PD-1 and PD-L1 expression is significantly associated with adverse clinicopathological features in CCRCC. Furthermore, PD-1 expression could be one of the biomarkers suggesting poor outcome in patients with metastatic CCRCC receiving molecular targeted therapies.

Background/Aim: The present study aimed to examine the influence of antibiotics (AB) on the clinical outcomes of Japanese patients treated with immune check point inhibitors (ICIs) for metastatic renal cell carcinoma (RCC) patients. Patients and Methods: A total of 31 patients with metastatic RCC treated with ICIs from November 2016 to April 2019 were retrospectively reviewed and analyzed. Results: Five patients were treated with AB prior to ICIs treatment. Median progression free survival (PFS) of patients treated with AB vs. patients not treated with AB was 2.8 months and 18.4 months, respectively. The difference between PFS was statistically significant (p=0.0004). In multivariate analyses, AB use (p=0.0377) and presence of immune related adverse events (p=0.0042) were independent prognostic factors for PFS in association with ICIs therapy. Conclusion: The use of AB before ICIs treatment was a predictor of poor ICIs response in metastatic RCC.Immune checkpoint inhibitors (ICIs) that target programmed cell death-1 (PD-1) protein, programmed cell death-ligand 1 protein, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), have changed the therapeutic landscape and are currently standard treatment options in patients with advanced and metastatic renal cell carcinoma (RCC) (1, 2). Despite the remarkable success of clinical applications, the efficacy of ICIs in RCC varies greatly across individual patients. Some researchers have reported biomarkers for predicting prognosis in patients treated with ICIs, such as PD-L1 and PD-L2 positivity, tumor mutation burden, and profile of immune-related genes (3). Furthermore, the association of immune related adverse events (irAEs) with prognosis in metastatic RCC has been recently reported (4, 5). Thus, it is critical to explore reliable predictors to improve prognosis of RCC patients treated with ICIs.Recently, several studies have demonstrated the crucial impact of human gut microbiota on ICIs therapies (6-9). It is well recognized that antibiotics (AB) alter the diversity and composition of gut microbiota and consequently shift their metabolic capacity (10). The hypothesis was that modulation of gut microbiota by AB may be associated with poor response to ICIs. However, the data on the association between AB use and clinical outcomes with ICIs are limited, especially in Japanese patients with genitourinary cancer.In the present study, we performed a retrospective analysis to examine the influence of AB on the clinical outcomes of Japanese patients treated with ICIs therapy for metastatic RCC patients. Patients and MethodsStudy design and patients. We retrospectively examined clinical information collected from 31 RCC patients treated with ICIs at Kurume University Hospital from November 2016 to April 2019. All patients received nivolumab or the combination of nivolumab and ipilimumab. Nivolumab was intravenously administered at 3 mg/kg or 240 mg/body every 2 weeks. Nivolumab and ipilimumab were administered intravenously at a dose of 240 mg/body and 1 mg/kg, respectiv...

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To investigate the relationships between whole-body vibration and changes in wakefulness,We measured the change of a subjective wakefulness level and electroencephalogram (EEG). Subjects are ten healthy male university students. The subjects were exposed to whole-body vibration with frequency (10 Hz) and acceleration level (0.6 ms -2 r.m.s.) for 12 min in the seated position. Subjective wakefulness level was evaluated using the questionnaire of VASS (Visual Analog Sleepiness Scale) and KSS (The Kwansei Gakuin Sleepiness Scale). For the electroencephalogram (EEG) measurement, AAT (Alpha Attenuation Test) which repeats three times each opened and closed eye for 1 min was conducted. Wakefulness levels were defined as the ratio of mean alpha-wave power during eyes closed versus eyes opened. VASS and KSS increased and subjective level of wakefulness decreased from pre-to post exposure in all subjects, regardless of vibration exposure. The objective wakefulness levels of AAT were reduced at the post-exposure test in all subjects. In the case with exposure to whole-body vibration was a significant difference from the case without exposure to whole-body vibration. It is suggested that a short-term exposure to whole-body vibration may cause a reduction of wakefulness level.

Previously, the preoperative neutrophil-to-lymphocyte ratio (NLR) has been demonstrated to be a beneficial prognostic marker in patients with upper tract urothelial carcinoma (UTUC). However, to the best of our knowledge, the postoperative NLR has rarely been investigated. Therefore, the present study evaluated the prognostic significance of postoperative NLR in patients with UTUC. Data of patients with UTUC who underwent surgical treatment at Kurume University hospital (Kurume, Japan) between 2004 and 2015 were retrospectively reviewed. Clinicopathological characteristics were analyzed, including pre-and postoperative NLRs. Overall survival (OS) and cancer-specific survival (CSS) rates were estimated using the Kaplan-Meier method and compared with a log-rank test. Multivariate proportional Cox regression models were applied for both endpoints to identify the independent prognostic significance of NLR. The median age of the 134 enrolled patients was 70 years. The postoperative NLR was elevated in 35 patients (26.1%). A high postoperative NLR of ≥2.5 was significantly associated with a high postoperative C-reactive protein level of ≥0.3 mg/dl, an advanced pathological T stage and positive lymphovascular invasion in surgical specimens (P<0.001, P=0.019 and P=0.024, respectively). The 5-year OS rates in patients with high and low postoperative NLR were 33.7 and 70.2%, respectively (P<0.001), and the 5-year CSS rates in patients with a high and low postoperative NLR were 33.7 and 80.7%, respectively (P<0.001). Multivariate analysis revealed that a high postoperative NLR was an independent prognostic marker for OS (hazard ratio, 4.66; 95% confidence interval, 2.11-10.00; P<0.001) and CSS (hazard ratio, 10.90; 95% confidence interval, 4.32-28.40; P<0.001), and the preoperative NLR was not identified as a prognostic marker. In conclusion, a high postoperative NLR is associated with a poor prognosis in patients with UTUC. Therefore, postoperative NLR may be a potential prognostic marker in patients with UTUC undergoing nephroureterectomy.