Fig. 1 in the Electronic Supplementary Material, ESM). The indications for ECMO support were respiratory failure and cardiogenic shock (54 vs. 46 % patients, respectively). Forty-nine and 22 patients were treated with venoarterial and veno-venous ECMO, respectively; 69 % used vasopressors and 33.8 % underwent continuous renal replacement therapy. The preECMO clinical variables and coagulation profiles did not differ significantly between the two groups (Table 1 in the ESM). The mean activated partial thromboplastin time, ACT, and heparin dose during ECMO were higher in group C than L (Fig. 2 in the ESM). The incidences of major bleeding and bleeding-induced death were higher in group C than L (71.0 vs. 20.0 %, p\ 0.001; 22.6 vs. 2.5 %, p = 0.008; respectively) (Fig. 1a). The cannulation site was the most common bleeding site. The incidences of cannula-site and gastrointestinal bleeding were higher in group C than L (Table 2 in the ESM).