Tokyo Metropolitan Geriatric Hospital

Abstract Extracorporeal membrane oxygenation (ECMO) provides life-saving support for patients with severe cardiac or respiratory failure, yet intra-circuit thrombosis remains a frequent and serious complication. Despite anticoagulation, thrombosis occurs in up to 35% of patients, impairing device performance, increasing morbidity and mortality, and often necessitating urgent circuit replacement. Current monitoring methods rely on visual inspection or indirect assays, which are insufficiently sensitive for early thrombus detection. Here we present a direct, quantitative, real-time strategy for large-scale image-based analysis of circulating platelets to monitor intra-circuit thrombogenesis during ECMO. Using an optofluidic time-stretch microscope with 780 nm spatial resolution and throughput exceeding 10, 000 events per second, we imaged circulating platelets in Capra hircus (goats) as a large animal model for long-term ECMO and analyzed them with deep learning. This enabled continuous tracking of single platelets, platelet–platelet aggregates, and platelet–leukocyte aggregates. Significant increases in the concentration of circulating platelet aggregates consistently preceded pump exchange events ( p = 0.0026), confirming their value as an early indicator of intra-circuit thrombosis. The method also distinguished thrombotic from inflammatory events, as only platelet–leukocyte aggregates rose during systemic inflammation, and aggregate levels correlated with lactate dehydrogenase, linking thrombosis to hemolysis or tissue injury. These findings demonstrate that high-throughput, image-based platelet phenotyping provides a sensitive, real-time tool for monitoring ECMO thrombosis, enabling early risk detection and supporting optimized anticoagulant management.

Abstract Beyond helping individuals and their families come to terms with a dementia diagnosis, appropriate informational support at the time of diagnosis may influence how they manage life with dementia in the years that follow. This study aimed to examine the impact of informational support provided at the time of diagnosis on the current caregiving burden experienced by family members. A self-administered survey was conducted in January 2025 with 164 family caregivers of individuals diagnosed at dementia medical centers and by certified dementia support physicians across Japan. The primary outcome was caregiver burden, assessed using the short version of the Japanese Zarit Caregiving Inventory (J-ZBI_8). Regression analyses controlled for care recipient characteristics, caregiver demographics, and caregiving context, while examining associations between nine types of informational support received at diagnosis and current caregiver burden. Caregivers most frequently reported receiving information about the disease itself (72.0%), long-term care services and Community General Support Centers (58.5%), and local medical institutions (37.2%). Practical information on legal, financial, or employment-related matters was less commonly provided. Among all types of support, only dementia-related information (B = –5.07, p < .001) and information about local medical institutions (B = –2.93, p = .02) were significantly associated with lower caregiver burden. These findings indicate that early, focused informational support—particularly regarding the disease and access to local dementia-specialized clinics—may enhance caregivers’ preparedness and ease anxiety about managing future care needs.

We investigated whether the same sympathetic nerves innervate arteries and neuromuscular junctions and aortic baroreceptor stimulation reduces muscle force in rats. Histological analysis with fluorescent labeling revealed nicotinic acetylcholine receptors, motor nerves, adrenergic nerves, and arteries in gastrocnemius muscle tissue. Whole-mount preparations revealed a potential extension of adrenergic nerves around an artery connected to the neuromuscular junction. Physiological analysis under anesthesia was conducted to examine the effects of baroreceptor activation on muscle contractility and contraction-induced lumbar sympathetic reflex discharges following tetanic motor nerve stimulation. Intravenous phenylephrine injection increased mean arterial pressure to ∼150 mmHg and reduced both tetanic force and sympathetic reflex discharges when the aortic depressor nerves were intact. Bilateral aortic nerve denervation nearly abolished these effects. These findings indicate that aortic baroreceptor afferent signaling decreases hindlimb muscle contractility, most likely by inhibiting the contraction-induced sympathetic reflex. Sympathetic nerves distributed to arteries and neuromuscular junctions may underlie this modulation.

72歳男性，扁平上皮癌cT1cN0M0に対し右肺下葉切除ND2a-1を施行，術後23日目に胸痛・息切れを自覚，定期受診時に右胸水と炎症を認めた．入院でドレナージ・抗生剤加療したが間欠熱持続と胸水培養でグラム陰性桿菌を認め，無瘻性膿胸の診断で胸腔鏡下膿胸腔掻把術を施行した．手術は急性膿胸を認め，初回手術で縦隔脂肪を被覆した気管支断端が視認でき，断端内腔は膿性付着物に覆われ，断端瘻による膿胸が疑われたが，明らかな気瘻は確認できず．術直後から持続性気瘻があり，CTで被覆脂肪内に気管支断端瘻を認めた．ドレナージで経時的に改善を得たため，術後1ヵ月で退院，術後2ヵ月でドレーンを全て抜去し，現在再燃なし．気管支断端瘻の程度や経過は様々で，治療法を迷う症例にも遭遇する．また断端被覆の効能は様々だが，今回は気管支断端への被覆脂肪内の気瘻減衰が保存加療継続の決め手となった．当方の過去被覆例や文献を踏まえ断端瘻保存加療を考察した．

Digital bioanalysis enables highly sensitive detection of biomolecules at the single-molecule level, making it a widely used technique in biomedical research. However, conventional approaches typically rely on fluorescence detection of single-enzyme reactions, which limits molecular selectivity and the ability to analyze multiple targets simultaneously. To address these limitations, we developed a digital bioanalysis platform based on surface-enhanced Raman scattering spectroscopy and microchamber arrays decorated with silver nanoparticles. This platform achieves a million-fold amplification of Raman signals from products generated by single-enzyme reactions, enabling precise digital counting of enzyme biomarkers with high molecular selectivity and multiplexing capability. We applied this platform to detect and distinguish two closely related enzyme biomarkers, acetylcholinesterase (AChE) and butyrylcholinesterase. By leveraging the sharp and distinct Raman spectral signatures of the reaction products, the platform achieved multiplexed biomarker quantification with femtomolar-level sensitivity. As a proof-of-concept, the platform successfully quantified AChE in human cerebrospinal fluid within 8.5 min, highlighting its potential utility in clinical diagnostics, particularly for differentiating types of dementia based on subtle differences in enzyme levels. Hence, this study presents a valuable alternative to fluorescence-based digital bioanalysis by offering enhanced molecular selectivity and multiplexing capability. Its application extends the scope of digital bioanalysis and broadens its capacity to quantify multiple biomarkers in complex biological samples with high precision and efficiency.

Ensuring a high quality of death (QOD) and family satisfaction is crucial for advanced cancer patients receiving home-based care. While home deaths are associated with better QOD and family satisfaction, key contributing factors remain unclear. This study aimed to identify key factors of QOD and family satisfaction among cancer patients at home using a nationwide mortality follow-back survey and bereavement questionnaire. A secondary analysis of a nationwide, cross-sectional mortality follow-back survey was conducted. Data were collected from bereaved family members of cancer patients who died at home in 2017-2018. The primary outcomes were QOD in the last month of life, assessed via the Good Death Inventory (GDI), and family satisfaction at the last place before death. Multivariate regression analyses examined associations between QOD, family satisfaction, and factors such as medical and nursing care, end-of-life (EOL) discussions, and caregiver burden. Among 30,205 surveyed families, 18,505 responded (61.3%). Adequate patient-physician discussions on the place of death were positively associated with GDI and family satisfaction (β = 6.22, p < 0.001; OR = 2.69, p < 0.001), as were regular physician home visits (β = 1.57, p < 0.001; OR = 1.58, p < 0.001). Conversely, ambulance use (β = - 1.68, p < 0.001; OR = 0.69, p < 0.001) and caregiver burden (β = - 3.06, p < 0.001; OR = 0.85, p < 0.001) were negatively associated with both outcomes. Regular physician visits and EOL discussions significantly positively associated with QOD and family satisfaction. Minimizing caregiver burden and avoiding ambulance use may further enhance QOD and family satisfaction at home.

Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis in AD compared with those in other eczematous dermatitis and inflammatory skin diseases by using immunohistochemical methods. Infiltration of IDECs (CD11c+ cells and/or CD206+ cells) and T-lymphocytes, accompanied by degenerated keratinocytes and aggregated LCs (CD207+ cells), was frequently observed as a common feature of spongiosis in multiple conditions. However, IDECs expressing IgE were identified exclusively in IgE-mediated AD. Aggregation of IDECs was predominantly observed in the spongiosis of adaptive immune-mediated eczematous disorders, such as AD and allergic contact dermatitis. These IDEC aggregations constituted the major components of the epidermal dendritic cell clusters seen in AD and other eczematous or eczematoid dermatoses, and may serve as a useful distinguishing marker from Pautrier collections seen in cutaneous T-cell lymphoma. These findings suggest that IDECs, in cooperation with other immune cells, may play a pivotal role in spongiosis formation in AD and various skin diseases, although the underlying immunopathological mechanisms differ among these conditions.

Abstract Spinocerebellar ataxias (SCAs) are a group of progressive neurodegenerative disorders caused by pathogenic variants in more than 40 genes with diverse cellular functions. In this study, we identified the c.247C&gt;T p.(Arg83Trp) variant in RAB3A, encoding a small GTPase involved in membrane-associated regulated exocytosis, in two families with cerebellar ataxia. Affected individuals presented with adult-onset, gradually progressive cerebellar symptoms, often accompanied by mild gait spasticity and tremors. Variable features of neurodevelopmental disorders were also observed. Brain MRI consistently revealed cerebellar atrophy, often accentuated in the vermis, and neuropathological examinations demonstrated diffuse cerebellar cortical degeneration. Functionally, the R83W mutation lies within the conserved switch II region of Rab3A, a domain critical for effector interaction. Although the mutant Rab3A R83W retained GTP-binding affinity, it failed to bind the key effector proteins RIM1 and Rabphilin-3A, highlighting the functional importance of R83 in effector complex formation, as supported by structural analysis. In PC12 cells, the R83W mutant exhibited diffuse cytoplasmic localization, in contrast to the vesicle- and neurite-tip localization of the wild-type and GTP-bound Rab3A mutant. The concordant localization pattern of R83W and GDP-bound Rab3A mutants suggests that R83W-induced mislocalization results from a failure to engage downstream effector proteins. In frozen sections of the mouse cerebellum, Rab3A was predominantly localized to parallel fiber terminals and was absent from postsynaptic Purkinje cells. These findings suggest that disruption of the interaction between Rab3A and its effector proteins may underlie disease pathogenesis, possibly involving presynaptic dysfunction at parallel fiber–Purkinje cell synapses mediated by the Rab3A–RIM1 complex.