These observations suggest that locally produced MCP-1 may be involved in the development of advanced diabetic nephropathy, especially in the formation of tubulointerstitial lesions possibly through Mphi recruitment and activation. Moreover, up-regulation of MCP-1 may be a common pathway involved in the progressive tubulointerstitial damage in diabetic nephropathy as well as inflammatory renal diseases.

The aim of this study was to investigate the clinical impact of sarcopenia on the efficacy of programmed death (PD)-1 inhibitors. We retrospectively reviewed the medical records of all patients treated with nivolumab or pembrolizumab between January 2016 and September 2018 for previously treated advanced non–small cell lung cancer (NSCLC). The cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on baseline computed tomography was assessed to calculate the psoas muscle index (PMI). Sarcopenia was defined based on PMI cut-off values for Asian adults (6.36 cm 2 /m 2 for males and 3.92 cm 2 /m 2 for females). A total of 42 patients were analysed. The prevalence of sarcopenia was 52.4%. Sarcopenia was significantly associated with poorer progression-free survival (PFS) (median, 2.1 vs. 6.8 months, p = 0.004). Compared to patients with sarcopenia, those without sarcopenia had a higher overall response rate (40.0% vs. 9.1%, p = 0.025) and 1-year PFS rate (38.1% vs. 10.1%). In conclusion, sarcopenia at baseline as determined using computed tomography is a significant predictor of worse outcome in patients with advanced NSCLC receiving PD-1 blockade. Screening for sarcopenia may help identify patients more likely to achieve a long-term response in routine clinical practice.

BACKGROUND. The PD-1–blocking antibody nivolumab persists in patients several weeks after the last infusion. However, no study has systematically evaluated the maximum duration that the antibody persists on T cells or the association between this duration and residual therapeutic efficacy or potential adverse events.METHODS. To define the duration of binding and residual efficacy of nivolumab after discontinuation, we developed a simplified strategy for T cell monitoring and used it to analyze T cells from peripheral blood from 11 non–small cell lung cancer patients previously treated with nivolumab. To determine the suitability of our method for other applications, we compared transcriptome profiles between nivolumab-bound and nivolumab-unbound CD8 T cells. We also applied T cell monitoring in 2 nivolumab-treated patients who developed progressive lung tumors during long-term follow-up.RESULTS. Prolonged nivolumab binding was detected more than 20 weeks after the last infusion, regardless of the total number of nivolumab infusions (2–15 doses) or type of subsequent treatment, in 9 of the 11 cases in which long-term monitoring was possible. Ki-67 positivity, a proliferation marker, in T cells decreased in patients with progressive disease. Transcriptome profiling identified the signals regulating activation of nivolumab-bound T cells, which may contribute to nivolumab resistance. In 2 patients who restarted nivolumab, T cell proliferation markers exhibited the opposite trend and correlated with clinical response.CONCLUSIONS. Although only a few samples were analyzed, our strategy of monitoring both nivolumab binding and Ki-67 in T cells might help determine residual efficacy under various types of concurrent or subsequent treatment.TRIAL REGISTRATION. University Hospital Medical Information Network Clinical Trials Registry, UMIN000024623.FUNDING. This work was supported by Japan Society for the Promotion of Science KAKENHI (JP17K16045, JP18H05282, and JP15K09220), Japan Agency for Medical Research and Development (JP17cm0106310, JP18cm0106335 and JP18cm059042), and Core Research for Evolutional Science and Technology (JPMJCR16G2).

A new method of nesting a high-resolution limited area model (LAM) in a low-resolution global model (GCM) is proposed for the purpose of conducting.regional climate simulations. It is tested with a few feasibility studies of month-long time integrations of the LAM.The conventional method of embedding a LAM in a larger area model is to couple the inner to the outer model in terms of lateral boundary conditions in real space. In the present method, the concept of a spectral boundary in wavenumber space is the key to joining a high-resolution LAM to a low-resolution GCM.In practice the new technique of combining the two different resolution models is to replace the large-scale fields of the LAM with the corresponding large-scale fields supplied externally from the GCM at a selected regular time interval.The present experiments showed that the time integration was very smooth over a period of one month, and that the mesoscale features associated with the large-scale supplied from the GCM were well simulated, suggesting that the new method is encouraging for regional mesoscale climate simulations.