Tottori University Hospital

In this nationwide retrospective study, we sought to evaluate the oncologic and functional outcomes and safety of transoral surgery (TOS) for hypopharyngeal and laryngeal squamous cell carcinomas in Japan and to clarify the appropriate indications for various TOS modalities. Data were obtained from the Head and Neck Cancer Registry of Japan. Patients who underwent transoral or endoscopic resection between 2011 and 2016 were selected. Detailed clinical information was collected from 55 institutions using web-based case report forms. Surgical modalities analyzed included endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), endoscopic laryngopharyngeal surgery (ELPS), transoral laser microsurgery (TLM), and transoral videolaryngoscopic surgery (TOVS). In total, 1825 patients were included (hypopharyngeal cancer, 62.5 %; laryngeal cancer, 37.5 %). Most cases (77.5 %) were T1 or lower, and 90.8 % were Stage II or earlier. TLM is predominantly used for glottic cancers, ELPS/ESD for superficial hypopharyngeal lesions, and TOVS for more advanced tumors, reflecting distinct indications for each modality. The 5-year disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS) were 97.1 %, 84.3 %, and 85.4 %, respectively. The laryngeal preservation rate was 98.2 %. Tracheostomy was performed in 5.0 % of cases, mainly for airway protection; major complications, including pneumonia (2.4 %), hemorrhage (1.1 %), fistula formation (0.4 %), and vocal cord fixation (2.6 %), occurred in <3 % of patients. Postoperative functional outcomes were favorable, with persistent dysphagia (Functional Outcome Swallowing Scale stage ≥ 3) in 1.6 % and tube feeding dependence in 1.8 %. Non-robot-assisted TOS demonstrated excellent oncologic control and functional preservation of the larynx with low complication rates in early-stage hypopharyngeal and laryngeal cancers. Each surgical modality has distinct indications depending on the tumor site, depth of invasion, and institutional expertise. These findings support the use of TOS as a safe and effective treatment option for selected patients. Further procedural standardization and data accumulation are required to refine the indications and facilitate their broader adoption in clinical practice.

We evaluated the long-term outcomes of children undergoing thoracotomy lung resection for congenital lung malformations in terms of lung function, complications, and health-related quality of life (HRQOL). We retrospectively reviewed 27 children who underwent thoracotomy at Osaka University Hospital (1992-2017) with at least five years of follow-up and postoperative lung function testing after six years of age. We compared the percent predicted vital capacity (%VC), percent predicted forced expiratory volume in 1s (%FEV1), and FEV1 to FVC ratio (FEV1/FVC) as indicators of the lung function. Longitudinal changes in the lung function, pulmonary and musculoskeletal morbidities, and HRQOL were assessed using the Pediatric Quality of Life Inventory. %VC and FEV1/FVC remained within the normal range but were significantly lower than the controls; %FEV1 was below the normal range. No significant longitudinal changes in the lung function were observed. Asthma‑like symptoms appeared in 37.0% of the patients and persisted beyond adolescence. Musculoskeletal morbidities occurred in 33.3% of the patients, with five pectus excavatum cases requiring correction. HRQOL did not differ from that of the healthy controls. In our study, children undergoing thoracotomy lung resection for congenital lung malformations exhibited a significantly lower lung function than the healthy controls, and these impairments persisted over an extended follow-up period. Long-term complications and a reduced lung function were not reflected in the subjective HRQOL.

• Frailty subtypes were assessed using the Kihon Checklist in older adults. • Housebound status independently predicted future fractures in a 9-year cohort. • A single KCL item on going out weekly identified high fracture risk. • KCL may serve as a simple screening tool for fracture prevention in the community. • Findings support including social frailty in fracture risk assessment models. This study aims to determine whether frailty, assessed using the simple multidimensional frailty assessment tool, the Kihon Checklist (KCL), is associated with future fractures and, if so, to identify which frailty subtypes exhibit the strongest association with fracture incidence. This study recruited local residents who visited government-organized examination sites for specific health check-ups for older adults, conducted over a three-day period each year and 468 community-dwelling older adults from 2014 to 2023 in Hino Town, Tottori Prefecture, Japan. Characteristics, physical structure and performance, and frailty were assessed at the baseline assessment. Frailty was assessed using KCL and categorized into six subtypes: lower motor function, malnutritional, lower oral function, housebound, reduced cognitive function, and possible depression. Self-Reported incidence fracture was determined through annual follow-up surveys. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the association between frailty subtypes and fracture incidence. A total of 352 participants were followed for fracture incidence over a mean period of 6.9 years. During the follow-up period, 41 participants experienced at least one fracture, resulting in an incidence rate of 1.69 per 100 person-years. Both lower motor function and housebound were significantly associated with fracture incidence. However, after adjusting for previous fall history, and lower bone mass, housebound (HR = 2.436, 95 % CI: 1.125–5.271) remained significantly associated with fracture incidence. Unlike previous studies emphasizing musculoskeletal frailty, our findings highlight housebound status as a factor associated with fractures. Fracture prevention strategies should integrate social engagement interventions alongside conventional musculoskeletal management.

Introduction: Adipose-derived mesenchymal stem cells (AD-MSCs) cultured under hypoxic conditions are known to secrete extracellular vesicles (EVs) with protective effects against ischemia. In this study, we aimed to evaluate the enhanced therapeutic potential of these EVs—emerging as a promising cell-free strategy for cardiac regeneration—when derived from hypoxia-conditioned AD-MSCs. Materials and Methods: MSCs were isolated from the adipose tissue of Lewis rats and cultured under normoxic (20% O2) or hypoxic (5% O2) conditions. EVs were collected from conditioned media via ultracentrifugation. EV marker protein expression assessed the quantity of EVs, and comprehensive miRNA profiling was performed. To evaluate therapeutic efficacy, myocardial infarction (MI) was induced in Lewis rats via ligation of the left anterior descending artery. Two weeks after MI, rats were divided into three groups: normoxic EVs (N-EV), hypoxic EVs (H-EV), and PBS control. Each treatment was locally injected around the infarct border zone. Four weeks later, cardiac function was assessed by echocardiography and histological analyses were conducted. Results: There was no significant difference in the amount of EVs, as assessed by Alix quantification, between the hypoxic-and normoxic groups (p = 0.25)(Figure 1A). There were no significant differences in the median particle size (70.5nm vs 65.5nm, p = 0.51) or concentration (4.59×10 12 /mL vs 3.05×10 12 /mL, p = 0.70) of EVs between the hypoxic and normoxic groups. (Figure 1B). miRNA sequencing revealed that hypoxia-derived EVs contained more miRNAs associated with anti-fibrotic gene regulation (Figure 1C and 1D). In the rat ICM (Ischemic Cardiomyopathy) model, echocardiographic assessment at 4 weeks post-administration revealed that the H-EV group exhibited significantly greater prevention of left ventricular diastolic diameter enlargement (7.3mm vs 8.0mm, p = 0.004) and systolic diameter enlargement (5.7mm vs 6.5mm, p = 0.0004), as well as improved ejection fraction (50% vs 43%, p = 0.0069), compared to the N-EV group (Figure 2A). Histologically, Picro-Sirius Red staining demonstrated a greater reduction in myocardial fibrosis in the H-EV group (7.3% vs 12.0%, p=0.044) (Figure 2B). Conclusions: In a rat model of ICM, EVs derived from hypoxic MSC cultures were enriched in anti-fibrotic miRNAs and exhibited superior therapeutic effects in terms of remodeling suppression and functional recovery compared to normoxic EVs.

Immune checkpoint inhibitors (ICIs) improve cancer survival but can induce immune-related adverse events (irAEs). Pre-existing autoantibodies, particularly antinuclear antibodies (ANAs), have been suggested as predictive biomarkers for irAE development. However, prior studies have yielded mixed results. Furthermore, the predictive value of specific ANA staining patterns has remained unexplored. We aimed to investigate the relationship between baseline autoantibody levels and irAE development. This retrospective observational study included 626 patients with cancer receiving ICI therapy between November 2020 and August 2024 at the Tottori University Hospital. irAEs were graded using Common Terminology Criteria for Adverse Events v5.0, with grade ≥ 2 considered clinically significant. Logistic regression analysis assessed the association between baseline factors and irAE development. Receiver operating characteristic (ROC) curve analysis evaluated model performance. Elevated ANA titers (≥ ×40), speckled ANA staining pattern, and combination ICI therapy were significantly associated with an increased risk of grade ≥ 2 irAEs in both univariable and multivariable analyses. The predictive performance of the area under the ROC curve for the multivariable models using either elevated ANA titers or the speckled pattern was similar (approximately 0.617). Baseline ANA titer and speckled ANA pattern are potential predictive biomarkers for grade ≥ 2 irAEs, particularly in patients receiving combination ICI therapy. Comprehensive ANA testing may improve risk stratification and inform personalized irAE management.

Abstract Background and Aims Cisplatin is one of the most widely used chemotherapy drugs. However, its potential side effects in normal organs, including kidneys, limit its use and related platinum-based chemotherapies. Various approaches to protect kidneys against nephrotoxicity have been discovered. N-acetylcysteine (NAC) and hydrogen sulfide are among such reno-protective agents, but their effects are partial, suggesting the need for another strategies. The mechanisms of cisplatin nephrotoxicity include mitochondrial injury caused by the production of reactive oxygen species (ROS). Recent researches have revealed the important role of cysteinyl tRNA synthetase-2 (CARS2) on regulation of mitochondrial homeostasis through cysteine polysulfide production. As cysteine polysulfide is a strong mediator of redox status, endogenous production of cysteine polysulfide by CARS2 may be involved in cisplatin-induced nephrotoxicity. However, the association between CARS2 and renal injury under cisplatin treatment is not fully elucidated. This study aimed to investigate the role of CARS on cisplatin-induced nephrotoxicity. Method In this in-vivo study, wild type (WT) and Cars2+/− mice were prepared, because Cars2−/− mice are embryonic lethal. Male mice (14 to 16 weeks old; n = 5, each) were intraperitoneally injected cisplatin (20 mg/kg) once to induce renal injury. The mice were sacrificed 72 hours after the injection. Urine, blood from the heart, and the kidneys were collected and stored for the analysis. Biochemical, histological were performed to investigate the differences in renal injury between the groups. Western blot analysis was performed to compare protein expressions. This animal experiment is approved by the authorized ethical committee. Results At baseline, the Cars2+/− mice showed significantly lower levels of CARS2 mRNA and protein in the kidney, and urinary polysulfide level was significantly lower in the Cars2+/− mice. Periodic acid Schiff (PAS) staining showed no significant difference between groups at baseline. Serum creatinine after cisplatin was significantly higher in the Cars2+/− mice suggesting that CARS2 deficient mice were susceptible to cisplatin nephrotoxicity. PAS staining showed remarkable renal tubular injury, represented by vacuolization, desquamated epithelial cells, and exudative alterations, in the Cars2+/− mice. Apoptotic cells were significantly abundant in the Cars2+/− mice. Protein analysis revealed that Kidneys from Cars2+/− mice showed significantly higher levels of cytochrome c and activated form of caspase-9. No significant change could be observed in BAX level. Conclusion This study demonstrated that CARS2 is involved in the apoptosis pathways in the mitochondria under cisplatin-induced nephrotoxicity. Further investigation is needed to clarify whether cysteine polysulfide has protective effect on cisplatin nephrotoxicity.

Hospital pharmacists play vital roles in patient care, with career satisfaction influenced by work environment, career advancement opportunities and personal aspirations. Addressing these factors in Japan is essential to attract and retain hospital pharmacists. This study aimed to identify factors associated with hospital pharmacists' satisfaction with their current careers in Japan. A nationwide cross-sectional questionnaire survey was distributed through the Japanese Society of Hospital Pharmacists website, journal and newsletter. Responses were collected from 14 June to 31 July 2024, using Google Forms. Ordinal logistic regression analysis was applied to evaluate the association between career satisfaction and individual-related factors, including background, work style and environment. Of the 712 respondents, 710 provided consent for analysis. Pharmacists in their 30s, 40s and 50s reported significantly higher career satisfaction than those in their 20s (OR: 2.311, 95% CI: 1.323 to 4.038; OR: 2.148, 95% CI: 1.128 to 4.092; and OR: 2.077, 95% CI: 1.048 to 4.116, respectively). Conversely, mid-level and senior managerial roles and certifications were associated with lower satisfaction (OR: 0.354, 95% CI: 0.200 to 0.627; OR: 0.258, 95% CI: 0.158 to 0.421; and OR: 0.668, 95% CI: 0.478 to 0.934, respectively). Structured mentorship programmes, financial support for advanced training and systems to reduce workload and improve flexibility could enhance career satisfaction among hospital pharmacists in Japan.