Association between immune-related adverse events and prognosis in patients with metastatic renal cell carcinoma treated with nivolumab.

OBJECTIVES: Immune-related adverse events (irAEs) develop in a subset of patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors. The relationship between presence of irAEs and prognosis in these patients remains unknown. Thus, we evaluated the prognostic impact of irAEs caused by nivolumab therapy in mRCC patients who had received prior molecular-targeted therapies. METHODS: We retrospectively evaluated 47 patients with mRCC who were treated with nivolumab after receiving at least 1 molecular-targeted therapy. The irAEs assessed in this study included cutaneous, gastrointestinal, endocrine, pulmonary, hepatobiliary, renal, and other (rheumatic disease and pancreatitis) manifestations. The grade of irAEs was defined based on the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: In total, 23/47 patients (48.9%) experienced 29 irAEs. The most frequent irAE was rash/pruritus (12/23, 52.2%). The median progression-free survival (PFS) and overall survival after the initiation of nivolumab therapy were significantly longer in patients with irAEs than in those without irAEs (PFS: 13.1 vs. 4.87 months, P < 0.0001; overall survival: 26.0 vs. not reached, P = 0.0072). The multivariate analysis of PFS showed that irAE development was an independent prognostic factor (hazard ratio: 0.25, P = 0.0009). Additionally, the 2-cycle landmark analysis showed that PFS was significantly longer in patients with irAEs than in those without irAEs (median: not reached vs. 6.28 months, P = 0.0279). CONCLUSIONS: This retrospective study revealed a significant association between nivolumab-associated irAEs and prognosis in previously treated mRCC. Further prospective studies are necessary to confirm our findings.

A new method for enhanced expectoration of sputum by vibratory stimulation of the cervical trachea.

BACKGROUND: Expectoration of sputum can be difficult for patients with respiratory conditions such as chronic obstructive pulmonary disease, chronic bronchitis, or bronchiectasis because of the effects of decreased pulmonary function, respiratory muscle fatigue, altered sputum properties, and impaired ciliary function. We developed a new method for the vibratory stimulation of the cervical trachea and this study aimed to compare it with the Acapella (a current oscillation device) method. METHODS: Patients with chronic productive cough and difficulty with expectoration were recruited for the study. The tracheal vibration and Acapella methods were applied for 4 weeks each, according to a crossover design with an intervening 4-week washout period. To perform the tracheal vibration method, an electronic artificial larynx (Yourtone®) was applied to the cervical trachea for up to 5minutes. Patient preference for the two devices was determined from the performance scores recorded for each device and by using a visual analogue scale. RESULTS: Twelve patients were recruited in the study. According to the performance scores assigned by the subjects, the tracheal vibration method was effective in 9 patients, while the Acapella method was effective in 10 patients. Both methods were effective in 8 patients, among whom the tracheal vibration method was more effective in 5 patients. Both methods were found to be ineffective in 1 patient. CONCLUSIONS: The tracheal vibration method may be effective at removing central airway sputum and does not require repeated forced expiratory effort, which can otherwise cause exhaustion in patients with decreased lung function. Further investigation is required to confirm its use as a new oscillation technique.

The effects of daily bathing on symptoms of patients with bronchial asthma.

BACKGROUND: The influence of bathing in asthma patients is not yet fully known. OBJECTIVE: We conducted an observational study to investigate changes in symptoms and their degree by bathing in asthmatic patients. METHODS: A questionnaire focusing on ever experienced bathing-induced symptom changes and their degree, as well as contributing factors, was designed and administered to asthmatic patients in the outpatient department of our institute between January 2012 and November 2013. RESULTS: Two hundred fifteen cases were recruited. In 60 cases (27.9%), asthmatic symptoms appeared, including 20 cases of chest discomfort (33.3%), 19 cases of cough (31.7%), and 21 cases of wheezing (35.0%). The triggering factors included vapor inhalation (32 cases, 53.3%), hydrostatic pressure on the thorax due to body immersion in the bathtub (26 cases, 43.3%), and sudden change of air temperature (16 cases, 26.7%). Thirty-eight cases (17.7%) experienced improvement in active asthmatic symptoms by bathing. Vapor inhalation was the most common contributing factor (34 cases, 89.5%), followed by warming of the whole body (13 cases, 34.2%). There was no relationship between asthma severity and the appearance of bathing-induced symptoms or improvement of active asthmatic symptoms by bathing. CONCLUSION: The effects of bathing in asthmatic patients widely differed from patient to patient and their etiology includes several factors. For those who suffer from bathing-induced asthma symptoms, preventive methods, such as premedication with bronchodilators before bathing, should be established. This study is registered in the University Hospital Medical Information Network (UMIN) clinical trials registry in Japan with the registration number UMIN000015641.

Bronchoscopy for Pulmonary Peripheral Lesions With Virtual Fluoroscopic Preprocedural Planning Combined With EBUS-GS: A Pilot Study.

BACKGROUND: Virtual fluoroscopic preprocedural planning (VFPP) is a figure in which the trace lines between the trachea and the target lesions are constructed along the connecting bronchus on Ray Summation image similar to fluoroscopy. The lines can be displayed at any angle with 3D imaging. This system was applied to bronchoscopy as a reference for forceps guidance under the fluoroscopy, as a new type of navigation. The objective of this study was to demonstrate the feasibility of VFPP. METHODS: Patients with pulmonary peripheral lesions (PPLs) with long axis ≤30 mm were recruited. Bronchoscopy with endobronchial ultrasonography with a guide sheath (EBUS-GS) was performed by using simultaneous display of VFPP. RESULTS: For 27 patients with 27 lesions, endobronchial ultrasonography with a guide sheath with simultaneous display of VFPP was performed. The median lesion size was 20.2 mm (range, 10 to 30 mm). The median examination time was 24.5 minutes (range, 12 to 50 min). Diagnosis was made for 17 lesions of the total 27. Lung cancer was diagnosed in 12 lesions, nontuberculous mycobacterial disease in 1 lesion, lymphoid hyperplasia in 1 lesion, and inflammation in 3 lesions. In 10 lesions, no diagnosis was made. The diagnostic rate of the procedure was 63.0%. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for malignant disease were 66.7%, 100%, 45.5%, 100%, and 73.9%, respectively. CONCLUSION: VFPP was easy to prepare and useful for selecting target bronchi. This study confirms feasibility of the VFPP as an adjunct to minimally invasive transbronchial biopsy of pulmonary peripheral lesions.