Respiratory Virus Infections during the COVID-19 Pandemic Revealed by Multiplex PCR Testing in Japan.

Under the strict quarantine policy imposed to combat the COVID-19 (coronavirus disease 2019) pandemic in Japan, the prevalence of respiratory infections by viruses other than SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been largely unknown. However, such information on viral circulation is important in order to develop better management policies that are based on scientific data. Here, we retrospectively investigated respiratory virus infections in individuals who visited a community hospital with respiratory symptoms between June of 2020 and September of 2021 with the use of the BioFire FilmArray Respiratory Panel 2.1. Virus was detected in 65 out of a total of 328 subjects, with SARS-CoV-2 (67.7%), rhino/enterovirus (18.5%), and parainfluenza virus 3 (7.7%) accounting for most of the infections. No influenza virus or respiratory syncytial virus (RSV) infections were detected. The monthly cases of rhino/enterovirus infection were highest from winter to spring, with this temporal pattern differing from that of SARS-CoV-2. SARS-CoV-2 was detected more frequently (P < 0.001) in subjects with cough (31/104 cases, 29.8%) than in those without cough (13/224 cases, 5.8%), suggesting that cough might contribute to the prediction of COVID-19. Our findings also suggest that testing for rhino/enterovirus and parainfluenza virus 3, in addition to SARS-CoV-2, may be important for the rigorous diagnosis of respiratory virus infections. IMPORTANCE Influenza virus, RSV, adenovirus, and rhino/enterovirus were the major respiratory viruses before COVID-19 pandemic. Circulating respiratory viruses may have been affected by our strong quarantine policy during the COVID-19 pandemic. We checked the circulating respiratory viruses from our outpatients by using a multiplex PCR kit that had recently been released. SARS-CoV-2 was the most frequently detected virus, and it was followed by rhino/enterovirus and parainfluenza virus 3. No influenza virus or RSV infections were detected during our study period, suggesting that influenza virus and RSV became almost extinct. COVID-19 cases frequently experienced cough, and this frequency was statistically significantly higher than that observed in the cases without SARS-CoV-2 detection. The cough can be an indicator of COVID-19.

Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease implicated as an independent risk factor for lung cancer. However, optimal treatment for advanced lung cancer with IPF remains to be established. We performed a randomised phase 3 trial (J-SONIC) to assess the efficacy and safety of nintedanib plus chemotherapy (experimental arm) compared with chemotherapy alone (standard-of-care arm) for advanced nonsmall cell lung cancer (NSCLC) with IPF. METHODS: Chemotherapy-naïve advanced NSCLC patients with IPF were allocated to receive carboplatin (area under the curve of 6 on day 1) plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) (100 mg·m-2 on days 1, 8 and 15) every 3 weeks with or without nintedanib (150 mg twice daily, daily). The primary end-point was exacerbation-free survival (EFS). RESULTS: Between May 2017 and February 2020, 243 patients were enrolled. Median EFS was 14.6 months in the nintedanib plus chemotherapy group and 11.8 months in the chemotherapy group (hazard ratio (HR) 0.89, 90% CI 0.67-1.17; p=0.24), whereas median progression-free survival was 6.2 and 5.5 months, respectively (HR 0.68, 95% CI 0.50-0.92). Overall survival was improved by nintedanib in patients with nonsquamous histology (HR 0.61, 95% CI 0.40-0.93) and in those at GAP (gender-age-physiology) stage I (HR 0.61, 95% CI 0.38-0.98). Seven (2.9%) out of 240 patients experienced acute exacerbation during study treatment. CONCLUSIONS: The primary end-point of the study was not met. However, carboplatin plus nab-paclitaxel was found to be effective and tolerable in advanced NSCLC patients with IPF. Moreover, nintedanib in combination with such chemotherapy improved overall survival in patients with nonsquamous histology.

Final Results from a Phase II Trial of Osimertinib for Elderly Patients with Epidermal Growth Factor Receptor t790m-Positive Non-Small Cell Lung Cancer That Progressed during Previous Treatment.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used for treating EGFR-mutated lung cancer, and osimertinib is effective in cases that acquired T790M mutations after treatment with the first- and second-generation EGFR-TKIs. However, no study has evaluated its safety and efficacy in older patients. This phase II trial (jRCTs071180002) evaluated osimertinib in T790M mutation-positive Japanese patients who were ≥75 years old and had experienced relapse or progression after previous EGFR-TKI treatment. Our previous report that enrolled 36 patients showed the overall response rate (58.3%) and disease control rate (97.2%), while this report describes the results for the progression-free survival (PFS), overall survival (OS), and safety analyses. The median PFS was 11.9 months (95% confidence interval (CI): 7.9-17.5), and the median OS was 22.0 months (95% CI: 16.0 months-not reached). The most frequent adverse events were anemia/hypoalbuminemia (27 patients, 75.0%), thrombocytopenia (21 patients, 58.3%), and paronychia/anorexia/diarrhea/neutropenia (15 patients, 41.7%). Pneumonitis was observed in four patients (11.1%), including two patients (5.6%) with Grade 3-4 pneumonitis. These results suggest that osimertinib was relatively safe and effective for non-small cell lung cancer that acquired T790M mutations after previous EGFR-TKI treatment, even among patients who were ≥75 years old.

Longitudinal monitoring of somatic genetic alterations in circulating cell-free DNA during treatment with epidermal growth factor receptor-tyrosine kinase inhibitors.

BACKGROUND: The aim of this study was to evaluate the potential of liquid biopsy for prediction of the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment and for assessment of the changes in genetic alterations during such treatment. METHODS: Plasma samples were prospectively collected from non-small cell lung cancer patients with EGFR-activating mutations during EGFR-TKI treatment until disease progression and were analyzed for such mutations with droplet digital polymerase chain reaction and for other somatic alterations with next-generation sequencing. RESULTS: One hundred patients, including 87 who were EGFR-TKI naïve, were enrolled. Median progression-free survival was significantly shorter for EGFR-TKI-naïve patients with EGFR-activating mutations detected in plasma at baseline than for those without them (7.9 vs 19.0 months; P < .001), with the values being significantly longer for initially positive patients who became negative for these mutations at 12 or 24 weeks than for those who remained positive. An increase in the number of alleles positive for EGFR-activating mutations in plasma during treatment was associated with disease progression, with a hazard ratio of 4.72 (95% CI, 2.07-10.79; P < .001) for EGFR-TKI-naïve patients showing an increase within 36 weeks. For 55 patients with available samples, the total number of somatic alterations (other than activating mutations or T790M of EGFR) in plasma was higher at disease progression than at baseline (33 vs 19; P = 0.04). CONCLUSION: Liquid biopsy shows potential for prediction of EGFR-TKI efficacy and elucidation of clonal tumor evolution during targeted therapy.

Meteorological effects on severe hemoptysis: A hospital-based observational study.

BACKGROUND: Although some meteorological factor are likely to contribute to the onset of hemoptysis, few studies have investigated this issue, with none conducted in the Asia-Pacific region. Therefore, the present study aimed to evaluate the associations of meteorological factors with the occurrence of hemoptysis. Differences in the frequency of hemoptysis among several calendar variables were also assessed. METHODS: A total of 47 hemoptysis patients aged ≥ 20 years undergoing bronchial artery embolization in Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers from January 2012 to December 2017 were included in the study. All hemoptysis events were assembled in a single time series, and the proportion of hemoptysis days was 2.1%. The associations of meteorological variables with hemoptysis days were estimated as odds ratios with 95% confidence intervals by using multivariable-adjusted logistic regression models. The frequency of hemoptysis days was compared among several calendar variables using a chi-square test. RESULTS: Mean relative humidity was negatively associated with hemoptysis (P for trend = 0.02). The inverse association remained significant when only the hemoptysis events with no infectious lung diseases were used (P for trend=0.02). No significant difference was observed in the occurrence of hemoptysis among seasons, months, or other calendar variables (all P ≥ 0.21). CONCLUSIONS: Lower relative humidity was a significant risk factor for the development of hemoptysis. Clinicians should be aware of the potential for increases in hemoptysis events on days with low ambient humidity.

Osimertinib in Elderly Patients with Epidermal Growth Factor Receptor T790M-Positive Non-Small-Cell Lung Cancer Who Progressed During Prior Treatment: A Phase II Trial.

LESSONS LEARNED: Non-small-cell lung cancer (NSCLC) represents 85% of lung cancer in elderly patients.In the present study performed in the 36 elderly subjects with epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, osimertinib 80 mg demonstrated statistically significant improvement in the objective response rate, which was comparable to those in the nonelderly population.Osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC with EGFR mutation; further research in larger scale is warranted. BACKGROUND: Previous findings suggest the possibility of relatively safe use of osimertinib for patients with T790M-positive non-small-cell lung cancer (NSCLC), with few serious adverse events for the elderly in comparison with conventional endothelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and with an antitumor effect. METHODS: This phase II study was performed to prospectively investigate the efficacy and safety of osimertinib for elderly patients aged ≥75 years with ineffective prior EGFR TKI treatment or with recurrence in T790M EGFR TKI resistance mutation-positive NSCLC. RESULTS: A total of 36 patients were included in the analyses. Among the 36 subjects, 63.9% were female, with mean age of 79.9 years. The objective response rate (ORR) was 58.3% (95% confidence interval [CI], 42.2%-72.9%), demonstrating statistically significant efficacy of osimertinib (p = .0017). The median duration of response (DOR) was 27.9 weeks (95% CI, 21.1-82.0). Complete response (CR) and partial response (PR) were 2.8% and 55.6%, respectively. Disease control rate (DCR) was 97.2%. A waterfall plot revealed that 33 (91.6%) subjects exhibited tumor shrinkage during treatment, including 12 of 14 subjects who had stable disease (SD). All adverse events were not reason for discontinuation of the study drug. CONCLUSION: Osimertinib may be an effective and safe treatment option in elderly patients with advanced NSCLC with EGFR mutation.

Seasonal and meteorological impacts on primary spontaneous pneumothorax.

BACKGROUND: Although several studies have suggested that primary spontaneous pneumothorax (PSP) might occur in clusters, only a few studies have found seasonal variations in PSP occurrence. Some meteorological parameters might be related to the occurrence of PSP occurrence, however, the effects of weather variations on the onset of PSP are still controversial. METHODS: We examined seasonal differences in the occurrence of PSP and the meteorological risk factors for PSP. All PSP patients aged <40 years who were admitted to Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers from April 2007 through March 2013 were included in the study. RESULTS: The incidence rates of PSP were 16.7 and 2.1 per 100,000 person-years in men and women, respectively. The frequency of PSP days among months and seasons was significantly different with a peak in September and autumn. Daily changes in maximum wind speed had positive associations with PSP days [crude OR =1.11 (95% CI: 1.02-1.21) per 1 m/s, P=0.02; multivariable-adjusted OR =1.11 (95% CI: 1.00-1.23) per 1 m/s, P=0.05]. CONCLUSIONS: PSP tends to cluster seasonally. Increased wind speed may play a role in the development of PSP.

Emphysematous Pyelonephritis and Cystitis: Unusual Adverse Events during Concurrent Chemoradiotherapy for Lung Cancer.

Various adverse events can occur during antineoplastic therapy. A 67-year-old diabetic woman developed an emphysematous urinary tract infection (UTI) associated with chemoradiotherapy for lung cancer. She had received weekly carboplatin plus paclitaxel with thoracic radiotherapy and developed a fever on day 19. Computed tomography showed a large quantity of gas within the urinary tract. She was therefore diagnosed with emphysematous UTI. Poor diabetes control due to the weekly administration of dexamethasone, an existing urinary tract obstruction, and bone marrow suppression were involved in her serious infection. The potential development of emphysematous UTI during chemoradiotherapy should be considered in at-risk patients.

Efficacy of aprepitant in patients with advanced or recurrent lung cancer receiving moderately emetogenic chemotherapy.

AIMS AND BACKGROUND: To evaluate the efficacy of a combination of aprepitant and conventional antiemetic therapy in patients with advanced or recurrent lung cancer receiving moderately emetogenic chemotherapy (MEC). METHODS: Patients with advanced or recurrent lung cancer who were treated with MEC regimens at the Department of Respiratory Medicine, Fukuoka University Hospital, were included and classified into the following groups: control group (treatment: 5-HT3 receptor antagonists + dexamethasone) and aprepitant group (treatment: 5-HT3 receptor antagonists + dexamethasone + aprepitant). The presence or absence of chemotherapy-induced nausea and vomiting (CINV) was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0; patients with grade 1 or above were considered positive for CINV. Food intake per day, completion of planned chemotherapy, and progression-free survival (PFS) achieved by chemotherapy were investigated. RESULTS: The complete suppression rate of nausea in the aprepitant group was significantly higher than that in the control group (p = 0.0043). Throughout the study, the food intake in the aprepitant group was greater than that in the control group, with the rate being significantly higher, in particular, on day 5 (p = 0.003). The completion rate of planned chemotherapy was also higher in the aprepitant group (p = 0.042). PFS did not differ significantly, but tended to be improved in the aprepitant group. CONCLUSIONS: The aprepitant group showed significantly higher complete suppression of nausea, food intake on day 5, and completion of planned chemotherapy than the control group.