Mie University Hospital

Background: Candidemia remains a life-threatening infection with high mortality despite advances in antifungal therapy. Malnutrition has been suggested as an important contributor to poor outcomes; however, the prognostic value of different nutritional assessment tools in candidemia has not been fully clarified. This study aimed to evaluate the impact of nutritional status on prognosis in patients with candidemia and to identify the most reliable nutritional assessment tool. Method: We conducted a retrospective cohort study of adult patients diagnosed with candidemia at a tertiary teaching hospital in Japan between 2014 and 2024. A total of 170 patients were included, with a mean age of 73 years. Nutritional status was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria and Controlling Nutritional Status (CONUT) score. The primary outcome was 30-day mortality. Results: According to the GLIM criteria, 72% of patients were classified as malnourished. The 30-day and in-hospital mortality rates were 35% and 44%, respectively. The CONUT score demonstrated good prognostic performance for 30-day mortality (Area under the Receiver operating characteristic 0.723, p < 0.001), with an optimal cut-off value of 12. Patients with higher CONUT scores had significantly shorter overall survival (Log-rank test p < 0.001). In multivariate analysis, a CONUT score ≥ 12, SOFA score ≥ 5, and the European Confederation of Medical Mycology Quality of Clinical Candidemia Management (EQUAL) Candida score ≥ 10 were independent predictors of 30-day mortality, whereas malnutrition defined by the GLIM criteria was not. Conclusions: The CONUT score is a useful prognostic indicator for short-term mortality in patients with candidemia, outperforming the GLIM criteria.

Abstract Background Although it is known that cardiovascular magnetic resonance (CMR)-derived right ventricular ejection fraction (RVEF) is significantly associated with adverse events in patients with cardiovascular diseases (CVDs), little is known about whether its association is stronger than that of left ventricular ejection fraction (LVEF). Purpose We aimed to investigate and compare the prognostic value of LVEF and RVEF in predicting adverse outcomes in patients with CVDs using systematic review and meta-analysis. Methods We searched three electronic databases for articles reporting hazard ratios (HRs) for both CMR-derived LVEF and RVEF in patients with CVDs on September 26, 2025. We rescaled the HRs by standard deviation (SD) within each study, and then calculated the HRs per 1-SD decrease in LVEF and RVEF. We also calculated the ratio of HRs to directly compare LVEF and RVEF. Results A total of 114 articles, including 25,839 patients, were eligible for inclusion in this study and were categorized into 14 CVDs. Although the HR per 1-SD reduction in LVEF showed no statistically significant association with adverse events in the heart failure with preserved ejection fraction (HFpEF) (HR: 1.00, 95% confidence interval [CI]: 0.87-1.14), non-ischemic cardiomyopathy (NICM) (HR: 1.47, 95% CI: 0.91-2.36), arrhythmogenic right ventricular cardiomyopathy (ARVC) (HR: 1.40, 95% CI: 0.93-2.09), myocarditis (HR: 1.41, 95% CI: 0.76-2.60) and valvular heart disease (VHD) (HR: 1.16, 95% CI: 0.88-1.53), the other nine CVDs showed significant associations with adverse outcomes. Conversely, the HR per 1-SD reduction in RVEF was statistically significant for all CVDs (HR: 1.29-1.79) except for myocarditis (HR: 1.29, 95% CI: 0.62-2.67). Additionally, the ratio of HR for RVEF to LVEF was significantly greater than 1 in congenital heart disease (CHD) (HR: 1.24, 95% CI: 1.00-1.54), HFpEF (HR: 1.27, 95% CI: 1.10-1.47), ARVC (HR: 1.24, 95% CI: 1.02-1.49) and pulmonary hypertension (PH) (HR: 1.22, 95% CI: 1.11-1.33). Conclusion Reduced RVEF was associated with adverse outcomes in all specific types of CVDs except myocarditis. However, reduced LVEF was not shown to significantly impact prognosis in HFpEF, NICM, ARVC, myocarditis and VHD. In CHD, HFpEF, ARVC and PH, lower RVEF was more strongly associated with adverse clinical outcomes than lower LVEF.Table 1:HR for each CVDs Figure 1:Forest plot of ratio of HR

To investigate the prevalence of radiologic classifications of the sinus tympani (ST), subtympanic sinus (STS), and facial sinus (FS) in a pediatric population using ultra-high-resolution photon-counting detector CT (PCD-CT). Retrospective, cross-sectional analysis. Single academic medical center. PCD-CT scans of 86 temporal bones from pediatric patients aged 0 to 14 years without prior otologic surgery or congenital malformations. Radiological assessment. Prevalence of ST, STS, and FS classifications (type A, B, C) based on their morphological relationship to the mastoid segment of the facial nerve. For the ST, type C was the most frequent classification, observed in 49 of 86 cases (57%), with its prevalence being particularly high in infants (86%). For the STS, Type A was the most common, found in 66 of 86 cases (78%). Similarly, for the FS, type A was the most prevalent, identified in 45 of 86 cases (52%). The predominance of type A for both the STS and FS was a consistent trend across all pediatric age groups. The pediatric retrotympanum is characterized by a high prevalence of deep, posteriorly extended (Type C) ST, which differs significantly from established adult anatomy. In contrast, the STS and FS are predominantly shallow (type A).

TPS244 Background: Comprehensive genomic profiling (CGP) using next-generation sequencing is recommended in metastatic colorectal cancer (mCRC) to identify actionable alterations. In Japan, CGP is reimbursed only once in a patient’s lifetime and generally after completion of standard systemic therapy, limiting its ability to capture temporal genomic changes. Liquid biopsy using circulating tumor DNA (ctDNA) enables repeated, minimally invasive genomic assessment and may detect emerging or disappearing actionable alterations during the disease course. There have been few prospective studies to assess the frequency and clinical impact of such changes before and after first-line chemotherapy in mCRC. We are therefore conducting a prospective observational study to evaluate the clinical utility of serial CGP testing using ctDNA. Methods: This is a prospective, multicenter observational study conducted at approximately 10 Japanese cancer genomic core and hub hospitals. Eligible patients are adults (≥18 years) with histologically confirmed unresectable mCRC, ECOG performance status 0–1, no prior systemic chemotherapy for metastatic disease, and adequate organ function. Patients undergo ctDNA analysis using the Guardant360 CDx assay at two time points: prior to initiation of first-line chemotherapy and after radiologic confirmation of disease progression on first-line therapy. Results are reviewed by institutional expert panels and returned to patients per local practice, including via telemedicine where applicable. The primary endpoint is the proportion of patients with a change in actionable genomic alterations (defined as OncoKB therapeutic level 1, 2, or R1, excluding variants of unknown significance/synonymous variants) between baseline and post–first-line testing. Secondary endpoints include: proportion of patients with actionable alterations at each time point; proportion with expert panel–recommended therapy and those who receive such therapy; objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) from expert panel–recommended therapy; and feasibility of telemedicine-based result disclosure. Based on prior retrospective data suggesting ~20% change in actionable alterations after systemic therapy, the target sample size is 200 patients, with ≥123 patients expected to have evaluable post–first-line ctDNA results. The study has 90% power at a one-sided α of 0.025 to detect a change proportion ≥15% versus a threshold of 6%. Patient enrollment began in November 2025, with a 12-month accrual period and 18-month follow-up. This trial will clarify the clinical utility of serial ctDNA CGP in mCRC and may support policy change to allow repeated CGP testing during the disease course. Clinical trial information: TBD .

ABSTRACTPurposeDensity gradient centrifugation (DGC) enriches motile sperm but may increase sperm DNA fragmentation (SDF), whereas microfluidic sperm sorting devices, such as ZyMōt and CA0, enable centrifugation‐free selection with lower SDF. Direct comparisons are limited, and their relative clinical efficacy remains unclear. We compared sperm parameters and SDF after DGC, ZyMōt, and CA0 to evaluate sperm selection performance and assessed the clinical utility of ZyMōt and CA0 based on intracytoplasmic sperm injection (ICSI) outcomes.MethodsSeventeen semen samples were aliquoted into three groups and processed using DGC, ZyMōt, or CA0. Sperm parameters and SDF were evaluated before and after selection. ICSI was performed using ZyMōt or CA0‐selected sperm, inseminating 108 oocytes with ZyMōt and 64 with CA0, followed by the comparative analysis of embryo development.ResultsZyMōt‐selected sperm exhibited higher motility, average path velocity, and amplitude of lateral head displacement than DGC (p < 0.01); CA0‐selected sperm showed higher linearity and wobble. ZyMōt achieved higher rates of fertilization, blastocyst formation, and good‐quality blastocysts, and a lower percentage of poor‐quality cleavage‐stage embryos than CA0 (all p < 0.05).ConclusionsZyMōt demonstrated superior sperm quality compared with DGC and CA0, and favorable ICSI outcomes further support its potential clinical applicability.Trial RegistrationThe study (H2023‐230) was registered in the Japan Registry of Clinical Trials (jRCT) Clinical Trials Registry in Japan (jRCT1040230045)

ABSTRACTObjectives:Non-older adults are at risk of developing sarcopenia, and exercise and increased physical activity are effective preventive interventions. Digital interventions, including gamification, may enhance the effects of exercise interventions. This systematic review and meta-analysis examined the effects of digital health interventions on muscle strength, muscle mass, and physical function in non-older adults at risk of sarcopenia.Methods:We conducted a systematic review of randomized controlled trials that evaluated the effects of digital health interventions on outcomes related to sarcopenia. Literature searches were performed in MEDLINE (Ovid), Web of Science Core Collection, and CENTRAL databases. Risk of bias was assessed according to established guidelines, and meta-analyses were conducted. The certainty of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.Results:In total, 28 studies were analyzed. The pooled results indicated that digital health interventions led to improvements in grip strength, performance in the chair-stand test, walking speed, Dynamic Gait Index, and Timed Up-and-Go test. In contrast, lower limb muscle strength and lean body mass did not show meaningful improvements. Although no major risks of bias were identified, the strength of the evidence remained limited because of the small number of studies and participants included.Conclusions:This systematic review suggests that digital health interventions may lead to modest improvements in muscle strength, muscle mass, and physical function in non-older adults at risk of sarcopenia, although the current evidence remains inconclusive. Further studies are needed to establish their effect.

ABSTRACTBackgroundLenvatinib‐related hypothyroidism occurs in 16%–22% of patients with hepatocellular carcinoma and may affect treatment management. Previous studies have reported elevated serum thyroid stimulating hormone (TSH) levels despite levothyroxine therapy, indicating the need for research on the optimal levothyroxine dose during lenvatinib therapy.AimsWe aimed to explore the effect of lenvatinib on thyroid function, focusing on lenvatinib pharmacokinetics and factors influencing hypothyroidism development.Methods and ResultsA retrospective cohort study involving 56 patients with hepatocellular carcinoma treated with lenvatinib was conducted at the Mie University Hospital. The primary outcome was grade ≥ 2 hypothyroidism. Demographic data, treatment details, and clinical outcomes were analyzed to identify factors associated with lenvatinib‐related hypothyroidism. In addition, we assessed the levothyroxine dose administered during treatment and the dose required to achieve TSH levels < 10 mIU/L. Twelve patients (21%) developed hypothyroidism during lenvatinib therapy. The median levothyroxine dose and time to onset of hypothyroidism were 25.0 [25.0–50.0] μg/day and 81.0 [15.0–208.0] days, respectively. Levothyroxine therapy was initiated at either a low or recommended dose, with 10 patients achieving TSH levels < 10 mIU/L. Significant predictors of hypothyroidism included age ≤ 63 years and a higher daily lenvatinib dose (≥ 0.152 mg/kg/day).ConclusionInitiation of levothyroxine therapy, even at lower doses, may be effective in managing lenvatinib‐related hypothyroidism. Underweight patients (e.g., body weight < 50 kg) require particular attention due to their increased susceptibility to hypothyroidism. Even though this study has limitations such as a small sample size and the lack of multivariate analysis, it provides valuable information for managing lenvatinib‐related hypothyroidism.

Although zinc oxide ointment is commonly used to treat diaper dermatitis in infants, there exists limited evidence of pharmacists suspecting hyperzincemia due to zinc oxide ointment and early intervention for mitigation of severity. This case study is female infant who was born at 27 weeks and 1 d of gestation and weighing 542 g. On postnatal 49 d, the serum zinc concentration was 65 µg/dL. Thereafter, treatment with oral zinc acetate hydrate (2 mg/kg/d) began on 56 d for ameliorating hypozincemia. Zinc oxide ointment was administered on 86 d as a treatment for diaper dermatitis. Despite of attaining hyperzincemia (427 µg/dL), treatment with zinc acetate hydrate and zinc oxide ointment continued because diarrhea and nausea had not developed. On 105 d, the serum zinc concentration was 199 µg/dL and the dermatitis conditions showed a marked improvement. Consequently, the pharmacist considered that zinc oxide ointment might have contributed to the hyperzincemia and consulted with the physician. Subsequently, both the zinc acetate hydrate and zinc oxide ointment were discontinued. Although zinc acetate hydrate was restarted on 114 d, serum zinc concentration was 101 µg/dL on 128 d. The Naranjo Adverse Drug Reaction Probability Scale score was 9 points, which is categorized as "definitive." Administration of zinc oxide ointment to diaper dermatitis with decrease skin barrier may have increased percutaneous absorption of zinc, resulting hyperzincemia. The pharmacist may be able to conduct early intervention for hyperzincemia by monitoring not only serum zinc concentration but also changes in the dermatitis conditions in infant patients.