Shusaku Haranaga

Adjunctive Systemic Corticosteroids for Hospitalized Community-Acquired Pneumonia: Systematic Review and Meta-Analysis 2015 Update

Previous randomized controlled trials (RCTs) and meta-analyses evaluated the efficacy and safety of adjunctive corticosteroids for community-acquired pneumonia (CAP). However, the results from them had large discrepancies. The eligibility criteria for the current meta-analysis were original RCTs written in English as a full article that evaluated adjunctive systemic corticosteroids adding on antibiotic therapy targeting typical and/or atypical pathogen for treating hospitalized human CAP cases. Four investigators independently searched for eligible articles through PubMed, Embase, and Cochrane databases. Random model was used. The heterogeneity among original studies and subgroups was evaluated with the I2 statistics. Of 54 articles that met the preliminary criteria, we found 10 eligible RCTs comprising 1780 cases. Our analyses revealed following pooled values by corticosteroids. OR for all-cause death: 0.80 (95% confidence interval (95% CI) 0.53–1.21) from all studies; 0.41 (95% CI 0.19–0.90) from severe-case subgroup; 0.21 (95% CI 0.0–0.74) from intensive care unit (ICU) subgroup. Length of ICU stay: −1.30 days (95% CI (−3.04)−0.44). Length of hospital stay: −0.98 days (95% CI (−1.26)–(−0.71)). Length to clinical stability: −1.16 days (95% CI (−1.73)–(−0.58)). Serious complications do not seem to largely increase by steroids. In conclusion, adjunctive systemic corticosteroids for hospitalized patients with CAP seems preferred strategies.

Computed tomographic features of 23 sporadic cases with Legionella pneumophila pneumonia

OBJECTIVE To describe the chest computed tomographic (CT) findings of Legionella pneumophila pneumonia. METHODS CT scans obtained from 23 sporadic cases of L. pneumophila pneumonia were retrospectively reviewed. Chest CT findings were analyzed with regard to the patterns and distributions of pulmonary abnormalities. We also analyzed the histopathology of lungs from guinea pigs with experimentally induced L. pneumophila pneumonia. RESULTS Consolidation and ground-glass opacity (GGO) were the main findings of CT scans in L. pneumophila pneumonia. The distribution of opacities was categorized as non-segmental (n=20) and segmental (n=4). Non-segmental distribution may follow an onset of segmental distribution. Pleural effusion was observed in 14 (58.3%) patients, of which 13 were accompanied with non-segmental distribution. Abscess formation was observed in only one immunocompromised patient. In the animal pneumonia model, the lesions comprised of terminal bronchioles, alveolar spaces, and interstitia. Small bacilli were observed to be contained by many macrophages within the alveoli. CONCLUSION Non-segmental distribution was significantly more frequent than segmental distribution in L. pneumophila pneumonia. It is possible that L. pneumophila infection initially results in segmental pneumonia, which progresses to typical non-segmental distribution.

Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone

BackgroundLegionella pneumophila pneumonia often exacerbates acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells.MethodsNuclear deoxyribonucleic acid (DNA) fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP)-biotin nick end labeling method (TUNEL method) and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila.ResultsThe virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining) and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1) protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 μM) did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells.ConclusionInfection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a major virulence factor of L. pneumophila, is involved in the effects we measured in alveolar epithelial cells. Methyl prednisolone may modulate the interaction of Legionella and these cells.

An Autopsy Case of Two Distinct, Acquired Drug Resistance Mechanisms in Epidermal Growth Factor Receptor-mutant Lung Adenocarcinoma: Small Cell Carcinoma Transformation and Epidermal Growth Factor Receptor T790M Mutation.

We herein describe the case of a 63-year-old man who died from relapsed epidermal growth factor receptor gene (EGFR) exon 19 deletion lung adenocarcinoma treated with erlotinib. According to the autopsy results, he was confirmed to have small cell carcinoma without the EGFR T790M mutation in his pancreas and left kidney metastatic specimens, while the adenocarcinoma metastatic lesion in his right kidney had the EGFR T790M mutation; both retained the somatic EGFR exon 19 deletion. We herein report an autopsy case of resistance to an EGFR tyrosine kinase inhibitor via small cell carcinoma transformation and the EGFRT790M mutation in separate metastatic organs.

Implementation of bronchoalveolar lavage using a high-flow nasal cannula in five cases of acute respiratory failure

In recent clinical practice, high-flow nasal cannula (HFNC) therapy has been used to improve oxygenation in adults with acute respiratory failure (ARF). However, bronchoscopy using HFNC in ARF has not yet been reported. Herein, we describe 5 cases of ARF where bronchoalveolar lavage (BAL) was employed successfully using an HFNC. We were able to discontinue or reduce the HFNC fraction of inspired oxygen (FiO2) 30 min after completion of the bronchoscopy. Only 1 patient needed non-invasive positive pressure ventilation for 16 h after bronchoscopy. The HFNC may be a useful tool for ARF patients who require bronchoscopy.

Immunopathological characteristics of immune reconstitution inflammatory syndrome caused by Mycobacterium parascrofulaceum infection in a patient with AIDS.

Immune reconstitution inflammatory syndrome (IRIS) caused by mycobacterium in patients with AIDS is often experienced in clinical practice. There is, however, a paucity of data documenting the histopathological findings and the pathogenesis. We determined the immunopathological characteristics of IRIS associated with Mycobacterium parascrofulaceum infection in an AIDS patient. A patient presented with pulmonary lymphadenitis and involvement of the pulmonary lingular segment. Portions of the involved lymph nodes and lung were excised, and the immunological properties were analyzed by immunohistochemical assays. The histological characteristics of lymph nodes showed a caseous necrosis. Histopathologically, the pulmonary lesion was composed of exudative and proliferative lesions. CD4(+), CD8(+), CD57(+), and CD25(+)/FoxP3(+) cells were observed in both types of lesions. Clusters of CD20(+) cells and GATA3(+) cells were predominantly observed in exudative lesions, while T-bet(+) cells were dominant in proliferative lesions. ROR-γ(+) cells were also observed in exudative lesions. These results indicate that the cellular immunity to mycobacteria was recovering in the lung tissue. In M. parascrofulaceum pulmonary infection, the exudative lesion had characteristics of Th2 and Th17-type immunities. In contrast, the proliferative lesion had characteristics of Th-1 type immunity. Our data provide the first evidence to reveal the status of the axis of distinctive immunity in the process of granuloma formation caused by a mycobacterium-related infection.

The prevalence of airway obstruction among Japanese HIV-positive male patients compared with general population; a case-control study of single center analysis.

BACKGROUND AND OBJECTIVE Previous studies have suggested that human immunodeficiency virus (HIV) infection and/or the airway colonization of Pneumocystis jirovecii (Pcj) impact on the progression of airway obstruction, such as chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the relationship between HIV infection, airway colonization of Pcj and airway obstruction in Japanese male patients. METHODS Case-control study of 49 HIV-positive and 257 HIV-negative men were enrolled in this study. Airway obstruction was determined by spirometry. Cigarette smoking was determined by a self report. Laboratory data were obtained from medical records. Among HIV positive patients, the airway colonization of Pcj was evaluated by induced sputum using the real time polymerase chain reaction method. RESULTS Forty-eight out of 49 (97.9%) HIV-positive patients received antiretroviral therapy, and their median CD4 cell counts were 491/μL (79-935). The prevalence of airway obstruction as determined by spirometry was 10.2% (5/49) in HIV-positive subjects and 2.4% (5/208) in HIV-negative subjects (p = 0.024). Compared with the control group, HIV-positive patients were significantly younger (median age 44 vs 40, p = 0.019). After adjusting for age, pack-years of smoking, HIV infection was an independent risk factor for airway obstruction (OR; 10.93, 95%CI 1.99-60.1, p = 0.006). None of patient was detected the airway colonization of Pcj. CONCLUSIONS HIV infection was an independent risk factor for airway obstruction regardless of airway colonization of Pcj. Health-care providers should be aware of the increased likelihood of airway obstruction among HIV-positive patients.

A Case of Pulmonary and Hepatic Cystic Echinococcosis of CE1 Stage in a Healthy Japanese Female that Was Suspected to Have Been Acquired During Her Stay in the United Kingdom

We herein report a case of a young Japanese female who was confirmed to have cystic echinococcosis (CE) 1 stage based on the World Health Organization Informal Working Group on Echinococcosis pathological classification of CE, and she was also suspected to be infected with eggs of the G1 Echinococcus granulosus sensu stricto during her stay in the United Kingdom and therefore, suffered from synchronous pulmonary and hepatic CE. Oral albendazole was administered initially, but rupture of a lung hydatid cyst was observed. To avoid additional rupture, we performed two surgeries. CE is very rare in Japan; all CE cases in Japan during the past two decades have been confirmed to be imported, and almost all cases are hepatic CE. This case is the first case report of a Japanese patient who had concomitant giant lung and liver CE with early-stage CE1 and was successfully treated by surgery and pharmacotherapy with a serological follow-up.

Beta-lactam plus macrolides or beta-lactam alone for community-acquired pneumonia: A systematic review and meta-analysis.

It is unclear whether in the treatment of community‐acquired pneumonia (CAP) beta‐lactam plus macrolide antibiotics lead to better survival than beta‐lactam alone. We report a systematic review and meta‐analysis. Trials and observational studies published in English were included, if they provided sufficient data on odds ratio for all‐cause mortality for a beta‐lactam plus macrolide regimen compared with beta‐lactam alone. Two investigators independently searched for eligible articles. Of 514 articles screened, 14 were included: two open‐label randomized controlled trials (RCTs) comprising 1975 patients, one non‐RCT interventional study comprising 1011 patients and 11 observational studies comprising 33 332 patients. Random‐model meta‐analysis yielded an odds ratio for all‐cause death for beta‐lactam plus macrolide compared with beta‐lactam alone of 0.80 (95% CI 0.69–0.92, P = 0.002) with substantial heterogeneity (I2 = 59%, P for heterogeneity = 0.002). Severity‐based subgroup analysis and meta‐regression revealed that adding macrolide had a favourable effect on mortality only for severe CAP. Of the two RCTs, one suggested that macrolide plus beta‐lactam lead to better outcome compared with beta‐lactam alone, while the other did not. Subgrouping based on study design, that is, RCT versus non‐RCT, which was almost identical to subgrouping based on severity, revealed substantial inter‐subgroup heterogeneity. Compared with beta‐lactam alone, beta‐lactam plus macrolide may decrease all‐cause death only for severe CAP. However, this conclusion is tentative because this was based mainly on observational studies.

Role of neuraminidase inhibitor chemoprophylaxis in controlling nosocomial influenza: an observational study

Please cite this paper as: Higa et al. (2012) Role of neuraminidase inhibitor chemoprophylaxis in controlling nosocomial influenza: an observational study. Influenza and Other Respiratory Viruses 6(4), 299–303.