Go Sano

Efficacy of Bacteriophage Therapy against Gut-Derived Sepsis Caused by Pseudomonas aeruginosa in Mice

ABSTRACT We evaluated the efficacy of bacteriophage (phage) therapy by using a murine model of gut-derived sepsis caused by Pseudomonas aeruginosa that closely resembles the clinical pathophysiology of septicemia in humans. Oral administration of a newly isolated lytic phage strain (KPP10) significantly protected mice against mortality (survival rates, 66.7% for the phage-treated group versus 0% for the saline-treated control group; P < 0.01). Mice treated with phage also had lower numbers of viable P. aeruginosa cells in their blood, liver, and spleen. The levels of inflammatory cytokines (tumor necrosis factor alpha TNF-α, interleukin-1β [IL-1β], and IL-6) in blood and liver were significantly lower in phage-treated mice than in phage-untreated mice. The number of viable P. aeruginosa cells in fecal matter in the gastrointestinal tract was significantly lower in phage-treated mice than in the saline-treated control mice. We also studied the efficacy of phage treatment for intraperitoneal infection caused by P. aeruginosa and found that phage treatment significantly improved the survival of mice, but only under limited experimental conditions. In conclusion, our findings suggest that oral administration of phage may be effective against gut-derived sepsis caused by P. aeruginosa.

Comparison of clinical characteristics and prognostic factors of combined pulmonary fibrosis and emphysema versus idiopathic pulmonary fibrosis alone

The results of studies examining the outcome and the factors predicting prognosis in combined pulmonary fibrosis and emphysema (CPFE) have so far been contradictory. Our objective was to determine prognosis and the prognostic factors for CPFE.

Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation.

Background: Germline alterations in the proapoptotic protein Bcl-2–like 11 (BIM) can have a crucial role in tumor response to treatment. To determine the clinical utility of detecting BIM deletion polymorphism in non–small-cell lung cancer positive for epidermal growth factor receptor (EGFR) mutation, we examined outcomes of patients with and without BIM alterations. Methods: We studied 70 patients with EGFR mutation-positive non–small-cell lung cancer who were treated with an EGFR tyrosine kinase inhibitor between January 2008 and January 2013. BIM deletion was analyzed by polymerase chain reaction in 58 samples of peripheral blood and 24 formalin-fixed paraffin-embedded slides of surgical specimens (20 of lung tissue and four of brain tissue); both blood and tissue specimens were available for 12 patients. We retrospectively analyzed clinical characteristics, response rate, toxicity, and outcomes among patients with and without BIM deletion. Results: BIM deletion was present in 13 of 70 patients (18.6%). There were no significant differences between patients with and without BIM deletion in clinical characteristics, rate of response to EGFR tyrosine kinase inhibitor, or incidence of adverse events. Patients with BIM deletion had significantly shorter progression-free survival (PFS) than those without BIM deletion (median, 227 versus 533 days; p < 0.001). Multivariate Cox regression analysis showed that BIM deletion was an independent indicator of shorter PFS (hazard ratio, 3.99; 95% confidence interval, 1.864–8.547; p < 0.001). Conclusions: Polymerase chain reaction successfully detected BIM deletion in samples of peripheral blood and formalin-fixed paraffin-embedded slides of surgical specimens. BIM deletion was the most important independent prognostic factor in shorter PFS.

Effectiveness of combined therapy with pirfenidone and inhaled N-acetylcysteine for advanced idiopathic pulmonary fibrosis: a case-control study.

Treatment with pirfenidone may slow the decline in vital capacity and increase progression‐free survival (PFS) in idiopathic pulmonary fibrosis (IPF). The effects of combination therapy with inhaled N‐acetylcysteine (NAC) and pirfenidone are unclear. We assessed the effects of this combination therapy in patients with advanced IPF.

Pathological response and prognosis of stage III non-small cell lung cancer patients treated with induction chemoradiation.

Aim:  The aim of this study was to clarify the relationship between pathological effects and the prognosis of patients with stage III non‐small cell lung cancer (NSCLC) treated with induction chemoradiation.

Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and β-d-Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis

ABSTRACT We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a β-d-glucan (βDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and βDG testing of BALF, respectively. The sensitivity and specificity of the GM test, βDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and βDG tests had the highest diagnostic odds ratio. The combination of the GM and βDG tests on BALF was more useful than any single test for diagnosing CPA.

Characterization and evaluation of a novel immunochromatographic assay for pharyngeal Mycoplasmapneumoniae ribosomal protein L7/L12 antigens.

Point-of-care testing for Mycoplasma pneumoniae infection may be ideal and useful because significant numbers of the cases will be seen as outpatients. Recently, a new immunochromatographic method (ICM) targeting M. pneumoniae ribosomal protein L7/L12 (RP-L7/L12) in pharyngeal swabs became available in Japan, although clinical data and basic information regarding efficacy and characterization of this ICM are limited. The present study examined the fate of M. pneumoniae RP-L7/L12 during in vitro growth and the correlation between M. pneumoniae concentration in clinical specimens and the sensitivity of the ICM test. The usefulness of the ICM was investigated in patients suspected of having M. pneumoniae pneumonia and upper respiratory tract infection (137 children and 39 adults). The limit of detection for the ICM test was 1.1×104 c.f.u. ml-1 of M. pneumoniae. Bacterial production of RP-L7/L12 correlated positively with the viable M. pneumoniae concentration in vitro; antigen was then degraded in culture broth, with an in vitro half-life of approximately 2 days. Five other Mycoplasma spp. and 14 representative respiratory pathogens were ICM assay negative at bacterial concentrations of 106 c.f.u. ml-1. The clinical sensitivity and specificity of the ICM assay were 57.1 % (20/35) and 92.2 % (130/141), respectively, in comparison with bacterial culture. Clinical specimens containing ≥106 c.f.u. ml-1 of M. pneumoniae burden were ICM positive in 13 of 18 cases (72.2 %). The ICM is a poorly sensitive but reasonably specific means for detecting M. pneumoniae infections.

Role of fluoro‐2‐deoxyglucose positron emission tomography for the detection of gastrointestinal tract lesions in patients with lung cancer

Background:  The purpose of this study was to clarify the clinical characteristics of lung cancer patients with abnormal accumulation of fluoro‐2‐deoxyglucose (FDG) in the gastrointestinal tract imaged by positron emission tomography (PET).

New risk scoring system for predicting acute exacerbation of interstitial pneumonia after chemotherapy for lung cancer associated with interstitial pneumonia

BACKGROUND Fatal acute exacerbation (AE) of interstitial pneumonia (IP) sometimes occurs after chemotherapy for lung cancer. We developed and evaluated a scoring system for assessing AE risk after chemotherapy in patients with lung cancer associated with IP. METHODS A review of medical records identified 109 patients with primary lung cancer associated with IP who had received chemotherapy at our center during the period from June 2007 through September 2017. We developed a model to score AE risk after chemotherapy in this patient group, and logistic regression was used to evaluate the model. RESULTS The anticancer agent score was determined by using AE rates reported in past studies. The risk score was calculated with the following formula: (1 × anticancer agent score) + (3 × smoking history [>70 pack-years]) + (4 × history of steroid use) + (3 × %diffusing capacity of lung carbon monoxide [<50%]). Patients were then classified into three groups. The AE incidence rate was 12% for a risk score of 0-5, 47% for a score of 6-10, and 66.7% for a score of ≥11. The sensitivity of the scoring system was 78.6% and specificity was 67.8%. CONCLUSIONS The present scoring system was able to identify IP patients at high risk for AE after chemotherapy for lung cancer associated with IP.

Clinical Evaluation of Severe Asthma Attacks Requiring Tracheal Intubation and Mechanical Ventilation

BACKGROUND Although the number of patients requiring hospitalization due to asthma attacks has decreased over the years, there are many who still require hospitalization for tracheal intubation and mechanical ventilation following a severe asthma attack. Therefore, we evaluated the characteristics of patients with asthma who required tracheal intubation and mechanical ventilation in our hospital. METHODS We evaluated 20 patients who had severely exacerbated asthma, requiring tracheal intubation and mechanical ventilation. An evaluation was made based on their smoking history, the number of days from the onset of the asthma attack to admission, the level of asthma control, treatments before presenting to our hospital, the frequency of hospital visits, the reason for tracheal intubation and mechanical ventilation, and outcome. RESULTS Of the 20 patients with asthma 13 were men and 7 women, with a mean age of 48.7 years. The characteristics of patients who required tracheal intubation and mechanical ventilation were as follows: (1) smokers, (2) not taking or irregularly taking medication, (3) using inhaled short-acting beta(2)agonist (SABA) alone as needed, and (4) not using inhaled corticosteroids (ICS). CONCLUSIONS Our findings suggest that treatment mainly using ICS, in addition to increased awareness of the dangers of asthma among the patients themselves, are important in preventing severe asthma attacks requiring tracheal intubation and mechanical ventilation.