Hiroyasu Kobayashi

Mie University, Tu, Mie, Japan

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Publications (12)45.03 Total impact

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    ABSTRACT: Background. Optimal empiric therapy for hospitalized healthcare-associated pneumonia (HCAP) patients is uncertain. Methods. We prospectively applied a therapeutic algorithm, based on the presence of risk factors for multidrug-resistant (MDR) pathogens in a multicenter- cohort study of 445 pneumonia patients, including both community-acquired pneumonia (CAP, n=124) and HCAP (n=321). Results. MDR pathogens were more common (15.3% vs 0.8%, p<0.001) in HCAP patients than in CAP patients, including Staphylococcus aureus (11.5% vs 0.8%, p<0.001) ; methicillin-resistant Staphylococcus aureus (MRSA) (6.9% vs 0%, p=0.003); Enterobacteriaceae (7.8% vs 2.4%, p=0.037); and Pseudomonas aeruginosa (6.9% vs 0.8%, p=0.01). Using the proposed algorithm, HCAP patients with>2 MDR risks, one of which was severity of illness (n=170), vs. HCAP with 0-1 risk (n=151) had a significantly higher frequency of MDR pathogens (27.1% vs 2%, p<0.001). 93.1% of HCAP patients were treated according to the therapy algorithm, with only 53% receiving broad-spectrum empiric therapy, yet 92.9% received appropriate therapy for the identified pathogen. 30-day HCAP mortality was significantly higher than for CAP (13.7% vs. 5.6%, p=0.017), but among HCAP patients with 0-1 MDR risks, mortality was lower than with ≥2 MDR risks (8.6% vs. 18.2%, p=0.012). In multivariate analysis, initial treatment failure, but not inappropriate empiric antibiotic therapy, was a mortality risk factor (odds ratio 72.0). Conclusions. Basing empiric HCAP therapy on its severity and the presence of risk factors for MDR pathogens is a potentially useful approach that achieves good outcomes without excessive use of broad-spectrum antibiotic therapy.
    Clinical Infectious Diseases 09/2013; · 9.37 Impact Factor
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    ABSTRACT: Apart from its role in the coagulation system, thrombin plays an important role in the inflammatory response through its protease-activated receptor(PAR)s. However, the role of thrombin in the immune response is not clear. We evaluated if thrombin has a modulatory role in allergic bronchial asthma. Bronchial asthma was induced in mice by intraperitoneal sensitization and inhalation challenge with ovalbumin. Thrombin or its inhibitors were administered by inhalation before each allergen challenge. Mice with low but sustained coagulation activation had reduced allergic inflammation and allergic asthma was inhibited by low doses but worsened by high doses of thrombin. Allergic asthma was worsened by antithrombin, argatroban, hirudin and anti-thrombomodulin antibody. Mice with an increased concentration of an inhibitor of both thrombin and activated protein C had worsened disease. Heterozygous PAR-1 mice had less allergic inflammation but PAR-1 agonist worsened it. Allergic bronchial inflammation was worsened in mice that received adoptive transfer of PAR-1 agonist-treated Th2 cells compared to controls. Low concentrations of thrombin suppressed but high-dose of it enhanced maturation and secretion of cytokines in dendritic cells. The effects of thrombin on allergic asthma are dose-dependent with detrimental effects at high dose and protective ones at low dose. These data demonstrate that thrombin modulates the outcome in allergic bronchial asthma. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 08/2013; · 6.08 Impact Factor
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    ABSTRACT: Interstitial lung diseases (ILD) are characterized by progressive interstitial pulmonary fibrosis and a decline in lung function. Fibrocytes are bone marrow-derived mesenchymal progenitor cells that may play a role in the pathogenesis of pulmonary fibrosis. Circulating fibrocyte numbers have been correlated with the prognosis of patients with idiopathic pulmonary fibrosis. The aim of the present study was to evaluate the relationship between circulating fibrocytes, and parameters of disease activity and progression in several groups of patients with ILD. The study population comprised 41 patients with ILD and seven healthy control subjects. Circulating CD45(+) collagen-I(+) fibrocytes were evaluated by flow cytometry. The number of circulating fibrocytes was significantly increased in all patients with ILD and particularly in patients with idiopathic interstitial pneumonitis and interstitial pneumonitis associated with collagen vascular disease as compared with healthy control subjects. The numbers of circulating fibrocytes were significantly correlated with pulmonary function test parameters and with serum levels of sialylated carbohydrate antigen, a marker of disease activity. Temporal changes in circulating fibrocyte numbers were evaluated in two patients, and the results suggested that these changes correlated with the activity of ILD. The results from this study provide further evidence for the role of circulating fibrocytes in fibrotic lung diseases.
    Respirology 03/2012; 17(4):693-8. · 2.78 Impact Factor
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    ABSTRACT: Bronchial asthma is an inflammatory disease of the airways. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase that besides inhibiting fibrinolysis, also regulates inflammatory processes. The only validated substrate known for TAFI is fibrin. In the present study we evaluated the role of TAFI in bronchial asthma by comparing the development of allergic bronchial asthma between wild-type (WT) and TAFI-deficient mice (KO). Asthmatic inflammation was induced by sensitization and challenge with ovalbumin in WT (WT/OVA) and TAFI KO (KO/OVA) mice. WT mice (WT/SAL) and TAFI KO (KO/SAL) were used as controls. Cytokines, markers of inflammation, and coagulation were measured in bronchoalveolar lavage fluid (BALF). Airway hyperresponsiveness was worse in KO/OVA mice than in WT/OVA mice or control mice. Markers of lung injury were significantly increased in BALF from KO/OVA mice compared to WT/OVA mice. Airway hyperresponsiveness and the BALF concentrations of IL-5 and osteopontin were significantly increased in KO/OVA mice compared to WT/OVA mice. Treatment of WT/OVA and KO/OVA mice with a C5a receptor antagonist significantly decreased hyperresponsiveness along with the BALF concentrations of total protein and C5a compared to untreated asthmatic mice. The results of this study suggest that TAFI plays a protective role in the pathogenesis of allergic inflammation probably by inhibiting the complement system.
    Beiträge zur Klinik der Tuberkulose 10/2011; 190(2):189-98. · 2.06 Impact Factor
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    ABSTRACT: A 64-year-old diabetic man was admitted because his general condition had not improved despite the admini stration of voriconazole in another hospital, and his condition had become critical. Chest CT demonstrated a large fungus ball and consolidation around a cavity in the right lung. Aspergillusfumigatus was detected on a sputum culture. Based on these findings, we diagnosed invasive aspergillosis and administered high-dose (5mg/kg) liposomal amphotericin B (L-AMB) for 8 weeks, which resulted in the improvement of his general condition and the disappearance of the fungus ball, without severe adverse events.
    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 07/2011; 49(7):496-500.
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    ABSTRACT: A macrolide-resistant Mycoplasma pneumoniae strain was isolated from two patients with community-acquired pneumonia. The pneumonia severity score of both patients was mild, and rapid clinical improvement was seen after administration of fluoroquinolone. Clinical features of macrolide-resistant M. pneumoniae pneumonia were identical to those of macrolide-sensitive M. pneumoniae pneumonia. An A-to-G transition at position 2063 and 2064, respectively, in domain V of the 23S rRNA gene was identified. The minimum inhibitory concentration of erythromycin of these isolates was greatly elevated. In Japan, macrolide-resistant M. pneumoniae infections are common in pediatric patients but not in adults. However, physicians should pay attention to macrolide-resistant M. pneumoniae not only in children but also in adults.
    Journal of Infection and Chemotherapy 02/2011; 17(1):114-8. · 1.55 Impact Factor
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    ABSTRACT: Benign metastasizing leiomyoma in the lung is a very rare disease characterized by the growth of uterine leiomyoma tissue. In most cases there is a previous history of hysterectomy for uterine leiomyoma. A 50-year-old Asian woman underwent a total abdominal hysterectomy for uterine leiomyoma at the age of 37 years old. She was referred to our hospital because of sudden anterior chest pain. A chest computed tomography scan revealed a ground-glass opacity in her left S10 lung segment and a solitary small nodule in her left bronchial segment, S4. We performed a left lower lobectomy and an upper lung partial resection in order to make a definitive diagnosis and to enable us to determine a further therapeutic strategy. The ground-glass opacity in her left S10 was a primary lung adenocarcinoma, while the small nodule in her left S4 was diagnosed as a benign metastasizing leiomyoma. No additional therapy was done and our patient was followed up with chest computed tomography. Up to date, repetitive evaluation by chest computed tomography has shown no sign of benign metastasizing leiomyoma or lung cancer recurrence. This is a very rare case of benign metastasizing leiomyoma of the lung associated with primary lung cancer. This comorbid association should be considered in the differential diagnosis when a solitary lung nodule is detected in a patient with a history of uterine leiomyoma.
    Journal of Medical Case Reports 01/2011; 5:500.
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    ABSTRACT: To determine the efficacy of a 23-valent pneumococcal polysaccharide vaccine in people at high risk of pneumococcal pneumonia. Prospective, randomised, placebo controlled double blind study. Nursing homes in Japan. 1006 nursing home residents. Participants were randomly allocated to either 23-valent pneumococcal polysaccharide vaccine (n=502) or placebo (n=504). The primary end points were the incidence of all cause pneumonia and pneumococcal pneumonia. Secondary end points were deaths from pneumococcal pneumonia, all cause pneumonia, and other causes. Pneumonia occurred in 63 (12.5%) participants in the vaccine group and 104 (20.6%) in the placebo group. Pneumococcal pneumonia was diagnosed in 14 (2.8%) participants in the vaccine group and 37 (7.3%) in the placebo group (P<0.001). All cause pneumonia and pneumococcal pneumonia were significantly more frequent in the placebo group than in the vaccine group: incidence per 1000 person years 55 v 91 (P<0.0006) and 12 v 32 (P<0.001), respectively. Death from pneumococcal pneumonia was significantly higher in the placebo group than in the vaccine group (35.1% (13/37) v 0% (0/14), P<0.01). The death rate from all cause pneumonia (vaccine group 20.6% (13/63) v placebo group 25.0% (26/104), P=0.5) and from other causes (vaccine group 17.7% (89/502) v placebo group (80/504) 15.9%, P=0.4) did not differ between the two study groups. The 23-valent pneumococcal polysaccharide vaccine prevented pneumococcal pneumonia and reduced mortality from pneumococcal pneumonia in nursing home residents. Trial registration Japan Medical Association Center for Clinical Trials JMA-IIA00024.
    BMJ (online) 01/2010; 340:c1004. · 17.22 Impact Factor
  • The Journal of The Japanese Association for Chest Surgery. 01/2009; 23(1):2-7.
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    ABSTRACT: Radiological and histological correlation was evaluated in patients with malignant tumors of the lung that underwent radiofrequency ablation (RFA). One of the patients had a primary lung tumor and another patient had three metastatic lung tumors. RFA was performed under computed tomography (CT) fluoroscopic guidance. CT showed ground glass shadows around the tumoral lesions immediately after RFA, but one week later homogenous opacification without tumoral enhancement was noted. Two months after RFA, most lesions showed cystic changes without activity on FDG-PET. Histological evaluation showed massive coagulation necrosis throughout the tumor and some viable cells at the peripheral areas in all lesions. Although RFA is a promising therapeutic approach for malignant lung tumors, some viable cells may persist in peripheral areas of the tumor.
    Internal Medicine 09/2005; 44(8):865-9. · 0.97 Impact Factor
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    ABSTRACT: Lung radiofrequency (RF) ablation was performed for the treatment of a primary lung cancer measuring 2.5 cm in maximum diameter in a 78-year-old man. A contrast-enhanced computed tomography (CT) study performed 3 months after RF ablation showed incomplete ablation of the lung tumor and the appearance of a chest wall tumor 4.0 cm in maximum diameter that was considered to be the result of needle-tract seeding. RF ablation was performed for the treatment of both the lung and the chest wall tumors. Although tumor enhancement was eradicated in both of the treated tumors, follow-up CT studies revealed diffuse intra-pulmonary metastases in both lungs 2 months after the second RF session. He is currently receiving systemic chemotherapy.
    CardioVascular and Interventional Radiology 05/2005; 28(4):530-2. · 2.14 Impact Factor
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    ABSTRACT: The occurrence of thrombotic complications is commonly associated with poor prognosis in patients with malignancy. However, the prognostic significance of the subclinical activation of the clotting system, frequently observed in cancer patients, is unknown. The purpose of the present study was to evaluate the value of the pre-thrombotic state for predicting survival of lung cancer patients. This investigation comprised 70 lung cancer patients without clinical or laboratory diagnosis of intravascular coagulation. There were 49 cases with non-small and 21 with small cell carcinomas. Samples taken in controls were available for comparison. The clotting system was assessed measuring thrombin-antithrombin III complex (TAT) and plasmin-α2-plasmin inhibitor complex (PAP). The independent value of these clotting markers to predict survival was evaluated in relation with previously well-established prognostic factors for lung cancer patients. Plasma concentration of each parameter was significantly higher in cancer patients as compared to that of controls. The plasma level of PAP was a predictor of survival independently from the stage of disease, sex, age, histological type, performance status, tumor size and the presence of distant metastasis. Discriminant analysis of PAP plasma concentration identified 2 groups with significant difference in survival rate in all patients, cases in advanced stages of disease and in those with small and non-small cell lung cancer. The results of the present study showed prognostic significance of the subclinical activation of the clotting system, particularly of the fibrinolytic pathway, in lung cancer. Newly developed markers of fibrinolysis might be potentially applicable for predicting outcome in malignancy.
    Clinica Chimica Acta 01/1996; · 2.85 Impact Factor