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Kanako Azuma,1 Takashi Kawaguchi,2 Takuhiro Yamaguchi,3 Sayuri Motegi,1 Kimito Yamada,4 Kenji Onda,5 Satoru Iwase,6 Sakae Unezaki,2 Hironori Takeuchi1 1Department of Pharmacy, Tokyo Medical University Hospital, Tokyo, Japan; 2Department of Practical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; 3Division of Biostatistics, Tohoku University Graduate School of Medicine, Miyagi, Japan; 4Department of Breast Surgery, Tokyo Medical University Hospital, Tokyo, Japan; 5Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; 6Department of Emergency & Palliative Medicine, Faculty of Medicine, Saitama Medical University, Saitama, JapanCorrespondence: Takashi Kawaguchi Email tkawa@toyaku.ac.jpPurpose: The importance of shared decision-making (SDM) between physicians and patients is increasingly recognized. In Japan, patients have shown more willingness to participate in treatment if medical professionals provide sufficient information; however, relationships between physicians and patients have traditionally been asymmetric, with patients accepting information from physicians without discussion. To explore the benefits of SDM in cancer treatment, including confidence in treatment decisions, satisfaction with treatment, and trust in healthcare providers, this study developed Japanese versions of the Control Preference Scale (CPS) and Information Needs Questionnaire (INQ).Patients and Methods: Reliability and validity of the CPS and INQ were tested with 49 breast cancer patients.Results: The CPS showed good test–retest reliability (kappa coefficient: 0.61, weighted kappa coefficient: 0.61, Kendall’s tau coefficient: 0.61) and acceptable criterion validity. The INQ showed adequate consistency; the mean number of circular triads and coefficient of consistency were 3 (range 0– 19) and 0.9 (range 0.37– 1), respectively. Using the CPS and INQ to identify patients’ roles in decision-making and information needs, results further suggested that breast cancer patients in Japan want to participate in SDM. Medical issues, including disease spread and cure, were found to be of high interest, while social and psychological issues, including sexual attractiveness, genetic risk, and family impact, tended to be low.Conclusion: The Japanese CPS and INQ can be used to assess patients’ needs to improve care. Further, as patients’ information needs change along the care trajectory, these tools should be used throughout treatment.Keywords: shared decision-making, breast cancer, treatment option, control preference scale, information needs questionnaire

Recently, steroid reduction/withdrawal regimens have been attempted to minimize the side effects of steroids in renal transplantation. However, some recipients have experienced an increase/resumption of steroid administrations and acute graft rejection (AR). Therefore, we investigated the relationship between the individual lymphocyte sensitivity to steroids and the clinical outcome after steroid reduction/withdrawal. We cultured peripheral blood mononuclear cells (PBMCs) isolated from 24 recipients with concanavalin A (Con A) in the presence of methylprednisolone (MPSL) or cortisol (COR) for four days, and the 50% of PBMC proliferation (IC50) values and the PBMC sensitivity to steroids were calculated. Regarding the experience of steroid increase/resumption and incidence of AR within one year of steroid reduction/withdrawal, the IC50 values of these drugs before transplantation in the clinical event group were significantly higher than those in the event-free group. The cumulative incidence of steroid increase/resumption and AR in the PBMC high-sensitivity groups to these drugs before transplantation were significantly lower than those in the low-sensitivity groups. These observations suggested that an individual’s lymphocyte sensitivity to steroids could be a reliable biomarker to predict the clinical outcome after steroid reduction/withdrawal and to select the patients whose dose of steroids can be decreased and/or withdrawn after transplantation.

An SN2 mechanism was proposed for highly stereoselective glycosylation of benzoic acid with unprotected α-d-glucose under Mitsunobu conditions in dioxane, while an SN1 mechanism was indicated for nonstereoselective glycosylation in DMF. The SN2-type stereoselective Mitsunobu glycosylation is generally applicable to various unprotected pyranoses as glycosyl donors in combination with a wide range of acidic glycosyl acceptors such as carboxylic acids, phenols, and imides, retaining its high stereoselectivity (33 examples). Glycosylation of a carboxylic acid with unprotected α-d-mannose proceeded also in an SN2 manner to directly afford a usually less accessible 1,2-cis-mannoside. One- or two-step total syntheses of five simple natural glycosides were performed using the glycosylation strategy presented here using unprotected α-d-glucose.

Background Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations. Methods The study included 83 patients who received consecutive living-donor kidney transplants at our facility from June 2013 to December 2016. Comparisons were made between 48 cases of induction with TacER and 35 cases of induction with cyclosporine (CyA). The observation period was 3 months after transplantation. Transplanted kidney function, rejection, infectious disease, lipid abnormalities, and glucose tolerance were compared. Results The 2 groups showed no significant difference in donor background or transplanted kidney function. Within the 3-month observation period, an acute rejection response was observed in 2 cases in the TacER group and in 8 cases in the CyA group. After transplantation, hyperlipidemia requiring medication was observed more frequently in the CyA group. The 2 groups did not show a marked difference in systemic infection or renal calcineurin inhibitor toxicity in histopathologic examination of the transplanted kidneys 3 months after surgery. Discussion Proactive use of TacER leads to improved adherence while yielding immunosuppressive potency equivalent to that of conventional tacrolimus preparations; however, tacrolimus has a potent blood sugar-elevating effect; thus, direct comparison with the CyA group is important for assessing the side effects. Conclusion TacER has the potential to also reduce side effects in the early stages after surgery, suggesting its potential as a drug of first choice.

An SN2 mechanism was proposed for highly stereoselective glycosylation of benzoic acid with unprotected α-D-glucose under Mitsunobu conditions in dioxane, while an SN1 mechanism seems to be responsible for non-stereoselective glycosylation in DMF. The SN2-type glycosylation can be applicable to various unprotected pyranoses as glycosyl donors and a wide range of carboxylic acids, phenols, and imides as glycosyl acceptors, retaining its high stereoselectivity (34 examples). Glycosylation of a carboxylic acid with unprotected α-D-mannose proceeded also in an SN2 manner to directly afford a usually less accessible 1,2-cis-mannoside. An extremely short-step total synthesis of a middle molecule (1874 Da) natural glycoside with antitumor activity, coriariin A, was achieved via a double SN2 glycosylation strategy with two molecules of unprotected α-D-glucose.

A short-step total synthesis of the natural glycosides pterocarinin C and tellimagrandin II (eugeniin) has been performed by sequential and site-selective functionalization of free hydroxy groups of unprotected D-glucose. The key reactions are β-selective glycosidation of a gallic acid derivative using unprotected D-glucose as a glycosyl donor and catalyst-controlled site-selective introduction of a galloyl group into the inherently less reactive hydroxy group of the glucoside.