Estrogens attenuate renal injury induced by ischemia/reperfusion (I/R), an effect that is related to nitric oxide production in the post-ischemic kidney. The compound 17beta-estradiol (E(2)-beta) acting via estrogen receptors (ERs) is known to activate endothelial nitric oxide synthase (eNOS) through the phosphatidylinositol-3 kinase (PI3K)/Akt pathway. We determined if this pathway contributes to the renoprotective effect of E(2)-beta in the uninephrectomized ischemia reperfusion rat model of acute renal injury. Treatment with E(2)-beta suppressed the I/R-induced increases in blood urea nitrogen, plasma creatinine, urine flow, and fractional excretion of sodium while augmenting creatinine clearance, renal blood flow, and urine osmolality, indicating attenuation of renal injury. Phosphorylation of Akt and eNOS protein was significantly increased 30-60 min after reperfusion in estradiol-treated compared to vehicle-treated rats. The protective effects of E(2)-beta and protein phosphorylation were reversed by the PI3K inhibitor wortmannin or the ER antagonist tamoxifen. Furthermore, the E(2)-beta-induced renoprotective effects were not seen in eNOS knockout mice with renal injury. We conclude that the E(2)-beta-induced renoprotective effect is due to activation of the PI3K/Akt pathway followed by increased eNOS phosphorylation in the post-ischemic kidney.

Using Naϩ /Ca 2ϩ exchanger (NCX1)-deficient mice, the pathophysiological role of Ca 2ϩ overload via the reverse mode of NCX1 in ischemia/reperfusion-induced renal injury was investigated. Because NCX1 Ϫ/Ϫ homozygous mice die of heart failure before birth, we used NCX1 ϩ/Ϫ heterozygous mice. NCX1 protein in the kidney of heterozygous mice decreased to about half of that of wild-type mice. Expression of NCX1 protein in the tubular epithelial cells and Ca 2ϩ influx via NCX1 in renal tubules were markedly attenuated in the heterozygous mice. Ischemia/ reperfusion-induced renal dysfunction in heterozygous mice was significantly attenuated compared with cases in wild-type mice. Histological renal damage such as tubular necrosis and proteinaceous casts in tubuli in heterozygous mice were much less than that in wild-type mice. Ca 2ϩ deposition in necrotic tubular epithelium was observed more markedly in wild-type than in heterozygous mice. Increases in renal endothelin-1 content were greater in wild-type than in heterozygous mice, and this reflected the difference in immunohistochemical endothelin-1 localization in necrotic tubular epithelium. When the preischemic treatment with KB-R7943 was performed, the renal functional parameters of both NCX1 ϩ/ϩ and NCX1 ϩ/Ϫ acute renal failure mice were improved to the same level. These findings strongly support the view that Ca 2ϩ overload via the reverse mode of Na ϩ /Ca 2ϩ exchange, followed by renal endothelin-1 overproduction, plays an important role in the pathogenesis of ischemia/reperfusion-induced renal injury.Renal ischemia is characterized by the depletion of ATP and the development of intracellular acidosis, which alter cellular ionic homeostasis. In particular, elevated intracellular Ca 2ϩ concentration causes cellular injury during ischemia and leads to irreversible renal damage during reperfusion (Schrier et al., 1987). An increase in the intracellular Na ϩ concentration has been shown to correlate with Ca 2ϩ

Background: Palliative care is highly relevant for patients with heart failure (HF), and there is a need for quantitative information on quality of care. Accordingly, this study aimed to develop a set of quality indicators (QIs) for palliative care of HF patients, and to conduct a practical pilot measurement of the proposed QIs in clinical practice. Methods and Results: We used a modified Delphi technique, a consensus method that involves a comprehensive literature review, face-to-face multidisciplinary panel meeting, and anonymous rating in 2 rounds. A 15-member multidisciplinary expert panel individually rated each potential indicator on a scale of 1 (lowest) to 9 (highest) for appropriateness. All indicators receiving a median score ≥7 without significant disagreement were included in the final set of QIs. Through the consensus-building process, 35 QIs were proposed for palliative care in HF patients. Practical measurement in HF patients (n=131) from 3 teaching hospitals revealed that all of the proposed QIs could be obtained retrospectively from medical records, and the following QIs had low performance (<10%): "Intervention by multidisciplinary team", "Opioid therapy for patients with refractory dyspnea", and "Screening for psychological symptoms". Conclusions: The first set of QIs for palliative care of HF patients was developed and could clarify quantitative information and might improve the quality of care.

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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity worldwide. Patients with severe COPD often fail to receive adequate palliative care and are subject to undesired hospital transfers and cardiopulmonary resuscitation. Although promoting advance care planning (ACP) in the community can help ensure the optimal delivery of palliative care for patients with COPD, the key challenges to routinely implementing ACP are not known. The aim of this study was to identify the perception of healthcare professionals with regard to ACP for adults living with severe COPD and the challenges to facilitating ACP. A multicenter qualitative study design was used. In-depth semistructured interviews were held involving 38 healthcare professionals from 19 institutions in Japan. Text data were analyzed by content analysis. Five main themes capturing the challenges to routine implementation of ACP were identified: daily decision-making; sense of ethical decision-making; in-depth interviewing skills; collaborative information sharing among team members; and knowledge dissemination regarding ACP. The model demonstrates the complexity inherent in ACP facilitation for community-dwelling adults with severe COPD, with all the elements required for successful ACP implementation. We recommend an approach that recognizes the importance of stakeholder education, particularly educating professionals to develop the knowledge, attitudes, and skills required for ACP facilitation: in-depth interviewing, collaborative information sharing, and ethical analysis, focusing on decision-making concerning everyday life support.

Advance care planning is considered an important issue in end‐of‐life care for older adults. The ongoing COVID‐19 pandemic has interrupted the healthcare system and end‐of‐life care tremendously. This review aimed to explore available articles on advance care planning amid the pandemic and analyze qualitatively. PubMed and Google Scholar were searched on February 2021 using the relevant keywords. Retrieved articles were screened applying inclusion criteria. Any article describing advance care planning during the COVID‐19 era was included. A qualitative content analysis was conducted. In total, 20 articles incorporating 5542 participants from five countries were included. Among the articles, eight were primary studies and the rest were perspective papers or secondary analysis. From the qualitative content analysis six major themes emerged namely palliative care, lack of coordination among acute care, hospital palliative care, and long‐term care, community‐based advance care planning, real‐time dissemination of scientific information on the regional pandemic situation, online system and legislation. The COVID‐19 pandemic had decreased the uptake of advance care planning. Findings of the review suggested simplification of the procedure regarding advance care planning, implementation of community‐based advance care planning and utilization of online resources to enhance the process. Geriatr Gerontol Int 2021; 21: 779–787.

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Since the end of 2019, a life‐threatening infectious disease (coronavirus disease 2019: COVID‐19) has spread globally, and numerous victims have been reported. In particular, older persons tend to suffer more severely when infected with a novel coronavirus (SARS‐CoV‐2) and have higher case mortality rates; additionally, outbreaks frequently occur in hospitals and long‐term care facilities where most of the residents are older persons. Unfortunately, it has been stated that the COVID‐19 pandemic has caused a medical collapse in some countries, resulting in the depletion of medical resources, such as ventilators, and triage based on chronological age. Furthermore, as some COVID‐19 cases show a rapid deterioration of clinical symptoms and accordingly, the medical and long‐term care staff cannot always confirm the patient's values and wishes in time, we are very concerned as to whether older patients are receiving the medical and long‐term care services that they wish for. It was once again recognized that it is vital to implement advance care planning as early as possible before suffering from COVID‐19. To this end, in August 2020, the Japan Geriatrics Society announced ethical recommendations for medical and long‐term care for older persons and emphasized the importance of conducting advance care planning at earlier stages. Geriatr Gerontol Int 2020; 20: 1112–1119.