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Susumu Noguchi, Keiichiro Suminaga, Takahiro Kaki, Hiroaki Kawachi, Akari Fukao, Satoshi Terashita, Sadao Horikawa, Tatsuyoshi Ikeue, Takakazu Sugita Respiratory Medicine, Japanese Red Cross Wakayama Medical Center, Wakayama, JapanCorrespondence: Susumu NoguchiRespiratory Medicine, Japanese Red Cross Wakayama Medical Center, 20-4, Komatsubara Street, Wakayama City 640-8558, JapanTel +81-73-422-4171Fax +81-73-426-1168Email snoguchi515@gmail.comPurpose: The effects of immune checkpoint inhibitors have been reported to be linked with immune-related adverse events (irAEs). In patients with advanced non-small-cell lung cancer, who tested positive for programmed death-ligand 1 (PD-L1), pembrolizumab, an immune checkpoint inhibitor can be used as a treatment, and it was found to improve overall survival. However, there are only a few reports on the relationship between the therapeutic effects of pembrolizumab in patients with lung cancer and the irAEs of pembrolizumab. The purpose of this study was to determine the correlation between immune-related adverse events and the effects of pembrolizumab monotherapy in patients with non-small-cell lung cancer.Patients and Methods: From February 2017 to August 2019, we conducted a retrospective analysis of the effects of pembrolizumab treatment and immune-related adverse events in 94 patients with non-small-cell lung cancer treated with pembrolizumab only.Results: In 63 cases, irAEs were observed. The most common irAE was rash. PD-L1 positivity ≥ 50% tended to cause irAEs. The median progression-free survival (PFS) rates with and without irAEs were 371 days (95% CI, 184-NR) and 67 days (95% CI, 51– 87 days), respectively. In a multivariate analysis, irAEs and Eastern Cooperative Oncology Group performance status (PS) were the factors related to PFS.Conclusion: In patients with lung cancer, who were treated with pembrolizumab monotherapy, the development of irAEs was likely indicative of the positive effects of pembrolizumab. This novel finding appears to be useful for clinicians who work with pembrolizumab for lung cancer treatment.Keywords: lung cancer, pembrolizumab, adverse drug event, correlation study

Yuta Saito, 1–3 Miwa Sakata, 3 Moe Kobayakawa, 3 Hiroshi Kawachi, 4 Kazunori Kawaguchi, 3 Yoshiyuki Hiki, 3 Masao Kato, 1 Mayuko Mori, 1, 3 Midori Hasegawa, 1 Norimi Ohashi, 4 Yukio Yuzawa, 1 Nobuya Kitaguchi 3 1Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan; 2Graduate School of Medical Sciences, Fujita Health University, Toyoake, Aichi, Japan; 3Faculty of Clinical Engineering, School of Medical Sciences, Fujita Health University, Toyoake, Aichi, Japan; 4Ogaki Municipal Hospital, Ogaki, Gifu, JapanCorrespondence: Nobuya Kitaguchi 4-8-17, Yuzato, Higashisumiyosi-ku, Osaka 546-0013, JapanTel/Fax +81-6-3-4392-7087Email nkitaguc@fujita-hu.ac.jpPurpose: Amyloid-β protein (Aβ) is one of the causative proteins of Alzheimer’s disease. We have been developing extracorporeal blood Aβ-removal systems as a method for enhancing Aβ clearance from the brain. We reported previously that medical adsorbents and hemodialyzers removed Aβ monomers from peripheral blood, which was associated with influx of Aβ monomers from the brain into the bloodstream. Our intent here was to develop a method to promote clearance of Aβ oligomers and to provide an estimate of the molecular size of intact Aβ oligomers in plasma.Methods: Two hollow-fiber devices with different pore sizes (Membranes A and B) were evaluated as removers of Aβ oligomers with human plasma in vitro. The concomitant removal of Aβ oligomers and monomers was investigated by using Membrane B and hexadecyl alkylated cellulose beads or polysulfone hemodialyzers. Double-filtration plasmapheresis with Membrane A was investigated as an approach for the removal of plasma Aβ oligomers in humans.Results: Aβ oligomers were effectively removed by both Membranes A and B. The increase of Aβ oligomers in plasma was observed just after the removal of plasma Aβ oligomers in humans. The intact molecular size of major Aβ oligomers in the plasma was estimated to be larger than albumin at approximately 60 kDa or more. Additionally, the concomitant removal of Aβ monomers and oligomers evoked dissociation of larger Aβ oligomers into smaller ones and monomers.Conclusion: Aβ oligomers were cleared from plasma both in vitro and in human subjects by using hollow-fiber membranes with large pores, indicating that their intact sizes were mostly larger than 60 kDa. Aβ oligomers in peripheral circulation were increased after some clearances in human. Further investigation will determine whether the Aβ oligomers detected in circulation after clearance were via influx from the brain.Keywords: Aβ, amyloid beta, oligomer, Alzheimer’s disease, blood purification, membrane separation

Angus and Wagyu steers consuming high-roughage diets exhibit large differences in adipose tissue fatty acid composition, but there are no differences in terminal measures of stearoyl-CoA desaturase (SCD) activity or gene expression. Also, adipose tissue lipids of cattle fed corn-based diets have greater MUFA:SFA ratios than cattle fed hay-based diets. We hypothesized that any changes in SCD gene expression and activity would precede similar changes in adipose tissue lipogenesis between short- and long-fed end-points. Furthermore, changes in SCD activity and gene expression between production endpoints would differ between corn- and hay-fed steers and between Wagyu and Angus steers. Angus (n = 8) and Wagyu (n = 8) steers were fed a corn-based diet for 8 mo (short-fed; 16 mo of age) or 16 mo (long-fed; 24 mo of age), whereas another group of Angus (n = 8) and Wagyu (n = 8) steers was fed a hay-based diet for 12 mo (short-fed; 20 mo of age) or 20 mo (long-fed; 28 mo of age) to match the end point BW of the corn-fed steers. Acetate incorporation into lipids in vitro was greater (P < 0.01) in corn-fed steers than in hay-fed steers and tended (P = 0.06) to be greater in Wagyu than in Angus s.c. adipose tissue because the rate in Wagyu was twice that of Angus adipose tissue in the corn-fed, short-fed steers. There were diet x end point interactions for lipogenesis in i.m. and s.c. adipose tissues (both P < 0.01) because lipogenesis was 60 to 90% lower in the long-fed cattle than in short-fed cattle fed the corn-based diet. The greatest SCD enzyme activity in Angus s.c. adipose tissue was observed at 24 mo of age (corn-based diet), but activity in Wagyu adipose tissue was greatest at 28 mo of age (hay-based diet; breed x diet x end point interaction, P = 0.08). For short- vs. long-fed endpoints in Angus, s.c. adipose tissue SCD activity was less (hay diet) or the same (corn diet). Conversely, SCD gene expression was greatest in long-fed Wagyu steers fed the hay- or corn-based diets (breed x end point interaction; P < 0.01). Contrary to our hypotheses, SCD activity increased over time, whereas lipogenesis from acetate decreased. However, the developmental pattern of SCD gene expression and activity differed markedly between hay-fed Angus and Wagyu adipose tissues, which may explain the differences in the MUFA:SFA ratios observed in adipose tissues from these cattle. Key words: adipose tissue, bovine, lipogenesis, stearoyl-CoA desaturase