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A Scoping Review of the Current State and Reality of Papers on End-of-Life Care at Home in Japan: Toward a Study of the State of End-of-Life Care in Nara Prefecture
Get PDF本研究の目的は，日本国内の看取りの研究の現状と課題を明らかにして，奈良県内の看取りのあり方を探究する資料とすることである。研究方法は，スコーピングレビューを用いた。Patient (P) :在宅(療養者)死， Concept (C) :ケアの内容，現状と実態， Context (C) :日本，看取りとして， PCCのフレームワークを用いた。使用したデータベースは，医学中央雑誌であった。一次スクリーニングで抽出された論文をスコーピングレビューチームで精読し採用論文を決定した。結果，一次スクリーニングでは8件，二次スクリーニングでは4件採択された。へき地に暮らす高齢者は困りごととして話す人はいなかった。死亡場所確認および予後説明があると意思決定支援につながることがわかった。看取り件数が多くなると訪問看護師の満足度は低くなるが，介護職で、は高い結果であった。訪問看護師の肯定的感情を高めることがモチベーションの維持向上になり，看取り支援の質向上へとつながる可能性が示唆された。The purpose of this study was to clarify the current status and issues of research on end-of-life care in Japan，and to provide material for exploring the state of end-of-life care in Nara Prefecture. A scoping review was conducted using electronic databases including the Central Journal of Medicine. The PCC framework was used. The keywords were Patient (p): death at home (caregiver)，Concept (C): content of care，current status and actual conditions，and Context (C): Japan，and end-of-life care. The PRISMA statement (the Preferred Reporting Items for Systematic Review) was also consulted. We selected papers from the primary screening process for inclusion in the scoping review team. In accordance with the research question (RQ),the scoping review team conducted a close reading of the literature extracted from the primary screening. In secondary screening， the selected papers in the primary screening were carefully read by the scoping review team. In addition，the literature was examined for its suitability for the RQ. As a result，eight papers were selected in the primary screening and four papers were selected in the secondary screening. None of the elderly people living in remote areas talked about living there as a problem. It was found that confirmation of the place of death and explanation of the prognosis helped to support the person's decision-making. Satisfaction was lower among home care nurses as the number of end-of-life care cases increased，but was higher among caregivers. It was suggested that higher positive emotions among home care nurses may help them maintain their motivation and improve the quality of end-of-life care
microRNA-345の過剰発現は、MUC1およびTJP2の発現を抑制することにより、膵管腺癌細胞株の浸潤能に影響を及ぼす
Get PDFThe majority of pancreatic carcinomas are pancreatic ductal adenocarcinomas (PDAC), and
the presence of non-invasive pancreatic intraepithelial neoplasia or intraductal papillary mucinous
neoplasm, as an associated lesion, is considered important. These microscopic hyperplastic or grossly
papillomatous lesions exhibit varying degrees of morphological atypia and may develop into invasive
carcinomas. In this study, we investigated whether mucin-1 (MUC1) is involved in the progression of
pancreatic carcinoma and examined the mechanisms by which microRNAs regulate MUC1 expression
in vitro. In PDAC cell lines, suppression of MUC1 expression reduced cell proliferation and invasion;
PDAC cell lines transfected with an miR-345 precursor suppressed the expression of MUC1, and
reduced cell proliferation and invasion. Tight junction protein 2 (TJP2), a putative target of miR-345,
is regulated by MUC1. The suppression of TJP2 expression reduced cell proliferation by inducing
apoptosis. These results suggest that MUC1 and TJP2, the putative target molecules of miR-345,
are critical in maintaining the invasive potential of pancreatic carcinoma cells, and regulating their
expression may prevent the progression of non-invasive pancreatic intraductal lesions to invasive
carcinomas. This study provides new insights for the development of novel molecular targeted
therapies for pancreatic carcinomas.博士（医学）・甲第866号・令和5年3月15日© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
非機能性下垂体腺腫における経鼻内視鏡下経蝶形骨洞手術後の遅発性低ナトリウム血症の手術因子の検討
Get PDFPurpose Delayed hyponatremia can occur after pituitary surgery, resulting in prolonged hospitalization. However, the
influence of surgical factors after such a procedure has not been well established. The impact of surgery and related factors
on delayed hyponatremia was investigated.
Methods This was a retrospective analysis of 137 consecutive patients who underwent transsphenoidal surgery for a
nonfunctioning pituitary adenoma between 2008 and 2019. Preoperative (demographics, comorbidities), intraoperative
(resection extent, operation time, blood loss volume, cerebrospinal fluid leak, tumor consistency), and postoperative
[hematoma, meningitis, diabetes insipidus (DI), hormonal assessment] data were collected, with statistical analysis of each
factor performed.
Results Among the 137 patients, delayed hyponatremia occurred in 31 (22.6%). Multivariate analysis revealed that those
with hypertension had a significantly higher likelihood of avoiding delayed hyponatremia (p = 0.004). Although no correlations
of direct surgical factors with delayed hyponatremia were found, multivariate analysis of indirect surgical factors
showed that presence of a firm tumor, transient DI, and meningitis were significantly associated with delayed hyponatremia
(p = 0.014, 0.001, and 0.047, respectively). There was also a significant association of severe hyponatremia with appearance
of symptoms (p = 0.002).
Conclusion There was a tendency for hypertension to be associated with delayed hyponatremia avoidance, with indirect
surgical factors including tumor consistency, transient DI, and meningitis found to have an influence on delayed hyponatremia.
It was concluded that attention should be given to non-hypertensive patients with a firm tumor, transient DI, or
meningitis after pituitary surgery, as delayed hyponatremia may occur.博士（医学）・甲第871号・令和5年3月15日© The Author(s) 2022
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder
がん治療に伴う心機能障害における心筋の病理組織学的およびエピジェネティックな変化
Get PDFAims：Cancer therapy-related cardiac dysfunction (CTRCD) is commonly reported, but its histopathology, mechanisms, and risk factors are not known. We aimed to clarify the histopathology and mechanisms of CTRCD to identify risk factors.
Methods and results：We performed myocardial histopathological studies on 13 endomyocardial biopsies from CTRCD patients, 35 autopsied cancer cases with or without cardiac dysfunction, and controls without cancer (10 biopsies and 9 autopsies). Cardiotoxicity risk scores were calculated based on medication; and patient-related risk factors, fibrosis, and cardiomyocyte changes were scored; and p53 and H3K27ac histone modification were evaluated by histological score (H-score). In the biopsy cases, all histopathological changes and the p53 evaluation were significantly higher in the CTRCD group than in the controls [p53 H-score; 63 (9.109) vs. 33 (5.099), P 4.2 years), cellular abnormalities and p53 trended to a positive correlation and cardiotoxicity risk scores and p53 positively correlated (r = 0.95, P < 0.05). A year after biopsy, the short-term group had significant recovery of ejection fraction compared with the long-term group (P < 0.05). The CTRCD group had a significantly worse overall survival prognosis than the control group [hazard ratio 7.61 (95% confidence interval 1.30–44.6), P < 0.05]. Autopsy cases with cancer treatment also had a high grade of histopathological changes, with even more severe changes in patients with cardiac dysfunction, and had increased p53 and H3K27ac expression levels, compared with controls. H-scores of p53 and H3K27ac showed a positive correlation in the CTRCD group in biopsy cases (r = 0.62, P < 0.05) and a positive correlation in autopsy cases.
Conclusions：Our results indicate distinct morphological characteristics in myocardial histopathology associated with CTRCD. p53 and H3K27ac histone modification could be sensitive markers of CTRCD and suggest a mechanistic involvement of epigenetic changes.権利情報：© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes
肘の内外反変形に伴う尺骨神経の伸長度変化に関する生体力学的研究
Get PDFBackground: Cubital tunnel syndrome can be caused by overtraction and dynamic compression in elbow deformities.
The extent to which elbow deformities contribute to ulnar nerve strain is unknown. Here, we investigated ulnar
nerve strain caused by cubitus valgus/varus deformity using fresh-frozen cadavers.
Methods: We used six fresh-frozen cadaver upper extremities. A strain gauge was placed on the ulnar nerve 2 cm
proximal to the medial epicondyle of the humerus. For the elbow deformity model, osteotomy was performed at the
distal humerus, and plate fixation was performed to create cubitus valgus/varus deformities (10°, 20°, and 30°). Ulnar
nerve strain caused by elbow flexion (0–125°) was measured in both the normal and deformity models. The strains at
different elbow flexion angles within each model were compared, and the strains at elbow extension and at maximum
elbow flexion were compared between the normal model and each elbow deformity model. However, in the
cubitus varus model, the ulnar nerve deflected more than the measurable range of the strain gauge; elbow flexion
of 60° or more were considered effective values. Statistical analysis of the strain values was performed with Friedman
test, followed by the Williams’ test (the Shirley‒Williams’ test for non-parametric analysis).
Results: In all models, ulnar nerve strain increased significantly from elbow extension to maximal flexion (control:
13.2%; cubitus valgus 10°: 13.6%; cubitus valgus 20°: 13.5%; cubitus valgus 30°: 12.2%; cubitus varus 10°: 8.3%; cubitus
varus 20°: 8.2%; cubitus varus 30°: 6.3%, P < 0.001). The control and cubitus valgus models had similar values, but the
cubitus varus models revealed that this deformity caused ulnar nerve relaxation.
Conclusions: Ulnar nerve strain significantly increased during elbow flexion. No significant increase in strain 2 cm
proximal to the medial epicondyle was observed in the cubitus valgus model. Major changes may have been
observed in the measurement behind the medial epicondyle. In the cubitus varus model, the ulnar nerve was relaxed
during elbow extension, but this effect was reduced by elbow flexion.博士（医学）・甲第865号・令和5年3月15日© The Author(s) 2022.
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data
OCT で検出された冠動脈のlipid-richプラークに対する至適薬物療法施行後の臨床経過
Get PDFBackground: The aim of this study was to evaluate optical coherence tomography (OCT)-detected lipid-rich coronary plaques
(LRCPs) with coronary computed tomography angiography (CCTA) 10 months after optimal medical therapy (OMT).
Methods and Results: Baseline OCT detected 28 LRCPs in non-culprit lesions. High-risk plaque features (HRPFs), such as positive
remodeling, very low attenuation plaques, napkin-ring sign, and spotty calcification, were observed in 67.9%, 67.9%, 21.4%, and
64.3% of LRCPs, respectively, at the 10-month follow-up CCTA. Lesions with ≥3 HRPFs were defined as high-risk LRCPs (n=12);
the remaining were defined as low-risk LRCPs (n=16). The maximum lipid arc on baseline OCT was larger in high- than low-risk
LRCPs (221±62° vs. 179±44°, respectively; P=0.04). Receiver operating characteristic curve analysis indicated that a maximum lipid
arc >154° on baseline OCT was the optimal cut-off value to predict high-risk LRCPs 10 months after OMT. Patients with high-risk
LRCPs had worse clinical outcomes, defined as a composite of cardiac death, target lesion-related myocardial infarction, and target
lesion-related revascularization, during follow-up than those with low-risk LRCPs (33.3% vs. 0%; P=0.01).
Conclusions: A high-risk LRCP at follow-up CCTA was correlated with a larger maximum lipid arc on baseline OCT. Further
aggressive treatment for patients with large LRCPs may reduce vulnerable plaque features and prevent future cardiac events.博士（医学）・甲第869号・令和5年3月15日© 2022, THE JAPANESE CIRCULATION SOCIETY
This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license
慢性期末梢前庭障害に対する前庭リハビリテーションの身体活動量と主観的なめまい感に対する効果：6カ月間のランダム化比較試験
Get PDFIntroduction: The present study aimed to determine whether supervised vestibular
rehabilitation therapy (VRT) by physical therapists (PTs) affects subjective dizziness in
patients with chronic vestibular disorders, and whether supervised VRT-induced changes
in subjective dizziness are related to the changes in physical activity levels in daily life.
Methods: Patients (n = 47) with chronic peripheral vestibular disorders were randomly
divided into the VRT group (n = 25) and control group (n = 22). Patients in the VRT group
received weekly supervised visits from PTs for a period of 6 months. Every other month,
both groups were advised by neuro-otologists to increase the amount of activity in their
daily life. All patients wore an accelerometer device, which recorded their physical activity
for seven successive days before the end of the intervention. Patients also completed
the dizziness and unsteadiness questionnaires before and after the intervention.
Results: Subjective dizziness decreased significantly regardless of whether supervised
VRT was administered; however, dizziness evoked by social activity and head and body
movements improved more significantly in the VRT group than in the control group. In the
VRT group, there was a significant negative correlation between the increase in sedentary
behavior and improvement in subjective dizziness, and a significant positive correlation
between the increase in light physical activity and improvement in subjective dizziness at
the second month of intervention. The VRT group showed a significantly higher rate of
increase in light physical activity than the control group, after 6 months of intervention.
Conclusion: Supervised VRT could be highly effective in treating subjective dizziness
in patients with chronic peripheral vestibular disorders. We believe frequent (weekly) and
medium-term (6 months) PT-guided interventions may be highly effective in enhancing
physical activity in daily life, and may subsequently improve subjective dizziness in
these patients.
Trial registration: This clinical study was registered with University hospital Medical
Information Network (identification number: 000028832). https://www.umin.ac.jp/博士（医学）・甲第878号・令和5年3月15日© 2021 Shiozaki, Ito, Wada, Yamanaka and Kitahara.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
「Review」Function of non-tight junction claudin-4
No full textClaudin-4 (CLDN4) is a key component of tight junctions (TJs) in epithelial cells. CLDN4 is over-expressed in many epithelial malignancies and correlates with cancer progression. Changes in CLDN4 expression have been associated with epigenetic factors (such as hypomethylation of promoterD NA)，i nflammation associated with infection and cytokines, and growth factor signaling. CLDN4 helps to maintain the tumor microenvironment by forming TJs and acting as a bar rier to the entry of anticancer drugs into tumors. Decreased expression of CLDN4 is a potential marker of epithelial-mesenchymal transition (EMT), and decreased epithelial differentiation due to reduced CLDN4 activity is involved in EMT induction. Non-TJ CLDN4 also activates integrin beta 1 and YAP to promote proliferation, EMT, and stemness. These roles in cancer have led to investigations of molecular therapies targeting CLDN4 using anti-CLDN4 extracellular domain anti-bodies. gene knockdown. Clostridium perfringens enterotoxin (CPE). and the C-terminus domain of CPE (C-CPE), which have demonstrated the experimental efficacy of this approach. CLDN4 is strongly involved in promoting malignant phenotypes in many epithelial cancers and is regarded as a promising molecular therapeutic target
卵巣明細胞癌に対するプリチデプシンの前臨床活性
Get PDFBackground/Aim: To evaluate the antitumor effects of Plitidepsin against clear cell carcinoma (CCC) of the ovary. Materials and Methods: The expression of eEF1A2 in ovarian cancer was assessed by immunohistochemistry. Using ovarian CCC cell lines, the antitumor effect of Plitidepsin was assessed both in vitro and in vivo. By over-expressing or knocking down the eEF1A2 expression, we investigated the role of eEF1A2 in the sensitivity of CCC cells to Plitidepsin. Results: Immunoreactivity to eEF1A2 was observed in 76.2% of CCC, which was significantly higher than other histological subtypes of ovarian cancer. Plitidepsin exhibited significant antitumor activity toward chemonaive and chemoresistant CCC cells both in vitro and in vivo. Ectopic expression of eEF1A2 in CCC cells resulted in increased sensitivity to Plitidepsin. In contrast, eEF1A2 knockdown decreased sensitivity of CCC cells to plitidepsin. Conclusion: Plitidepsin, a novel anti-cancer agent that targets eEF1A2, may be a promising agent for treating ovarian CCC.Clear cell carcinoma (CCC) of the ovary is known to be less sensitive to platinum-based frontline chemotherapy, and advanced-stage CCC is known to be associated with a worse prognosis than the more common histological subtype of serous adenocarcinoma (SAC). The lack of an effective chemotherapy for recurrent CCC is another important clinical problem (1). Therefore, novel strategies for both first-line treatment for advanced-stage CCC and salvage treatment for recurrent disease are needed.
Plitidepsin (Aplidin®) is a novel anti-cancer agent currently investigated in late phases of clinical development. In 2018, the Australian regulatory agency approved Plitidepsin in combination with dexamethasone for the treatment of multiple myeloma. Plitidepsin was originally isolated from the Mediterranean tunicate Aplidium albicans in 1988: currently it is chemically synthesized by Pharma Mar (Madrid, Spain) (2). According to previous preclinical studies, Plitidepsin is active against a wide range of malignancies: hematological malignancies such as multiple myeloma, lymphoma, and leukemia, and solid tumors including non-small-cell lung carcinoma, pacncreas, breast, melanoma, sarcoma, gastric, and bladder cancer (3). Importantly, most reports demonstrated in vitro activity of Plitidepsin in a low nanomolar range. Accumulating evidence have suggested that Plitidepsin induces cell cycle arrest and apoptosis in a dose-dependent manner by inducing oxidative stress, decreasing intracellular levels of glutathione, upregulating the JNK and p38 MAPK pathways. In addition to cytotoxic and cytostatic activities, Plitidepsin is known to inhibit tumor-angiogenesis through the inhibition of vascular endothelial growth factor (VEGF) secretion from cancer cells. In ovarian cancer, Plitidepsin exhibited anti-proliferative activity in vitro, and significantly inhibited the growth of a xenograft in athymic mice. However, since most ovarian cancer cell lines used in the previous preclinical studies of Plitidepsin were derived from ovarian SAC, the therapeutic potential of Plitidepsin against ovarian CCC is unknown.
The translation factor eEF1A2 is a tissue-specific variant of the eukaryotic Elongation Factor 1. The expression of eEF1A2 is normally confined to muscles and neurons (4). However, eEF1A2 is frequently over-expressed in various human malignancies and has oncogenic properties. Anand et al. (5) were the first to show that eEF1A2, while not normally expressed in ovary, is expressed in 30% of ovarian tumors. When examined according to histological subtypes, eEF1A2 was highly expressed in clear cell ovarian tumors compared to other histological subtypes of ovarian cancer (6). A recent study demonstrated that approximately 75% of ovarian CCC showed over-expression of eEF1A2 at the protein level (7).
Although detailed mechanisms of action have not been completely investigated, Plitidepsin has been suggested to exert its antitumor activity by directly interacting with eEF1A2. Thus, plitidepsin might be a potential drug candidate for the treatment of CCC showing over-expression of eEF1A2.
In the current study, after investigating the expression rate of eEF1A2 in ovarian cancer specimens, we evaluated the in vitro and in vivo therapeutic efficacy of Plitidepsin as a single agent against both chemonaive and chemorefractory ovarian CCC cells.権利情報：© 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved