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Abstract Accurate prognostic tools for mortality in patients with healthcare-associated pneumonia (HCAP) are needed to provide appropriate medical care, but the efficacy for mortality prediction of tools like PSI, A-DROP, I-ROAD, and CURB-65, widely used for predicting mortality in community-acquired and hospital-acquired pneumonia cases, remains controversial. In this study, we conducted a systematic review and meta-analysis using PubMed, Cochrane Library (trials), and Ichushi web database (accessed on August 22, 2022). We identified articles evaluating either PSI, A-DROP, I-ROAD, or CURB-65 and the mortality outcome in patients with HCAP, and calculated the pooled sensitivities, specificities, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the summary area under the curves (AUCs) for mortality prediction. Additionally, the differences in predicting prognosis among these four assessment tools were evaluated using overall AUCs pooled from AUC values reported in included studies. Eventually, 21 articles were included and these quality assessments were evaluated by QUADAS-2. Using a cut-off value of moderate in patients with HCAP, the range of pooled sensitivity, specificity, PLR, NLR, and DOR were found to be 0.91–0.97, 0.15–0.44, 1.14–1.66, 0.18–0.33, and 3.86–9.32, respectively. Upon using a cut-off value of severe in those patients, the range of pooled sensitivity, specificity, PLR, NLR, and DOR were 0.63–0.70, 0.54–0.66, 1.50–2.03, 0.47–0.58, and 2.66–4.32, respectively. Overall AUCs were 0.70 (0.68–0.72), 0.70 (0.63–0.76), 0.68 (0.64–0.73), and 0.67 (0.63–0.71), respectively, for PSI, A-DROP, I-ROAD, and CURB-65 (p = 0.66). In conclusion, these severity assessment tools do not have enough ability to predict mortality in HCAP patients. Furthermore, there are no significant differences in predictive performance among these four severity assessment tools.

Abstract Background Syphilis is a chronic disease that progresses in the primary, secondary, latent, and tertiary stages. Pulmonary manifestations of syphilis are rare, and their histological features have not been well-described. Case presentation A 78-year-old man was referred to our hospital because of a solitary nodular shadow in the right middle lung field on a chest radiograph. Five years prior, a rash appeared on both legs. He was tested for syphilis at a public health center, and the non-treponemal test result was negative. When he was approximately 35 years old, he had unspecified sexual intercourse. Chest computed tomography showed a 13-mm nodule with a cavity in S6 of the right lower lobe of the lung. Robot-assisted resection of the right lower lobe was performed because of suspected localized right lower lobe lung cancer. A cicatricial variant of organizing pneumonia (CiOP) was observed, and immunohistochemistry identified Treponema pallidum inside the macrophages in the nodule cavity. The rapid plasma regain (RPR) value was negative, and the Treponema pallidum hemagglutination assay was positive. The patient was diagnosed as having secondary syphilis with pulmonary involvement. Insidious progression of secondary syphilis may result in CiOP and a negative RPR test result. Conclusions We report the first case of pulmonary syphilis with a histological pattern of CiOP. It may be asymptomatic and difficult to diagnose because the RPR test may be negative for a long period of time. When either non-treponemal or treponemal test results are positive, the possibility of pulmonary syphilis should be considered along with appropriate medical treatment.

Objectives: The combination of chemotherapy and immune checkpoint inhibitors (chemo-ICI) has become the new standard of treatment for extensive-stage small cell lung cancer (ES-SCLC). Recently, slight changes in interstitial shadows, defined as interstitial lung abnormalities (ILA), have been identified. In patients with ES-SCLC who received chemo-ICI, there are limited data on the incidence of drug-induced interstitial lung disease (D-ILD) in daily practice and the association between the development of D-ILD and ILA in the baseline computed tomography (CT). Materials and methods: A multicenter, retrospective study was conducted to investigate the incidence of D-ILD, the risk factors for developing D-ILD, progression-free survival (PFS), and overall survival (OS) in patients with ES-SCLC who received chemo-ICI between August 2019 and November 2021. Results: This study enrolled 70 patients (median age, 71 years; including 58 men) from nine institutions in Japan. There were 62 patients (89%) treated with carboplatin/etoposide/atezolizumab and 8 patients treated with carboplatin or cisplatin/etoposide/durvalumab. Twenty-nine patients (41.4%) were found to have ILA at baseline CT. Eleven patients (15.7%) developed D-ILD. The proportion of patients with ILA was significantly higher in the group who developed D-ILD than in the group who did not (9/11 (81.8%) vs. 20/59 (33.9%), respectively, P = 0.0057). In addition, the frequency of ground glass attenuation (GGA) and reticulation was higher in patients who developed D-ILD. There was no significant difference in PFS and OS between patients who developed D-ILD and those who did not (median PFS, 8.0 (95% confidence interval (CI), 5.5–9.5) months vs. 5.0 (95% CI, 4.5–5.6) months, respectively, P = 0.11 and median OS, not reached (NR) (95% CI, 8.7–NR) vs. 18.2 (95% CI, 13.2–NR) months, respectively, P = 0.20). Conclusion: The incidence of D-ILD in patients with ES-SCLC who received chemo-ICI in clinical practice was higher than that in clinical trials. Patients with pre-existing ILA were more likely to develop D-ILD.

Abstract Background Bronchoscopy can be a distress for the patient. There have been few studies on the combination of sedatives and opioids. The aim of this study was to demonstrate the usefulness and safety of administration of the combination of midazolam and pethidine during bronchoscopy. Methods In this prospective randomized single (patient)-blind study, we randomly assigned 100 patients who were scheduled to undergo bronchoscopy biopsy to receive treatment with either the midazolam/pethidine combination (combination group) or midazolam alone (midazolam group) during examinations. After the end of bronchoscopy, patients completed a questionnaire and the visual analogue scale was measured. The primary outcome was the patients’ acceptance of re-examination assessed by visual analogue scale. We also assessed pain levels, vital signs, midazolam use, xylocaine use, and adverse events. Univariate analyses were performed using Fisher’s exact test for categorical data, and the t-test or Mann-Whitney test was carried out for analysis of numeric data. All P-values were two-sided, and values

Abstract Objective This study aims to examine changes in patients’ perspectives and outlooks regarding the disease and their health after hospitalization for COVID-19 and investigate their discrimination and harassment experiences. This prospective observational study surveyed discharged patients who had been admitted to Hyogo Prefectural Tamba Medical Center in Japan for COVID-19. Patient characteristics, changes in outlook and behaviors after discharge, and incidents of discrimination and harassment were examined. The study was conducted in two waves: March–June 2020 and July–September 2020. Results Responses were obtained from 27 patients aged 50 ± 17 years, including 16 men (59.3%). We found most patients feared infection before hospitalization (88.5%) and had taken some preventive measures (96.3%), however after discharge, all (100%) practiced social distancing and infection prevention. Twenty patients (80%) considered changing their lifestyles, and 19 (79.2%) decided to use sick leave when they felt ill; these trends were more prominent during the second wave. Six patients (23.1%) reported experiencing discrimination or harassment after discharge. While most patients with COVID-19 had a strong fear of infection before hospitalization, their views about health and health behaviors changed after hospitalization.

Abstract Background We have shown that phospholipase Cε (PLCε), an effector of Ras and Rap1 small GTPases, plays pivotal roles in inflammation and inflammation-associated carcinogenesis by augmenting proinflammatory cytokine production from epithelial cells of various organs. The purpose of this study is to analyze its role in neutrophilic alveolar inflammation accompanying acute lung injury (ALI), focusing on that in alveolar epithelial cells (AECs), which are known to make a major contribution to the pathogenesis of ALI. Methods We examine the effect of the PLCε genotypes on the development of ALI induced by intratracheal administration of lipopolysaccharide (LPS) to PLCε wild-type (PLCε +/+ ) and knockout (PLCε ΔX/ΔX ) mice. Pathogenesis of ALI is analyzed by histological examination of lung inflammation and measurements of the levels of various cytokines, in particular neutrophil-attracting chemokines such as Cxcl5, by quantitative reverse transcription-polymerase chain reaction and immunostaining. Primary cultures of AECs, established from PLCε +/+ and PLCε ΔX/ΔX mice, are used to analyze the roles of PLCε, protein kinase D (PKD) and nuclear factor-κB (NF-κB) in augmentation of LPS-induced Cxcl5 expression. Results Compared to PLCε +/+ mice, PLCε ΔX/ΔX mice exhibit marked alleviation of lung inflammation as shown by great reduction in lung wet/dry weight ratios, accumulation of inflammatory cells in the alveolar space and thickening of alveolar walls as well as the number of neutrophils and the protein concentration in bronchoalveolar lavage fluid. Also, LPS-induced expression of the CXC family of chemokines, in particular Cxcl5, is substantially diminished in the total lung and AECs of PLCε ΔX/ΔX mice. Moreover, LPS-induced Cxcl5 expression in primary cultured AECs is markedly suppressed on the PLCε ΔX/ΔX background (p

Lung cancer is a leading cause of cancer-related death, and patients with lung cancer are a priority group for influenza vaccination. However, few studies have assessed the immunogenicity of the influenza vaccine in these patients. Here, we performed a prospective study to evaluate the immunogenicity of the influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy. Twenty-five patients with lung cancer undergoing anticancer chemotherapy and 26 patients with chronic obstructive pulmonary disease (COPD) as controls were enrolled. A trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012 was administered as a single subcutaneous injection. Serum samples were collected before vaccination, and at 4–6 weeks after vaccination. Levels of serum antibody to hemagglutinin were measured. Among patients with lung cancer, the seroprotection rate (postvaccination titer > 1:40) was 84% for both A(H1N1) and A(H3N2), similar to the levels observed in patients with COPD. However, the seroprotection rate for the B strain was significantly lower in patients with lung cancer than in patients with COPD (64% versus 92%). Even after adjustment for potential confounders, patients with lung cancer had a significantly lower odds ratio for seroprotection against the B strain than patients with COPD. Moreover, in patients with lung cancer, those receiving the platinum doublet treatment tended to exhibit a lower seroprotection rate than those receiving a single agent. Thus, patients with lung cancer undergoing anticancer chemotherapy showed acceptable immune responses to a trivalent influenza vaccine, supporting the recommendation for annual influenza vaccination in these patients.

Smoking causes various diseases and is a major public health threat worldwide. Therefore, promoting smoking cessation is the most important intervention contributing to maintaining the health of smokers and nonsmokers and saving enormous financial expense. We reviewed existing and emerging smoking-cessation pharmacotherapies from the Cochrane Database of Systemic Reviews, PubMed, Ovid, and ClinicalTrials.gov databases. A literature review revealed that bupropion may be appropriate for patients interested in reducing smoking who dislike, or who have failed, nicotine-replacement therapy (NRT). Additionally, varenicline and NRT are efficacious first-line smoking cessation treatments and should be given to all individuals unless contraindicated. The reviews of this paper are available via the supplementary material section.

BACKGROUND:Sphingosine kinase phosphorylates sphingosine to generate sphingosine 1 phosphate (S1P) following stimulation of the five plasma membrane G-protein-coupled receptors. The objective of this study is to clarify the role of S1P and its receptors (S1PRs), especially S1PR3 in airway epithelial cells. METHODS:The effects of S1P on asthma-related genes expression were examined with the human bronchial epithelial cells BEAS-2B and Calu-3 using a transcriptome analysis and siRNA of S1PRs. To clarify the role of CCL20 in the airway inflammation, BALB/c mice were immunized with ovalbumin (OVA) and subsequently challenged with an OVA-containing aerosol to induce asthma with or without intraperitoneal administration of anti-CCL20. Finally, the anti-inflammatory effect of VPC 23019, S1PR1/3 antagonist, in the OVA-induced asthma was examined. RESULTS:S1P induced the expression of some asthma-related genes, such as ADRB2, PTGER4, and CCL20, in the bronchial epithelial cells. The knock-down of SIPR3 suppressed the expression of S1P-inducing CCL20. Anti-CCL20 antibody significantly attenuated the eosinophil numbers in the bronchoalveolar lavage fluid (P

Nivolumab improves the survival of advanced non-small cell lung cancer (NSCLC), but a significant number of patients still fail to benefit from this treatment. In this study, we evaluated the efficacy of the time-series behavior of neutrophil-to-lymphocyte ratio (NLR) in a complete blood count from advanced NSCLC patients as a predictive marker of the anticancer effect of nivolumab.We performed a retrospective review of medical records and collected data on patients with advanced NSCLC treated with nivolumab as second- and further-line treatments from December 2015 to March 2017. The NLRs were calculated before each treatment cycle for four cycles. These parameters were tested for its association with the overall survival (OS), progression-free survival (PFS) and time to treatment failure (TTF).Nineteen patients were treated with nivolumab. Stratified by the response to nivolumab, the median OS was 2.8 months in progressive disease (PD) and 14.0 months in non-PD (p = 0.002). Before discontinuation of PD or toxicity, an NLR is rising from baseline in 5 out of 7 patients with PD and all of 4 patients with discontinuation due to toxicity. Patients with an >30% increase in NLR were associated with a significantly shorter TTF compared with those with stable or decrease in NLR both after first cycle (p = 0.014) and second cycle (p < 0.001).The NLR is suggested to be useful not only as a prognostic marker but also as a predictive marker for treatment with nivolumab. Further prospective study is warranted to develop a predictive algorithm to detect PD cases as early as possible by focusing the time-series behavior of NLR.

Extracellular vesicles (EVs) are circulating vesicles secreted by various cell types. EVs are classified into three groups according to size, structural components, and generation process of vesicles: exosomes, microvesicles, and apoptotic bodies. Recently, EVs have been considered to be crucial for cell-to-cell communications and homeostasis because they contain intracellular proteins and nucleic acids. Epithelial cells from mice suffering from bronchial asthma (BA) secrete more EVs and suppress inflammation-induced EV production. Moreover, microarray analyses of bronchoalveolar lavage fluid have revealed that several microRNAs are useful novel biomarkers of BA. Mesenchymal stromal cell-derived EVs are possible candidates of novel BA therapy. In this review, we highlight the biologic roles of EVs in BA and review novel EV-targeted therapy to help understanding by clinicians and biologists.

A 73-year-old Japanese man was histologically diagnosed with lung adenocarcinoma harboring an exon 19 deletion in the epidermal growth factor receptor. The patient was treated with gefitinib for 6 weeks until he developed substantially elevated hepatic enzyme levels that resulted in the discontinuation of gefitinib. Gefitinib was reintroduced with an intermittent treatment schedule after the transaminase levels normalized, but the patient's enzyme levels rose again, and the cancer progressed. Gefitinib was eventually replaced with erlotinib. There was stable disease for 7 weeks without any signs of liver toxicity. Thus, erlotinib may be a beneficial and well-tolerated treatment option for patients with gefitinib-related hepatotoxicity.