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This is the first report describing primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with the high expression of IgG4. The histological findings were compatible with the diagnostic criteria for MALT lymphoma and IgG4-related respiratory disease (IgG4-RRD). An unfixed sample for Southern blotting was not obtained since computed tomography findings showed multiple lung cysts, which is rare in patients with MALT lymphoma. However, polymerase chain reaction using paraffin sections showed the clonality of the immunoglobulin heavy chain variable region gene rearrangement, confirming a diagnosis of MALT lymphoma. This is an instructive case in which primary pulmonary MALT lymphoma was histologically compatible with IgG4-RRD.

Pulmonary alveolar proteinosis (PAP) is a rare disorder in which lipoproteinaceous materials accumulate in the alveolar compartments. A 72-year-old man was diagnosed with autoimmune PAP with severe respiratory failure. We decided to perform segmental lung lavage (SLL) with fiberoptic bronchoscopy under general anesthesia. If improvement was not significant, whole-lung lavage (WLL) would be done. SLL improved the respiratory failure and computed tomography findings. This case showed improvement in not only the area where lavage was done but also the non-lavaged area. SLL with fiberoptic bronchoscopy under general anesthesia might be an appropriate treatment option for patients with severe PAP.

Background Mesenchymal stromal cells (MSCs) are a potential therapeutic tool for pulmonary fibrosis. However, ex vivo MSC expansion using serum poses risks of harmful immune responses or unknown pathogen infections in the recipients. Therefore, MSCs cultured in serum-free media (SF-MSCs) are ideal for clinical settings; however, their efficacy in pulmonary fibrosis is unknown. Here, we investigated the effects of SF-MSCs on bleomycin-induced pulmonary inflammation and fibrosis compared to those of MSCs cultured in serum-containing media (S-MSCs). Methods SF-MSCs and S-MSCs were characterized in vitro using RNA sequence analysis. The in vivo kinetics and efficacy of SF-MSC therapy were investigated using a murine model of bleomycin-induced pulmonary fibrosis. For normally distributed data, Student’s t test and one-way repeated measures analysis of variance followed by post hoc Tukey’s test were used for comparison between two groups and multiple groups, respectively. For non-normally distributed data, Kruskal–Wallis and Mann–Whitney U tests were used for comparison between groups, using e Bonferroni’s correction for multiple comparisons. All tests were two-sided, and P Results Serum-free media promoted human bone marrow-derived MSC expansion and improved lung engraftment of intravenously administered MSCs in recipient mice. SF-MSCs inhibited the reduction in serum transforming growth factor-β1 and the increase of interleukin-6 in both the serum and the bronchoalveolar lavage fluid during bleomycin-induced pulmonary fibrosis. SF-MSC administration increased the numbers of regulatory T cells (Tregs) in the blood and lungs more strongly than in S-MSC administration. Furthermore, SF-MSCs demonstrated enhanced antifibrotic effects on bleomycin-induced pulmonary fibrosis, which were diminished by antibody-mediated Treg depletion. Conclusions SF-MSCs significantly suppressed BLM-induced pulmonary inflammation and fibrosis through enhanced induction of Tregs into the lungs and corrected the dysregulated cytokine balance. Therefore, SF-MSCs could be a useful tool for preventing pulmonary fibrosis progression without the demerits of serum use.

Cytotoxic chemotherapy-induced lung injury is a fatal complication in patients with lung cancer and interstitial lung disease (ILD). We aimed to evaluate the association between hyperglycemia and this form of lung injury in patients with lung cancer concomitant with ILD. From 1147 patients with advanced lung cancer, we retrospectively enrolled 98 patients with ILD whose hemoglobin A1c (HbA1c) levels were measured, and investigated the association between HbA1c levels and cytotoxic chemotherapy-induced lung injury. In 73 patients whose serum samples were retained, we measured serum levels of advanced glycation end products (AGE) and assessed the association of AGE levels with HbA1c levels and cytotoxic chemotherapy-induced lung injury. The incidence of cytotoxic chemotherapy-induced lung injury was significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels

Background/aim The significance of epidermal growth factor receptor (EGFR) mutation in untreated patients with non-small cell lung cancer (NSCLC) remains uncertain. We aimed to determine the significance of EGFR mutation in patients who received best supportive care (BSC) alone, and compare the outcomes of only EGFR- tyrosine kinase inhibitors (TKI)-treated vs. BSC patients. Patients and methods Between April 1991-August 2018, 1,197 patients diagnosed with unresectable NSCLC at our institutions were enrolled in the study. Results Among 226 patients who underwent EGFR mutation analysis and received BSC alone, 35 and 191 did and did not harbor the mutation, and the median survival times (MST) did not differ significantly between these groups. A comparison of only EGFR-TKI-treated and BSC patients with EGFR mutation revealed that the former had a three times longer MST than the latter. Conclusion Our results may help explain the benefit of EGFR-TKI for patients who would be directed towards BSC.

Vocal cord dysfunction (VCD) often coexists with asthma and exacerbates respiratory symptoms. A noninvasive method could be considered beneficial for the detection and follow-up of VCD complicated by asthma. Here, we report a case of VCD complicated by asthma, highlighting the effectiveness of colored three-dimensional (3-D) imaging of respiratory impedance using a broadband frequency forced oscillation technique (MostGraph).A 74-year-old woman with difficult-to-treat asthma, in whom mepolizumab treatment was ineffective, was referred to our hospital. Stridulous sounds were loudest over the anterior neck. Pulmonary function tests' results were normal; however, a flattening of the inspiratory flow-volume curve was detected.Remarkably, prominent spikes were observed in the inspiratory phase in the colored 3-D imaging of respiratory resistance, which was superimposed on increased respiratory resistance in the expiratory phase. Flexible laryngoscopy revealed the adduction of vocal cords on inspiration. The patient was diagnosed with asthma complicated by VCD. After successful treatment of VCD by speech therapy, inspiratory spikes of respiratory resistance disappeared, and normal vocal cord movement was observed on laryngoscopy.The present case report indicates the effectiveness of forced oscillometry in evaluating dynamic changes in respiratory resistance for detecting and monitoring VCD complicated by asthma.

Background No study has yet investigated the incidence of chemotherapy-induced acute exacerbation of interstitial pneumonia (AE-IP) in patients with autoantibody-positive IP and lung cancer. Herein, we retrospectively compared the incidence of chemotherapy-induced AE-IP in patients with lung cancer between those with autoantibody-positive and -negative IP. Patients and methods Between October 2003 and December 2018, patients with lung cancer who received chemotherapy, underwent serological test of antinuclear antibody or rheumatoid factor, and were diagnosed with IP were enrolled. Results A total of 81 patients were enrolled; autoantibody-positive cases were observed in 23.5%. Autoantibody positivity was an independent risk factor for chemotherapy-induced AE-IP at 6 months after initiation of chemotherapy for lung cancer. The time to onset of AE-IP was significantly shorter in autoantibody-positive patients than in the seronegative patients. Conclusion Chemotherapy-induced AE-IP developed earlier in patients with autoantibody than in those without. Therefore, the potential development of AE-IP in autoantibody-positive patients warrants monitoring.

Drug-induced immune hemolytic anemia (DIIHA) is a rare condition with an increasing incidence associated with the frequent use of certain drugs. An 85-year-old woman with lung adenocarcinoma prescribed alectinib complained of dyspnea on exertion at our hospital. Based on her laboratory tests results on admission, we focused on the clinical course of anemia and hemolysis progression after alectinib administration. The patient's anemia and hemolysis gradually improved after discontinuation of alectinib, leading to a diagnosis of alectinib-induced IHA, presented here as the first case encountered in a patient with lung adenocarcinoma. Furthermore, we discuss the importance of correlating clinical laboratory findings in DIIHA.

Pulmonary lymphangitic carcinomatosis is one rare pattern of pulmonary metastases in advanced cancers. Gastric cancer is one of the most common forms of cancer that causes pulmonary lymphangitic carcinomatosis. However, recurrent gastric cancer presenting as pulmonary lymphangitic carcinomatosis after surgery is extremely rare. Furthermore, recurrence is usually observed within 5 years. We present the first case of pulmonary lymphangitic carcinomatosis in a patient with recurrent gastric cancer, 19 years after resection. In patients with a history of gastric cancer and the presence of interstitial shadow, pulmonary lymphangitic carcinomatosis should be considered in the differential diagnosis even if several years have passed since surgery.

The incidence of central nervous system metastasis is known to be high among patients with lung cancer. The frequency of brain metastasis and carcinomatous meningitis during the entire clinical course of non-small cell lung cancer is reported to be about 40% and 5%, respectively. In contrast, the incidence of cranial nerve metastasis is extremely rare, and detailed reports of its clinical course remain limited. Herein, we report 2 patients diagnosed with cranial nerve metastasis of lung adenocarcinoma and treated with radiotherapy and systemic chemotherapy. Both patients had cranial nerve symptoms, and brain magnetic resonance imaging showed cranial nerve enhancement. However, no evidence of carcinomatous meningitis was noted on magnetic resonance imaging and cerebrospinal fluid cytology. Based on these observations, these patients were diagnosed with cranial nerve metastasis of lung adenocarcinoma. Radiotherapy and chemotherapy were performed in both cases. In both cases, neurological symptoms had not worsened and imaging findings did not indicate any deteriorations. Therefore, radiotherapy and systemic chemotherapy should be considered when treating cranial nerve metastasis of lung adenocarcinoma. Early therapeutic intervention may lead to attenuation of the cranial nerve dysfunction resulting from cranial nerve metastasis.

The standard treatment for locally advanced non‐small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by anti‐programmed cell death‐ligand 1 (anti‐PD‐L1) treatment. BIM deletion polymorphism induces the suppression of apoptosis resulting from epidermal growth factor (EGFR)‐tyrosine kinase inhibitors in EGFR‐mutated NSCLC patients. We aimed to examine the effects of BIM polymorphism on CRT and anti‐PD‐L1/PD‐1 treatment in NSCLC patients. In this retrospective study of 1312 patients with unresectable NSCLC treated at Higashi‐Hiroshima Medical Center and Hiroshima University Hospital between April 1994 and October 2019, we enrolled those who underwent CRT or chemotherapy using carboplatin + paclitaxel or cisplatin + vinorelbine, or anti‐PD‐L1/PD‐1 treatment. Of 1312 patients, 88, 80, and 74 underwent CRT, chemotherapy, and anti‐PD‐L1/PD‐1 treatment, respectively, and 17.0%, 15.2% and 17.6% of these patients showed BIM polymorphism. Among patients receiving CRT, the progression‐free survival was significantly shorter in those with BIM deletion than in those without. In the multivariate analyses, BIM polymorphism was an independent factor of poor anti‐tumor effects. These results were not observed in the chemotherapy and anti‐PD‐L1/PD‐1 treatment groups. In in vitro experiments, BIM expression suppression using small interfering RNA in NSCLC cell lines showed a significantly suppressed anti‐tumor effect and apoptosis after irradiation but not chemotherapy. In conclusion, we showed that BIM polymorphism was a poor‐predictive factor for anti‐tumor effects in NSCLC patients who underwent CRT, specifically radiotherapy. In the implementation of CRT in patients with BIM polymorphism, we should consider subsequent treatment, keeping in mind that CRT may be insufficient., We showed that progression‐free survival and overall survival durations were significantly shorter in the CRT‐treated NSCLC patients with BIM polymorphism than in those without. Our findings indicate that BIM polymorphism is associated with the efficacy of radiotherapy but not chemotherapy in patients with CRT.

Background To best employ radium‐223 dichloride (Ra‐223) for patients with castration‐resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone‐predominant status in patients treated with Ra‐223. Methods We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra‐223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra‐223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression‐free survival (PFS). Results During the median follow‐up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P 1 (HR 1.74, 95% CI 1.04‐2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02‐2.50, P = .043), and PSA doubling time (PSADT) of, We developed the risk assessment based on the types of dynamic changes of bone metastasis before the use of radium‐223 dichloride (Ra‐223). This risk assessment can be used to maximize the clinical benefits of Ra‐223 treatment for bone‐predominant metastasis.

Background The endogenous secretory receptor for advanced glycation end products (esRAGE) is a soluble isoform produced by alternative splicing of the RAGE gene. The isoform has anti-inflammatory properties due to its inhibition of the RAGE/ligand interaction and is reduced in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the association of esRAGE serum and bronchoalveolar lavage fluid (BALF) levels with progression of IPF. Methods This study included 79 IPF patients and 90 healthy controls. IPF and control serum esRAGE levels were compared, and the correlation between serum and BALF esRAGE levels was analyzed in 57 IPF patient samples. We also investigated the relationship of esRAGE serum and BALF levels with prognoses and lung function parameters in patients with IPF. Results Serum esRAGE levels in IPF patients were significantly lower than those in healthy controls (162.0 ± 102.4 ng/ml and 200.7 ± 107.3 ng/ml, p = 0.009), although the baseline characteristics of age and smoking history were not matched. Serum levels of esRAGE were correlated with BALF esRAGE levels (rs = 0.317). The BALF esRAGE levels were also correlated with diffusion capacity for carbon monoxide (rs = 0.406). A Kaplan-Meier curve analysis and univariate/multivariate Cox hazard proportion analysis revealed that lower levels of esRAGE in blood and BALF were significantly associated with poorer prognoses in patients with IPF. Conclusions Decreased esRAGE levels in BALF and blood were associated with poor prognoses in patients with IPF. These results suggest that esRAGE could be related to the pathophysiology of IPF and serum esRAGE could be a potential prognostic marker of IPF.

Background Bronchoalveolar lavage (BAL) is one of the fundamental examinations for the differential diagnosis of interstitial lung diseases (ILDs), and lymphocytosis strongly indicates alternative diagnoses rather than idiopathic pulmonary fibrosis. However, the BALF lymphocytosis is observed in several ILDs. We considered that quantitative evaluation of the BALF lymphocyte nuclear morphology would be useful in the differential diagnosis of ILDs with increased BALF lymphocyte fraction. Results One hundred and twenty-one patients with ILDs having increased BALF lymphocyte fraction were recruited (68 in the development cohort and 53 in the validation cohort). In the development cohort, BALF lymphocyte nuclei in sarcoidosis patients showed significantly smaller areas, shorter perimeters, lower radius ratios, and increased roundness than those of other ILD patients (p Conclusion This study is the first to demonstrate the usefulness of quantitative parameters of BALF lymphocyte nuclear morphology as novel biomarkers for sarcoidosis.

The safety and efficacy of anti-programmed cell death-1 (PD-1) antibodies in patients with granulomatosis with polyangiitis (GPA) still remain unclear. An 83-year-old man with GPA that was well controlled with immunosuppressive therapy was diagnosed with a postoperative recurrence of non-small cell lung cancer (NSCLC). Because the programmed cell death ligand 1 (PD-L1) tumor proportion score was 90%, pembrolizumab was administered. After 10 cycles, immune-related adverse events or GPA flare was not observed, and the patient showed an antitumor response. Anti-PD-1 antibody should therefore be considered a treatment option for PD-L1-high-expressing NSCLC patients with well-controlled GPA.

Approximately 5% of non-small cell lung cancer (NSCLC) patients develop immune checkpoint inhibitor (ICI)-induced interstitial lung disease (ICI-ILD), 10% of whom die. However, there are no established risk factors for its occurrence. Interstitial lung abnormalities (ILA) are areas of increased lung density on lung computed tomography (CT) in individuals with no known ILD. This study retrospectively investigated whether any patient characteristics, including ILA, were risk factors for ICI-ILD in patients with NSCLC.NSCLC patients who received anti-programmed death (PD)-1 antibody treatment at our hospital between September 2015 and December 2017 were enrolled. Information on patient characteristics before anti-PD-1 antibody administration, including chest CT findings and laboratory data, were obtained.Among 83 enrolled patients, the incidence of ICI-ILD was 16.9% (14/83). All ICI-ILD cases developed by the third line of treatment. The incidence of ICI-ILD was significantly higher in patients with pre-existing ILA than that in those without (p = 0.007). Furthermore, patients with ground glass attenuation (GGA) in ILA had a higher incidence of ICI-ILD than that in those without (p0.001). In univariate logistic analysis, ILA were significant risk factors for ICI-ILD (p = 0.005). Multivariate logistic analysis revealed that only GGA in ILA was a significant risk factor for ICI-ILD (p0.001).Pre-existing ILA are risk factors for ICI-ILD and GGA in ILA is an independent risk factor for ICI-ILD. Therefore, we should be more aware of the development of ICI-ILD in patients with ILA, especially those with GGA.

Background and purpose Patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies frequently experience complications of interstitial pneumonia (ARS-IP), and the computed tomography (CT) of ARS-IP frequently shows nonspecific interstitial pneumonia (NSIP) pattern. The CT pattern of ARS-IP might be different from that of idiopathic IP. However, the clinical differences in patients with ARS-IP and idiopathic IP showing the similar CT patterns have not yet been well studied. The objective of this study was to evaluate the clinical differences between patients with ARS-NSIP and idiopathic NSIP (I–NSIP). Methods Two groups of 34 patients each, with ARS-NSIP and I–NSIP, who visited Hiroshima University Hospital between January 2005 and December 2017, were enrolled. Clinical features and outcomes were retrospectively compared between the two groups. Results The ARS-NSIP group included more female patients and significantly younger patients than the I–NSIP group. The percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) was significantly higher, and the CD4/CD8 ratio in BALF was significantly lower in the ARS-NSIP group compared with the I–NSIP group. The proportion of patients with traction bronchiectasis detected by CT was significantly higher in I–NSIP compared with ARS-NSIP. The number of patients who received corticosteroid and/or immunosuppressant therapy was significantly larger in the ARS-NSIP group than in the I–NSIP group. In addition, the patients in the I–NSIP group who underwent the immunosuppressive therapy demonstrated shorter survival than those who underwent no treatment; this tendency was not observed in the ARS-NSIP group. The 10-year survival rate of patients in the ARS-NSIP group was significantly higher than that of patients in the I–NSIP group (91.8% vs. 43.0%; log-rank, p = 0.012). The multivariate survival analysis revealed that positive anti-ARS antibody was an independent favorable prognostic factor in the patients with NSIP (OR, [95% CI]:0.12 [0.02–0.55], p = 0.013). Conclusions Patients with ARS-NSIP had a significantly better prognosis than those with I–NSIP; this may be associated with the sensitivity to immunosuppressive therapies, and the different findings of BALF and HRCT between the two groups.

Plasminogen activator inhibitor‐1 (PAI‐1) promotes pulmonary fibrosis through increasing myofibroblast (MF) characteristics, expressing alpha‐smooth muscle actin (α‐SMA) in fibroblasts. Fibroblasts in the tumour stroma are called cancer‐associated fibroblasts (CAFs). Some CAFs have MF characteristics and substantially promote tumour progression and chemotherapy resistance. This study determined whether inhibition of PAI‐1 suppressed MF characteristics of CAFs and limited chemotherapy resistance in lung cancer. To investigate cellular PAI‐1 expression and its correlation with α‐SMA expression of CAFs, 34 patients’ paraffin‐embedded lung adenocarcinoma tissue sections were immunohistochemically stained for PAI‐1 and α‐SMA. Immunohistochemical analysis of lung adenocarcinoma tissues showed that PAI‐1 expression was correlated with that of α‐SMA (r = 0.71, p

Platinum doublet is the standard chemotherapy regimen for unresectable nonsmall-cell lung cancer (NSCLC) without a driver mutation. However, for squamous cell lung cancer, the most effective cytotoxic regimen is not yet established. Combination therapy of gemcitabine with a platinum agent is a highly effective treatment among the platinum doublet regimens and is promising as a treatment for advanced squamous cell lung carcinoma. In this study, we prospectively evaluated the efficacy of gemcitabine + platinum combination therapy followed by maintenance gemcitabine monotherapy in untreated advanced squamous cell lung cancer. Patients with squamous cell lung cancer received four cycles of gemcitabine + platinum combination therapy every 3 or 4 weeks. After the induction therapy, gemcitabine maintenance therapy was administered every 3 or 4 weeks until disease progression or unacceptable toxicity. Of 18 patients enrolled, the median progression-free survival was 3.9 months. Only six patients received maintenance chemotherapy with gemcitabine. The median survival time of all enrolled patients was 18.1 months. Cytopenia of any grade occurred in at least 70% of the enrolled patients. However, severe adverse events were observed in only a few cases. Gemcitabine maintenance therapy after gemcitabine plus platinum agents is a suggested treatment for unresectable squamous cell lung cancer. While the overall toxicity profile of this therapy is acceptable, attention should be paid to bone marrow suppression.

Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29–11.70] ng/mL vs. 3.55 [2.07–5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.

Fine crackles are frequently heard in patients with interstitial lung diseases (ILDs) and are known as the sensitive indicator for ILDs, although the objective method for analyzing respiratory sounds including fine crackles is not clinically available. We have previously developed a machine-learning-based algorithm which can promptly analyze and quantify the respiratory sounds including fine crackles. In the present proof-of-concept study, we assessed the usefulness of fine crackles quantified by this algorithm in the diagnosis of ILDs. We evaluated the fine crackles quantitative values (FCQVs) in 60 participants who underwent high-resolution computed tomography (HRCT) and chest X-ray in our hospital. Right and left lung fields were evaluated separately. In sixty-seven lung fields with ILDs in HRCT, the mean FCQVs (0.121 ± 0.090) were significantly higher than those in the lung fields without ILDs (0.032 ± 0.023, P

Introduction: Microbiome imbalance could be associated with the occurrence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). Aims: To investigate the association between oral bacterial flora and the occurrence of AE-IPF. Methods: We have prospectively collected 142 patients with IPF, 264 healthy subjects and 31 patients with bacterial pneumonia. Baseline serum antibody levels against 17 bacteria were measured by ELISA. The correlations between these values and the occurrence of AE-IPF were evaluated. An imbalance in the number of bacteria was defined as the number of pathogenic bacteria minus that of inhibitory bacteria. Results: We have identified 7 bacteria potentially promoting AE-IPF (Porphyromonas type I, III, IV, V, Helicobacter, Campylobacter, and Tannerella) and 3 bacteria potentially inhibiting AE-IPF (Prevotella, Fusobacterium, and Aggregatibacter). The baseline number of pathogenic bacteria was increased in patients with AE-IPF compared with those without AE-IPF (4.1±2.3 vs 2.9±2.4, p=0.0049), whereas the number of inhibitory bacteria was decreased (1.1±1.1 vs 1.6±1.1, p=0.007). The imbalance in the number of bacteria was increased in patients with AE-IPF (3.0±2.2 vs 1.3±2.2, p Conclusions: The imbalance of pathogenic and inhibitory bacteria was associated with the occurrence of AE-IPF.

Several interstitial lung diseases (ILDs) including hypersensitivity pneumonia (HP), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), collagen vascular disease-related ILD (CVD-ILD), drug-induced ILD (DILD) and sarcoidosis shows increase of lymphocyte fraction in bronchoalveolar lavage fluid (BALF). We performed the morphometric analysis in order to differentiate the BALF lymphocyte nuclear shape between sarcoidosis and the other ILDs. We recruited 68 patients with ILDs (16 of CHP, 5 of NSIP, 5 of COP, 10 of CVD-ILD, 14 of DILD and 18 of sarcoidosis) who showed 20% or more of lymphocyte fraction in BALF and measured the area, perimeter, radius ratio and roundness of the BALF lymphocyte nuclear by using the commercially available image analyzing software. As a result, among those with sarcoidosis, lymphocyte nuclear area was significantly smaller (p Based on these findings, we consider that the fraction of srLYM in BALF can be useful for the differential diagnosis of ILDs.

Background: Postoperative acute exacerbation of interstitial lung disease (AE-ILD) is a fatal complication in patients with lung cancer and ILD, and it needs to be overcome to improve the long-term outcomes of these patients. However, the molecular target for predicting and preventing this fatal complication remains unclear. High-mobility group box 1 (HMGB1), which is reported to increase due to surgical procedure, activates a pro-inflammatory response associated with acute lung injury. This study aimed to elucidate the association between postoperative AE-ILD and circulatory HMGB1, especially focusing on its predictive potential. Methods: This study included 152 patients with lung cancer and ILD, who underwent radical surgery between January 2011 and August 2019. We measured HMGB1 serum levels, and investigated the factors affecting HMGB1 and the predictive potential of HMGB1 for postoperative AE-ILD.Results: Postoperative AE-ILD was developed in 17 (11.2%) of 152 patients with lung cancer and ILD. HMGB1 serum levels in patients with AE-ILD were significantly higher than those in patients without (median [IQR]: 5.39 [3.29-11.70] ng/mL vs 3.55 [2.07-5.62] ng/mL). Logistic regression analysis revealed that HMGB1 higher levels and longer operative time was independently associated with a higher incidence of postoperative AE-ILD. Furthermore, when HMGB1 and operative time were incorporated into previously reported risk scoring system, the concordance index was 0.876 which is statistically higher than 0.715 calculated by reported scoring system only.Conclusions: Baseline levels of serum HMGB1 could be a promising biomarker for predicting postoperative AE-ILD, especially when combined with operative time. HMGB1 may be a molecular target of this fatal complication to be overcome.

The urinary antigen test (UAT) is a rapid diagnostic method for pneumococcal pneumonia, but the high false-negative rate of 30% may affect its reliability. To maximize the utility of UAT, it is necessary to investigate the patient factors affecting UAT results. However, there is no report elucidating the association between its utility and pre-existing lung abnormalities. We retrospectively reviewed 388 patients with pneumococcal pneumonia confirmed by blood and/or sputum culture tests. Finally, 94 of 388 patients who had the results of UAT and computed tomography scans were enrolled to evaluate the association between the utility of UAT and patient factors including pulmonary emphysema and fibrosis. The overall positive rate of UAT was 69.1%. The positive rates of UAT in the patients with emphysema were significantly lower than those in individuals without emphysema (33.3% and 77.6%, p

Background Pembrolizumab is recommended as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) and a Programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥50% without driver mutations. However, the safety and efficacy were not investigated among patients who were ≥75 years old. Methods This open-label single-arm phase II study is designed to evaluate pembrolizumab as first-line therapy for patients who are ≥75 years old with advanced NSCLC and a PD-L1 TPS of ≥50% without driver mutations. The primary endpoint is progression-free survival, and the secondary endpoints are overall survival, objective response rate, safety, and quality of life. Recruitment started in October 2017 and is expected to continue for approximately 3 years. Conclusions Given the currently poor prognosis of elderly patients with advanced NSCLC, we hope that the findings of this study will facilitate more effective treatment in this setting.

Several prognostic factors for pleuroparenchymal fibroelastosis (PPFE) have recently been reported. However, detailed high-resolution computed tomography (HRCT) findings have not yet been evaluated as prognostic factors. This study retrospectively investigated whether HRCT findings are prognostic factors in patients with PPFE compared to those with idiopathic pulmonary fibrosis (IPF).Patients with PPFE and IPF diagnosed at our hospital between January 2008 and December 2016 were enrolled. Clinical and HRCT characteristics were obtained. In addition to our patients, we also analyzed data of PPFE patients whose cause of death had been identified in previous studies.We enrolled 15 patients with PPFE and 75 patients with IPF. Consolidation and maximum pleural thickening were significantly higher in patients with PPFE than in those with IPF (both P .001). Fibrosis score, honeycomb area, and traction bronchiectasis were not significantly different between these patient groups but were significant prognostic factors in patients with PPFE in univariate analysis (P = .021, P = .017, and P = .014, respectively). The proportions of deaths by acute exacerbation or lung cancer were significantly lower in patients with PPFE than in those with IPF (P .001 and P = .001, respectively), whereas death by respiratory failure was significantly more frequent in PPFE patients (P .001).HRCT findings, such as fibrosis score, honeycomb area, and traction bronchiectasis, were independent prognostic factors in patients with PPFE. Respiratory failure, but not acute exacerbation and lung cancer, was the main cause of death in patients with PPFE.

Laser light sources have being used in sensing and medical applications, and it is required for higher power, high efficiency, good beam quality and high reliability. We demonstrated single-mode CW 200mW red laser diodes with wavelength of 660nm, 675nm, and 690nm. These were fabricated from AlGaInP-based material with narrow stripe. These showed good temperature characteristics that the highest power reached 250mW upto 70°C and 200mW at 90°C for 660nm laser, exceeded 250mW upto 90°C for 675nm and 690nm lasers. Each characteristic temperature T0 was 112K, 169K, and 201K, respectively. The wall plug efficiency exceeded 32% at 25°C. The far field pattern showed Gaussian-like single transverse mode. Stable operation at high temperature was demonstrated in 1,500hours at 60°C, CW 200mW for 660nm laser and in 1,000hours at 100°C, CW 200mW for 675nm and 690nm lasers. CW 200mW operation is the world’s first in single-mode 660nm to 690nm laser diodes to the best of our knowledge. In the case of AlGaInPbased material, although longer wavelength is concerned degrading crystal quality in the active layer due to increasing lattice mismatch, no degradation observed the characteristics and the reliability. These red laser diodes will contribute to progress for sensing and medical applications.

INTRODUCTION Airway resistance and reactance, measured by forced oscillometry, are used to measure the airway obstruction in patients with asthma. OBJECTIVES This study aimed to investigate the oscillometric bronchodilator responses in treated and untreated asthma and evaluate its association with airway inflammation and disease duration. MATERIALS AND METHODS This study included 30 nonsmoking patients with mild to moderate treated asthma, 25 patients with newly diagnosed untreated asthma and 29 control subjects. Spirometric and oscillometric measurements were performed before and after inhalation of 400 µg salbutamol. Disease duration was defined as the number of years since asthma diagnosis. RESULTS At airway resistance of 5 Hz (R5) and 20 Hz (R20), bronchodilator responses in patients with untreated and treated asthma were greater than those in control subjects. In patients with untreated asthma, higher fractional exhaled nitric oxide concentration (FeNO) levels were strongly correlated with greater reversibility of R20 (rs = -0.621, P < 0.001). In patients with treated asthma, there was no significant association between FeNO and oscillometric reversibility, whereas longer disease duration was significantly associated with lesser bronchodilator response at R20 (rs = 0.441, P < 0.05). Treated asthma patients with longer disease duration (≥10 years) showed significantly higher post-bronchodilator R5 and R20 than the treated asthma patients with shorter disease duration (

The technology for restoring a damaged road system is critical for reaching victims and reconstructing damaged areas in large-scale natural disasters caused by earthquake and tsunami. Soil reinforcement technology with geocell materials can be useful in the above situation. This technology has been applied to road construction on soft soil ground, and its usefulness has been recognized. However, its reinforcement mechanism has not been investigated adequately. The current design method for geocell mattress under vertical load is based on classical pavement engineering and not on the actual mechanism of geocell reinforcement. Further technical investigation is required to achieve the rational design and construction of geocell mattress. The authors have developed a visualization technique for geocell mattress by using particle image velocimetry (PIV) analysis. The results obtained in the current stage are as follows: (1) mixing of colored sand with laboratory fill material is useful in visualizing the bearing capacity model test with PIV analysis. This paper proposes a method to determine the mixing ratio of two types of sand by conducting basic calibration tests. (2) This method can be used to visualize the behavior of soil confined by the geocell through a laboratory model test. This paper reports the results of the visualization.

Radiation-induced pulmonary fibrosis is a serious complication. Plasminogen activator inhibitor-1 (PAI-1) has been indicated to be a key factor in the progression of pulmonary fibrosis. In the present study, the effect of PAI-1 deficiency on radiation-induced pulmonary fibrosis was analyzed. Wild-type (WT) and PAI-1-deficient (PAI-1-/-) mice were treated with thoracic irradiation of 15 Gy to induce pulmonary fibrosis. Analyses of bronchoalveolar lavage (BAL) fluids were performed 0, 4, 12, 18, and 24 weeks after irradiation. The degree of pulmonary fibrosis was assessed according to the histology of lung tissues and hydroxyproline contents. The results demonstrated that the irradiation of WT mice increased PAI-1 expression in the lungs after 18 weeks and established lung fibrosis at 24 weeks. The number of total cells and transforming growth factor-β levels in BAL fluid were significantly lower at 24 weeks after irradiation in PAI-1-/- mice compared with WT mice. Furthermore, histological examination revealed that the extent of pulmonary fibrosis was attenuated in PAI-1-/- mice compared with that in WT mice. Hydroxyproline content was also significantly lower in PAI-1-/- mice compared with WT mice at 24 weeks after irradiation. In conclusion, PAI-1 serves an important role in the development of radiation-induced pulmonary fibrosis and may represent a novel therapeutic target for pulmonary fibrosis.

Severe leukopenia, thrombocytopenia, and bi-cytopenia due to nivolumab have been reported. In this report, we present the first case of nivolumab-induced severe pancytopenia in a patient with lung adenocarcinoma. A 56-year-old Japanese man with lung adenocarcinoma received nivolumab therapy as second-line treatment. After 3 cycles of this therapy, although computed tomography (CT) showed a reduced tumor size, laboratory findings revealed pancytopenia and a bone marrow biopsy showed a severely hypoplastic marrow. The pancytopenia was diagnosed as an adverse effect of nivolumab; filgrastim (75 μg/day), steroid-pulse therapy (intravenous methylprednisolone: 500 mg/day), and subsequently intravenous prednisolone (50 mg/day) were administered. Furthermore, intravenous administration of immunoglobulins was also performed. However, these treatments were ineffective. He was further diagnosed with fungal pneumonia and a catheter-related bloodstream infection. Anti-bacterial chemotherapy was administered. Two months after hospitalization, the neutrophil count improved to 1000/μL, but multiple red blood cell and platelet transfusions were needed. Therefore, further chemotherapy for lung adenocarcinoma could not be initiated, and the patient died due to progression of lung cancer 118 days after the onset of pancytopenia. The possibility of severe pancytopenia as an immune-related adverse event should be considered as a mandatory prerequisite for nivolumab therapy.

BackgroundA significant number of children with asthma show remission in adulthood. Although these adults are often diagnosed with COPD in later life, the effect of clinically remitted childhood asthma on the decline in lung function during adulthood is uncertain. We examined whether clinical remission of childhood asthma was associated with an accelerated decline in lung function in apparently nonasthmatic adults.Methods3584 participants (mean (range) age 48.1 (35–65) years) who did not have adulthood asthma and other lung diseases and had normal lung function at the baseline visit were included. They were categorised as those with remitted childhood asthma (n=121) and healthy controls (n=3463) according to their self-reported childhood asthma history. Spirometry was performed at baseline and follow-up visits.ResultsThe mean follow-up was 5.3 years. Multivariate regression analysis showed that remitted childhood asthma and smoking were independently associated with a rapid decline in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Smoking was an independent predictor of a rapid decline in FEV1/FVC. The annual decline in FEV1 and FVC was significantly greater in participants with remitted childhood asthma than in healthy controls, and the differences remained significant after adjusting for the propensity score.ConclusionsA history of clinically remitted childhood asthma is an independent risk factor for accelerated decline in lung function in adults. Remitted childhood asthma and smoking may additively accelerate the development of obstructive lung disease.

// Kakuhiro Yamaguchi 1 , Hiroshi Iwamoto 1 , Shinjiro Sakamoto 1 , Yasushi Horimasu 1 , Takeshi Masuda 1 , Shintaro Miyamoto 1 , Taku Nakashima 1 , Shinichiro Ohshimo 2 , Kazunori Fujitaka 1 , Hironobu Hamada 3 and Noboru Hattori 1 1 Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan 2 Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan 3 Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan Correspondence to: Hiroshi Iwamoto, email: iwamotohiroshig@gmail.com Keywords: AGER polymorphism, neutrophil-lymphocyte ratio, lung cancer, metastatic adenocarcinoma, disease susceptibility Received: April 25, 2017 Accepted: September 21, 2017 Published: October 10, 2017 ABSTRACT Background: The receptor for advanced glycation end-product (RAGE) is a multi-ligand receptor involved in inflammation. In the gene encoding RAGE ( AGER ), there are three well-known polymorphisms; rs2070600, rs1800624, and rs1800625, which potentially increase the risk of lung cancer. Remarkably, AGER rs2070600 polymorphism, which increases ligand-binding affinity, is a potential prognostic factor in non-small cell lung cancer, but the underlying mechanism is unclear. The neutrophil-lymphocyte ratio (NLR) reflects tumor-associated systemic inflammatory conditions; high ratios are associated with poor prognosis in multiple cancers. Additionally, some humoral factors via RAGE-signaling are associated with elevated NLR in cancer patients. Objectives: Associations of AGER polymorphisms with disease susceptibility, prognosis, and NLR were investigated in Japanese patients with lung adenocarcinoma. Methods: We included 189 patients with lung adenocarcinoma, 96 of which had distant metastases, and 303 healthy controls. The correlation between AGER polymorphisms (rs2070600, rs1800624, rs1800625) and disease susceptibility and factors elevating the mortality and NLR in patients with metastases were evaluated. Results: Only the minor allele of rs2070600 was associated with a higher NLR ( β = 0.209, p = 0.043) and a poor prognosis (Hazard ratio = 2.06, 95% Confidence interval = 1.09–3.77, p = 0.028) in patients with metastatic disease, independently of background characteristics, including EGFR mutation status. All three polymorphisms were not associated with the risk of lung adenocarcinoma. Conclusions: The AGER rs2070600 polymorphism was independently associated with systemic inflammation and poor prognosis in patients with metastatic lung adenocarcinoma.

Recently, sirolimus, an inhibitor of mammalian target of rapamycin, was reported to decrease chylous effusion in patients with lymphangioleimyomatosis (LAM). We herein report a case of a 34-year-old woman with LAM who developed refractory chylothorax and chylous ascites during sirolimus therapy. In this case, to reduce chylous effusion, we administered octreotide, which is often used to control postoperative chylous effusion, in addition to the sirolimus therapy. This combination therapy reduced the chylothorax and chylous ascites. For patients with LAM, octreotide therapy in addition to sirolimus may be effective for treating sirolimus-refractory chylous effusion.

Background and Objective: High mobility group box 1 (HMGB1) is known as a mediator of acute lung injury through the acceleration of pro-inflammatory signaling. Previous studies showed that HMGB1 is increased in the lung and circulation of patients with acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF). This study investigated the predictive value of circulatory HMGB1 for disease progression and prognosis of IPF in the stable phase and AE phase. Methods: Seventy-six patients with stable IPF, 17 patients with AE-IPF, and 74 healthy controls were included. Serum HMGB1 levels were compared among the three groups, and the associations of HMGB1 levels with lung function variables, the onset of AE, and prognosis were evaluated in patients with stable IPF. The prognostic value of HMGB1 was determined in AE-IPF. Results: Serum HMGB1 levels in patients with stable IPF were significantly higher than those in healthy controls; those in patients with AE-IPF were even higher when compared with levels in the other two groups (6.26 ± 16.77 ng/mL, 3.42 ± 2.69 ng/mL, and 19.20 ± 16.76 ng/mL, respectively). In patients with stable IPF, higher HMGB1 levels were associated with lower diffusion capacity for carbon monoxide (r= -0.248, p = 0.039) and earlier onset of AE (p = 0.030). In patients with AE-IPF, increased HMGB1 levels were associated with shorter survival (p= 0.001). Conclusions: Higher levels of serum HMGB1 predict earlier onset of AE in stable IPF and shorter survival in AE-IPF, indicating that HMGB1 is associated with acute deterioration of the disease.

Background: Chronic hypersensitivity pneumonitis (CHP) is characterized by lymphocytic inflammation and progressive fibrosis of the lung caused by a variety of inhaled antigens, and the prognosis of CHP patients is poor with the absence of established diagnosing criteria and effective therapeutic agent. Recently, we have founded that C-C motif chemokine ligand 15 (CCL15) mRNA highly expressed in CHP lung. Method: To investigate the usefulness of CCL15 as a clinical biomarker for CHP, CCL15 protein expression was investigated in lung tissue, serum and bronchoalveolar lavage fluid (BALF). Results: Immunohistochemistry investigations revealed high CCL15 expression in the lungs of CHP patients. Serum CCL15 levels in CHP patients (29.1 ± 2.1 μg/ml) were significantly higher than those in idiopathic pulmonary fibrosis patients (19.7 ± 1.3 μg/ml, p = 0.01) and in healthy subjects (19.5 ± 1.7 μg/ml, p = 0.003). When BALF CCL15 level was divided by BALF albumin level (BALF CCL15/Alb), it was significantly inversely correlated with forced vital capacity (β = -0.47, p = 0.0006), percentage of predicted carbon monoxide diffusion capacity of the lung (β = -0.41, p = 0.0048), and BALF lymphocyte count (β = -0.34, p = 0.01) in CHP patients. Multivariate Cox proportional hazards analysis revealed that high BALF CCL15/Alb and poor prognosis were statistically significantly independently correlated in CHP patients (HR = 1.1, 95% C.I. 1.03–1.18, p = 0.004). Conclusion: The results of the current study suggest that CCL15 may be a useful prognostic biomarker for CHP.

Introduction: Microbiome imbalance could be one of the risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). However, little is known about the role of the oral bacterial flora in AE-IPF. Aims: To investigate the significance of oral bacterial flora as a risk factor for AE-IPF. Methods: A total of 142 patients with IPF (77 German and 65 Japanese), 264 healthy subjects (164 German and 100 Japanese) and 31 Japanese patients with bacterial pneumonia were prospectively collected. Baseline serum levels of antibodies against 16 bacteria of the oral flora were measured by ELISA. The correlations between baseline serum levels of these antibodies and the incidence of AE-IPF were evaluated. Results: Baseline serum levels of Porphyromonas type III, IV, V, and Fusobacterium antibodies were significantly higher in the Japanese IPF patients compared with the other 4 groups (Japanese healthy, Japanese pneumonia, German healthy and German IPF). Baseline serum levels of several antibacterial antibodies (Porphyromonas type I, III, IV, V, Tannerella, and Campylobacter) were positively correlated with the occurrence of AE-IPF (AUC 0.554-0.608), whereas others (Aggregatibacter, Prevotella and Fusobcterium) were negatively correlated (AUC 0.400-0.441). Among them, the ratio of Tannerella to Aggregatibacter was significantly associated with the occurrence of AE-IPF (AUC 0.520-0.747, p=0.015). In the multivariate analysis, the ratio of Tannerella to Aggregatibacter > 0.72 and Japanese ethnicity were independent risk factors for AE-IPF (hazard ratio 2.23, p=0.03; 4.48, p=0.0002). Conclusions: An imbalance in the oral bacterial flora could be a risk factor for AE-IPF.

BACKGROUND/AIM In lung cancer (LC) patients, pre-existing interstitial lung disease (ILD) is a risk of chemotherapy-associated acute exacerbation of ILD (AE-ILD). AE-ILD shows a diverse clinical course varying from fatal respiratory failure to asymptomatic event, and the prognostic impact is still unclear. MATERIALS AND METHODS We retrospectively evaluated the association between the prognosis and AE-ILD in 86 LC patients with pre-existing ILD who were treated with cytotoxic chemotherapy, especially focusing on histological types of LC. RESULTS Thirty (34.9%) patients had AE-ILD, that was significantly associated with a poor prognosis in LC patients with ILD. When analyzed by histological types, a significant association of AE-ILD with shorter survival was observed only in the small cell LC (SCLC) group, but not in the non-small cell LC group. CONCLUSION The development of AE-ILD by cytotoxic chemotherapy is associated with poor prognosis in LC patients with ILD, especially in patients with SCLC.

Anti-programmed cell death receptor (PD)-1 antibody treatment results in better prognosis than standard chemotherapy in patients with non-small cell lung cancer (NSCLC), especially those with high PD-ligand 1 (PD-L1) expression. However, several studies have reported a lack of antitumor effect of PD-1 antibody, even in patients with high PD-L1 expression. Therefore, reliable predictors of treatment response are urgently needed. The albumin–globulin ratio (AGR) is associated with prognosis in several cancers. We aimed to determine whether AGR is a predictive biomarker of anti-PD-1 antibody response in patients with NSCLC. Seventy-four NSCLC patients treated with anti-PD-1 antibody were retrospectively enrolled. Patients with driver mutations were excluded. The mean AGR was significantly higher in the disease control (DC) group than in the progressive disease (PD) group (p

Laser light source projector becomes popular due to the features of high brightness, wide color gamut and long lifetime of laser light source. One of the key performances that the market continues to request is the higher output power from the single laser diode. To meet the market demand and accelerate the laser projector installation, we developed AlGaInP based 638nm 3.5W pulse / 2.4W CW red laser diode for projector light source. We designed new chip with dual emitters in one chip with each emitter width of 75μm. The chip was then assembled into diameter 9mm TO-CAN package. The highest power at high temperature achieved 45°C 3.9W, 55°C 3.1W under pulsed operation with frequency 120Hz duty 30%, in case of CW operation 45°C 3.0W, 55°C 2.1W. The wall plug efficiency (WPE) at 25°C was reached each 43% under pulsed operation and 42% under CW operation. As a result of life test at 20°C 3.5W 5,500hours under CW operation and 45°C 3.5W 1,500hours under pulsed operation with frequency 120Hz duty 35%, the estimated life was exceeded MTTF 20,000 hours under 45°C 3.5W pulsed operation. The 3.5W pulsed operation and WPE of 43% are the world’s highest in 638nm LD to the best of our knowledge. This newly developed LD is suitable for red light source for projector.

The use of trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis pneumonia (PcP) prophylaxis is often discontinued owing to adverse drug reactions. Half-dosage of TMP-SMX (40/200 mg daily) is considered more tolerable than the conventional dosage (80/400 mg daily). However, patient background characteristics that are associated with the discontinuation of TMP-SMX prophylaxis and suitable for reduced dosage remain unclear. In this study, we aimed to identify the risk factors for the discontinuation of and efficacy of different doses of TMP-SMX prophylaxis in patients with creatinine clearance higher than 30 mL/min.We retrospectively evaluated 318 immunocompromised non-human immunodeficiency virus (HIV)-infected patients (194 men and 124 women; median age, 68.5 [interquartile range, 59-75] years) who underwent TMP-SMX therapy as a primary PcP prophylaxis between July 2014 and August 2019. The patients were segregated into two groups on the basis of dosage: single-strength (SS; n = 244) and half-strength (HS; n = 74) groups. We evaluated PcP occurrence, TMP-SMX discontinuation rate, and discontinuation-related risk factors in these groups.PcP did not occur in either group. The univariate and multivariate Cox proportional hazards models revealed that the SS dosage and renal function (e.g. serum creatinine and creatinine clearance) were independently associated with prophylaxis discontinuation. At 24 weeks, the HS group presented significantly lower discontinuation rates than the SS group (P = 0.019, log-rank test). In the SS group, patients with mild renal impairment (e.g. serum creatinine ≥0.78 mg/dL or creatinine clearance ≤64.26 mL/min) presented significantly higher TMP-SMX discontinuation rates than those without such an impairment (P 0.05, log-rank test with Bonferroni correction). This difference was not significant in the HS group.Mild renal impairment might increase the risk of discontinuation of conventional TMP-SMX prophylaxis. In patients with a mild renal impairment, the HS dosage may improve tolerability while maintaining prophylactic efficacy.

Rationale: Cisplatin is one of the key drugs that is frequently used for treating various types of malignancies. Although renal and digestive toxicities are well-known cisplatin-related toxicities, attention should also be paid to acute aortic thrombosis, a relatively rare but potentially fatal disorder caused by cisplatin. Additionally, D-dimer is mainly measured to detect venous thromboembolism or disseminated intravascular coagulation, whereas its usefulness for detecting aortic thrombosis remains unclear. Here, we report a case of squamous cell lung cancer treated with cisplatin-based chemotherapy, wherein acute aortic thrombosis was diagnosed based on elevated D-dimer levels. Patient concerns: A 65-year-old man with stage IV squamous cell lung cancer presented with elevated D-dimer levels during treatment with second-line chemotherapy with cisplatin and S-1. Contrast-enhanced computed tomography (CT) revealed an intramural thrombus, which had not been previously identified, extending from the abdominal aorta to the common iliac artery. Diagnoses: We diagnosed the patient as having acute aortic thrombosis caused by cisplatin. Interventions: The patient received intravenous administration of unfractionated heparin for 9 days followed by oral warfarin. Outcomes: One month after initiating treatment, the patient's D-dimer levels decreased to the normal range, and contrast-enhanced CT revealed that the thrombi had nearly completely disappeared without any sequelae or organ damage. Lessons: Our findings revealed that cisplatin can cause acute aortic thrombosis and that regular measurements of D-dimer levels before and during chemotherapy may contribute to the early detection of acute aortic thrombosis.

Key Points Question Are interstitial lung abnormalities, which are minor interstitial shadows on lung computed tomography, associated with immune checkpoint inhibitor induced–interstitial lung disease in patients with nonlung cancers? Findings In this cohort study of 199 patients with advanced nonlung cancers treated with anti–programmed cell death 1 antibody monotherapy, patients with preexisting interstitial lung abnormalities had significantly increased risk of immune checkpoint inhibitor induced–interstitial lung disease. Meaning These findings suggest that greater attention should be accorded to the development of immune checkpoint inhibitor induced–interstitial lung disease in patients with nonlung cancers and interstitial lung abnormalities., This cohort study evaluates whether interstitial lung abnormalities are associated with immune checkpoint inhibitor–induced interstitial lung disease in patients with nonlung cancers., Importance Immune checkpoint inhibitor–induced interstitial lung disease (ICI-ILD) is clinically serious and life-threatening. Preexisting interstitial lung abnormalities have been shown to be risk factors for ICI-ILD in patients with lung cancer. Objective To evaluate whether interstitial lung abnormalities are associated with ICI-ILD in patients with nonlung cancers. Design, Setting, and Participants This cohort study was conducted between December 2015 and May 2019 at Hiroshima University Hospital. A total of 199 consecutive patients with head and neck cancer, malignant melanoma, oral cavity cancer, urological cancer, and gastrointestinal cancer who received anti–programmed cell death 1 (PD-1) antibody monotherapy were included. Data analysis was conducted from December 2015 to May 2019. Main Outcomes and Measures The associations between potential risk factors and the development of ICI-ILD were examined. Information on patient characteristics before antibody administration, including chest computed tomography findings, was obtained. The diagnosis of ICI-ILD was defined as abnormal computed tomography shadows occurring during treatment with anti-PD-1 antibodies. Results A total of 199 patients were enrolled in the study. The median (range) age was 66 (20-93) years, and most patients (133 [66.8%]) were men. Nineteen patients (9.5%) developed ICI-ILD. There was no significant difference in the baseline characteristics between patients with and without ICI-ILD. The logistic regression analyses revealed that interstitial lung abnormalities were associated with increased risk of ICI-ILD (odds ratio, 6.29; 95% CI, 2.34-16.92; P

e21736 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), are less toxic than conventional chemotherapy drugs, and benefit patients with EGFR-mutated non-small cell lung (NSCLC) cancer. However, there are a few patients who are not able to receive EGFR-TKI due to poor performance status, older age, or sever comorbidities. Here, we aimed to determine the prognostic significance of EGFR mutation in NSCLC patients who received best supportive care (BSC) alone, and compare the anti-tumor outcomes of only EGFR-TKI-treated patients vs. BSC patients. Methods: We retrospectively reviewed the medical records of patients diagnosed with NSCLC at Higashihiroshima Medical Center during April 1991–January 2019 and Hiroshima University Hospital during April 2008–August 2018. Results: A total of 1163 patients diagnosed with unresectable NSCLC were included in this analysis. Of these 1163 patients, 234 patients received BSC alone.Among 196 patients who underwent EGFR mutation analysis, 38 and 158 did and did not harbor an EGFR mutation, respectively, and the mean survival times (MST) did not differ significantly between these groups (121 vs. 85 days, p = 0.789). Consistent with the survival analysis, the multivariate Cox regression analyses showed EGFR mutation was not an independent prognostic factor. After propensity score matching, a comparison of only EGFR-TKI-treated (n = 35) and BSC patients (n = 35) with EGFR mutation revealed that the former had a significantly longer MST than the latter (372 vs. 121, p < 0.001). Conclusions: EGFR mutation itself was not a significant prognostic factor in untreated NSCLC patients. The patients who received EGFR-TKI had a significantly longer MST than their untreated counterparts. Our results may help to explain the benefit of EGFR-TKI, particularly for patients who would be directed towards treatment with BSC.