A 3D atlas of the human developing pancreas to explore progenitor proliferation and differentiation.

AIMS/HYPOTHESIS: Rodent pancreas development has been described in great detail. On the other hand, there are still gaps in our understanding of the developmental trajectories of pancreatic cells during human ontogenesis. Here, our aim was to map the spatial and chronological dynamics of human pancreatic cell differentiation and proliferation by using 3D imaging of cleared human embryonic and fetal pancreases. METHODS: We combined tissue clearing with light-sheet fluorescence imaging in human embryonic and fetal pancreases during the first trimester of pregnancy. In addition, we validated an explant culture system enabling in vitro proliferation of pancreatic progenitors to determine the mitogenic effect of candidate molecules. RESULTS: We detected the first insulin-positive cells as early as five post-conceptional weeks, two weeks earlier than previously observed. We observed few insulin-positive clusters at five post-conceptional weeks (mean ± SD 9.25±5.65) with a sharp increase to 11 post-conceptional weeks (4307±152.34). We identified a central niche as the location of onset of the earliest insulin cell production and detected extra-pancreatic loci within the adjacent developing gut. Conversely, proliferating pancreatic progenitors were located in the periphery of the epithelium, suggesting the existence of two separated pancreatic niches for differentiation and proliferation. Additionally, we observed that the proliferation ratio of progenitors ranged between 20% and 30%, while for insulin-positive cells it was 1%. We next unveiled a mitogenic effect of the platelet-derived growth factor AA isoform (PDGFAA) in progenitors acting through the pancreatic mesenchyme by increasing threefold the number of proliferating progenitors. CONCLUSIONS/INTERPRETATION: This work presents a first 3D atlas of the human developing pancreas, charting both endocrine and proliferating cells across early development.

Mason Caregivers Aiming for Resilience, Empowerment, and Support Study: Assessing Family Caregiver Burden Post-Intervention.

Background: Family caregivers of older adults living with dementia are known to experience higher burden levels. Methods: This empirical study conducted a sub-group analysis of burden levels of 97 family caregivers by the dementia severity of care recipients. Family caregivers were assessed before and after the 9-week Stress-Busting Program for Family CaregiversTM (SBP). Results: Family caregivers of older adults living with severe dementia had the highest baseline Zarit Burden Interview (ZBI) score of 27.7 which decreased to 25.0 (p < .05); family caregivers of those living with moderate dementia had a baseline ZBI score of 24.3 which decreased to 20.4 (p < .01); and family caregivers of those living with mild dementia had the lowest baseline ZBI score of 21.0, which decreased to 18.0 (p < .01). Conclusion: The SBP intervention was associated with a 15% reduction in burden scores for family caregivers of older adults living with dementia.

A Comprehensive Analysis of Litigation in Organ Transplantation for Allegations of Insufficient Policy Coverage, Discrimination and Malpractice.

Introduction: Transplantation is a field with unique medical and administrative challenges that involve an equally diverse array of stakeholders. Expectantly, the litigation stemming from this field should be similarly nuanced. There is a paucity of comprehensive reviews characterizing this medicolegal landscape. Design: The Caselaw Access Project Database was used to collect official court briefs of 2053 lawsuits related to kidney, liver, heart, lung, and pancreas transplantation. A thematic analysis was undertaken to characterize grounds for litigation, defendant type, and outcomes. Cases were grouped into policy, discrimination, poor or unsuccessful outcome, or other categories. Results: One hundred sixty-four court cases were included for analysis. Cases involving disputes over policy coverage were the most common across all organ types (N = 55, 33.5%). This was followed by poor outcomes (N = 51, 31.1%), allegations of discrimination against prison systems and employers (N = 37, 22.6%) and other (N = 21, 12.8%). Defendants involved in discrimination trials won with the greatest frequency (N = 29, 90.62%). Defendants implicated in policy suits won 65.3% (N = 32), poor outcomes 62.2% (N = 28), and other 70% (N = 14). Of the 51 cases involving poor outcomes, plaintiffs indicated lack of informed consent in 23 (45.1%). Conclusion: Reconsidering the informed consent process may be a viable means of mitigating future legal action. Most discrimination suits favoring defendants suggested previous concerns of structural injustices in transplantation may not be founded. The prevalence of policy-related cases could be an indication of financial burden on patients. Future work and advocacy will need to substantiate these concerns and address change where legal recourse falls short.

Chronic Health Conditions and Patient Portal Use in Caregivers of People With Alzheimer's Disease and Related Dementias.

This study aimed to investigate both chronic health conditions and the utilization of patient portals, focusing particularly on caregivers responsible for individuals with Alzheimer's disease and related dementias (ADRD). Data from the Health Information National Trends Survey 2018-2020 were analyzed, involving a sample of 304 family and unpaid caregivers of individuals with ADRD. Among caregivers of individuals with ADRD, 77.6% had at least one chronic disease. A significant proportion (46.6%) of ADRD caregivers had never accessed their patient portals. The limited utilization of patient portals among caregivers responsible for individuals with ADRD, particularly those with lower education, advanced age, and few chronic conditions, becomes apparent due to challenges associated with digital literacy and discomfort with computers. Recognizing the crucial role caregivers play for individuals with ADRD and their health risks, there's a need for tailored training to enhance their health management skills and caregiving capabilities.

Mental Health of Older Adults by Sexual Minority Status: Evidence From the 2021 National Health Interview Survey.

This study explored differences among older adults in mental health by sexual minority status. Data came from the 2021 U.S. National Health Interview Survey. The study sample included older adults (or those aged ≥50 years, N = 15,559), and of those, two percent (n = 380) self-identified as lesbian, gay, or bisexual (LGB). Older LGB adults had significantly higher odds of reporting a diagnosis of depression and anxiety and experiencing serious psychological distress than older non-LGB adults. Additionally, older LGB adults reported higher odds of experiencing depression and anxiety more frequently than older non-LGB adults. Significant covariates included age, sex, housing, food security, and social support. Increased risk for mental illness may be long-term consequences of stigma and discrimination that this population has experienced over the life course. The combination of structural interventions and affirming mental healthcare that recognizes the cumulative negative experience among older LGB adults is necessary to achieve mental health equity.

A tridimensional atlas of the developing human head.

The evolution and development of the head have long captivated researchers due to the crucial role of the head as the gateway for sensory stimuli and the intricate structural complexity of the head. Although significant progress has been made in understanding head development in various vertebrate species, our knowledge of early human head ontogeny remains limited. Here, we used advanced whole-mount immunostaining and 3D imaging techniques to generate a comprehensive 3D cellular atlas of human head embryogenesis. We present detailed developmental series of diverse head tissues and cell types, including muscles, vasculature, cartilage, peripheral nerves, and exocrine glands. These datasets, accessible through a dedicated web interface, provide insights into human embryogenesis. We offer perspectives on the branching morphogenesis of human exocrine glands and unknown features of the development of neurovascular and skeletomuscular structures. These insights into human embryology have important implications for understanding craniofacial defects and neurological disorders and advancing diagnostic and therapeutic strategies.

Prevalence of hyponatremia and associated factors in patients with chronic kidney disease: the Fukuoka Kidney Disease Registry (FKR) study.

BACKGROUND: Hyponatremia is a common and important electrolyte disorder. However, the prevalence and factors associated with hyponatremia in patients with chronic kidney disease (CKD) are unknown. METHODS: We studied the factors associated with hyponatremia (< 135 mEq/L) in CKD patients registered in the Fukuoka Kidney Disease Registry (FKR) study using a logistic regression model variable selected using the variable reduction method. RESULTS: We analyzed the baseline characteristics of 4367 participants with CKD (age, 64 ± 16 years; male, 56.1%). Hyponatremia was detected in 2.0% of the patients at baseline, and multivariate logistic analysis showed that the independent factors for hyponatremia were body mass index (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.85-0.97), prescription of benzodiazepine (OR 2.31; 95% CI 1.39-3.86), blood hemoglobin level (OR 0.76; 95% CI 0.65-0.88), and serum C-reactive protein level (OR 1.27; 95% CI 1.04-1.54). CONCLUSION: The cross-sectional analysis using baseline data from the FKR study revealed independent factors associated with hyponatremia in patients with decreased kidney function. Longitudinal analyses of the FKR cohort are needed to evaluate the effects of these factors on the prognosis of hyponatremia in patients with CKD.

Yolk sac cell atlas reveals multiorgan functions during human early development.

The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation. We reconstructed the emergence and decline of YS hematopoietic stem and progenitor cells from hemogenic endothelium and revealed a YS-specific accelerated route to macrophage production that seeds developing organs. The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds.

Opinion and Sentiment Analysis of Palliative Care in the Era of COVID-19.

During the COVID-19 pandemic, the value of palliative care has become more evident than ever. The current study quantitatively investigated the perceptions of palliative care emerging from the pandemic experience by analyzing a total of 26,494 English Tweets collected between 1 January 2020 and 1 January 2022. Such an investigation was considered invaluable in the era of more people sharing and seeking healthcare information on social media, as well as the emerging roles of palliative care. Using a web scraping method, we reviewed 6000 randomly selected Tweets and identified four themes in the extracted Tweets: (1) Negative Impact of the Pandemic on Palliative Care; (2) Positive Impact of the Pandemic on Palliative Care; (3) Recognized Benefits of Palliative Care; (4) Myth of Palliative Care. Although a large volume of Tweets focused on the negative impact of COVID-19 on palliative care as expected, we found almost the same volume of Tweets that were focused on the positive impact of COVID-19 on palliative care. We also found a smaller volume of Tweets associated with myths about palliative care. Using these manually classified Tweets, we trained machine learning (ML) algorithms to automatically classify the remaining tweets. The automatic classification of Tweets was found to be effective in classifying the negative impact of the COVID-19.

Characteristics of Nursing Facilities and Staff Willingness to Implement a Non-Pharmacological Intervention.

While non-pharmacological interventions could positively impact mood and behaviors of nursing-home residents who are living with dementia, some facilities are more willing to adopt such interventions than others. This study investigated the characteristics of Medicaid-funded nursing facilities that were associated with their willingness to implement a non-pharmacological intervention, personalized music. Using the publicly-available dataset (aka LTCfocus) from Brown University, this study examined characteristics of nursing homes in Virginia that have implemented or are in the process of implementing a personalized music intervention (n = 59) and that have decided not to implement it (n = 216). The findings indicate that nursing facilities with a higher proportion of long-term residents are more likely to implement the intervention. The findings can inform future research recruitment strategies. In addition, a greater understanding of the use of non-pharmacological interventions in relation to the characteristics of nursing facilities offers insight to policymakers and public health officials regarding resource allocations to facilities.

Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade.

BACKGROUND: Thyroid dysfunction is frequently caused by treatment with antiprogrammed cell death-1 ligand 1 antibodies (PD-L1-Abs) and anticancer drugs, including ramucirumab (RAM) and multitargeted tyrosine kinase inhibitors (multi-TKIs), which are often used prior to PD-L1-Ab treatment in cancer patients. METHODS: A total of 148 patients treated with PD-L1-Abs were evaluated for antithyroid antibodies at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then were observed until the visits stopped. RESULTS: Of the 148 patients, 15 (10.1%) developed thyroid dysfunction after PD-L1-Ab treatment (destructive thyroiditis in 8 and hypothyroidism without preceding thyrotoxicosis in 7). The prevalence of an elevated thyroid-stimulating hormone (TSH) level at baseline (3/15 [20.0%] vs 4/133 [3.0%], P < .05), positive antithyroglobulin antibodies (TgAbs) at baseline (4/15 [26.7%] vs 5/133 [3.8%], P < .05) and prior treatment with RAM or multi-TKIs (3/15 [20.0%] vs 5/133 [3.8%], P < .05) were significantly higher in patients with vs without thyroid dysfunction. In a multivariate analysis, elevated TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs were significantly associated with the development of thyroid dysfunction, with ORs of 7.098 (95% CI 1.154-43.638), 11.927 (95% CI 2.526-56.316), and 8.476 (95% CI 1.592-45.115), respectively. CONCLUSION: The results of this real-world study suggest that the risk of thyroid dysfunction induced by PD-L1-Abs can be predicted by the TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs.

Drug-induced thrombocytopenia associated with trastuzumab in a patient with HER2-positive recurrent gastric cancer.

Here, we report a 57-year-old female patient with HER2-positive recurrent gastric cancer who experienced drug-induced thrombocytopenia associated with trastuzumab, a humanized anti-HER2 monoclonal antibody. Shortly after the initiation of S-1, oxaliplatin, and trastuzumab chemotherapy, the patient experienced severe thrombocytopenia and did not respond to platelet transfusions. Based on the findings of increased numbers of polynuclear megakaryocytes in the bone marrow and an elevated level of platelet-associated IgG (PA-IgG), the patient was diagnosed with drug-induced thrombocytopenia (DITP). The platelet count recovered rapidly with oral prednisolone (1 mg/kg). Since we initially suspected oxaliplatin as the causal agent, S-1 was restarted as a monotherapy, followed by trastuzumab after a 3-week interval, without oxaliplatin. On the second day after the addition of trastuzumab, severe thrombocytopenia occurred again, which suggests that trastuzumab was responsible for the DITP. The patient no longer experienced severe thrombocytopenia during the subsequent S-1 and oxaliplatin chemotherapy, which supports this hypothesis.

Strategies for implementing music-based interventions for people with dementia in long-term care facilities: A systematic review.

OBJECTIVES: Research has found that music-based interventions can decrease behavioral and psychological symptoms of dementia or behaviors that challenge (BPSD/BtC). However, how to effectively implement these interventions is unclear. This study synthesizes available evidence regarding implementation strategies and outcomes of music-based interventions for people with dementia at residential long-term care facilities. METHODS: Study registered with PROSPERO (registration number: CRD42020194354). We searched the following databases: PsychInfo, PubMed, MEDLINE, CINAHL, and The Cochrane Library. Inclusion criteria included articles targeting music-based interventions conducted for people with dementia, studies conducted in residential long-term care facilities, and articles that reported implementation strategies and outcomes of the intervention. RESULTS: Of the included eight studies, half were studies of music therapy and the other half were on individualized music. 49 implementation strategies were reported. The most frequently reported category of strategies was planning (34.7%), followed by education (24.5%), quality management (24.5%), restructuring (12.2%), and finance (4.1%). No strategies under the category of attending to the policy context were reported. The most frequently reported implementation outcomes were appropriateness (27.3%), followed by adoption (22.7%), fidelity (22.7%), acceptability (9.1%), sustainability (9.1%), and cost (9.1%). No studies measured feasibility or penetration. CONCLUSIONS: Although various effective implementation strategies were identified, we were unable to examine the effectiveness of individual implementation strategies due to the designs of the selected studies. Less attention has been paid to strategies that aim at structural changes of intervention delivery systems. Future studies should investigate facilitators and barriers of implementing music-based interventions especially focusing on structural aspects.

Culturally Responsive Companion Program for a Japanese Woman with Dementia in a U.S. Nursing Home.

The older foreign-born population is predicted to increase in the United States. As a whole, this population in the long-term care setting is more likely to face greater challenges associated with loneliness and social isolation due to their smaller social networks, language and cultural differences. The benefits of person-centered care have been widely recognized and may be a potential remedy for such challenges felt by older immigrants. Using a qualitative case study approach, this study explored the staff perceptions of a culturally responsive companion program provided to an older Japanese woman with advanced dementia in the long-term care setting to understand the potential benefits of such a program. The first theme that emerged was that the client benefitted from the program in regard to her physical wellbeing, emotional wellbeing, language communication and cultural support. Given the support of Japanese companions, the client was able to express her needs and health symptoms effectively and the staff were subsequently able to provide culturally-sensitive care. The second theme that emerged was the perceived benefits received by the staff. The companion program improved the staff's ability to provide quality care for the resident. This study implies that culturally responsive companion programs may benefit foreign-born older individuals in improving their wellbeing in long-term care settings.

Advance care planning in medicare/medicaid-funded agencies: providing a training in cultural competence.

This study presents a training that was developed for staff members at Medicare/Medicaid agencies to improve their knowledge and comfort levels in working on advance care planning (ACP) with their clients in a culturally competent manner. The training was developed to address the need to clarify the different types and purposes of ACP and to help develop the skills needed to work with clients of diverse cultural backgrounds. The evaluation of findings from the training showed the positive impacts that it had on participants; in particular, they exhibited demonstrated improvement in their knowledge of and comfort levels with ACP. The participants also expressed interest in receiving continued training surrounding ACP to increase their cultural competency skills and to receive updated information on ACP policies and practices.

Caregiving Experience and Other Factors Associated With Having End-Of-Life Discussions: A Cross-Sectional Study of a General Japanese Population.

CONTEXT: The factors associated with end-of-life discussion (EOLD) are not well elucidated; an understanding of these factors may help facilitate EOLD. OBJECTIVES: To investigate the associations between EOLD and experiences of the death of and/or care for a loved one and other factors. METHODS: Data from a nationwide anonymous questionnaire survey of public attitudes toward end-of-life medical care, conducted in December 2017 in Japan, were used. Participants were randomly selected from the general population (age ≥ 20 years), and respondents who completed the questionnaire were analyzed (respondents: n = 836; effective response rate: 13.9%). Respondents were divided into two groups based on their experience of EOLD: those who had engaged in EOLD and those who had not. The main predictors were the experiences of the death of and care for a loved one. Multivariable logistic regression analyses were performed. RESULTS: Of the 836 respondents (male: 55.6%, aged 65 and over: 43.5%), 43.7% reported their engagement in EOLD. In the analyses, "having experience of caring for a loved one" was associated with EOLD compared with never having experience (odds ratio 1.88, 95% confidence interval 1.35-2.64). However, having experience of the death of a loved one had no association. CONCLUSION: For health-care providers, it may be worth recognizing that the care experience of their patient's caregiver might affect the caregiver's own EOLD in the future.

Triamterene in lithium-induced nephrogenic diabetes insipidus: a case report.

Lithium-induced nephrogenic diabetes insipidus (NDI) is a rare and difficult-to-treat condition. We describe the case of an 81-year-old woman with bipolar treated with lithium and no previous history of diabetes insipidus. She was hospitalized due to disturbance of consciousness and was diagnosed with, hypercalcemia, hyperparathyroidism, and NDI. Parathyroidectomy was contraindicated and parathyroid hormone level was improved insufficiently after cinacalcet initiation, percutaneous ethanol injection therapy was performed for the enlarged parathyroid gland. After improvement in hypercalcemia and unsuccessful indapamide treatment, triamterene was administrated to control polyuria. Lithium is one of the indispensable maintenance treatment options for bipolar disorder, but it has the side effect of NDI. Lithium enters the collecting duct's principal cells mainly via the epithelial sodium channel (ENaC) located on their apical membranes, ENaC shows high selectivity for both sodium and lithium, is upregulated by aldosterone, and inhibited by triamterene. To our knowledge, this is the first publication on triamterene use in lithium-induced NDI patients.

Chemotherapy for biliary tract cancer: real-world experience in a single institute.

The standard chemotherapy regimen for unresectable or recurrent biliary tract cancer is gemcitabine combined with cisplatin (GC). To evaluate the effectiveness and safety of chemotherapy in patients with unresectable or recurrent biliary tract cancer in the real world, we retrospectively analyzed the clinical courses of patients who underwent chemotherapy with GC from January 2015 to November 2019. Forty-eight patients underwent the GC regimen. One patient (2.1%) achieved a complete response, seven patients (14.6%) achieved a partial response, 26 patients (54.2) achieved stable disease, 11 patients (22.9%) achieved progressive disease, and 3 patients (6.3%) were not evaluable. The overall response rate was 16.7%. The median overall survival was 14.2 months (95% CI: 13.8-14.6), and the median progression-free survival was 7.7 months (95% CI: 4.2-11.2). Thirty-nine patients (81.3%) experienced grade 3 or higher severe adverse events as follows: 54.2% experienced neutropenia, 20.8% experienced anemia, 12.5% experienced thrombocytopenia and 20.8% experienced biliary tract infection. As a second-line chemotherapy, S-1 was used in seventeen patients, and stable disease was achieved in three patients (17.6%). The GC regimen for biliary tract cancer is effective and safe for unresectable or recurrent biliary tract cancer in routine clinical practice.

Comparison of immunogenicity between candidate influenza A(H3N2) virus vaccine strains in Japan: A randomized controlled trial using a monovalent vaccine of A/Saitama/103/2014 (CEXP-002) and A/Hong Kong/4801/2014 (X-263).

BACKGROUND: For the 2017-18 influenza season, A/Saitama/103/2014 (CEXP-002) (Saitama strain) was antigenically more similar to prior circulating strains than A/Hong Kong/4801/2014 (X-263) (Hong Kong strain) in a ferret model and was selected as the A(H3N2) vaccine virus strain in Japan. However, the Saitama strain grew poorly, and the Japanese government switched to the Hong Kong strain, raising public concerns of poor effectiveness. To enhance understanding of the correlation between antigenicity in experimental models and immunogenicity, as a surrogate measure of vaccine effectiveness, in the human population, we compared the immunogenicity of specially-prepared single dose monovalent influenza A(H3N2) vaccines containing the Saitama or the Hong Kong strain. METHODS: A randomized controlled trial of 100 healthy adults aged 20-64 years (n = 50/group) was conducted. Virus neutralization assay was performed on sera from days 0 (pre-vaccination) and 21 (post-vaccination). Geometric mean titer (GMT), mean fold rise (MFR), seroconversion proportion (SCP), and seroprotection proportion (SPP) were calculated for vaccine strains and a representative circulating A(H3N2) virus strain (A/Osaka/188/2017). RESULTS: For the Hong Kong strain, post-vaccination GMT was significantly higher in the Hong Kong vaccine recipients (1:546 vs 1:260, p < 0.01), but MFR, SCP, and SPP were similar for both vaccine groups. For the Saitama strain, post-vaccination GMT (1:116 vs 1:61, p = 0.01) and SPP (86% vs 68%, p = 0.03) were significantly higher in the Hong Kong vaccine recipients, but MFR and SCP were similar for both vaccine groups. Against A/Osaka/188/2017, post-vaccination GMT and MFR were similar in both vaccine groups, but SCP (32% vs 4%, p < 0.01) and SPP (28% vs. 6%, p < 0.01) were significantly higher in the Hong Kong vaccine recipients. CONCLUSION: The Hong Kong vaccine induced better or equivalent immunogenicity in comparison to the Saitama vaccine. Our trial showed that antigenic similarity in experimental models does not necessarily correlate with immunogenicity in the human population. CLINICAL TRIAL REGISTRATION: UMIN000029293.

Pharmacokinetics and Safety of Single-Dose Esaxerenone in Japanese Subjects with Mild to Moderate Hepatic Impairment.

INTRODUCTION: The mineralocorticoid receptor (MR) blocker esaxerenone is a new treatment for hypertension in Japan and under development for treatment of diabetic nephropathy. Hepatic impairment is known to impact the pharmacokinetics (PKs) of other MR blocking drugs. The aim of the present study was to characterise the PKs and safety of a single oral dose of esaxerenone in Japanese subjects with mild-moderate hepatic impairment. METHODS: In this open-label, parallel-group study, subjects with mild (Child-Pugh grade A) or moderate (grade B) hepatic impairment, and healthy controls with normal hepatic function matched by age and BMI (all groups n = 6), received a single 2.5-mg oral dose of esaxerenone. Plasma concentrations were measured by liquid chromatography-tandem mass spectrometry, and PK parameters were calculated using non-compartmental analysis. RESULTS: Geometric least-squares mean (GLSM) ratios (90% confidence intervals [CIs]) for area under the plasma concentration-time curve (up to the last quantifiable time, up to infinity) in subjects with mild hepatic impairment versus normal hepatic function were 0.837 (0.637, 1.099) and 0.824 (0.622, 1.092), respectively. Corresponding values for moderate hepatic impairment versus normal hepatic function were 1.078 (0.820, 1.415) and 1.098 (0.829, 1.454). GLSM ratios (90% CIs) for peak plasma concentration (Cmax) were 0.959 (0.778, 1.182) for mild hepatic impairment versus normal hepatic function and 0.804 (0.653, 0.992) for moderate hepatic impairment versus normal hepatic function. Time to Cmax and clearance values were comparable between groups. The incidence of adverse events (AEs) was 16.7% in the moderate hepatic impairment and normal hepatic function groups. One serious AE (hepatic encephalopathy) occurred in one subject with moderate hepatic impairment. CONCLUSIONS: Mild to moderate hepatic impairment had no clinically relevant effect on esaxerenone exposure. Esaxerenone dosage adjustment based on PKs is unlikely to be needed in patients with mild to moderate hepatic impairment. TRIAL REGISTRATION: JapicCTI-163339. FUNDING: Daiichi Sankyo Co., Ltd.