Iwate Medical University

Since the COVID-19 pandemic, the use of hypochlorous acid water has been spreading. However, limited studies have assessed its safety and efficacy when atomised in hospital environments. This study evaluated the disinfection performance of atomised hypochlorous acid water against Pseudomonas aeruginosa, a key pathogen in nosocomial infection control. Two test methods for P. aeruginosa, which is susceptible to drying, have been developed. In the first method, 10 μL of bacterial suspension was pipetted onto five spots in a Petri dish, allowed to dry, and solidified (bacterial suspension 'pipetting method'). The second method involved diluting the bacterial suspension 100-fold in saline and pouring 8 mL into a Petri dish (bacterial suspension 'pooling method'). In the pipetting method, no reduction in viable bacteria was observed following atomization of 40 ppm hypochlorous acid water, whereas a significant bactericidal effect (p < 0.001) was detected at 300 ppm. Conversely, in the pooling method, a significant reduction in viable bacteria (p < 0.01) was observed at 40 ppm, with bacterial counts falling below the detection limit at 300 ppm, clearly demonstrating a strong bactericidal effect. The effectiveness of the pooling method may be attributed to enhanced penetration of hypochlorous acid particles, which could promote oxidative action. These findings confirm the bactericidal efficacy of hypochlorous acid water atomization in hospital wards against P. aeruginosa. Furthermore, as a performance test, these methods were close to real clinical settings in terms of nutritional conditions and the pooling method could properly evaluate desiccation-sensitive bacteria.

Organ morphogenesis is essential for not only integrated organ functions in the body but also the determination of adult-tissue stem cells and their niche. Only hair follicle organs can cyclically regenerate in the variable bulbous germinative region as a form of programmed organ regeneration in adults. Here, we identified a cell population, hair follicle organ-intrinsic mesenchymal cells, with PDGFRα+/Sca1+/CD34high+ mesenchymal cells, from the boundary zone of the epithelial stem cell niche by using the organ germ method, which plays essential roles in entering and promoting the downgrowth phase of the hair cycle. The bioengineered hair follicle germ reconstituted from bulge region-derived epithelial stem cells, dermal papillae and mesenchymal cells has full functions, including downgrowth, full-size hair follicle regeneration and the hair cycle, both in in vitro artificial skin and after intracutaneous skin transplantation. This study provides significant contributions to the basic and medical science of adult organ-inductive potential stem cells and their niches in organ morphogenesis and the adult hair cycle.

Background: Catheter-related bloodstream infections, particularly central line-associated bloodstream infections (CLABSIs) involving central venous (CV) catheters, are major health care-associated infections, with Staphylococcus epidermidis ( S. epidermidis ) being the primary pathogen. However, the effect of catheter design, especially the section of the catheter and number of lumens, on bacterial adhesion remains unclear. The aim of the present study was to investigate S. epidermidis adhesion to various sections of double and triple-lumen CV catheters in an in vitro model. Materials and Methods: Bacterial suspensions of S. epidermidis were infused from the proximal port of double and triple-lumen CV catheters, and the number of adherent bacteria on the 6 catheter sections was quantified using a modified Brun-Buisson method. Statistical analysis was conducted to evaluate the differences in bacterial adhesion across catheter sections. Results: The highest level of bacterial adhesion was observed at the proximal port-opening section. A significantly greater number of bacteria adhered to this section than the other sections in both double and triple-lumen CV catheters, indicating that the proximal port-opening section is a critical site for potential contamination and infection risk. Conclusions: This finding highlights the importance of the proximal port region of CV catheters with regard to bacterial adhesion. Further research is warranted to explore the adhesion characteristics of other pathogens and evaluate various catheter designs to improve infection prevention strategies in clinical practices.

Objectives: This study aimed to prospectively investigate the associations among obesity, physical activity, and short-term high medical expenditures in Japanese employees and their dependents. Methods: Participants were 245,044 employees and their dependents aged 40-74 years who underwent the Specific Health Checkup in fiscal year 2008. Health checkup and medical expenditure data for 2008-2010 were provided by health insurers. They were divided into 12 groups according to the combination of body mass index categories (normal, overweight, and obesity) and engagement in exercise and/or daily physical activity (inactive, daily physical activity only, exercise only, and active). The multivariable-adjusted odds ratios of the groups for high total medical expenditures in the next year compared to the inactive normal body mass index group were estimated. High medical expenditures were defined as the top 5% of total annual expenditures, consistent with prior literature identifying high-cost users. Similar analyses were performed by sex and age (<65 years, ≥65 years). Results: Of the participants, 61.8% were men (mean age, 52.1 years). Multivariable-adjusted odds ratios were significantly high only in the inactive groups with overweight or obesity in men and younger individuals. In women and older individuals, the odds ratios were significantly high only in inactive women with obesity; however, the odds ratios were high in women who exercised only and in active older individuals, both with obesity. Conclusions: Exercise or daily physical activity might attenuate the possibility of incurring high short-term medical expenditures in men and younger individuals with overweight or obesity. These findings suggest that physical activity recommendations may need to be tailored for women and older individuals with obesity, and further longitudinal research is warranted.

BackgroundStaging laparoscopy (SL) for pancreatic ductal adenocarcinoma (PDAC) is considered useful in improving the accuracy of staging and resectability. However, currently, there are no standard criteria for selecting patients who may benefit from SL prior to determining the appropriate treatment. In this report, we aimed to determine the role of SL before therapy in patients with PDAC.MethodsThis study was a single-center, prospective cohort study comprising patients with PDAC at Iwate Medical University Hospital during the period from November 2021 to June 2025. SL was performed in all patients with PDAC with no radiological distant metastasis before they underwent pancreatic resection or chemotherapy or chemoradiotherapy. The baseline characteristics, operative outcomes, changes of resectability status, complete resection rate and mid-term survival were examined.Results102 patients were finally included in the present study. Before SL, according to resectability status, 45 patients (44.1%) were classified as resectable (R), 36 (35.0%) as borderline resectable (BR), and 21 (20.6%) as unresectable locally advanced (UR-LA). SL revealed distant metastasis in 24 (23.5%) patients. The univariate analysis revealed that the factors of CEA positive and CA19-9 ≥ 150, U/mL were associated with a significantly higher risk of occult metastasis. The multivariate analysis revealed that having a CEA positive and CA19-9 ≥ 150, U/mL were the only factors that were independently associated with occult metastasis. For patients with R PDAC before SL, distant metastasis was found after SL in 17.8% of patients. Even in cases where none of the tumor markers were elevated, one case was found to have distant metastasis after SL. There was no morbidity and mortality in this case series. In the intention-to-treat population, the median overall survival (OS) were not reached [95% CI: 22.0 months–not estimable (NE)]. The median DFS was 22.0 months (95% CI: 15.0 months–27.0 months). Of the patients with UR-LA PDAC, despite stage migration, no improvement in OS was observed after SL.ConclusionSL is safe and effective in determining accurate staging, which may allow for more appropriate treatment. Therefore, SL is actively recommended for patients with R PDAC or BR PDAC who are planning to undergo complete resection shortly to avoid unnecessary surgical exploration, especially those CEA positive or with CA19-9 ≥ 150 U/mL.

Accurate clinical staging of upper tract urothelial carcinoma (UTUC) remains challenging, and discrepancies between clinical and pathological T stages may result in missed opportunities for appropriate treatment. This study aimed to elucidate real-world discrepancies between clinical and pathological T staging in UTUC, emphasizing the diagnostic uncertainty associated with clinical T2 (cT2) disease. A retrospective analysis was conducted involving 739 patients with cTa–4N0M0 UTUC who underwent radical nephroureterectomy (RNU) at multiple institutions. Patients who received neoadjuvant therapy or had missing pathological T stage data were excluded. Discrepancies between clinical and pathological staging, treatment patterns, and survival outcomes were evaluated. Among 739 patients, substantial discrepancies between clinical and pathological T stages were observed, with an overall diagnostic concordance rate of 44.7%. Only 16% of cT2 cases were pathologically confirmed as pathological T2 (pT2), whereas most were either down-staged to ≤pT1 or up-staged to ≥pT3, indicating marked diagnostic uncertainty. Clinical heterogeneity within the cT2 group resulted in marked survival differences based on pathological stage, as pT3 patients had significantly worse outcomes than pT2 patients. Within the pT3 subgroup, lymphovascular invasion independently correlated with poor prognosis, whereas adjuvant therapy improved survival. However, only approximately one-third of patients with pT3 disease received adjuvant therapy, indicating a treatment gap in this high-risk population. This multicenter study identified real-world discrepancies between clinical and pathological staging in UTUC. cT2 disease represents a heterogeneous and diagnostically uncertain category, requiring careful interpretation for appropriate treatment planning.

Background: The principal glial cells of the retina, Müller glia, play a central role in retinal regeneration in teleost fish and have recently attracted attention as potential sources of neuronal regeneration in mammals. Objectives: In this study, we examined whether SV40-immortalized rat Müller glia could be directed toward neuronal differentiation using a non-genetic approach with defined culture conditions. Methods: Comprehensive transcriptomic profiling by RNA sequencing indicated that changes in culture medium alone could induce transcriptional reprogramming toward a neuronal lineage. Results: Specifically, expression of Müller glia-related genes decreased, while a subset of photoreceptor-related transcription factors and specific genes showed altered expression, suggesting early-stage induction toward a photoreceptor-like fate. This finding suggests that even immortalized cells may exhibit activation of neuronal genes through non-genetic culture interventions. Gene set enrichment analysis further revealed upregulation of pathways related to the synaptic vesicle cycle, metabolic activation, oxidative stress defense, and lysosomal function, consistent with initiation of neuronal differentiation. Conversely, pathways associated with cell cycle regulation and stemness signaling were downregulated, reflecting a transition from a proliferative to a differentiation-prone state. Collectively, these results provide preliminary molecular markers for early neuronal induction and potential targets for chemical screening. Conclusions: Importantly, this strategy enables neuronal-like differentiation of Müller glia without genetic manipulation, offering a safe and cost-effective platform. Overall, our findings may support the development of in vitro models for retinal neuroregeneration and facilitate research toward regenerative therapies for retinal disorders.

FLAIR vessel hyperintensities (FVH)-Alberta Stroke Program Early CT Score (ASPECTS) is an imaging marker but its clinical implications remain unclear. We estimated the correlation between FVH-ASPECTS and clinical outcomes in patients with wake-up stroke or unknown time of stroke onset. The THrombolysis for Acute Wake-up and Unclear-onset Strokes with Alteplase at 0.6 mg/kg (THAWS) trial was a multicenter, randomized controlled trial conducted at 40 sites in Japan between 2014 and 2018. Patients with unknown stroke onset and diffusion-weighted imaging (DWI)-FLAIR mismatch were randomly assigned to receive either intravenous alteplase (0.6 mg/kg) or standard medical treatment. FVH-ASPECTS, a semiquantitative scoring system assessing FVH prominence in the seven cortical ASPECTS regions, was evaluated for its association with favorable outcomes (modified Rankin Scale 0-2 at 90 days). The optimal FVH-ASPECTS threshold was determined using receiver operating characteristic (ROC) analysis and its correlation with favorable outcomes was assessed. Among 131 patients (mean age, 76 ± 13 years; 42% women), 71 received alteplase and 60 did not. Median NIHSS score was 7 (interquartile range [IQR] 4-13), and median FVH-ASPECTS was 4 (IQR 2-4). ROC analysis identified FVH-ASPECTS 3 or more as predictive of favorable outcomes (sensitivity 80%, specificity 51%, area under the ROC curve [AUC] 0.717). A significant correlation was observed between FVH-ASPECTS 3 or more and favorable outcomes (adjusted odds ratio [OR] 4.50, 95% confidence interval [CI] 1.89-10.75; p < 0.001). FVH-ASPECTS could offer an indicator for achieving favorable clinical outcomes among stroke patients with unknown time of onset, with a threshold of 3 or more.

683 Background: Enfortumab vedotin (EV) is a standard therapy for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy and immune checkpoint inhibitors. However, optimal early dosing strategies remain unclear in real-world practice. Maintaining relative dose intensity (RDI) may influence efficacy, yet the prognostic role of early RDI (eRDI) and its relationship with adverse event–related dose modification (AE-DM) are not well defined. Clarifying whether early dose modification affects outcomes is crucial for balancing efficacy and tolerability in EV therapy. Methods: We retrospectively analyzed 119 patients with mUC treated with EV monotherapy at multiple Japanese institutions from 2021 to 2024. Among them, 84 patients who underwent at least one post-baseline radiographic assessment and did not show early progressive disease (PD) were included in the efficacy analysis. Early RDI was defined as the mean RDI during the first three months. AE-DM was defined as any reduction, delay, or interruption due to toxicity. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method and compared using the log-rank test, stratified by AE-DM status (positive or negative). Results: In the PD-excluded cohort, patients with eRDI ≥80% had significantly longer PFS and OS than those with eRDI &lt;80% (median PFS: 8.5 vs 4.3 months, p=0.008; OS: not reached vs 11.2 months, p=0.012). Among AE-DM–negative patients, low eRDI predicted worse outcomes (median PFS: 11.7 vs 4.2 months, p=0.001; OS: not reached vs 13.8 months, p=0.021). Conversely, in AE-DM–positive patients, survival did not differ between eRDI groups, suggesting that clinically guided dose modification did not compromise efficacy. Conclusions: Early RDI predicted survival in patients who tolerated standard dosing without AE-DM, whereas dose modification for toxicity preserved efficacy. Maintaining early intensity is important for fit patients, while individualized dose modification may ensure safety and effectiveness in those with AE-DM. eRDI may serve as a practical early indicator in real-world EV therapy. Survival outcomes according to eRDI and AE-DM status. Cohort n Median PFS (months, eRDI ≥80% vs &lt;80%) p-value Median OS (months, eRDI ≥80% vs &lt;80%) p-value All PD-excluded 84 8.5 vs 4.3 0.008 NR vs 11.2 0.012 AE-DM (−) 49 11.7 vs 4.2 0.001 NR vs 13.8 0.021 AE-DM (+) 35 6.3 vs 6.1 0.67 15.1 vs 14.9 0.82 PFS, progression-free survival; OS, overall survival; eRDI, early relative dose intensity; PD, progressive disease; AE-DM, adverse event-related dose modification; NR, not reached.

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018 and updated in 2022 (Ozaki et al. in Cardiovasc Interv Ther 33:178-203, 2018), (Ozaki et al. in Cardiovasc Interv Ther 37:1-34, 2022). Following the publication of the 2023 European Society of Cardiology (ESC) Guidelines for the management of acute coronary syndromes, the CVIT Task Force released another revised version in 2024 (Ozaki et al. in Cardiovasc Interv Ther 39:335-375, 2024). In light of new clinical evidence and technological advances that have emerged since then, the Task Force now proposes an updated expert consensus document for the management of ACS focusing on procedural aspects of primary PCI in 2026 version.