Nagasaki University Hospital

Introduction: Hazard scenarios during torrential rain disasters in Japan involve a high proportion of elderly people and accidents indoors. One of the reasons for this is the lack of available workers at welfare facilities for the elderly. The purpose of this study is to examine the factors that affect the attitudes of staff toward onsite attendance at welfare evacuation shelters. Methods: Thirty welfare evacuation shelters were randomly sampled from 89 shelters in a city, and a self-administered, anonymous questionnaire survey was conducted by mail. The levels of disaster preparedness and disaster awareness were measured from responses, and their relationship to attitudes toward onsite attendance during disasters was analyzed. Results: A total of 113 staff subjects were analyzed. Responses of walking to work in the event of a disaster (p=0.002, x2test), being aware of a disaster manual (p=0.004, x2test), and having defined roles at the facility in the event of a disaster (p=0.034, x2test) were associated with onsite attendance. Disaster preparedness was associated with the ability to visualize disaster situations (p=0.009, Mann-Whitney U test), the ability to sense impending disasters (p=0.019, Mann-Whitney U test), and concern regarding disasters (p=0.001, Mann-Whitney U test). Compared to non-attendees, attendees were more concerned (OR 1.261; 95% CI: 1.025, 1.551) and less anxious (OR: 0.846; 95% CI: 0.719, 0.996) about disasters. Conclusion: The results suggest that encouraging facility staff to be more familiar with disaster preparedness and make firmer decisions to act in the event of a disaster can improve attitudes toward onsite attendance during disasters.

Abstract Background: Tumor-infiltrating lymphocytes (TILs) reflect host immune response and are associated with prognosis and treatment response in HER2-positive and triple-negative breast cancer (TNBC). While the International Immuno-Oncology Biomarker Working Group recommends evaluating stromal TILs in tumor areas, intratumoral heterogeneity and small sample size in core needle biopsy (CNB) specimens limit consistent assessment. It remains unclear whether central tumor (CT) or invasive margin (IM) regions should be prioritized and what cut-off values are clinically relevant. Ultrasonographic (US) features may also reflect the immune microenvironment. We previously proposed a TILs-US score based on three US features that predicts lymphocyte-predominant breast cancer (LPBC). This study evaluated the clinical utility of TILs assessment from CT and IM regions, appropriate cut-off values for predicting response in HER2-positive and TNBC using CNB, and explored optimal biopsy targeting through pathologic and US comparisons. Methods: In this multicenter retrospective study, we analyzed 239 patients (124 HER2-positive, 115 TNBC) with cT1-3/cN0-2 breast cancer who underwent surgery after neoadjuvant chemotherapy (NAC). TILs were evaluated using CNB specimens obtained before NAC and assessed separately in the central tumor (CT) and invasive margin (IM) regions. The IM was defined as a 1-mm-wide area centered on the interface between the tumor and surrounding stroma, while the CT was defined as the remaining intratumoral area within the IM boundary. TILs were analyzed using binary cut-offs of 30% and 50%, as well as a three-tier classification: low (0-10%), intermediate (11-49%), and high (≥50%). Pre-treatment ultrasound (US) findings included tumor shape (scored 0-2), internal echo (0-2), and posterior echo (0-3), which were used to calculate a composite TILs-US score ranging from 0 to 7. Associations between TIL levels, US features, and pathological complete response (pCR) were analyzed. Results: Overall, 104 patients achieved pCR (HER2-positive: 39; TNBC: 65). Using a 30% cut-off, TILs were evenly distributed both CT and IM, while ≥50% cases were relatively rare especially CT (CT: 10%; IM: 20%). CT TILs ≥30% was significantly associated with pCR (p=0.001), whereas the ≥50% cut-off was not (p=0.128). In contrast, both 30% and 50% cut-offs in the IM region were predictive of pCR (p<0.001 and p=0.009, respectively). Subtype analysis revealed that in TNBC, TILs ≥30% in both CT and IM regions were significantly correlated with pCR. In HER2-positive cases, however, only IM TILs ≥30% was predictive of pCR. Similar trends were observed with the three-tier classification. Among US features, a small lobulated shape was associated with high TILs levels in both CT and IM regions, while an enhanced posterior echo was correlated with high TILs in the IM region. Conclusion: Our findings suggest that TILs assessment should include the IM in addition to the CT, especially in CNB specimens as provide valuable information. Given the limited tissue area available in CNB specimen, using a 30% cut-off for TILs may offer a clinically meaningful threshold to predict treatment response. In cases where US findings suggest central fibrosis, targeting only the tumor center may result in sampling fibrotic areas with sparse immune and tumor cells, potentially hindering proper evaluation. Therefore, selecting the biopsy target based on US imaging is essential. Especially in HER2-positive breast cancer, as well as TNBC, it is important for operators to consider the optimal needle insertion angle and sampling site to ensure appropriate sampling of viable tumor tissue and immune microenvironment for accurate pathological and immunological evaluation. Citation Format: Y. Kimura, R. Yamaguchi, K. Fukui, A. Kanou, M. Noma, S. Akashi-Tanaka, K. Arihiro, N. Iwamoto, Y. Ohta, T. Okuno, S. Kashiwagi, Y. Kamei, Y. Tanada, S. Nakano, A. Nagata, A. Murakami, Y. Mochitomi, A. Yamakawa, M. Yamaguchi, H. Shima, A. Emi. Ultrasound-guided biopsy-based tils assessment at tumor margins as a predictive biomarker of neoadjuvant treatment response in early her2-positive and triple-negative breast cancer: a multicenter study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-18.

BackgroundChronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by airflow limitation and exertional dyspnea, leading to reduced exercise tolerance and physical inactivity. Nasal high-flow (NHF) therapy delivers heated and humidified gas at a high flow rate through a nasal cannula, washing out anatomical dead space, providing a small degree of positive airway pressure, improving ventilation efficiency, and reducing the work of breathing. In addition, adequate humidification may enhance ciliary clearance. The AIRVO3TM (Fisher & Paykel Healthcare, Auckland, New Zealand) is a novel portable NHF device that incorporates these features and can be used during ambulation. Using AIRVO3TM during exertion may improve exercise tolerance in patients with COPD; however, its safety and effectiveness in ambulatory patients have not yet been established.MethodsThis is a single-center, early-phase, open-label, randomized, two-period crossover pilot trial conducted at Nagasaki University Hospital, designed to evaluate the acute, within-day effects of AIRVO3TM on exercise tolerance during a single visit. Twenty patients with moderate to severe COPD will perform two 6-minute walk tests (6MWT) in a randomized order: one with AIRVO3TM and one without the device. The primary outcome is the 6-minute walk distance (6MWD). Secondary outcomes include percutaneous oxygen saturation (SpO2), transcutaneous partial pressure of carbon dioxide (PtcCO2), respiratory rate, pulse rate, Borg dyspnea scale score, time to desaturation (SpO2 ≤90%), time to PtcCO2 ≥45 mmHg, time to respiratory rate ≥22/min, walking distance to the first rest, patient-reported comfort, and subjective symptoms. Safety outcomes include the incidence of SpO2 <90%, adverse events (AEs), device-related discomfort, and withdrawal or dropout. Data will be analyzed primarily using paired t-tests and mixed-effects models that are appropriate for a crossover design.DiscussionThis trial will evaluate whether a portable NHF device increases exercise tolerance and is safe during ambulation in patients with COPD who do not require long-term oxygen therapy. By using room air [finspiratory oxygen fraction (FiO2) 21%] and focusing on high flow rather than high oxygen concentration, this study will clarify the pure effects of high-flow nasal therapy on exertional capacity. If the AIRVO3TM device is shown to be effective and acceptable, it may expand the options for pulmonary rehabilitation and daily physical activity in patients with COPD. Because all assessments are performed during a single study visit, this trial specifically evaluates short-term, acute responses to AIRVO3TM rather than long-term training effects of repeated use.Trial RegistrationThe study is registered in the Japan Registry of Clinical Trials (jRCT; trial ID jRCTs072240116; registered on February 20, 2025; https://jrct.mhlw.go.jp/latest-detail/jRCTs072240116). This article describes the protocol version 1.1 (March 11, 2025).

Abstract Background Whole-genome sequencing (WGS) has been increasingly used for antimicrobial resistance (AMR) surveillance and molecular epidemiology. However, variability in AMR gene detection across databases may impact clinical interpretation. This study compared three AMR gene databases using WGS data on methicillin-resistant Staphylococcus aureus (MRSA) and assessed their correlation with antimicrobial susceptibility testing (AST) results. Methods We analyzed WGS data from 270 MRSA bloodstream infection isolates collected through nationwide surveillance in Japan. AMR genes were identified using AMRFinderPlus, CARD, and ResFinder. AST for erythromycin, minocycline, and levofloxacin was performed by broth microdilution, applying breakpoints defined by CLSI and EUCAST guidelines. Statistical analyses were conducted using GraphPad Prism 10. Results The numbers of AMR genes detected by AMRFinderPlus, CARD, and ResFinder were 48, 53, and 42, respectively. The average number of AMR genes detected per strain was 8.3 ± 0.2 in AMRFinderPlus, 18.6 ± 0.1 in CARD, and 7.1 ± 0.2 in ResFinder. Despite all isolates being MRSA, mecA detection rates varied among databases, with detection rates of 82.2%, 98.1%, and 100% by AMRFinderPlus, CARD, and ResFinder, respectively. Figure 1 shows the positive detection rates of AMR genes for erythromycin, minocycline, and levofloxacin at different MIC levels. The detection rates increased with higher MIC levels. The performance of WGS-based AMR gene detection in predicting AST results is summarized in Table 1. Sensitivity varied across antimicrobial classes and databases, with CARD demonstrating the highest sensitivity overall. LR⁺ values indicated that CARD had the strongest diagnostic accuracy for predicting AST-confirmed resistance. Sensitivity increased when considering resistance gene detection in at least one of the three databases, but this was accompanied by a decrease in the positive likelihood ratio (LR⁺). Conclusion CARD demonstrated high sensitivity for erythromycin, minocycline, and levofloxacin. However, it did not detect mecA in a few isolates, raising concerns about MRSA identification. Integrating WGS-based AMR gene detection into clinical practice will require ongoing validation to ensure accuracy and reliability. Disclosures All Authors: No reported disclosures

The aim of this study is to evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride/sodium ferrous citrate (5-ALA-HCl/SFC) in patients with adult-onset Still's disease (AOSD) refractory to glucocorticoids during the maintenance treatment period of a phase II investigator-initiated randomized, double-blind, parallel-group clinical trial. This multicenter, open-label, continuous trial was limited to participants from the preceding study, which was planned for 30 enrollees but was stopped early after four enrollees because of slow recruitment. The current trial maintained a 16-week treatment period and remained double-blind until the previous study database was locked and unblinded. Two dose groups were used: 5-ALA-HCl/SFC 100 and 300 mg. Participants previously assigned to placebo were re-randomized 1:1 to either dose group. The dosage and administration were identical to those of the previous protocol. The primary endpoint was the achievement of adapted ACR 30 at week 16. All four participants achieved the primary endpoints. Secondary outcomes, including the adapted ACR 90/100 and the change in serum ferritin levels, showed numerically greater improvement in the participant who received the high-dose compared with the other. Eleven adverse events occurred in three participants, including one serious event and one discontinuation; all were deemed unrelated to the study drug, and no deaths were reported. This study identified potential efficacy signals, particularly in the high-dose group. However, because of premature termination and a very limited sample size, the data were insufficient to establish the efficacy and safety profile of 5-ALA-HCl/SFC in refractory AOSD. Larger studies are required to confirm these findings.

Cowden syndrome is an autosomal-dominantly inherited rare condition caused by germline pathogenic variants of the PTEN gene. Multiple tumor development at a younger age in this syndrome may warrant different modalities of fertility preservation. Here we report that women with this syndrome gave successful live birth with frozen-thaw embryo transfer that was cryopreserved before the start of chemotherapy for breast cancer. This woman also suffered from endometrial cancer that developed during hormonal treatment with GnRH agonist and tamoxifen for breast cancer. The lesion was well controlled with oral MPA therapy and hysteroscopic resection. She could receive fertility preservation for breast cancer and endometrial cancer before fertility treatment and pregnancy. This is the first report of live births after multiple fertility preservation therapy for metachronous breast and uterine cancer in Cowden syndrome. Appropriate genetic counseling may help the patient's decision making. The treatment plan should be discussed with diverse professionals such as oncologists, reproductive physicians, perinatologists, geneticists, and genetic counselors.

58歳女性，突然の頭痛を主訴に前医へ救急搬送され，頭部CTにてくも膜下出血の診断，造影CTにて出血源が特定できなかったため当院へ転院搬送された．脳血管造影を施行し，左椎骨動脈—後下小脳動脈分岐部遠位に膨隆を認め，血腫の局在も一致することから同病変が出血源であると判断し親血管塞栓術を企図した．塞栓術終了後マイクロカテーテルを抜去したところコイル数本が逸脱し遠位血管へ迷入した．遠位血管へマイクロカテーテルを誘導後，ステントリトリーバーを展開，逸脱したコイルをステントリトリーバーとマイクロカテーテルの間に挟み込む様にマイクロカテーテルをリシースすることで逸脱したコイルを回収した．小口径血管や屈曲した血管へ細径カテーテルが誘導できれば，ステントリトリーバーを用いたコイル回収は有効な治療法と考えられた．

The concept of "HER2-negative" breast cancer is evolving, with the recognition of HER2-low and HER2-ultralow subsets. These subsets are clinically relevant regarding treatment with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd), which has shown survival benefit in patients with metastatic carcinoma with minimal HER2 protein expression that lack HER2 gene amplification by in situ hybridization. In clinical trials using T-DXd, HER2-low was defined as an immunohistochemistry (IHC) score 1+ or an IHC score 2+ without HER2 gene amplification. HER2-ultralow was defined as faint or barely perceptible, incomplete membrane staining in >0% to ≤10% of tumor cells (IHC score 0+/with membrane staining) and HER2-null as the complete absence of staining (IHC score 0/absent membrane staining). These results now necessitate more detailed evaluation and reporting of traditional "HER2-negative" results to identify patients with metastatic breast cancer who may benefit from T-DXd therapy. Both the US Food and Drug Administration and the European Medicines Agency have extended the regulatory approval of T-DXd to patients with metastatic breast cancer showing HER2-low or HER2-ultralow expressions. Updated clinical management guidelines now, therefore, incorporate the spectrum of HER2 results into treatment selection algorithms in the metastatic setting. To align histopathologic practice with these developments, the College of American Pathologists has issued a new biomarker-reporting template that recommends explicit distinction between IHC 0/absent membrane staining and IHC 0+/with membrane staining. Key concerns among pathologists include assay variability, scoring reproducibility, and quality assurance standards for accurately detecting such low levels of HER2 expression. This manuscript provides expert consensus, evidence-based practical recommendations for identifying and reporting tumors with HER2-low and HER2-ultralow expression. We emphasize standardized testing protocols, validated assays, robust internal and external controls, and focused training for pathologists. A universal structured pathology report is proposed to highlight the accurate distinction between IHC 0 (null), IHC 0+ (ultralow), and HER2-low expressions.