Efficacy and safety of lascufloxacin for nursing- and healthcare-associated pneumonia: A single-arm, open-label clinical trial.

BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.

Association between Telomere-Related Polymorphisms and the Risk of IPF and COPD as a Precursor Lesion of Lung Cancer: Findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) Registry.

BACKGROUND: Lung cancer coexisting with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) can lead to poor prognosis.  Telomere-related polymorphisms may be implicated in the pathogenesis of these three lung diseases.  As to elucidate the mechanism of lung cancer via IPF or COPD may enable early detection and early treatment of the disease, we firstly examined the association between telomere-related polymorphisms and the risk of IPF and COPD in a case-control study. MATERIALS AND METHODS: A total of 572 patients with IPF (n = 155) or COPD (n = 417), who were derived from our on-going cohort study, and controls (n = 379), who were derived from our previous case-control study, were included in this study.  Telomerase reverse transcriptase (TERT) rs2736100, telomere RNA component (TERC) rs1881984, and oligonucleotide/oligosaccharide-binding fold containing1 (OBFC1) rs11191865 were genotyped with real-time PCR using TaqMan fluorescent probes. Unconditional logistic regression was used to assess the adjusted odds ratios and 95% confidence intervals. RESULTS: TERT rs2736100 was significantly associated with the risk of IPF; increases in the number of this risk allele increased the risk of IPF (Ptrend = 0.008).  Similarly, TERT rs2736100 was associated with the risk of COPD.  In regard to the combined action of the three loci, increasing numbers of "at-risk" genotypes increased the risk of IPF in a dose-dependent manner (P trend=0.003). CONCLUSIONS: TERT rs2736100 was associated with the risks of both IPF and COPD in a Japanese population. A combination of the "at-risk" genotypes might be important to identify the population at risk for IPF more clearly.

Pulmonary Mycobacterium abscessus Infection with Reactive AA Amyloidosis: A Case Report and Brief Review of the Literature.

We herein report a case involving a 64-year-old Japanese woman with a pulmonary Mycobacterium abscessus infection complicated by reactive AA amyloidosis, which, to our knowledge, has not been reported to date. The patient underwent gastrointestinal endoscopy for diarrhea during the treatment of pulmonary M. abscessus infection and was diagnosed with AA amyloidosis according to the histopathological findings from the endoscopic specimen. She died four months later. The prognosis of AA amyloidosis associated with pulmonary M. abscessus infection may be very poor, and physicians should pay attention to this rare condition when difficult-to-treat diarrhea occurs in patients with pulmonary M. abscessus infection.

[Efficacy and Safety of Carboplatin/Nanoparticle Albumin-Bound Paclitaxel Combination Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer or Recurrent Non-Small-Cell Lung Cancer Following Surgery].

OBJECTIVE: A retrospective analysis on carboplatin(CBDCA)/nanoparticle albumin-boundpaclitaxel(nab-PTX)combination chemotherapy was conducted in patients with non-small-cell lung cancer(NSCLC)to evaluate both the efficacy and toxicity based on age, treatment line, histology, and underlying diseases. SUBJECTS: A total of 27 patients with advanced or recurrent NSCLC following surgery who receivedCBDCA /nab-PTX as first- andsecond -line combination chemotherapy, respectively, were investigatedfrom March 2013 to December 2015. RESULTS: The overall response rate, median progressionfree survival, andmed ian overall survival of all patients were 37.0%, 5.5 months, and 11.4 months, respectively. With regard to toxicity, 3.7%and 14.8%of all patients had peripheral disorder and interstitial lung disease(ILD), respectively. Treatmentrelatedd eaths were not observed. No difference in the efficacy basedon age, treatment line, histology, andund erlying diseases was observed. CONCLUSION: CBDCA/nab-PTX combination chemotherapy was safe for elderly patients and those with ILD. However, the occurrence of new interstitial lung lesions should be carefully considered.

Pleurisy Caused by Mycobacterium abscessus in a Young Patient with Dermatomyositis: A Case Report and Brief Review of the Literature.

M. abscessus is a rapidly growing mycobacteria (RGM) and is the most common cause of pulmonary RGM infection. M. abscessus pleurisy is extremely rare. We herein report the case of a young patient with M. abscessus pleurisy without any lung lesions. A laboratory analysis of the pleural effusion revealed lymphocyte predominance and increased adenosine deaminase, similar to the findings observed in tuberculous pleurisy. The patient was initially treated for tuberculous pleurisy, which resulted in the partial improvement of the patient's symptoms and pleural effusion. M. abscessus pleurisy should be considered, especially in immunocompromised individuals, even in the absence of pulmonary involvement.

Smoking Status and a Pulmonary Function Test in Patients with Rotator Cuff Tears.

Although chronic obstructive pulmonary disease (COPD) affects one in several smokers, only a few patients are correctly diagnosed compared to the estimated number of patients. Several recent reports indicate that the development of rotator cuff tears is related to smoking. In this study, we investigated smoking status in patients with rotator cuff tears and evaluated the possibility of undiagnosed COPD by a pulmonary function test. The subjects were 150 consecutive patients over 40 years old, who had been diagnosed with rotator cuff tears and had been examined by a pulmonary function test before surgery in our orthopedic department between April 2011 and June 2015. They consisted of 96 men and 54 women, which included 59 non-smokers (39.3%), 62 ex-smokers (41.3%), and 29 smokers (19.3%). The smoking rate of the subjects was the same as that of the general Japanese population. However, the ever-smokers who smoked more than 21 cigarettes per day were 31.9%, which was high compared to the Japanese ever-smokers population, i.e. 15.2% of men and 5.5% of women. Twenty-five subjects (16.7%) showed airflow limitation, and they consisted of 7 cases of COPD, 3 cases of bronchial asthma, one case of bronchiectasis, and 14 undiagnosed cases. The undiagnosed cases consisted of 7 non-smokers, 5 ex-smokers, and 2 smokers. Their stages of COPD were stage 1 in 11 cases and stage 2 in 3 cases. The prevalence of airflow limitation increased with increasing age: 0% for 40's, 8.3% for 50's, 20.7% for 60's, and 25.6% for over 70's. From these results, we recognized that paying attention to the numbers of cigarettes smoked per day are important in addition to the smoking history, for the patients with rotator cuff tears. Also, sharing the data of a pulmonary function test before surgery can contribute to the early diagnosis of COPD.

IgG4-related Lung Disease Associated with Autoimmune Hemolytic Anemia: A Case Report and a Literature Review.

We herein report a case of IgG4-related lung disease (IgG4-RLD) associated with autoimmune hemolytic anemia (AIHA). A 73-year-old Japanese female visited our hospital for an examination following an abnormal chest X-ray in 1999. She was diagnosed with bronchiolitis and AIHA, and treatment with prednisolone was started. After seven years, she visited our department due to a cough. Chest computed tomography (CT) demonstrated focal consolidation with ground-glass attenuations and thickened bronchial walls in the bilateral lungs. She was clinically diagnosed and treated for bronchial asthma. CT findings had shown no changes, and a lung biopsy was performed using video-assisted thoracic surgery at eleven years from the first diagnosis of AIHA. The pathological findings demonstrated the presence of peribronchovascular lymphoplasmacytic infiltrates with stromal fibrotic changes, admixed with many IgG4-positive plasma cells. Furthermore, the patient's serum IgG4 level was high, and her CT findings did not show any obvious abnormal findings in the any organs other than the lungs. She was diagnosed with IgG4-RLD based on the findings. We believe that this case report of IgG4-RLD associated with AIHA is clinically helpful for a better understanding of these diseases, although there are five reported cases of IgG4-related disease associated with AIHA.

Adrenal Insufficiency Associated with Small Cell Lung Cancer: A Case Report and Literature Review.

A 78-year-old Japanese man with fatigue, appetite loss, skin hyperpigmentation, hypotension and hypoglycemia, visited our hospital to evaluate an abnormal chest X-ray and adrenal gland swelling in echography in February 2015. Chest computed tomography showed a mass lesion in the right lower lobe and bilateral adrenal swellings, and small cell lung cancer (SCLC) with bilateral adrenal metastasis was diagnosed after bronchoscopy. According to low levels of serum cortisol, elevated adrenocorticotropic hormone (ACTH) and rapid ACTH test, the diagnosis of adrenal insufficiency associated with SCLC was made. Treatment with hydrocortisone (20 mg/day) was started in addition to systemic chemotherapy with carboplatin and etoposide. The patient's symptoms were slightly improved, however, systemic chemotherapy was discontinued according to the patient's request after 1 course of chemotherapy. Thereafter, he received only supportive care, and his general condition gradually worsened and he ultimately died in August 2015. Adrenal insufficiency associated with SCLC, which is caused by tissue destruction more than 90% of the adrenal glands, is rare although adrenal metastasis is not rare in patients with lung cancer. The findings such as general fatigue, appetite loss, hypotension, and hyponatremia are often got follow up as findings of advanced cancer, but appropriate therapy for adrenal insufficiency, supplement of the adrenal corticosteroid hormone, may lead to a significant improvement in the symptoms and quality of life in clinical practice of lung cancer. Therefore, physicians must consider potential adrenal insufficiency in lung cancer patients with bilateral adrenal metastasis.

[Three Cases of Bacteremia due to Helicobacter cinaedi Infection and the Usefulness of Gene Analysis of Isolated Bacteria].

Helicobacter cinaedi is typically isolated from immunocompromised patients. Some reports of infection caused by H.cinaedi have been found in recent years. We experienced three cases of H.cinaedi bacteremia in one year and ten months in our hospital, although the detection of H.cinaedi in blood cultures is extremely rare. In case 1, a 77-year-old female had been treated with a steroid and immunosuppressive agent for interstitial pneumonia. In cases 2 and 3, two 71-year-old men had been treated with chemotherapy for lung cancer. Although the identification of the bacteria could not be performed by the culture method in the three cases, H.cinaedi bacteremia was diagnosed by a 16S rRNA gene sequencing analysis in case 1, and by nested PCR in cases 2 and 3. H.cinaedi bacteremia often tends to recur and also requires prolonged antimicrobial therapy. We believe that gene analysis is useful in the identification of H.cinaedi.

Primary Pulmonary Angiosarcoma Presenting with Hemoptysis and Ground-Glass Opacity: A Case Report and Literature Review.

Angiosarcoma originates from the vascular endothelium and accounts for only 1-2% of all sarcomatous malignancies. The skin is one of the most common primary sites. However, primary pulmonary angiosarcoma is rare, and only 31 cases of primary pulmonary angiosarcoma have been reported. A 79-year-old Japanese female developed bloody sputum, and chest X-ray and chest computed tomography (CT) showed consolidation with ground-glass opacity (GGO) on the right middle and lower lung fields. The bronchoscopic findings demonstrated bleeding from the right B(4) and B(5), and bronchial arterial embolization was subsequently performed. However, the CT findings demonstrated new pulmonary nodules with GGO in the left lung, and she presented with hemosputum and a progression of anemia. Right hemothorax also occurred, and surgical lung resection was performed to control the bleeding. The pathological analysis of the resected lung revealed the focal growth of atypical alveolar epithelioid-like cells that were positive for CD31 and negative for epithelial membrane antigen, and these atypical cells were replacing the endothelium of the pulmonary artery. Based on these findings, the patient was diagnosed with pulmonary angiosarcoma, which might originate from the endothelium of the pulmonary artery. No abnormal findings were observed except for the pulmonary involvement on systemic CT scanning. However, the patient passed away due to respiratory failure with compression of the brainstem caused by brain metastasis three months after the first visit. Early surgical resection is the important treatment for patients with angiosarcoma. In addition, we review the literature reporting the patients with primary pulmonary angiosarcoma.

The clinical features of respiratory infections caused by the Streptococcus anginosus group.

BACKGROUND: The Streptococcus anginosus group (SAG) play important roles in respiratory infections. It is ordinarily difficult to distinguish them from contaminations as the causative pathogens of respiratory infections because they are often cultured in respiratory specimens. Therefore, it is important to understand the clinical characteristics and laboratory findings of respiratory infections caused by the SAG members. The aim of this study is to clarify the role of the SAG bacteria in respiratory infections. METHODS: A total of 30 patients who were diagnosed with respiratory infections which were caused by the SAG bacteria between January 2005 and February 2015 were retrospectively evaluated. RESULTS: Respiratory infections caused by the SAG were mostly seen in male patients with comorbid diseases and were typically complicated with pleural effusion. Pleural effusion was observed in 22 (73.3%) patients. Empyema was observed in half of the 22 patients with pleural effusion. S. intermedius, S. constellatus and S. anginosus were detected in 16 (53.3 %), 11 (36.7 %) and 3 (10.0 %) patients, respectively. Six patients had mixed-infections. The duration from the onset of symptoms to the hospital visit was significantly longer in "lung abscess" patients than in "pneumonia" patients among the 24 patients with single infections, but not among the six patients with mixed-infection. The peripheral white blood cell counts of the "pneumonia" patients were higher than those of the "lung abscess" patients and S. intermedius was identified significantly more frequently in patients with pulmonary and pleural infections (pneumonia and lung abscess) than in patients with bacterial pleurisy only. In addition, the patients in whom S. intermedius was cultured were significantly older than those in whom S. constellatus was cultured. CONCLUSIONS: Respiratory infections caused by the SAG bacteria tended to be observed more frequently in male patients with comorbid diseases and to more frequently involve purulent formation. In addition, S. intermedius was mainly identified in elderly patients with having pulmonary infection complicated with pleural effusion, and the aspiration of oral secretions may be a risk factor in the formation of empyema thoracis associated with pneumonia due to S. intermedius.

A Case of Rapid Exacerbation of Pulmonary Mycobacterium Avium Complex Infection Mimicking Pulmonary Aspergillosis.

We herein report a case of pulmonary Mycobacterium avium complex (MAC) infection with pulmonary multiple nodules and the "halo sign" on chest computed tomography (CT) in which the patient showed rapid exacerbation seven years after undergoing bone marrow transplantation (BMT). A 68-year-old Japanese female visited our hospital due to a productive cough and dyspnea. She had undergone allogeneic BMT for acute myelocytic leukemia and received both prednisolone (2 mg/day) and cyclosporine (30 mg/day). Chest CT demonstrated no abnormal findings on admission; however, multiple pulmonary nodules and the "halo sign" were detected three weeks later. Although a fungal infection was initially suspected, a bronchoscopic examination revealed pulmonary MAC infection. In the present case, pulmonary MAC infection exhibited rapid progression with unique CT findings. Physicians should consider MAC infection in the differential diagnosis in patients who receive BMT and/or immunosuppressive agents, even if the clinical and radiological findings are atypical of the disease.

Case of immunoglobulin G4 (IgG4)-related disease diagnosed by transbronchial lung biopsy and endobronchial ultrasound-guided transbronchial needle aspiration.

A 62-year-old Japanese man was admitted to our hospital for evaluation of bilateral chest abnormal shadow.His lacrimal, submandibular and parotid glands had been swollen for several years. His serum immunoglobulin G4 (IgG4) level was >1,500 mg/dl, and chest computed tomography showed bilateral reticular opacities with enlarged mediastinal lymph nodes. Transbronchial lung biopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results suggested IgG4-related disease. This is the first report, to our knowledge, in the English literature showing EBUS-TBNA to be useful for diagnosing IgG4-related disease.

[Efficacy and safety of levofloxacin in patients with nursing and healthcare-associated pneumonia].

Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.