Distinct clinical features and prognosis between persistent and temporary thyroid dysfunctions by immune-checkpoint inhibitors
Hidefumi Inaba, Hiroyuki Ariyasu, Hiroshi Iwakura, Chiaki Kurimoto, Ken Takeshima, Shuhei Morita, Hiroto Furuta, Muneki Hotomi, Takashi Akamizu
Vol 68 No. 2
Immune-related adverse events in the thyroid glands (thyroid irAEs) during treatment with immune-checkpoint inhibitors (ICIs) are most frequent endocrine irAE. Thyroid irAE can be divided into that requiring continuous therapy for thyroid dysfunction (P-THY), and that requiring only temporal treatment (T-THY). However, predictive factors for those differential outcomes are unknown, and susceptibility of human leukocyte antigen (HLA) to thyroid irAE has never been investigated. This study aimed to elucidate clinical courses and prognosis of P-THY in comparison with T-THY in the aspect of thyroid immunity and HLA. Patients with P-THY (n = 15) that required L-T4 supplemental therapy for hypothyroidism for more than 3 months, and patients with T-THY who required no therapy or therapy within 1 month were enrolled in the study. Lower-value of TSH, higher-value of FT4, and lower value of TSH/FT4 were thought to be predictive markers to estimate P-THY. In addition, anti-thyroglobulin antibody (TgAb) levels were significantly higher in patients with P-THY than those in patients with T-THY. HLA-DPA1*01:03 and HLA-DPB1*02:01 allele, and their haplotype frequencies were significantly higher in patients with P-THY than those in controls. P-THY had better survival rate than T-THY. Pre-existing thyroid autoimmunity, the extent of thyroid dysfunction, and predisposing HLA were associated with the differential course of thyroid irAEs. It was suggested that thyroid function tests, TgAb, and HLA typing tests are useful for prediction of clinical course in thyroid irAEs.
Effects of resistance training using elastic bands on muscle strength with or without a leucine supplement for 48 weeks in elderly patients with type 2 diabetes
Yutaro Yamamoto, Yoshio Nagai, Shin Kawanabe, Yoshiaki Hishida, Koji Hiraki, Masakatsu Sone, Yasushi Tanaka
Vol 68 No. 3
Type 2 diabetes is associated with sarcopenia. Resistance training and appropriate nutritional therapy are reported to be effective for muscle strength and mass. This study aimed to evaluate the effect of resistance training using elastic bands at home combined with a leucine-rich amino acid supplement on muscle strength, physical function, and muscle mass in elderly type 2 diabetes. We conducted a 48-week prospective single-center randomized controlled trial in 60 patients who were randomly allocated to one of three groups: control (C), resistance exercise (R), and resistance exercise plus supplement (RL). R and RL groups performed daily bodyweight resistance training with elastic bands exercises at home, and the RL group also took 6 g of a leucine-rich amino acid supplement daily. Knee extension strength (muscle strength), grip strength, usual gait speed (physical function), muscle mass, and cognitive function were assessed at 0 and 48 weeks. Although the change in knee extension strength from baseline was significantly increased by 6.4 Nm (95% CI 1.0, 11.7) in the RL group (p = 0.036), no significant difference was observed among the three groups (p = 0.090). Physical function, muscle mass, and cognitive function also had no changes during the study period among the three groups. No additive effect of a leucine-rich amino acid supplement on muscle strength or mass was observed. Although a post hoc analysis comparing with or without resistance training (C group vs. R + RL group) found that knee extension strength was significantly increased (p = 0.028), and cognitive decline was less (p = 0.046) than in the C group.
The revised clinical practice guidelines on the management of thyroid tumors by the Japan Associations of Endocrine Surgeons: Core questions and recommendations for treatments of thyroid cancer
Yasuhiro Ito, Naoyoshi Onoda, Takahiro Okamoto
Vol. 67 No. 7
The Japan Associations of Endocrine Surgeons has developed the revised version of the Clinical Practice Guidelines for Thyroid Tumors. This article describes the guidelines translated into English for the 35 clinical questions relevant to the therapeutic management of thyroid cancers. The objective of the guidelines is to improve health-related outcomes in patients with thyroid tumors by enabling users to make their practice evidence-based and by minimizing any variations in clinical practice due to gaps in evidential knowledge among physicians. The guidelines give representative flow-charts on the management of papillary, follicular, medullary, and anaplastic thyroid carcinoma, along with recommendations for clinical questions by presenting evidence on the relevant outcomes including benefits, risks, and health conditions from patients' perspective. Therapeutic actions were recommended or not recommended either strongly (◎◎◎ or XXX) based on good evidence (😊)/good expert consensus (+++), or weakly (◎, ◎◎ or X, XX) based on poor evidence (😣)/poor expert consensus (+ or ++). Only 10 of the 51 recommendations given in the guidelines were supported by good evidence, whereas 35 were supported by good expert consensus. While implementing the current guidelines would be of help to achieve the objective, we need further clinical research to make our shared decision making to be more evidence-based.
Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men
Junichiro Irie, Emi Inagaki, Masataka Fujita, Hideaki Nakaya, Masanori Mitsuishi, Shintaro Yamaguchi, Kazuya Yamashita, Shuhei Shigaki, Takashi Ono, Hideo Yukioka, Hideyuki Okano, Yo-ichi Nabeshima, Shin-ichiro Imai, Masato Yasui, Kazuo Tsubota, Hiroshi Itoh
Vol 67 No. 2
Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NAD+) levels causes aging-related disorders and therapeutic approaches increasing cellular NAD+ prevent these disorders in animal models. The administration of nicotinamide mononucleotide (NMN) has been shown to mitigate aging-related dysfunctions. However, the safety of NMN in humans have remained unclear. We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men. A single-arm non-randomized intervention was conducted by single oral administration of 100, 250, and 500 mg NMN. Clinical findings and parameters, and the pharmacokinetics of NMN metabolites were investigated for 5 h after each intervention. Ophthalmic examination and sleep quality assessment were also conducted before and after the intervention. The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature. Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN. Results of ophthalmic examination and sleep quality score showed no differences before and after the intervention. Plasma concentrations of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration. The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects. Thus, the oral administration of NMN was found to be feasible, implicating a potential therapeutic strategy to mitigate aging-related disorders in humans.