Aomori Prefectural Central Hospital

Chemotherapy-induced nausea and vomiting (CINV) remain major challenges during concurrent chemoradiotherapy (CCRT) for cervical cancer. Mannitol and furosemide are agents widely used to prevent cisplatin-induced nephrotoxicity; however, the differences in their effect on CINV have not been characterized. This study aimed to evaluate the impact of concomitant diuretic administration (mannitol versus furosemide) on the incidence and timing of vomiting in patients with cervical cancer undergoing CCRT. This multicenter, retrospective study evaluated the impact of concomitant diuretic administration on CINV in 485 patients receiving weekly, cisplatin-based CCRT between 2016 and 2024, including 206 who received mannitol and 279 who received furosemide. Vomiting occurred more frequently in the mannitol group than in the furosemide group (18.4% vs. 10.4%). Time-to-event analysis found that vomiting occurred earlier with mannitol during the entire CCRT course. These findings may reflect mannitol's osmotic properties and the increased, intestinal permeability associated with CCRT-related mucosal injury. To the best of our knowledge, this study is the largest investigation to date comparing diuretic agents in this setting. The results suggested that furosemide may be a more appropriate option for patients with a high risk of CINV.

Introduction:Although several clinical prediction models (CPMs) have been developed for identifying acute dizziness with central causes, their application in clinical practice remains unclear. This study aimed to evaluate the accuracy and clinical utility of four CPMs in identifying dizziness with central lesions.Methods:This single-center, retrospective, diagnostic accuracy study was conducted at the ED of Aomori Hospital, Japan, from April to March 2023. The area under the receiver operating characteristic curve (AUROC) of four risk stratification models (ABCD2, TriAGe+, PCI, and Sudbury) in predicting dizziness with central causes were evaluated considering the brain imaging (computed tomography (CT) scan and magnetic resonance imaging (MRI)) findings, interpreted by a neurologist or neurosurgeon, as the gold standard. Calibration was evaluated visually using calibration plots. Additionally, analyses of efficacy, safety, and clinical utility using a decision curve were conducted.Results:Of the 3,606 patients identified, 2,958 with the mean age of 65.3 ± 16.4 (range: 15-97.) years were included in the final analysis (64.7% female). 155 (5.2 %) were diagnosed with central lesions. The AUROCs were 0.67 (95% confidence interval (CI): 0.62–0.71) for ABCD2, 0.80 (95% CI: 0.76–0.84) for TriAGe+, 0.82 (0.78-0.86) for PCI, and 0.85 (95% CI: 0.82–0.88) for Sudbury. TriAGe+, PCI, and Sudbury demonstrated good calibration. Among these, the Sudbury model demonstrated the highest diagnostic efficiency, was the only model to meet safety criteria, and provided the highest net benefit in decision curve analysis, particularly at lower predicted prevalence thresholds.Conclusion: The TriAGe+, PCI, and Sudbury models demonstrated strong discriminatory performance and reliable calibration when applied during ED admission at a community hospital. Particularly, the Sudbury model may reduce false-negative outcomes for central lesions, thereby potentially minimizing the need for unnecessary neuroimaging in patients identified as low-risk.

現行の血液製剤使用実態調査は，国内の適正使用推進に重要な役割を果たしてきたが，その包括的側面から，質問数の多さを含む回答者負担の大きさが懸念されてきた．最新の令和5年度分を含む計15回の調査の質問数と内容を分析した．平均質問数は298.7問で，その数は増加傾向にあった．内容面では，当初の調査目的である「院内輸血管理体制」や「製剤使用量」の質問に，各種ガイドラインに基づく「適正使用状況」や病院外・へき地・離島などの「状況別の輸血状況」の質問が経時的に加えられていた．使用実態の質問では，製剤種・診療科別に複数データを入力する「複数の質問への回答と同等の労力を要する質問」も多く含まれていた．質問数と回答率の年次推移に明らかな関連は見られなかった．最新調査での自由意見（参加施設の6%が回答）の約6割は否定的内容で，その多くが調査の形式面，特に回答者負担の大きさに言及していた．国内の輸血実施施設の多くは小規模施設であるがその回答率は大規模施設より低いままである．本分析より，回答者負担に配慮して調査を効率化していくことが，特に小規模施設での管理体制整備状況の把握・改善につながる可能性が示唆された．

Background:EGFR L858R mutation is associated with poorer efficacy of EGFR-tyrosine kinase inhibitors (TKIs) than EGFR Ex19del in patients with non-small cell lung cancer (NSCLC). However, ramucirumab (RAM) + erlotinib (ERL) therapy exhibited comparable efficacy between patients with L858R mutation and Ex19del mutation (median progression-free survival (PFS): 19.6 vs 19.4 months) in the RELAY study, with favorable PFS for both gene mutations at 19.4 months in the Japanese subset. Meanwhile, the FLAURA study revealed shorter PFS with osimertinib (OSI) for L858R mutation than Ex19del mutation, with poorer PFS in the Japanese subset than in the overall population. The treatment discontinuation rates of RAM + ERL and OSI in Japanese patients were 18% and 29%, respectively. Consequently, RAM + ERL may exhibit superior efficacy and safety in Japanese patients with the L858R mutation.Objectives:To evaluate the therapeutic efficacy and safety of RAM + ERL as a first-line treatment for advanced or recurrent NSCLC harboring the L858R mutation in Japanese patients.Design:A multicenter, noninterventional, retrospective cohort study.Methods and analysis:This study will involve patients with advanced or recurrent NSCLC (ECOG PS score 0–2) with L858R mutation who received RAM + ERL between November 1, 2020 and August 31, 2023, with the planned sample size of 200 patients. The primary endpoint is time to treatment failure, and the secondary endpoints are overall survival, PFS, PFS2, time to discontinuation of any EGFR-TKI, time to failure of strategy, objective response rate, disease control rate, and safety. Exploratory endpoints are effects of ERL and RAM on PD-L1 expression and neutrophil-to-lymphocyte ratio.Discussion:To the best of our knowledge, this is the first retrospective study focusing on L858R mutations associated with the RELAY regimen, providing the corresponding real-world data.Trial registration:UMIN Clinical Trials Registry identifier: UMIN000052047.

BackgroundHyperbaric hyperoxia exposure improves skeletal muscle capillary rarefaction and mitochondrial activity in diabetes mellitus (DM). However, the hyperbaric environment is limited, and normobaric hyperoxia exposure effects on skeletal muscle capillaries and mitochondrial activity in DM are unknown. We determined normobaric hyperoxia exposure effects on skeletal muscle capillary density and mitochondrial activity in type 1 DM rats.MethodsSeven-week-old male Wistar rats were randomly divided into control, DM, DM with 40% oxygen exposure (DM40), and DM with 50% oxygen exposure (DM50) groups. A single intraperitoneal injection of streptozotocin was administered to induce type 1 DM. DM40 and DM50 exposures were conducted daily for 60 min for 4 weeks. The soleus muscle, extensor digitorum longus muscle, and plantaris muscle samples were sectioned. The capillary-to-fiber ratio was measured using alkaline phosphatase staining. Succinate dehydrogenase (SDH) activity was measured by SDH staining. Scheffe’s test was performed for multiple comparisons, and Pearson’s correlation coefficients between the ratio and SDH activity were calculated. Statistical significance was set at < 5%.ResultsThe ratio in the soleus and extensor digitorum longus muscles was significantly higher in DM40 and DM50 rats than in DM rats (all p < 0.01). Moreover, SDH activity in the soleus muscle was significantly higher in DM40 rats than in DM rats; the same was found for the plantaris muscle (all p < 0.01). A significant positive correlation was observed between the ratio and SDH activity in the soleus and plantaris muscles (all p < 0.05).ConclusionsNormobaric hyperoxia affected all skeletal muscles, reflecting their fiber characteristics. Skeletal muscle capillary density was associated with mitochondrial activity, suggesting improved DM metabolism.

We aimed to investigate the impact of skin adverse events (AEs) of enfortumab vedotin (EV) on prognosis in patients with locally advanced or metastatic urothelial carcinoma in real-world practice. This study analyzed data from 115 patients with locally advanced or metastatic urothelial carcinoma. We evaluated the association between EV dose and skin AEs in these patients. The impact of skin AEs on progression-free survival (PFS) and overall survival (OS) was assessed using Kaplan-Meier curves and Cox regression analysis. The median PFS and OS were 8.1 and 14.5 months, respectively. EV dose reduction was observed in 68 (59.1%) patients. An estimated dose amount in the first, second, and seventh cycles was 95%, 85%, and 81%, respectively. We observed skin AEs in 69 (60%) cases, and they were observed within 1 month in 53 (76.8%) of cases. Patients with skin AEs had significantly longer PFS and OS compared to those without skin AEs. Multivariable Cox regression analysis showed a significant association of skin AEs with prolonged PFS and OS. Skin AEs were significantly associated with prolonged prognosis compared to those without skin AEs, although EV dose reduction was required in 59.1% of patients. Careful dose adjustment of EV may be crucial for long-term use and optimizing oncological outcomes.

788 Background: Local recurrence and/or pelvic lymph node metastases after radical cystectomy (RC) are often observed in patients with muscle-invasive bladder cancer (MIBC). Although chemotherapy and immune checkpoint inhibitors are the main treatment strategies in such patients, radiation therapy (RT) to the recurrence sites might be one of the treatment options. However, its effects on oncological outcomes remain unclear. Methods: This multi-institutional retrospective study included 106 patients who experienced local recurrence and/or pelvic lymph node metastases without distant metastases after RC. Patients were divided into two groups: patients who were treated with RT to the recurrence sites (RT group) and without (non-RT group). Multivariable Cox-proportional hazards regression analyses were performed to evaluate the effects of RT on cancer-specific survival (CSS) and overall survival (OS) after recurrence. Results: The median age at recurrence was 72 years, and the median follow-up period after recurrence was 13 months. Of the 106 patients, 65 (61%) received neoadjuvant chemotherapy (NAC) and 30 (28%) were treated with RT after recurrence. CSS and OS were not significantly different between the two groups ( P = 0.569 and P = 0.456, respectively). In univariable analyses, NAC, pure urothelial carcinoma, tumor grade, and lymphovascular invasion were significantly associated with CSS. Similarly, NAC, pure urothelial carcinoma, tumor grade, lymphovascular invasion, and pathological lymph node involvement were significantly associated with OS. After adjustment for these confounding variables, RT to recurrence sites was not significantly associated with prolonged CSS and OS (Table). Conclusions: RT to recurrence sites might have no effects on oncological outcomes in patients who experienced local recurrence and/or pelvic lymph node metastases after RC. Multivariable analyses for CSS and OS. CSS Factor P value HR 95% CI NAC Received 0.080 0.649 0.400–1.053 Pure urothelial carcinoma Positive 0.059 0.577 0.326–1.022 Tumor grade Grade 3 0.644 1.167 0.606–2.247 LVI Positive 0.003 2.407 1.353–4.283 Radiation therapy Positive 0.244 0.735 0.438–1.234 OS Factor P value HR 95% CI NAC Received 0.030 0.552 0.323–0.944 Pure urothelial carcinoma Positive 0.113 0.574 0.289–1.141 Tumor grade Grade 3 0.694 0.868 0.428–1.759 LVI Positive 0.005 2.438 1.305–4.556 Pathological N stage ≥ pN1 0.328 1.372 0.728–2.584 Radiation therapy Positive 0.161 0.652 0.359–1.186