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Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Mirii Harada,2 Shingo Tamura,7 Akihiro Miura,1 Hiroki Komori,1 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi, Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan, Tel +81-92-541-3231, Fax +81-92-551-4585, Email nobumduro@gmail.comBackground: To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab.Materials and Methods: This retrospective study analyzed 105 advanced UC patients treated with pembrolizumab after disease progression on platinum-based chemotherapy between January 2018 and June 2021. The association between the occurrence of irAEs and the efficacy of pembrolizumab was investigated. The change in the REC from before the initiation of pembrolizumab therapy, to three weeks after treatment and the incidence of irAEs were determined.Results: Overall irAEs were associated with a significantly higher objective response rate (ORR) (58.8% vs 25.4%, P< 0.001), a longer progression-free survival (PFS) (25.1 months vs 3.1 months, P< 0.001) and overall survival (OS) (31.2 months vs 11.5 months, P< 0.001) compared to patients without irAEs; however, grade ≥ 3 irAEs were not associated with the ORR (36.4% vs 36.2%, P=0.989), PFS (9.5 vs 5.5 months, P=0.249), or OS (not reached vs 13.7 months, P=0.335). Compared to a decreased REC at 3 weeks after pembrolizumab, an increased relative REC at 3 weeks was not associated with the incidence of any-grade irAEs (32.3% vs 32.5%, P=0.984) or of grade ≥ 3 irAEs (10.8% vs 10.0%, P=0.900). Multivariate analyses revealed a female sex (P=0.005), Eastern Cooperative Oncology Group Performance Status ≥ 1 (P=0.024), albumin < 3.7 g/dl (P< 0.001), decreased REC (3 weeks later) (P< 0.001), and the absence of irAEs of any grade (P=0.002) to be independently associated with a worse OS.Conclusion: Patients with irAEs showed a significantly better survival compared to patients without irAEs in advanced UC treated with pembrolizumab. An increased posttreatment REC may be a marker predicting improved clinical outcomes and it had no significant relationship with the incidence of irAEs.Keywords: urothelial carcinoma, pembrolizumab, immune-related adverse events, relative eosinophil count

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Shingo Tamura,7 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki FurubayashiDepartment of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email nobumduro@gmail.comBackground: To evaluate the association of clinical outcomes with posttreatment changes in the relative eosinophil count (REC) and neutrophil-to-eosinophil ratio (NER) in patients with advanced urothelial cancer (UC) treated with pembrolizumab.Materials and Methods: We retrospectively analyzed 105 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The REC and NER before and three weeks after pembrolizumab were recorded. A receiver operating characteristic curve was used to determine the optimal cut-off values for analyzing the risk.Results: There were no significant differences in the overall survival (OS) between the REC ≥ 4.8% and < 4.8% groups and the NER ≥ 13.7 and < 13.7 groups before pembrolizumab (p=0.997 and 0.669, respectively). However, a significant difference in the OS was confirmed between the increased and decreased REC groups and between the decreased and increased NER groups at 3 weeks after pembrolizumab (p< 0.001 and 0.002, respectively). Multivariate analyses revealed that an Eastern Cooperative Oncology Group Performance Status ≥ 2 (P=0.003), albumin < 3.7 g/dl (p=0.002), LDH > 246 U/L (p=0.011), disease site ≥ 3 organs (p=0.019), decreased posttreatment REC (3 weeks later) (p=0.002) and increased posttreatment NER (3 weeks later) (p=0.022) were independent prognostic factors for a worse OS.Conclusion: An increased REC and decreased NER after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.Keywords: urothelial carcinoma, pembrolizumab, eosinophil, neutrophil-to-eosinophil ratio

Three composites composed of the cobalt terpyridine complex [CoII(MeO-terpy)2] and the diblock copolypeptide amphiphiles 1 and 2 or the polypeptide 3 (including glutamic acid and leucine) were prepared. Supramolecular structures such as rectangular morphologies were obtained from composites of 1 and 2. A perfectly reversible reverse spin transition was successfully generated in the case of composites made with 1.

Two of the most intensively studied processes in the field of ecological physiology are the limits to metabolic performance and the energetics of temperature acclimation. A major emphasis currently is the examination of relationships among basal metabolic rate (BMR), maximum metabolic rate (MMR), and the sizes of vital organs and tissues such as kidneys, liver, heart, and skeletal muscle. We examined these relationships in house finches (Carpodacus mexicanus) that were maintained in the laboratory at two different acclimation temperatures. Birds in the cold-acclimation (CA) group were maintained at [5.sup.f] C, and those in the warm-acclimation (WA) control group at [25.sup.f] C, for six weeks following capture in New York in June. All metabolic rate values were measured as oxygen consumption in an open-circuit respirometry system. MMR was determined by two methods for each animal: exercise maximum in a running wheel chamber and thermogenic maximum during exposure to cold temperatures in a helium-oxygen (heliox) atmosphere. The body mass of CA birds (20.1 [+ or -] 0.5 g) was significantly greater (p [is less than] 0.001) than that of WA birds (18.4 [+ or -] 0.3 g). Even when adjusted for differences in body mass, the BMR of CA birds was 15% greater than that of WA individuals (p [is less than] 0.01). However, there was no effect of acclimation temperature on either exercise or cold-induced MMR. Exercise-induced MMR values were 17.5% greater than those obtained using the heliox protocol (p [is less than] 0.01). The relationships among organ sizes and metabolic measurements will be discussed.