Objectives: To clarify the preferences for survival time (ST) or quality of life (QOL) in the treatments for advanced cancer. Method: Patients with breast cancer, oncologists, and healthcare-providers including nurses, pharmacists and medical clerks were asked to anonymously complete a survey: The survey included questions regarding 1) priority among treatment options for a fictitious cancer patient, 2) preference of treatment aggressiveness for fictitious cancer patients by age group, 3) preference of treatment among options, with different weight on ST and QOL. Results: 1) Cancer patients' priority regarding ST and QOL was clearer than healthcare providers. 2) Oncologists tended to prioritize ST than cancer patients and other medical staffs in elderly patients. 3) Patients and oncologists tended to prioritize ST, whereas and other medical staffs prioritized QOL. Conclusion: Cancer patients and healthcare providers may have different perception regarding a treatment goal, which should be recognized in the practice of oncology.

Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

Effects of anti-oketsu drug, Keishibukuryogan (Gui-zhi-fu-ling-wan) and Tokishakuyakusan (Dang-gui-shao-yao-san) in vivo and in vitro on platelet aggregation were investigated in normal volunteers.
Of 20 volunteers who were given Keishibukuryogan, there were 6, 3 and 11 subjects whose dose-response curves of collagen-induced aggregations were shifted to the right, to the left, or who had no shift, respectively. The control aggregations of these 20 people were in the same range. In ADP-induced aggregation, there were 5 curves shifted to the right. Their potencies in the control aggregation were higher than those of 9 subjects who were not affected by the drug. There were 6 curves shifted to the left, and their potencies were lower than those of the 9 unaffected subjects. Of 12 volunteers who were given Tokishakuyakusan, there were 2, 2 and 8 subjects whose dose-response curves in collagen-induced aggregation were shifted to the right, the left, or who had no shift respectively. With ADP-induced aggregation, there were 1, 1 and 10 subjects whose doseresponse curves were shifted likewise. In vitro, Keishibukuryogan caused inhibition of ADP-induced aggregation but not that of collagen-induced aggregation.

BACKGROUND: Oral food challenge (OFC) tests are conducted in both specialized institutions and general hospitals. We aimed to compare the severity of the conditions of the patients between these 2 types of institutions in order to consider the role of such institutions in society. OBJECTIVE: We evaluated the results of OFC tests for hen's egg, cow's milk, and wheat that were conducted in a specialized institution (Aichi Children's Health and Medical Center [ACHMC], n = 835) and in 4 general hospitals (n = 327) in Aichi prefecture, Japan. METHODS: The symptoms provoked were scored using the total score (TS) of the Anaphylaxis Scoring Aichi scoring system in combination with the total ingested protein dose (Pro) before the appearance of allergic symptoms. RESULTS: The total ingested dose of the challenge-positive patients in ACHMC was significantly less than that in the general hospitals (p < 0.01). The median TS of the provoked symptoms in ACHMC and the general hospitals did not differ to a statistically significant extent in the hen's egg or cow's milk challenges; however, the median TS in ACHMC was significantly lower than that in the general hospitals for the wheat challenge (p = 0.02). The median TS/Pro values in ACHMC were almost identical to the upper 25% of the TS/Pro values in the general hospitals, suggesting that the specialized institution usually managed more severe patients. CONCLUSION: The specialized institution performed OFC tests at a lower threshold dose, but provoked similar TSs to the general hospitals. This evaluation may help in optimizing the distribution of patients to general hospitals and specialized institutions.
Anaphylaxis ; Child Health ; Hospitals, General ; Hospitals, Special ; Humans ; Japan ; Milk ; Ovum ; Severity of Illness Index ; Triticum

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

Background: Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear. Methods: In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021. Results: Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset. Conclusion Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

Background/Aims: Mirikizumab is a p19-directed anti-interleukin-23 antibody with potential efficacy against ulcerative colitis (UC). We evaluated the efficacy and safety of mirikizumab in a Japanese subpopulation with moderately to severely active UC from the LUCENT-1 and LUCENT-2 studies. Methods: LUCENT-1 and LUCENT-2 were phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab therapy in adults with moderately to severely active UC. LUCENT-1 was a 12-week induction trial where patients were randomized 3:1 to receive intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W). Patients achieving a clinical response with mirikizumab following the induction study were re-randomized 2:1 to double-blind treatment with either mirikizumab 200 mg or placebo subcutaneously Q4W during the 40-week maintenance study. The primary outcomes were clinical remission at week 12 of LUCENT-1 and week 40 of LUCENT-2. Results: A total of 137 patients enrolled in Japan were randomized to mirikizumab (n = 102) or placebo (n = 35). Compared with placebo, patients who received mirikizumab showed numerically higher clinical remission at week 12 of induction (32.4% [n = 33] vs. 2.9% [n = 1]) and at week 40 of maintenance (48.9% [n = 23] vs. 28.0% [n = 7]). A greater number of patients achieved key secondary endpoints in the mirikizumab group compared with placebo. The frequency of treatment-emergent adverse events was similar across mirikizumab and placebo groups. Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population. Conclusions Mirikizumab induction and maintenance treatments were effective in Japanese patients with moderately to severely active UC. No new safety concerns were identified.

BACKGROUND/AIMS: There are few reports on the correlation between chewing gum and the gastrointestinal functions. But previous report showed use of chewing gum to be an effective method for controlling gastrointestinal symptoms. The aim of this study was to determine the correlation between chewing gum and gastric emptying using the continuous real time 13C breath test (BreathID system). METHODS: Ten healthy male volunteers participated in this randomized, 2-way crossover study. The subjects fasted overnight and were randomly assigned to chewing gum (Xylish, 2-3/1 tablet) for an hour following intake of a test meal (200 kcal/200 mL) or intake of the test meal alone. Gastric emptying was monitored for 4 hours after administration of the test meal by the 13C-acetic acid breath test performed continually using the BreathID system. RESULTS: No significant differences in the calculated parameters, namely, T1/2 (median, 111.82 vs 109.26 minutes; P = 0.575), Tlag (median, 53.28 vs 56.53 minutes; P = 0.333), gastric emptying coefficient (median, 3.58 vs 3.65; P = 0.285), regression-estimated constant beta (median, 1.85 vs 1.80; P = 0.575) and regression-estimated constant kappa (median, 0.61 vs 0.62; P = 0.959) were observed between the test meal alone group and the test meal and chewing gum group. CONCLUSIONS: This study showed that chewing gum had no effect on the rate of gastric emptying. Therefore, since chewing gum did not enhance the speed of gastric emptying, it may ameliorate gastrointestinal symptoms through other mechanisms, such as saliva and autonomic nervous system.
Autonomic Nervous System ; Breath Tests ; Chewing Gum ; Cross-Over Studies ; Gastric Emptying ; Humans ; Male ; Mastication ; Meals ; Saliva

BACKGROUND/AIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test. METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (beta and kappa), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically. RESULTS: No significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or beta and kappa, were observed between the 2 test conditions. CONCLUSIONS: The present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.
Breath Tests ; Cross-Over Studies ; Eating ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Incretins ; Male ; Meals ; Pyrazines ; Triazoles ; Sitagliptin Phosphate