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BACKGROUND Hepatitis B virus (HBV) and hepatitis C virus (HCV) are suspected of being associated with non-Hodgkin lymphoma (NHL); however, persuasive data are lacking. Hence, a nested large-population case-control study was performed to investigate such associations in Koreans. METHODS Data were collected from 929 patients with NHL and 3716 healthy subjects, who were matched 1:4 for age, sex, income, and region of residence, from the Korean Health Insurance Review and Assessment Service-National Sample Cohort. The diagnoses of NHL and HBV/HCV infection were based on the International Classification of Diseases (version 10) codes. Conditional logistic regression models were used to assess odds ratios (ORs) for NHL with respect to HBV or HCV with adjustment for the Charlson comorbidity index. RESULTS HBV and HCV rates were higher in the NHL group (3.3% and 1.3%, respectively) than in the control group (0.9% and 0.3%, respectively; P

Pleomorphic adenoma is the most common type of salivary gland tumor. Although it rarely affects the trachea and bronchus, it usually grows in the airway and presents as an endobronchial mass. We recently experienced a case of pleomorphic adenoma originating in the bronchus and growing outward into the mediastinum. We present this case with review of the computed tomography (CT) scan of the patient's chest, the endoscopic ultrasound (EUS), and the histopathology report.

Summary Varying coefficient regression models are known to be very useful tools for analysing the relation between a response and a group of covariates. Their structure and interpretability are similar to those for the traditional linear regression model, but they are more flexible because of the infinite dimensionality of the corresponding parameter spaces. The aims of this paper are to give an overview on the existing methodological and theoretical developments for varying coefficient models and to discuss their extensions with some new developments. The new developments enable us to use different amount of smoothing for estimating different component functions in the models. They are for a flexible form of varying coefficient models that requires smoothing across different covariates' spaces and are based on the smooth backfitting technique that is admitted as a powerful technique for fitting structural regression models and is also known to free us from the curse of dimensionality.

Endotracheal metastasis of primary lung cancer is extremely rare. We report the case of a 51-year-old male patient who had undergone right pneumonectomy for squamous cell carcinoma one year earlier. The post-operative chest computed tomography (CT) image revealed a very small endotracheal nodule with contrast enhancement. This finding was erroneously regarded as endotracheal phlegm because of the nodular size and the rarity of endotracheal metastases from primary lung cancer. This case indicates that a thorough evaluation should be performed with a high level of suspicion for malignancy when a nodule-like lesion with contrast enhancement or tracheal thickening is detected on follow-up CT scan, in patients who undergo surgery for lung cancer.

Lee KG, Lee H, Ha JM, Lee YK, Kang HJ, Park C-G, Kim SJ. Increased human tumor necrosis factor-α levels induce procoagulant change in porcine endothelial cells in vitro. Xenotransplantation 2012; 19: 186–195. © 2012 John Wiley & Sons A/S. Abstract: Background: Intravascular thrombosis and systemic coagulation abnormalities are major hurdles to successful xenotransplantation and are signs of acute humoral rejection. Increased expression of tissue factor (TF) is associated with the development of microvascular thrombosis in xenografts. To develop an effective strategy to prevent accelerated coagulation in xenografts, we investigated the mechanism by which porcine endothelial cells (PECs) become procoagulant after contact with human blood. Methods: The changes in TF mRNA levels and activity in PECs after incubation with 20% human serum or human bioactive molecules, including C5a, tumor necrosis factor-α (TNFα) and interleukin (IL)-1α, were evaluated using real-time PCR and the factor Xa chromogenic assay, respectively. The procoagulant changes in PECs by these agonists were evaluated by measuring the coagulation time of human citrated plasma suspended with PECs pretreated with each agonist. TF expression and coagulation times were also assessed in PECs transfected with short interfering RNA (siRNA) designed to knock down porcine TF. We also examined the production of proinflammatory cytokines in human whole-blood or plasma after contact with PECs, which were screened using the cytometric bead array system. TNFα levels were measured using ELISA in whole-blood after contact with PECs, with or without the addition of xenoreactive antibodies or C1 esterase inhibitor. Results: Porcine TF mRNA and activity in PECs were up-regulated in response to human TNFα and IL-1α but were not affected by C5a or 20% human serum. Up-regulation of TF expression by human TNFα or IL-1α shortened PEC-induced coagulation time, while siRNA-mediated knockdown of TF expression prolonged coagulation time. The incubation of PECs with human whole-blood led to a significant increase in human TNFα levels in the blood, which was promoted by the addition of xenoreactive antibodies and prevented by C1 esterase inhibitor. Conclusions: Human TNFα level increases in human blood after contact with PECs, which is attributed to xenoreactive antibody binding and subsequent complement activation. Human TNFα induces procoagulant changes in PECs with increased TF expression. This study suggests that human TNFα may be one of the mediators linking complement activation with procoagulant changes in the xenoendothelium.

Summary Background: Patients with chronic obstructive pulmonary disease (COPD) show different spirometric response patterns to bronchodilator, such that some patients show improvement principally in expiratory flow (forced expiratory volume in 1 s; FEV1), whereas others respond by improvement of lung volume (forced vital capacity; FVC). The mechanisms of these different response patterns to bronchodilator remain unclear. We investigated the associations between bronchodilator responsiveness and quantitative computed tomography (CT) indices in patients with COPD. Methods: Data on a total of 101 patients with stable COPD were retrospectively analysed. Volume and flow responses to bronchodilator were assessed by FVC and FEV1 changes before and after inhalation of salbutamol (400 μg). Volumetric CT was performed to quantify emphysema, air trapping and large airway thickness. Emphysema was assessed by the volume fraction of the lung under −950 Hounsfield units (HU; V950) at full inspiration and air trapping by the ratio of mean lung density (MLD) at full expiration and inspiration. Airway wall thickness and wall area percentage (WA%; defined as wall area/[wall area + lumen area] × 100), were measured near the origin of right apical and left apico-posterior bronchus. Results: Among quantitative CT indices, the CT emphysema index (V950 insp) showed a significant negative correlation with postbronchodilator FEV1 change (R = −0·213, P = 0·004), and the CT air-trapping index correlated positively with postbronchodilator FVC change(R = 0·286, P≤0·001). Multiple linear regression analysis showed that CT emphysema index had independent association with postbronchodilator FEV1 change and CT air-trapping index with postbronchodilator FVC change. Conclusion: The degrees of emphysema and air trapping may contribute to the different response patterns to bronchodilator in patients with COPD.

Several groups have demonstrated that a submicroscopic gene deletion in Ph+ chronic myelogenous leukemia (CML) is associated with a poor prognosis and reduced response to treatment. To assess the variation between detection methods in the interpretation of a submicroscopic gene deletion, we performed an extra signal (ES)-FISH BCR/ABL and double-FISH (D-FISH) BCR/ABL on frozen bone marrow cells from 79 patients with CML (63 in the chronic phase, 6 in the accelerated phase, and 10 in blast crisis) and 30 patients with a BCR/ABL-negative myeloproliferative disorder as determined by RT-PCR. The normal cutoff values were 0.22% for ES-FISH and 0.25% for D-FISH. The cutoff values for false-positive signals from a juxtaposition of the BCR and ABL gene were 11% in ES-FISH and 13% in D-FISH. Of the 14 patients who showed an ABL gene deletion by ES-FISH, 5 had an ABL deletion only, 5 had both a BCR and an ABL deletion, but 4 proved to have a classic BCR/ABL rearrangement without a submicroscopic deletion, as determined by D-FISH. Discrepant results between ES- and D-FISH were observed in 12 of the 79 patients (15.8%), and the main causes of a discrepancy were a false-positive ABL deletion (4 of 12, 33%), a variant Philadelphia chromosome (3 of 12, 25%), an inversion of derivative chromosome 9 at the very breakpoint of the ABL gene (9q32) (1 of 12, 8.3%), a cryptic variant Ph chromosome (1 of 12, 8.3%), and a marker chromosome (1 of 12, 8.3%). Although there was no significant difference in the sensitivity for the detection of the fusion signal between ES- and D-FISH, ES-FISH showed a high percentage of cells with false-positive fusion signals (1 orange, 1 green, 1 yellow), which makes it difficult to interpret the submicroscopic ABL deletion. In conclusion, an interpretation of the submicroscopic deletions of the BCR or ABL gene should not depend on ES-FISH.

Purpose: To evaluate normal tissue sparing in intra-cranial HF-SRT, comparing various arc configurations with the Synergy Beam Modulator (SynBM) and Agility linacs, the latter incorporating leaf interdigitation and backup jaws. Methods: Five patients with multiple brain metastases (BMs), (5 BMs (n=2), 3 BMs (n=3)) treated with HF-SRT using 25 Gy (n=2) or 30 Gy (n=3) in 5 fractions, were investigated. Clinical treatment plans used the SynBM. Each patient was retrospectively re-planned on Agility, employing three planning strategies: (A) one isocenter and dedicated arc for each BM; (B) a single isocenter, centrally placed with respect to BMs; (C) the isocenter and arc configuration used in the SynBM plan, where closely spaced (