Establishment of a trastuzumab-resistant extramammary Paget disease model: loss of PTEN as a potential mechanism.

BACKGROUND/OBJECTIVES: Extramammary Paget disease (EMPD) is a rare, cutaneous intraepithelial adenocarcinoma typically treated with wide local excision. Unfortunately, a number of patients with metastases show poor responses to chemotherapy. While some studies have explored trastuzumab's effectiveness against EMPD positive for human epidermal growth factor receptor 2 (HER2), trastuzumab resistance (TR) may emerge after anti-HER2 therapy. METHODS/SUBJECTS: In this study, we established TR EMPD patient-derived xenografts (PDX) that replicated the histological and HER2 expression traits of naive EMPD tumours. RESULTS: Cancer gene analyses revealed a loss of the PTEN gene in TR tumours, which was further confirmed by immunohistochemical staining and immunoblotting to test for protein expression levels. Reduced PTEN levels correlated with increased protein kinase B (Akt) phosphorylation and p27 downregulation, suggesting a potential mechanism for trastuzumab resistance in EMPD cells. In the trastuzumab-sensitive EMPD-PDX mouse model, PTEN inhibitors partially restored trastuzumab-mediated tumour regression. The TR EMPD-PDX responded favourably to targeted therapy (lapatinib, abemaciclib, palbociclib) and chemotherapy (eribulin, docetaxel, trastuzumab deruxtecan). CONCLUSIONS: This study demonstrates an innovative TR EMPD-PDX model and introduces promising antineoplastic effects with various treatments for TR EMPD tumours.

The disaster liaison for pediatric and perinatal medicine: A new system in Japan.

BACKGROUND: Worldwide, children, newborns, and pregnant or postpartum women are vulnerable to disasters and emergency situations, and providing support to this population is of great concern. Japan is located in a disaster-prone area, so disaster response and risk reduction strategies are important priorities. METHODS: We introduce a system called the Disaster Liaison for Pediatric and Perinatal Medicine (DLPPM). This was created with a specific focus on perinatal children and pregnant women in Japan. We report the details of its activities, discuss its challenges, and draw on lessons learned for the further development of perinatal support systems, particularly for children. RESULTS: The lessons learned from the activities of the DLPPM include the following: (1) establish a support system for emergency specialists beyond those with pediatric and perinatal specialties; (2) mitigate the risk of indirect damage caused by primary disasters; and (3) establish a networking function linked to existing pediatric and perinatal medicine facilities. CONCLUSIONS: By establishing similar systems, we believe that it will be feasible to address pediatric and perinatal care needs in disaster response contexts in other countries and regions around the world.

Challenges and solutions for discharge support of elderly people in the acute care ward: Interviews with community-based integrated care supporters and patients in Tokyo, Japan.

Japan, which has become the country with the longest-living people in the world due to rapid population aging, has an insurer function for each local government and socialized long-term care under a public system. Japan aims to build a Community-based Integrated Care System (CICS) for each municipality with the goal of integrating medical care and long-term care. However, despite the policy and management studies, the challenges and solutions for discharge support by the parties have not yet been clarified. This study aimed to obtain suggestions on challenges and solutions for discharge support in the acute care wards for the elderly for community-based integrated care support providers and patients in Kita Ward, Tokyo. Semi-structured interviews were conducted, and the obtained data were a priori analyzed by a deductive thematic analysis using a conceptual framework for integrated care based on the integrative functions of primary care. The challenges were found to include: i) disparity between medical and lifestyle perspectives, ii) competencies of medical and care workers at homes, iii) discharge support challenges related to the elderly themselves, iv) nursing care dependent on family; and v) the impact of payment of medical service in the health insurance system and payment of long-term care services. The solution that can be applied at the local government level was community connection. While aiming to build a CICS for each local government, there was a contradiction in that the challenges and solutions required examination at the national and prefectural levels.

The role of community nurse in the implementation of health policy for the elderly in Thailand.

In the implementation of the policy for the elderly, the nurses who have the competency to pull out their potential power to continue living with several stakeholders' support are required to provide care in the community. Community nurse in Thailand has the responsibility to deliver adequate medical care and also social care for the elderly. The study aimed to identify the role of community nurse in the implementation of Thai health policy for the elderly. Codes regarding the role of community nurse in the implementation of Thai health policy for the elderly were extracted from descriptive data interviewed with 15 policy implementors in Thailand. The codes were categorized by similarities using thematic analysis. The role of community nurse was 16 categories and 102 codes out of factors promoting implementation of Thai health policy for the elderly, with 27 categories and 416 codes. The main roles were Coordination, Service delivery, and Monitoring and evaluation, composing seven categories and 45 codes, eight categories and 51 codes, and one category and six codes, respectively. It was conspicuous in coordination mechanisms, especially between the organizations and disciplines in providing Primary Health Care. Both health promotion activities and medical treatment were crucial roles for community nurses. The role of community nurse was one of promoting factors of Thai health policy for the elderly. The community nurse acts as a lubricant between the hospital and the community, which means that the community nurse implements seamless service delivery for the elderly integrating medical care and welfare.