The utility of three-dimensional computed tomography for prediction of tumor invasiveness in clinical stage IA lung adenocarcinoma

BackgroundIt is critical to have an accurate measurement of solid tumor size in order to predict the invasiveness of small lung adenocarcinomas. Some lesions cannot be measured accurately via High-resolution computed tomography (HRCT) due to their irregular shape and unclear borders. For this reason, we evaluated the relative efficacy of three-dimensional (3D) CT for predicting invasive adenocarcinoma.MethodsWe evaluated 195 patients with clinical stage IA adenocarcinomas, including 109 with lesions documented as invasive that were surgically resected at our institute during 2017. All lesions were categorized as either (I) lesions that were difficult to evaluate (i.e., hazy lesions; HL) or (II) more typical lesions (TL). The relationships between solid tumor size as determined by HRCT, solid tumor volume as determined by 3D CT and pathologic diagnosis were evaluated.ResultsFifty-seven patients (29%) were diagnosed with HL. We set the cut-off value for the solid volume at 225 mm³ as predictive for invasive adenocarcinoma. When evaluating all 195 patients as a group, the accuracy, sensitivity, and specificity based on the solid tumor volume were similar to those based on the solid tumor size. When we limit our analysis to the HL group, the specificity based on solid tumor volume (65.5%) was higher than that based on solid tumor size (44.8%) with a difference that approached statistical significance (P=0.070).Conclusions3D CT was equivalent to HRCT for predicting invasive adenocarcinoma and may be particularly useful for diagnosing lesions that are difficult to evaluate on HRCT.     

Long-term follow-up of adalimumab monotherapy for rheumatoid arthritis in Japanese patients: a report of six cases

We present six cases of patients with Japanese rheumatoid arthritis (RA) treated with a tumor necrosis factor (TNF)-alpha blocking agent, adalimumab as monotherapy for 220?weeks. All six patients were women, and the median age was 54.0?±?7.07?years old. The median duration of the disease was 7.43?±?11.1?years, and the median disease activity score (DAS28-CRP) was 5.35?±?0.69. Three of six patients were able to continue to receive this treatment for 220?weeks successfully, and the DAS28-CRP decreased to 1.89?±?0.75. Two patients withdrew because of lack of efficacy, and one patient withdrew because of adverse events (non-Hodgkin lymphoma). Adalimumab resulted in a sustained clinical response in RA patients during 220-week follow-up.     

Reduced difference of α<Subscript>2</Subscript>-plasmin inhibitor levels between plasma and serum in patients with severe factor XIII deficiency,including autoimmune hemorrhaphilia due to anti-factor XIII antibodies

Coagulation factor XIII/13 (FXIII/13) stabilizes fibrin molecules by creating crosslinks with other fibrin molecules as well as with α₂-plasmin inhibitor (α₂-PI). “Hemorrhagic acquired FXIII/13 deficiency” was formerly considered rare, but has been increasing recently in Japan. During the 10 months of our nationwide campaign, we diagnosed five new patients with “acquired hemorrhaphilia due to anti-FXIII/13 autoantibodies,” after examining 20 newly suspected cases of “hemorrhagic acquired FXIII/13 deficiency.” When FXIII/13 activity was reduced to less than 50% of normal, it was proportional to the difference in α₂-PI levels between plasma and serum (plasma–serum α₂-PI), likely due to its cross-linking to fibrin by activated FXIII/13. Accordingly, decreased amounts of the plasma–serum α₂-PI ex vivo may reflect reduced FXIII/13 activity in vivo. The plasma–serum α₂-PI may thus also be a useful diagnostic marker for severe FXIII/13 deficiency.     

Transdermal tulobuterol patch, a long-actingβ(2)-agonist

Tulobuterol patch (HokunalinTM Tape), which contains a β(2)-adrenergic agonist, is the first bronchodilator to be available as a transdermal patch. This drug delivery system ensures that the time at which the peak drug concentration in the blood is reached coincides with the morning dip in respiratory function. The use of the patch also prevents excessive increase in blood drug concentrations, thereby reducing the incidence of systemic adverse reactions. Since 1998, when it was first approved in Japan and worldwide, the tulobuterol patch has been used widely in the treatment of bronchial asthma and chronic obstructive pulmonary disease (COPD), and evidence collected since it was approved has confirmed its clinical efficacy and safety. Because the patch is easy to use and requires only once-daily application, treatment adherence of patients using the patch is good. In this article, we discuss the rationale behind the development of the tulobuterol patch, evaluate data on its clinical efficacy and safety in the treatment of asthma and COPD, and examine the treatment adherence in individuals using the patch.     

Efficacy and safety of indacaterol 150 and 300 µg in chronic obstructive pulmonary disease patients from six Asian areas including Japan: a 12-week, placebo-controlled study

Background and objective: The efficacy and safety of indacaterol, a novel inhaled once daily ultra long‐acting β₂‐agonist was evaluated in COPD patients in six Asian countries/areas. This study was primarily designed to obtain the regulatory approval of indacaterol in Japan. Methods: Moderate‐to‐severe COPD patients were randomized to indacaterol 150 µg, indacaterol 300 µg or placebo once daily. Efficacy variables: trough FEV₁ (average of 23 h 10 min and 23 h 45 min post‐dose values), health status (St. George's Respiratory Questionnaire) and transition dyspnoea index at week 12. Safety/tolerability was evaluated. Results: A total of 347 patients were randomized (96.5% male, mean (SD) age 66.7 (8.38) years, post‐bronchodilator FEV₁% predicted: 53.7 (12.50)); 88.8% completed. The least squares means (LSM) trough FEV₁ at week 12 for indacaterol 150 µg, indacaterol 300 µg and placebo were 1.34 L, 1.37 L and 1.17 L, respectively, with differences versus placebo exceeding the prespecified minimal clinically important difference of 0.12 L (0.17 L and 0.20 L for indacaterol 150 µg and 300 µg, respectively, both P < 0.001). The week 12 LSM transition dyspnoea index score was statistically superior for both indacaterol doses versus placebo (differences of 1.30 and 1.26, P < 0.001; both exceeding the minimal clinically important difference of 1). At week 12, both indacaterol doses provided statistically significant (P ≤ 0.005) and clinically meaningful (≥4 units) improvements in LSM St. George's Respiratory Questionnaire total score versus placebo (differences: ?4.8 and ?5.7 units). Adverse events for indacaterol (49.1%, both doses) were lower than placebo (59.0%) and were mostly mild/moderate in severity; no deaths were reported. Conclusions: Indacaterol provided clinically significant bronchodilation and improvements in dyspnoea and health status in Asian COPD patients.     

Diagnostic performance of labial minor salivary gland flow measurement for assessment of xerostomia

ObjectiveMinor salivary gland flow rate (MF) has been proposed as a key feature of xerostomia (subjective feeling of dry mouth). To assess its diagnostic performance, MF was compared in xerostomia and control subjects.DesignSixty-six subjects with xerostomia and 30 controls were enrolled. MF was measured in the lower labial mucosa using the iodine–starch filter paper method. Stimulated whole salivary flow rates were also measured using the gum test (stimulated-WF).ResultsBoth labial-MF and stimulated-WF were significantly lower in xerostomia subjects than in controls. There was a positive correlation between labial-MF and stimulated-WF in control but not xerostomia subjects. In xerostomia subjects compared to controls, there was a significantly larger reduction in labial-MF than in stimulated-WF. Xerostomia was most accurately diagnosed using a labial-MF cutoff value of 0.25 μL/cm²/min. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy at this cutoff value were 1.00, 0.87, 0.93, 1.00, and 0.96, respectively. Compared to respective values of 0.64, 1.00, 1.00, 0.56, and 0.75 for stimulated-WF at the traditional cutoff of 1.0 mL/min, these data indicate the higher sensitivity, negative predictive value, and diagnostic accuracy of labial-MF.ConclusionsXerostomia was more strongly related to reduction of labial-MF than to that of stimulated-WF. Xerostomia was most likely triggered at a labial-MF cut-off value of 0.25 μL/cm²/min based on results from the iodine–starch method.