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Background Patients with clinically amyopathic dermatomyositis (CADM) with anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) frequently develop rapidly progressive interstitial pneumonia (RPIP), often with fatal outcomes. Therapeutic plasma exchange (TPE) has been reported as effective against CADM-RPIP refractory to conventional immunosuppressive therapy. However, the detailed mechanisms by which TPE improves disease activity of CADM-RPIP remain unclear. Aim To elucidate the clinical and demographic characteristics of patients with anti-MDA5 Ab-positive CADM-RPIP treated with TPE and to analyze changes in laboratory findings before, during, and after TPE. Materials & methods Patients hospitalized for CADM-RPIP and treated with TPE in 2017 and 2018 were analyzed retrospectively. Results Three patients were successfully treated with TPE, with good tolerance. Anti-MDA5 Ab titers decreased significantly over the course of TPE. Conclusion We emphasize that TPE could represent an effective treatment option for CADM-RPIP refractory to traditional therapy. Removal of anti-MDA5 Ab and other pathogenic factors may facilitate favorable outcomes.

Background and objective Nursing and healthcare-associated pneumonia (NHCAP) is a category of healthcare-associated pneumonia modified for the healthcare system in Japan. To date, only a few studies have examined the prognostic factors of NHCAP in a prospective cohort. This study aimed to investigate the prognostic factors related to 30-day mortality in patients with NHCAP by analyzing prospective data. Methods We analyzed patients hospitalized for NHCAP who were enrolled between October 2010 and February 2017. Age, sex, comorbidities, vital signs and laboratory findings were used as prognostic variables. The primary outcome was 30-day mortality. Results Of 817 NHCAP patients identified, the mean age was 78.0 ± 11.1 years, 580 (71.0%) were men and 30-day mortality was 13.1% (107/817). On multivariate analysis, male sex (odds ratio [OR]: 2.07, 95% confidence interval [CI]: 1.18–3.63), malignancy (OR: 2.35, 95%CI: 1.38–4.01), performance status (PS) (OR: 1.55, 95%CI: 1.23–1.96), body temperature (OR: 0.77, 95%CI: 0.61–0.97), heart rate (OR: 1.02, 95%CI: 1.01–1.03), respiratory rate (OR: 1.04, 95%CI: 1.01–1.08), serum albumin (Alb) (OR: 0.45, 95%CI: 0.30–0.66) and blood urea nitrogen (BUN) (OR: 1.02, 95%CI: 1.01–1.03) were significantly related to 30-day mortality. On the other hand, the risk factors for involvement by drug-resistant pathogens predicted a better prognosis (OR: 0.39, 95%CI: 0.19–0.82). Conclusions Male sex, malignancy, poor PS, hypothermia, tachycardia, tachypnea, low serum Alb and high BUN are worse prognostic factors. Thus, the risk of drug-resistant pathogens is not necessarily related to poor prognosis.

Objectives: The usefulness of serial procalcitonin (PCT) measurements for predicting the prognosis and treatment efficacy for hospitalised community-acquired pneumonia (CAP) patients was investigated. Methods: This prospective, multicentre, cohort study enrolled consecutive CAP patients who were hospitalised at 10 hospitals in western Japan from September 2013 to September 2016. PCT and C-reactive protein (CRP) were measured on admission (PCT D1 and CRP D1), within 48–72 h after admission (PCT D3 and CRP D3), and within 144–192 h after admission. CURB-65 and the Pneumonia Severity Index (PSI) were assessed on admission. The primary outcome was 30-day mortality; secondary outcomes were early and late treatment failure rates. Results: A total of 710 patients were included. The 30-day mortality rate was 3.1%. On multivariate analysis, only PCT D3/D1 ratio >1 [odds ratio (95% confidence interval): 4.33 (1.46–12.82),P = 0.008] and PSI [odds ratio (95% confidence interval): 2.32 (1.07–5.03), P = 0.03] were significant prognostic factors. Regarding treatment efficacy, PCT D3/D1 >1 was a significant predictor of early treatment failure on multivariate analysis. PCT D3/D1 with the PSI significantly improved the prognostic accuracy over that of the PSI alone. Conclusions: PCT should be measured consecutively, not only on admission, to predict the prognosis and treatment efficacy in CAP. Keywords: Biomarker, C-reactive protein, Pneumonia, Procalcitonin, Prognosis

Background Idiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP. Methods Japanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis. Results Overall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11–0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13–0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value. Conclusions BAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.

Background Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved. Methods We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions. Results Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR. Conclusions Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.

Immune checkpoint inhibitor-associated interstitial lung disease (ICI-ILD) is a serious immune-related adverse event. We aimed to evaluate the impact of ICI-ILD severity and imaging patterns or post-ILD cancer therapy on prognosis in patients with non-small-cell lung cancer (NSCLC). We retrospectively analysed NSCLC patients who developed ICI-ILD in our institution between January 2016 and March 2019. The primary objective was to report prognosis following onset of ICI-ILD, stratified by severity grade or imaging pattern. The secondary objective was the analysis of cancer therapy after ICI-ILD. Among 222 patients treated with ICI, 27 (12.2%) developed ICI-ILD. No trend for different prognosis depending on severity grade was seen unless ICI-ILD was fatal. Most patients (91.3%) with organising pneumonia (OP) or nonspecific interstitial pneumonia pattern on imaging showed grade 1 or 2, while all patients with a diffuse alveolar damage (DAD) pattern showed grade 3 or higher, and one reached grade 5. Among patients who overcame ICI-ILD, eight patients (30.8%) have been followed up without chemotherapy because of long-term disease control and seven had shown an OP pattern on imaging at onset of ICI-ILD. Three patients underwent ICI rechallenge, but two showed ICI-ILD recurrence and no patient achieved response to rechallenge treatment. The DAD pattern may predict short-term adverse prognosis for ICI-ILD. Once ICI-ILD is overcome, severity grade is not associated with prognosis. Even if initial immunotherapy proves effective, ICI rechallenge requires careful consideration.

Background: There has been no study so far on gemcitabine continuous maintenance therapy targeting only squamous non-small-cell lung cancer (NSCLC) patients. This study aimed to assess the efficacy and safety of cisplatin plus gemcitabine followed by maintenance gemcitabine for chemotherapy- naïve Japanese patients with advanced squamous NSCLC. Methods: The patients received 4 cycles of gemcitabine (1,000 mg/m2, days 1 and 8) and cisplatin (80 mg/m2, day 1) every 3 weeks, followed by gemcitabine alone as maintenance therapy every 3 weeks until disease progression or unacceptable toxicity. The primary end point of the study was progression-free survival (PFS) from the date of registration. Results: From May 2013 to October 2018, 26 patients were enrolled, and 25 patients received ≥1 cycle of planned treatment. Eighteen patients (69.2%) received 4 cycles of cisplatin plus gemcitabine, and 16 patients (61.5%) received ≥1 cycle of maintenance gemcitabine. The median PFS from the date of registration was 5.3 months (95% CI 2.9–7.3 months). In 16 patients who received ≥1 cycle of maintenance gemcitabine, the median PFS from the date of maintenance gemcitabine initiation was 3.8 months (95% CI 2.3–5.2 months). Their median overall survival from the date of registration was 11.9 months (95% CI 7.5–26.5 months). During the maintenance therapy, adverse events (AEs) were mostly Common Terminology Criteria for AE grade 1. Conclusions: While this trial did not meet the primary endpoint, the sufficient efficacy and feasibility of gemcitabine maintenance therapy were suggested.

The number of patients with pulmonary nontuberculous mycobacterial disease complicated by chronic pulmonary aspergillosis (CPA) has been increasing. Additionally, CPA is reportedly associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). In the present study, we aimed to identify risk factors for developing CPA and stratify the risk for CPA development in patients with MAC-LD.We retrospectively examined 361 patients newly diagnosed with MAC-LD. Risk factors for CPA development were examined using multivariate Cox proportional hazards regression analyses. A risk stratification system was established using the risk factors and receiver operating characteristic curve analyses.CPA developed in 20 (5.5%) of the 361 patients. Independent risk factors for CPA development included the presence of pulmonary emphysema, baseline steroid use, a serum albumin level3.5 g/dL, and the presence of MAC-LD cavities. A 4-point scoring system was established to stratify patients into low-risk (0-1 point) and high-risk (2-4 points) groups. The 5-year incidence rates of CPA were 2.2% and 31% in the low- and high-risk groups, respectively (P 0.001).We identified independent predictors of CPA development and established a simple risk stratification system for identifying patients with MAC-LD who were at a high risk of developing CPA.

Introduction Nivolumab has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials. Methods We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016. Results Of 613 patients included in our study, 141 had poor performance status (PS) and 106 were EGFR mutation – or ALK rearrangement-positive. The response and disease control rates were 20% and 44%, respectively; the estimated 1-year progression-free survival (PFS) was 18%. Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK rearrangement as independent negative predictors of PFS. The most frequently reported grade ≥3 adverse event was pneumonitis (5% of patients). Severe pneumonitis (grade ≥3) occurred significantly earlier than mild pneumonitis (1.6 vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months, respectively; P = 0.002). Conclusions Smoking status, PS, and EGFR mutation/ALK rearrangement were independent predictors of PFS. Our study elucidated nivolumab's efficacy in previously underreported patient populations; i.e., those with poor PS and/or with driver oncogenes. We also found that pneumonitis is not infrequent, and carries key implications for outcomes. These data should be useful for improving the clinical courses of nivolumab-treated patients with NSCLC.

Background Because of a limited number of reports, we aimed to investigate the clinical characteristics of patients with Legionella pneumonia due to non-Legionella pneumophila serogroup 1 and the diagnostic usefulness of the six-point scoring system for such patients compared with patients with pneumonia caused by L. pneumophila serogroup 1. Methods We retrospectively analysed patients diagnosed with Legionella pneumonia due to non-L. pneumophila serogroup 1 between March 2001 and June 2016. We examined the clinical characteristics, including symptoms, laboratory findings, radiologic findings, pneumonia severity, initial treatment and prognosis. We also calculated scores using the six-point scoring system in these patients. Furthermore, we compared the clinical characteristics and six-point scores between non-L. pneumophila serogroup 1 patients and L. pneumophila serogroup 1 patients among hospitalized community-acquired pneumonia patients enrolled prospectively between October 2010 and July 2016. Results Eleven patients had pneumonia due to non-L. pneumophila serogroup 1; their median age was 66 years and 8 patients (72.7%) were male. The most common pathogen was L. pneumophila serogroup 3 (6/11), followed by L. pneumophila serogroup 9 (3/11), L. pneumophila serogroup 6 (1/11) and L. longbeachae (1/11). Non-specific symptoms, such as fever and cough, were common. Six patients (54.5%) had liver enzyme elevation, but no patient developed hyponatraemia at

Background There have been few data on the chemotherapy in elderly advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS), and usefulness of chemotherapy for such patients remains unclear. The objective of this study was to identify factors that predicted the survival benefit of chemotherapy. Methods All consecutive elderly patients (≥75 years) with advanced NSCLC, Eastern Cooperative Oncology Group PS ≥2, EGFR mutation wild type/unknown, and newly diagnosed from January 2009 to December 2012 at a tertiary hospital were retrospectively reviewed. Results We enrolled 59 patients, and 31 patients received at least one chemotherapy regimen (chemotherapy group). However, 28 patients received best supportive care (BSC) alone (BSC group). The proportion of PS 2 and serum albumin levels was significantly higher in the chemotherapy group than in the BSC group. In the chemotherapy group, log-rank testing did not show statistically significant differences in overall survival (OS) between the single-agent therapy group and carboplatin-based doublet therapy group; however, the OS of patients receiving chemotherapy for only 1 cycle (early termination) was significantly shorter than patients receiving chemotherapy for ≥2 cycles. Hypoalbuminemia was not only a risk factor for the early termination of chemotherapy but also an independent prognostic factor in the chemotherapy group. A receiver operating characteristic curve analysis showed that the best cut-off value was 3.40 g/dL. In patients with serum albumin levels ≥3.40 g/dL, OS was significantly better in the chemotherapy group than in the BSC group (p = 0.0156), however, patients with serum albumin levels

Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). An Aspergillus-positive respiratory specimen often reflects colonization, and thus the clinical significance of Aspergillus isolation in MAC-LD patients is not well understood. The objective of this study was to investigate the clinical characteristics and outcomes of MAC-LD patients in whom Aspergillus was isolated from respiratory specimens. We performed a retrospective review of the medical records of 329 MAC-LD patients. We compared the characteristics and mortality rates between patients with Aspergillus isolation and those without. All Aspergillus species detected from respiratory specimens within the follow-up period were reviewed. Aspergillus was detected in 40 (12.2%) of the 329 patients. There were no significant differences in the clinical characteristics and mortality rates between patients with and without Aspergillus isolation. Among the 40 patients with Aspergillus isolation, 9 (22.5%) developed CPA. CPA was most often caused by A. fumigatus. In the 40 Aspergillus-positive patients, patients with A. fumigatus isolation had a significantly higher mortality rate than those without (P

Background Chronic fibrosing idiopathic interstitial pneumonia (CFIIP) has a potential risk of acute exacerbation (AE). However, the usefulness of cellular analysis of bronchoalveolar lavage fluid (BALF) has never been evaluated. This study aimed to evaluate the impact of the lymphocyte differential count > 15% in BALF on the mortality of patients with AE of CFIIP. Methods We retrospectively analysed 37 patients with AE of CFIIP who underwent BAL on admission. Patients were divided into two groups: one group consisting of those with a lymphocyte differential count > 15% and the other consisting of those with a lymphocyte differential count ≤ 15%. We compared the 90-day mortality between the two groups as the primary outcome, using the two-tailed log-rank test. Results The median follow-up duration was 6.9 months. Twenty-four patients had a lymphocyte differential count > 15%. The 90-day mortality was significantly higher in the group with a lymphocyte differential count ≤ 15% than in the group with a lymphocyte differential count > 15% (long rank test, p = 0.003). In the multivariate analysis a lymphocyte differential count > 15% was shown to be an independent favourable prognostic factor for 90-day mortality (HR: 0.125; 95% CI: 0.0247–0.589; p = 0.009). Conclusions A lymphocyte differential count > 15% in BALF may be associated with favourable outcomes in patients with AE of CFIIP. Electronic supplementary material The online version of this article (doi:10.1186/s12890-017-0412-8) contains supplementary material, which is available to authorized users.

Whether macrolide combination therapy reduces the mortality of patients with severe community-acquired pneumonia (CAP) hospitalized in the non-intensive care unit (ICU) remains unclear. Therefore, we investigated the efficacy of adding azithromycin to β-lactam antibiotics for such patients. This prospective cohort study enrolled consecutive patients with CAP hospitalized in the non-ICU between October 2010 and November 2016. The 30-day mortality between β-lactam and azithromycin combination therapy and β-lactam monotherapy was compared in patients classified as mild to moderate and severe according to the CURB-65, Pneumonia Severity Index (PSI), and Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) criteria. Inverse probability of treatment weighting (IPTW) analysis was used to reduce biases. Based on the CURB-65 and PSI, combination therapy did not significantly reduce the 30-day mortality in either group (179 patients in the combination group, 952 in the monotherapy group). However, based on the IDSA/ATS criteria, combination therapy significantly reduced the 30-day mortality in patients with severe (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.007–0.57), but not non-severe pneumonia (OR 1.85, 95% CI 0.51–5.40); these results were similar after IPTW analysis. Azithromycin combination therapy significantly reduced the mortality of patients with severe CAP who met the IDSA/ATS criteria.

Introduction Previous studies have described an association between immune-related adverse events (irAEs) and better outcomes in patients administered nivolumab for advanced non–small-cell lung cancer. However, the patients in previous studies were not stratified by potential predictive factors, such as programmed cell death ligand 1 status and treatment lines. Additionally, little is known of whether the timing and type of irAEs can inform the prediction of outcomes. Patients and Methods We prospectively investigated the association between irAEs and outcomes in the single-center cohort that included patients administered nivolumab in the second or later line of therapy. Subsequently, we confirmed these findings in a retrospective multicenter cohort that included patients with programmed cell death ligand 1 tumor proportion score of ≥ 50% who had received first-line pembrolizumab. The primary outcome was progression-free survival (PFS). Results In the prospective cohort (n = 76), the median PFS was significantly longer for the patients experiencing irAEs within 2 weeks of beginning nivolumab compared with the PFS for those who did not (median, 5.0 months [95% confidence interval (CI), 2.1-8.6 months] vs. median, 2.0 months [95% CI, 1.9-2.5 months]; P = .046). The association was stronger with earlier (within 2 weeks) than with later (within 6 weeks) irAEs. In the retrospective cohort (n = 148), the median PFS was significantly longer for the patients with early irAEs (within 3 weeks) than for those without (median, not reached [95% CI, 5.9 months to not reached] vs. median, 6.9 months [95% CI, 4.2-9.7 months]; P = .04). Rash was common and a better predictor of outcomes in both cohorts. Conclusion Our results have provided firmer evidence of the association between the occurrence of irAEs and outcomes and suggest that early irAEs (especially rash) might better predict outcomes.

The usefulness of existing pneumonia severity indices for predicting mortality in nursing and healthcare-associated pneumonia (NHCAP) is unclear. This study compared the usefulness of existing pneumonia severity indices for predicting mortality in NHCAP and community-acquired pneumonia (CAP). Consecutive hospitalized pneumonia patients including NHCAP and CAP patients were prospectively enrolled between October 2010 and November 2017. Admission pneumonia severity was assessed using CURB-65, Pneumonia Severity Index (PSI), A-DROP, Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria, and I-ROAD. The primary outcome was 30-day mortality. The discriminatory ability of each severity index was evaluated by receiver operating characteristic curve analysis. Overall, 828 patients had NHCAP, and 1330 patients had CAP. Thirty-day mortality was 12.8% and 5.6% in NHCAP and CAP patients, respectively. The area under the curve of PSI (0.717, 95% confidence interval 0.673–0.761) was the highest among all pneumonia severity indices, with significant differences compared with CURB-65 (0.651, 95% confidence interval 0.598–0.705, P = 0.02) and IDSA/ATS severe pneumonia criteria (0.659, 95% confidence interval 0.612–0.707, P = 0.03). The predictive abilities for 30-day mortality of the pneumonia severity indices, excluding PSI and I-ROAD, were significantly inferior for NHCAP than for CAP. PSI may be the most useful pneumonia severity score for predicting mortality in NHCAP. However, the predictive ability for mortality of each pneumonia severity score was worse for NHCAP than for CAP; therefore, the prognostic factors in NHCAP need to be identified for better management of NHCAP patients.

The impact of EGFR tyrosine kinase inhibitors (TKI) on the tumor immune microenvironment (TME) in non-small cell lung cancer (NSCLC) is unclear.We retrospectively identified 138 patients withThe proportion of patients with a PD-L1 expression level of ≥50% (high) increased from 14% before to 28% after EGFR-TKI (EGFR-TKI treatment was associated with changes in the TME of

Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor clinical outcomes. We surveyed clinical outcomes of MRSA pneumonia in daily practice to identify risk factors for the clinical failure and mortality in patients with MRSA pneumonia. This multicenter prospective observational study was performed across 48 Japanese medical institutions. Adult patients with culture-positive MRSA pneumonia were recruited and treated with anti-MRSA antibiotics. The relationships between clinical and microbiological characteristics and clinical outcomes at test of cure (TOC) or 30-day all-cause mortality were analyzed. In total, 199 eligible patients, including nursing and healthcare-associated pneumonia (n = 95), hospital-acquired pneumonia (n = 76), and community-acquired pneumonia (n = 25), received initial treatment with anti-MRSA agents such as vancomycin (n = 135), linezolid (n = 36), or teicoplanin (n = 22). Overall clinical failure rate at TOC and the 30-day mortality rate were 51.1% (48/94 patients) and 33.7% (66/196 patients), respectively. Multivariable logistic regression analyses for vancomycin-treated populations revealed that abnormal white blood cell count (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.31–14.39) was a risk factor for clinical failure and that no therapeutic drug monitoring (OR 3.10, 95% CI 1.35–7.12) and abnormally high C-reactive protein level (OR 3.54, 95% CI 1.26–9.92) were risk factors for mortality. In conclusion, this study provides evidence that majority of MRSA pneumonia patients are initially treated with vancomycin in Japan, and the absence of therapeutic drug monitoring for vancomycin is significantly associated with the mortality in patients with MRSA pneumonia.

The aim of the present study was to investigate the predictors of targeted therapy (TT) for pneumococcal community-acquired pneumonia (PCAP) with a positive urinary antigen test (UAT) and compare the outcomes with those of nontargeted therapy. This prospective cohort study enrolled consecutive PCAP patients with a positive UAT who were hospitalized at Kurashiki Central Hospital from October 2010 to November 2019. A total of 286 patients were included. Of them, 56 patients (19.6%) were included in the TT group. On multivariate analysis, identification of Gram-positive diplococci by Gram stain (OR [95% CI]: 2.46 [1.32-4.63]) was a positive predictor, whereas aspiration pneumonia (0.17 [0.03-0.59]) and CURB-65 score (0.59 [0.42-0.81]) were negative predictors of TT. Initial treatment failure and 30-day mortality were not significantly different. The UAT is not used enough for TT, and TT for PCAP did not have worse outcomes.

This study aimed to investigate the usefulness of procalcitonin-guided therapy in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening prognosis.352 hospitalized community-acquired pneumonia patients in an observational cohort study in which procalcitonin was measured three times serially, on admission (Day 1) and 2-3 days (Day 3) and 6-8 days (Day 7) after admission, between October 2010 and February 2016 were reviewed retrospectively. Antibiotics could be stopped if Day 7 procalcitonin was0.25 ng mLUsing theoretical procalcitonin guidance, antibiotic duration could be reduced from 12.6 to 8.6 days (P 0.001), while costs could be reduced from 45,833 to 38,952 yen (P = 0.005). Among the patients in whom theoretical procalcitonin guidance could be adopted, recurrence rates (5.6% vs. 8.1%, P = 0.15) and mortality rates (0% vs. 5.1%, P = 0.07) did not worsen between the group having the same antibiotic durations as with theoretical procalcitonin guidance in actual practice (N = 71) and the group having durations more than 2 days longer in actual practice than in theoretical procalcitonin guidance (N = 198). There was no significant difference in pneumonia severity using A-DROP, CURB-65, and PSI between two groups.Procalcitonin-guided therapy may be useful in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening the prognosis.

Background and objectives It can be difficult to treat respiratory tract infections caused by Mycobacterium abscessus ( M. abscessus ) as there is no established treatment strategy. Complications involving other nontuberculous mycobacterial infections such as Mycobacterium avium complex (MAC) are also commonly observed. Methods We investigated the clinical background and course of 18 cases of pulmonary M. abscessus infection treated over 8 years at Kurashiki Central Hospital. Radiological evaluation was performed using NICE scoring system, a method of semi-quantitative evaluation of imaging findings of pulmonary MAC infection. Results The mean age of the 18 patients (males, 6; females, 12) was 74.7 years. The median follow-up period was 1316 days (95% confidence interval; 720–1675 days), and 11 patients were concomitantly infected with pulmonary MAC. Among the patients that underwent antibacterial treatment for M. abscessus , there was one MAC-complication case and one non-MAC-complication case. All MAC-complication cases underwent antibacterial treatment including clarithromycin. Chest X-ray NICE scores for all cases were 8.50 ± 5.45 and 10.94 ± 6.03 at baseline and follow-up, respectively ( p = 0.0063). For MAC-complication cases, scores were 8.36 ± 4.74 and 12.00 ± 6.02 at baseline and follow-up, respectively ( p = 0.00818), and for non-MAC-complication cases, scores were 8.71 ± 6.82 and 9.29 ± 6.13 at baseline and follow-up, respectively ( p = 0.356). MAC-complication cases were significantly further exacerbated than non-MAC-complication cases ( p = 0.027). Conclusions Some cases of pulmonary M. abscessus infection progressed well without undergoing antibacterial treatment. In particular, results suggested that the clinical course of MAC-complication and non-MAC-complication cases differs.

Objectives Afatinib is an effective treatment in patients who have epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), but its toxicities often require dose adjustment. Exploratory analyses of previous trials have suggested that reducing the dose of afatinib can decrease treatment-related adverse events without negatively affecting effectiveness. The aim of this study was to assess the efficacy and safety of low starting dose of afatinib with dose modification according to its toxicity in patients with EGFR mutation-positive NSCLC. Materials and methods This study was a multicenter, single-arm, open-label phase II trial. Treatment-naive patients with advanced NSCLC positive for common EGFR mutations received afatinib starting in a dose of 20 mg/day. If tolerated, the dose was increased in 10-mg increments up to 50 mg/day. The primary endpoint was progression-free survival (PFS). Results From February 2015 through March 2016, 46 patients were enrolled. The median age was 73 years (range, 43–86), and 35 patients (72%) were women.EGFR mutation subtypes included exon 19 deletion (54%) and Leu858Arg point mutation (46%). Most patients had a performance status of 0 or 1 (91%) and a histological diagnosis of adenocarcinoma (98%). As of the data cut-off date of June 2017, the median follow-up was 18.9 months. The median PFS was 15.2 months (95% CI: 13.2–not estimable). The 1-year overall survival rate was 95.6% (95% CI: 89.7%–100%). The objective response rate was 81.8% (95% CI, 81.3%–98.6%). Adverse events of grade 3 or higher occurred in 14 patients (30.4%) and included rash/acne in 4 patients (8.7%), paronychia in 4 patients (8.7%), diarrhea in 2 patients (4.3%). There was no treatment-related death. Conclusions Low starting dose of afatinib therapy showed promising clinical efficacy and good tolerability. Further investigations are warranted.

Background Baloxavir marboxil (baloxavir) is an antiviral drug that inhibits the viral "cap-snatching" step in virus RNA transcription initiation. In Phase 2 study, baloxavir significantly shortend the time to alleviation of symptoms (TTAS) and showed significantly greater reduction in influenza virus titer compared with placebo. This provides additional outcomes including efficacy against virus types/subtypes and pharmacokinetic/pharmacodynamic (PK/PD) analysis. Methods Subgroup analyses by virus types/subtype were conducted for the primary and key secondary endpoints. Blood samples were collected totally at 2 to 5 points including Day 2 after baloxavir dosing. PK/PD analyses were conducted for TTAS and change in virus titer using the liner model and the Emax model, respectively. Results The median TTAS in each baloxavir dose group was significantly shorter than in the placebo group for patients with A/H1N1pdm virus, and was numerically shorter than the placebo group for patients with A/H3N2 and type B virus. Baloxavir significantly reduced virus titer within 1 day after treatment: for A/H1N1pdm, A/H3N2, and B virus, all 3 doses of baloxavir marboxil reduced virus titer on Day 2 to a greater extent than placebo. No clear PK/PD relationships were found for the TTAS, but the larger reduction in virus titer was observed in increasing C24. Conclusion These results support that baloxavir marboxil will be effective against a range of virus types/subtypes.

Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression.We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors-defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors-defined second progressive disease or death.Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001).Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression.

Background Most patients with acute eosinophilic pneumonia (AEP) show rapid improvement. However, some cases of AEP prove fatal. The aims of this study were to determine the clinical, radiographic, and pathologic characteristics of patients in whom AEP has a fatal outcome and to identify predictors of a poor prognosis. Methods We retrospectively identified the medical records of all patients diagnosed with AEP at our institution in Japan from July 2005 to July 2013. Results There were four deaths among 41 patients diagnosed to have AEP during the study period. All the patients who died were male; three cases were idiopathic and one was medication-related. The median bronchoalveolar lavage eosinophil differential count was 59%. An autopsy was performed on the patient with medication-related AEP who died and the pathologic finding was diffuse alveolar damage with eosinophilic infiltration. Diffuse ground-glass attenuation and traction bronchiectasis (TBE) were identified on high-resolution computed tomography in the four patients with fatal AEP. TBE was observed in six patients (five with idiopathic AEP, one with medication-related AEP), and 67% of these patients died. None of the patients with smoking-related AEP had TBE; all these patients had better responses to treatment and survived. Conclusions We observed the characteristics of patients with fatal AEP who did not respond to treatment. TBE was observed in all fatal cases and may be associated with a poor prognosis.

BACKGROUND Empiric therapy of pneumonia is currently based on the site of acquisition (community or hospital), but could be chosen, based on risk factors for multidrug-resistant (MDR) pathogens, independent of site of acquisition. METHODS We prospectively applied a therapeutic algorithm based on MDR risks, in a multicenter cohort study of 1089 patients with 656 community-acquired pneumonia (CAP), 238 healthcare-associated pneumonia (HCAP), 140 hospital-acquired pneumonia (HAP), or 55 ventilator-associated pneumonia (VAP). RESULTS Approximately 83% of patients were treated according to the algorithm, with 4.3% receiving inappropriate therapy. The frequency of MDR pathogens varied, respectively, with VAP (50.9%), HAP (27.9%), HCAP (10.9%), and CAP (5.2%). Those with ≥2 MDR risks had MDR pathogens more often than those with 0-1 MDR risk (25.8% vs 5.3%, P < .001). The 30-day mortality rates were as follows: VAP (18.2%), HAP (13.6%), HCAP (6.7%), and CAP (4.7%), and were lower in patients with 0-1 MDR risks than in those with ≥2 MDR risks (4.5% vs 12.5%, P < .001). In multivariate logistic regression analysis, 5 risk factors (advanced age, hematocrit

SETTING Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality worldwide. While interactions among bacterial pathogens in the respiratory tract have been studied, the impact of polybacterial aetiology on mortality has not been fully elucidated. OBJECTIVE To investigate the impact of polybacterial aetiology on mortality, prevalence, microbial patterns and clinical characteristics among CAP patients. DESIGN Retrospective data analysis. RESULTS Bacterial aetiology was established in 711 (46.0%) of 1544 enrolled hospitalised CAP patients. Of these, polybacterial aetiology was identified in 89 (12.5%): Streptococcus pneumoniae was the most frequently identified pathogen (n = 55, 61.8%). The most prevalent microbial combination was S. pneumoniae and Haemophilus influenzae (n = 19, 21.3%). Alcoholism and lack of previous antibiotic therapy were independent predictors of polybacterial aetiology. The proportion of patients with severe pneumonia was significantly higher in the polybacterial aetiology group than in the monobacterial group. Multivariate analysis showed that polybacterial aetiology was a predictor of 30-day mortality (OR 2.14, 95%CI 1.07-4.24, P = 0.030), independently of severe pneumonia status, pneumonia severity index, chronic obstructive pulmonary disease and inappropriate empirical therapy. CONCLUSION Polybacterial CAP tends to advance in severity, and indicates adverse outcomes.

Introduction Epidermal growth factor receptor (EGFR) mutation T790M accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor (TKI). Because T790M is mediated by TKI exposure, its penetration and "on–off" may affect T790M status. Methods We retrospectively reviewed T790M status and clinical course of patients who had undergone multiple rebiopsies after acquired resistance to EGFR-TKI. Results Of 145 patients with EGFR-mutant NSCLC receiving rebiopsy after acquired resistance, 30 underwent multiple site rebiopsies, and 24 received repeated rebiopsies at the same lesion. In 22 patients who underwent rebiopsies from both central nervous system (CNS; 20 cerebrospinal fluids [CSF] and 2 brain tumoral tissues) and thoracic lesions (7 lung tissues, 14 pleural effusions, and 1 lymph node), 12 were thoracic-T790M-positive. Of these 12 patients, 10 were CNS-T790M-negative, despite exhibiting thoracic-T790M-positive. All 10 thoracic-T790M-negatives were CNS-T790M-negative. Three patients revealed a spatial heterogeneous T790M status among their thoracic lesions. In 24 patients receiving repeated rebiopsies at the same lesion (12 lung tissues, 6 CSFs, and 6 pleural effusions), T790M status of lung lesions varied in five patients after TKI-free interval. In all five patients whose T790M status changed from positive to negative, EGFR-TKI rechallenge was effective. In three of these five patients, after further TKI exposure, T790M status changed from negative to positive again. There was also a patient whose CSF T790M status changed from negative to positive after high-dose erlotinib therapy. Conclusions T790M status in an individual patient can be spatiotemporally heterogeneous because of selective pressure from EGFR-TKI.

Background The aim of the study was to describe the epidemiology, clinical features, antimicrobial treatment, and outcomes of bedridden pneumonia patients receiving home healthcare. Methods A 3-year prospective observational study of poor performance status (PS) 3–4 patients receiving long-term home healthcare and hospitalized at a single center with pneumonia between October 2010 and September 2013 was conducted, and their clinical characteristics were compared with non-bedridden community-acquired pneumonia (CAP) patients. Results A total of 131 CAP patients with PS 3-4, and 400 CAP patients with PS 0-2 were evaluated. The PS 3–4 patients were older, and exhibited a higher frequency of underlying diseases. Aspiration was thought to be associated with pneumonia in 77.1% of the PS 3–4 patients. Streptococcus pneumoniae was the leading pathogen in both groups, whereas the frequency of streptococci and polymicrobial infections was higher in the PS 3-4 group. The incidence of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa was lower than in previous healthcare-associated pneumonia reports. The in-hospital mortality and recurrence rates were significantly higher in the PS 3-4 group than in the good PS group (17.6% vs. 6.0%, p Conclusions The clinical characteristics of pneumonia in poor PS patients were similar to healthcare-associated pneumonia (HCAP), except for the frequency of drug-resistant pathogens. Hence, it might be beneficial to categorize pneumonia in home residents with poor PS separately from pneumonia in CAP patients who were previously healthy or experienced mild comorbidities.

Legionella species are important causative pathogens for severe community-acquired pneumonia (CAP). Most cases of Legionella pneumonia are due to Legionella pneumophila serogroup 1, and CAP due to L. pneumophila serogroup 9 is rare. A fourth case of CAP due to L. pneumophila serogroup 9 has been reported, and initial treatment using single-dose oral azithromycin appeared useful. Azithromycin or fluoroquinolone injection is usually recommended for the treatment of Legionella pneumonia, and no previous reports have shown the effectiveness of single-dose oral azithromycin. This case report is therefore valuable from the perspective of possible treatment for mild to moderate Legionella pneumonia using single-dose oral azithromycin.

High-resolution computed tomography (HRCT) parenchymal patterns have been used to predict prognosis in patients with interstitial lung disease (ILD). In idiopathic pulmonary fibrosis, the fibrosis score (i.e. the combined extent of reticulation and honeycombing) has been associated with worse survival. This study aimed to identify HRCT patterns and patient characteristics that can predict poor prognosis in rheumatoid arthritis-related ILD (RA-ILD).We retrospectively analysed 65 patients with newly diagnosed RA-ILD from 2007 to 2016 at Kurashiki Central hospital. Using univariate and bivariate Cox regression analysis, associations with mortality, were identified.During a median follow-up of 56.5 months, 16/65 (24.6%) patients died. Univariate analysis identified six significant poor prognostic factors: lower baseline % predicted forced vital capacity, total interstitial disease score, reticulation score, traction bronchiectasis score, fibrosis score, and definite UIP pattern. Fibrosis score remained to be an independently significant poor prognostic factor of survival on bivariate analysis. Patients with a fibrosis score20% had higher mortality (HR, 9.019; 95% CI, 2.87-28.35; p .05).This study showed that fibrosis score is strongly associated with worse survival in RA-ILD, and patients with fibrosis score20% had a 9.019-fold increased risk of mortality.

Background Pneumococcal pneumonia causes high morbidity and mortality among adults. This study aimed to identify risk factors for bacteremic pneumococcal pneumonia, and to construct a prediction model for the development of bacteremia in patients with community-acquired pneumococcal pneumonia. Methods We retrospectively analyzed data from patients hospitalized with community-acquired pneumococcal pneumonia between April 2007 and August 2015. Logistic regression models were applied to detect risk factors for pneumococcal bacteremia, and a receiver operating characteristic curve was used to devise a prediction model. Results Based on the results of sputum cultures, urine antigen tests, and/or blood cultures, 389 patients were diagnosed with pneumococcal pneumonia, 46 of whom had bacteremia. In the multivariate analysis, age 20 mg/dL were identified as independent risk factors for the development of pneumococcal bacteremia. The bacteremia prediction score based on receiver operating characteristic curve analysis had a sensitivity of 0.74 and a specificity of 0.78 in patients with two risk factors. The area under the receiver operating characteristic curve was 0.77 (95% confidence interval (CI), 0.70–0.85). Conclusions Age

BACKGROUND Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents. METHODS We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population. RESULTS In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P

Objective The goals of this study were to assess the efficacy and tolerability of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) and to identify predictors of tolerability to pirfenidone. Methods We conducted a retrospective observational study. When the patient showed deterioration in the percent forced vital capacity (%FVC) or experienced acute exacerbations or severe adverse events, treatment of the patient with pirfenidone was discontinued. We classified the patients who did not display progression following six months of pirfenidone treatment as the tolerant group and the patients who did display progression as the intolerant group. We retrospectively analyzed differences between the two groups in terms of baseline characteristics. The efficacy of pirfenidone was evaluated by the changes in vital capacity (VC) and %FVC before and after the start of treatment in the tolerant group. Patients A total of 20 patients who had been diagnosed with IPF were treated with pirfenidone. Results In the tolerant group, the baseline %FVC (p=0.01) and the percentage diffusing capacity of the lungs for carbon monoxide (DLCO, p=0.02) were significantly higher, and the baseline composite physiologic index (CPI) was significantly lower (p=0.009) than in the intolerant group. In the tolerant group, pirfenidone significantly reduced the decline in VC and %FVC of the patients after treatment. In the intolerant group, five patients discontinued pirfenidone treatment because of anorexia. Conclusion We found that pirfenidone was better tolerated in patients with milder disease symptoms, as indicated by their baseline CPI, %FVC and %DLCO, and that patients in the tolerant group could benefit from the use of pirfenidone.

Background To identify the prognostic factors for survival in patients with interstitial pneumonia with autoimmune features (IPAF) who meet the serological domain of the IPAF criteria. Methods We retrospectively analysed 99 IPAF patients who met the serological domain and were hospitalised at the Respiratory Medicine Unit of Kurashiki Central Hospital from 1999 to 2015. The high-resolution computed tomography findings were usual interstitial pneumonia (UIP; n = 1), non-specific interstitial pneumonia (NSIP; n = 63), NSIP with organizing pneumonia (OP) overlap (n = 15), and OP (n = 20). One patient who had radiological UIP pattern, and met the serological and clinical domains was excluded. The clinical characteristics, radiological findings, administered therapy, and prognosis of the remaining 98 IPAF patients who met the serological and morphological domains were analysed. Results The median age of the 98 IPAF patients was 68 years, and 41 (41.8%) of them were men. Twelve (12.2%) of the 98 IPAF patients developed other characteristics and were diagnosed with connective tissue disease (CTD) later during the median follow-up of 4.5 years. Univariate Cox analysis revealed systemic sclerosis (SSc)-specific and SSc-associated antibodies (ANA nucleolar pattern, ANA centromere pattern, anti-ribonucleoprotein and anti-Scl-70) positive IPAF, radiological NSIP pattern, bronchoalveolar lavage fluid lymphocytes >15%, and age as significant prognostic factors for survival. Multivariate Cox analysis revealed radiological NSIP pattern (hazard ratio [HR], 4.48; 95% confidence interval [CI], 1.28–15.77, p = 0.02) and age (HR, 1.07; 95% CI, 1.02–1.11, p = 0.01) were significantly associated with worse survival. Conclusions We confirmed that radiological NSIP pattern and age are poor prognostic factors for the survival of IPAF patients. This study suggested that the autoantibodies that are highly specific for certain connective tissue diseases might be less important for the prognosis of IPAF compared with the radiological-pathological patterns. The relatively high proportion of IPAF patients who developed CTD later suggests the importance of careful observation for evolution to CTD in IPAF.

Background Patients with Mycobacterium avium complex (MAC) lung disease (LD) have a heterogeneous prognosis. This study aimed to develop and validate a prognostic scoring model for these patients using independent risk factors for survival. Methods We retrospectively analyzed the data of patients with MAC-LD from two hospitals (cohort 1, n = 368; cohort 2, n = 118). Cohort 1 was evaluated using a multivariate Cox proportional hazards model to identify independent risk factors for overall survival (OS). A prognostic scoring model composed of these factors was developed, and cohort 1 was stratified into three groups according to risk using the log-rank test. Finally, the prognostic scoring model was validated using the data of cohort 2. Results Seven independent risk factors for OS were selected from cohort 1, including the male sex, age ≥ 70 years, the presence of a malignancy, body mass index

Background To date, only few studies have examined the prognostic factors of community-acquired pneumonia (CAP) defined according to the latest criteria, which excludes healthcare-associated pneumonia (HCAP). Therefore, we aimed to investigate the factors that affect prognosis, and evaluate the usefulness of existing pneumonia severity scores for predicting the prognosis of CAP. Methods We retrospectively analyzed patients with CAP, excluding HCAP, who were enrolled prospectively between April 2007 and February 2016. Four patients who used macrolides other than azithromycin (AZM) were excluded. We used age, sex, comorbidities, laboratory findings and antimicrobial therapy as prognostic variables. The primary outcome was 30-day mortality and secondary outcome was ICU admission. We also performed receiver operating characteristic curve analysis of Pneumonia Severity Index (PSI), Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) severe criteria, CURB-65 and A-DROP pneumonia severity scores. Results Among 1834 CAP patients, mean age was 73.5 ± 14.3 years; 1281 (69.8%) were men; and 30-day mortality was 6.7% (122/1834). In total, 1830 patients were analyzed. Multivariate analysis identified age [Odds Ratio (OR): 1.04, 95% Confidence Interval (CI): 1.02–1.07], chronic obstructive pulmonary disease (COPD) [OR: 1.77, 95% CI: 1.13–2.76], malignancy (OR: 2.25, 95% CI: 1.25–4.06), body temperature (OR: 0.81, 95% CI: 0.67–0.99), respiratory rate (OR: 1.04, 95% CI: 1.01–1.07), PaO2/FiO2 ≤ 250 (OR: 3.15, 95% CI: 1.93–5.14), Alb (OR: 0.27, 95% CI: 0.19–0.39), BUN (OR: 1.01, 95% CI: 1.00–1.02), and mechanical ventilation (OR: 2.99, 95% CI: 1.75–5.12) as prognostic factors. AZM and β-lactam combination therapy significantly reduced 30-day mortality (OR: 0.50, 95% CI: 0.26–0.97). Areas under the curve of PSI, IDSA/ATS severe criteria, CURB-65 and A-DROP were 0.759, 0.746, 0.754 and 0.764, respectively. Conclusions Increasing age, presence of COPD and malignancy as comorbidities, hypothermia, tachypnea, PaO2/FiO2 ratio ≤250 mmHg, low Alb level, high BUN level and mechanical ventilatory support predict a worse prognosis; AZM combination therapy should be considered for CAP, excluding HCAP. All four pneumonia severity scores are useful for assessing the severity of CAP defined by the latest criteria. Trial registration UMIN-CTR UMIN000004353. Registered 7 October 2010. Retrospectively registered. Electronic supplementary material The online version of this article (doi:10.1186/s12890-017-0424-4) contains supplementary material, which is available to authorized users.

We performed a postmarketing surveillance study to determine the efficacy and safety of the oral quinolone antibacterial agent, garenoxacin (Geninax R Tablets 200 mg), against bacterial pneumonia. Between October 2009 and March 2011, patients with community-acquired pneumonia visited 174 facilities in Japan; we collected survey forms from 739 patients of these patients who were suspected with bacterial pneumonia on the basis of factors, e.g., the presence of purulent sputum or suspected presence of bacterial pathogens in clinical specimens. We examined the safety in 730 patients and the efficacy in 535 patients. The efficacy rate of garenoxacin for bacterial pneumonia was 92.8% (479/516 patients). The eradication rates for Streptococcus pneumoniae and Haemophilus influenzae, the major pathogens of bacterial pneumonia, were 98.5% (65/66 strains) and 100% (65/65 strains), respectively. The incidence of adverse drug reactions (including abnormal laboratory tests) was 7.9% (58/730 patients). Among the main adverse drug reactions, abnormal laboratory tests were observed in 2.1% patients (15/730), hepatobiliary disorders were observed in 1.8% patients (13/730), and skin and subcutaneous tissue disorders were observed in 1.6% patients (12/730). In conclusion, garenoxacin showed an efficacy rate of greater than 90% for bacterial pneumonia and is considered to be useful in daily practice., Journal of Infection and Chemotherapy, 20(9), pp.549-557; 2014

Unlike elderly patients with community-acquired pneumonia whose outcomes are markedly affected by their background characteristics, it appears that the severity of the infection itself contributes to outcomes in younger patients with community-acquired pneumonia. In order to identify clinical characteristics of severe community-acquired pneumonia in younger patients under 60 years old, among such cases prospectively collected at our hospital over a period of 18 years, those meeting the criteria for severe community-acquired pneumonia, as defined in the Infectious Diseases Society of America/American Thoracic Society Guidelines for community-acquired pneumonia, were retrospectively examined and compared to elderly patients with severe community-acquired pneumonia. Younger patients with severe pneumonia accounted for 12.9% of younger hospitalized patients. Although the incidence of severe pneumonia in younger patients was lower than that in elderly patients, its severity may be underestimated by severity assessment based on the conventional guidelines. Thus, attention is required. While Streptococcus pneumoniae and Legionella species were important causative pathogens, atypical pathogens and viruses were also frequently detected. There were only 11 deaths over a period of 18 years. Based on multivariate analysis, the risk factors for aggravation of community-acquired pneumonia among younger patients were age 50 years or older, diabetes mellitus, chronic liver disease, and Legionella pneumonia. Although the mortality rate from community-acquired pneumonia is extremely low in previously healthy younger patients, outcomes might be poor for patients with underlying diseases and those with rapid progression. Multimodal treatments including respiratory management may be appropriate.

Shigeru Kohno, Yoshifumi Imamura, Yuichiro Shindo, Masafumi Seki, Tadashi Ishida, Shinji Teramoto, Junichi Kadota, Kazunori Tomono, Akira Watanabe Unit of Molecular Microbiology and Immunology, Nagasaki University, Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501 Japan Institute for Advanced Research, Nagoya University, and Department of Respiratory Medicine, Nagoya University, Graduate School of Medicine, Japan Division of Infection Control and Prevention, Osaka University Hospital, Japan Department of Respiratory Medicine, Kurashiki Central Hospital, Japan Hitachinaka Medical Education and Research Center, University of Tsukuba, Japan Department of Internal Medicine II, Oita University Faculty of Medicine, Japan Division of Anti-Infective Agents, Institute of Development, Aging and Cancer, Tohoku University, Japan

Background Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe systemic hypersensitivity reaction caused by specific drugs, in which herpesvirus reactivations and organ dysfunction occur during the course of the disease. Although recent reports have documented the development of autoimmune disease after complete resolution of DIHS/DRESS, relatively little is known about long-term outcomes after complete resolution of the disease. Objective The aim of this study was to retrospectively analyze complications and sequelae in the early and late phases of DIHS/DRESS according to treatment. Methods In all, 34 patients were classified into 2 groups: 14 patients with oral corticosteroid treatment; and 20 with noncorticosteroid treatment. The disease time course was divided into 2 periods: the first 6 months after onset of the drug reaction (early phase); and the period thereafter (late phase). Investigations to detect the presence of viral/bacterial infectious diseases, organ dysfunction, and autoantibodies were performed in both early and late phases. Results Herpesvirus infections and pneumonia were detected in 6 and 2 patients, respectively, in the corticosteroid treatment group in the early phase. In the noncorticosteroid treatment group, 2 patients developed autoimmune diseases, namely lupus erythematosus and autoimmune thyroiditis. Autoantibodies were detected in 44.4% of patients examined in the late phase of the disease. Limitations This study only evaluated a small number of autoantibodies. Conclusion The need for anti-inflammatory effects from systemic corticosteroids should be balanced with the risk of infectious diseases and the benefits of preventing the appearance of later autoimmune conditions in patients with DIHS/DRESS.

Interstitial lung disease (ILD) is a common pulmonary manifestation of systemic sclerosis (SSc). It is unknown whether radiographic fibrosis score predicts mortality in SSc-associated ILD (SSc-ILD). We retrospectively analysed patients with SSc-ILD to evaluate whether radiographic fibrosis score was a useful predictor of mortality.We identified SSc-ILD patients evaluated at Kurashiki Central Hospital (Japan) from 2006 to 2016, and radiographic fibrosis scores based on the extent of reticulation and honeycombing on high-resolution computed tomography (HRCT) scanning were calculated by manually tracing around each fibrotic area. Independent predictors of overall survival were determined using the Cox proportional hazards model.The study included 48 patients, of whom 19 had usual interstitial pneumonia on HRCT. The median follow-up period was 56.6 months, and over the follow-up period 15 patients died. The 5-year survival was 72.4%. In the multivariate analysis, radiographic fibrosis score, age, being male and forced vital capacity were independently associated with an increased risk of death, while HRCT pattern was not.A high radiographic fibrosis score was a poor prognostic factor in SSc-ILD. More widespread fibrosis was associated with an increased risk of death, independent of HRCT pattern.

The efficacy of programmed death-1 blockade in epidermal growth factor receptor gene (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR.We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A). Programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) density in tumor specimens obtained after acquisition of EGFR-TKI resistance were determined by immunohistochemistry. Whole-exome sequencing of tumor DNA was carried out to identify gene alterations. The relation of T790M status to PD-L1 expression or TIL density was also examined in an independent cohort of 60 patients (cohort B).In cohort A, median progression-free survival (PFS) was 2.1 and 1.3 months for T790M-negative and T790M-positive patients, respectively (P = 0.099; hazard ratio of 0.48 with a 95% confidence interval of 0.20-1.24). Median PFS was 2.1 and 1.3 months for patients with a PD-L1 expression level of ≥1% or 1%, respectively (P = 0.084; hazard ratio of 0.37, 95% confidence interval of 0.10-1.21). PFS tended to increase as the PD-L1 expression level increased with cutoff values of ≥10% and ≥50%. The proportion of tumors with a PD-L1 level of ≥10% or ≥50% was higher among T790M-negative patients than among T790M-positive patients of both cohorts A and B. Nivolumab responders had a significantly higher CD8+ TIL density and nonsynonymous mutation burden.T790M-negative patients with EGFR mutation-positive NSCLC are more likely to benefit from nivolumab after EGFR-TKI treatment, possibly as a result of a higher PD-L1 expression level, than are T790M-positive patients.

We describe a 55-year-old man who received stereotactic radiotherapy (SRT) for the treatment of brain metastasis from lung adenocarcinoma. Fourteen months after SRT, right-sided hemiparesis developed, and magnetic resonance imaging revealed progression of perifocal edema and an enhanced lesion. Cerebral radiation necrosis was diagnosed, and treatment with bevacizumab was initiated. The lesion clearly responded to bevacizumab therapy, but reenlarged 8 months later and was surgically resected. Histopathological analysis of the resected specimen revealed large areas of necrosis; however, viable tumor cells were detected in the necrotic areas. Reenlargement of the necrotic lesion was attributed to the recurrence of lung cancer.

Objective The aim of this study was to describe the epidemiology, clinical features, antimicrobial treatment, and outcomes of patients with nursing and healthcare-associated pneumonia (NHCAP); a new category of pneumonia proposed by the Japanese Respiratory Society. Methods We conducted a retrospective analysis of a prospectively collected database of patients with NHCAP and community-acquired pneumonia (CAP) hospitalized at a single center between January 2008 and December 2010, and compared their clinical characteristics. The criteria for NHCAP were as follows: (1) residence in a nursing home or an extended-care ward, (2) a discharge from a hospital in the preceding 90 days, (3) an elderly or handicapped patient who needs long-term care, (4) a patient who regularly requires vascular access in an outpatient setting. Results A total of 442 NHCAP patients and 451 CAP patients were evaluated. The NHCAP patients were older and had a higher frequency of underlying diseases. Aspiration was thought to be associated with the NHCAP in 63% of patients. Streptococcus pneumoniae was the leading pathogen in both groups, whereas the frequency of multidrug-resistant pathogens was higher in the NHCAP patients. The most frequently used antimicrobials in NHCAP patients were penicillins with beta-lactamase inhibitors. The in-hospital mortality and recurrence rates were significantly higher in NHCAP patients than in CAP patients (13.1% vs. 5.1%, p

Diaphenylsulfone (DDS: Dapsone) is used for Pneumocystis pneumonia (PCP) prophylaxis, and methemoglobinemia has rarely been reported as a side effect of DDS. We herein report two cases of DDS-related methemoglobinemia in an 81-year-old man with organizing pneumonia and an 84-year-old woman with eosinophilic pneumonia under treatment with prednisolone. Both patients initially received trimethoprim/sulfamethoxazole for PCP prophylaxis and were switched to DDS due to side effects and subsequently exhibited a clinically unexplainable decrease in SpO2. Methemoglobinemia was diagnosed based on the findings of arterial blood gas analyses. In both cases, the methemoglobinemia improved after discontinuing DDS.

Background Recent reports have suggested that erlotinib therapy after gefitinib failure requires optimal patient selection to obtain clinical benefits in relapsed non-small cell lung cancer (NSCLC). However, insufficient evidence exists to determine which clinical factors best identify patients who benefit from erlotinib therapy. Methods One hundred twenty-five patients with relapsed NSCLC who had received erlotinib therapy after gefitinib failure were retrospectively evaluated between January 2008 and May 2009. Results The response rate (RR), disease control rate (DCR), and median progression-free survival (PFS) for all patients were 9% (95% confidence interval [CI], 5–15%), 44% (95% CI, 35–53%), and 2.0 months (95% CI, 1.4–2.5 months), respectively. The median survival time was estimated to be 11.8 months (95% CI, 6.4–16.0 months). Using multivariate analysis, good performance status (PS), EGFR mutation-positive status, and benefit from prior gefitinib therapy were identified as significant predictive factors for disease control. Using a proportional hazards model, benefit from prior gefitinib therapy, good PS, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies emerged as significant predictive factors for longer PFS. Thirty-two patients with concomitant PS 0/1, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies benefitted more from erlotinib therapy: RR, 25% (95% CI, 12–43%); DCR, 72% (95% CI, 53–86%); and median PFS, 3.4 months (95% CI, 2.4–4.9 months). Conclusions Higher efficacy of erlotinib after gefitinib failure can be achieved with proper patient selection criteria, including good PS, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies.

A 50-year-old man with a 30-year occupational history of welding presented with low-grade fever, fatigue and persistent dry cough. Computed tomography (CT) of the chest revealed interlobular septal thickening and bilateral non-segmental patchy ground-glass opacities except in the sub-pleural zone. He revealed that he had inhaled nickel fumes 3 days previously at work. These findings suggested a diagnosis of pneumonitis induced by inhalation of nickel fumes. Fewer reports describe pneumonitis associated with the inhalation of nickel compared with zinc fumes. Although nickel compounds are particularly pernicious among the transition metals and more toxic than zinc compounds, nickel fume inhalation rarely induces lethal acute respiratory distress syndrome. Our patient was successfully treated with corticosteroid.

Introduction: Mutation of the epidermal growth factor receptor (EGFR) gene can predict the efficacy of EGFR-tyrosine kinase inhibitors. Different mutations have been shown to co-occur in a single tumor. However, the frequency of these so-called "complex mutations" and the efficacy of gefitinib in treating patients with these mutations are unclear. Methods: We investigated the frequency of complex mutations in 783 patients with non-small cell lung cancer seen at our institutes between April 2006 and May 2009. Mutational analysis was performed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. Gefitinib efficacy was evaluated in patients found to have complex mutations. Results: EGFR mutations were detected in 318 (41%) patients, with 21 (6.6%) of these individuals having complex mutations. Sixteen of these 21 patients received gefitinib. The response rate (RR) was 67% (95% confidence interval [CI], 35–90%) and median progression-free survival was 12.2 months (95% CI, 1.3 months to undeterminable). Analysis of RR according to mutation type revealed that patients with deletional mutation in exon 19 (Del-19) and a point mutation in exon 21 (L858R) had a better RR (86%, 6 of 7) than those with other complex mutation patterns such as a point mutation in exon 18 (G719S) + L858R (40%, 2 of 5) (p = 0.2222). The median progression-free survival was also longer in these patients (16.5 months; 95% CI, 1.1 months to undeterminable versus 3.8 months; 95% CI, 0.7–10.0 months) (p = 0.0459). Conclusions: Complex EGFR mutations are not rare. Gefitinib has different efficacy according to the type of complex EGFR mutations. Patients with Del-19 and L858R mutations may benefit more from gefitinib than other types of complex mutations.

Background and objective The management of community-acquired pneumonia (CAP) depends, in part, on the identification of the causative agents. The objective of this study was to determine the potential of thin-section computed tomography (CT) in differentiating bacterial and non-bacterial pneumonia. Patients and methods Thin-section CT studies were prospectively examined in hospitalized CAP patients within 2 days of admission, followed by retrospective assessment by two pulmonary radiologists. Thin-section CT findings on the pneumonias caused by each pathogen were examined, and two types of pneumonias were compared. Using multivariate logistic regression analyses, receiver operating characteristic (ROC) curves were produced. Results Among 183 CAP episodes (181 patients, 125 men and 56 women, mean age ± S.D.: 61.1 ± 19.7) examined by thin-section CT, the etiologies of 125 were confirmed (94 bacterial pneumonia and 31 non-bacterial pneumonia). Centrilobular nodules were specific for non-bacterial pneumonia and airspace nodules were specific for bacterial pneumonia (specificities of 89% and 94%, respectively) when located in the outer lung areas. When centrilobular nodules were the principal finding, they were specific but lacked sensitivity for non-bacterial pneumonia (specificity 98% and sensitivity 23%). To distinguish the two types of pneumonias, centrilobular nodules, airspace nodules and lobular shadows were found to be important by multivariate analyses. ROC curve analysis discriminated bacterial pneumonia from non-bacterial pneumonia among patients without underlying lung diseases, yielding an optimal point with sensitivity and specificity of 86% and 79%, respectively, but was less effective when all patients were analyzed together (70% and 84%, respectively). Conclusion Thin-section CT examination was applied for the differentiation of bacterial and non-bacterial pneumonias. Though showing some potential, this examination at the present time would not be applicable for patients with underlying lung diseases, severe conditions of pneumonia, or immunocompromised conditions.