Hamamatsu University Hospital

Abstract Uric acid (UA) is traditionally regarded as a metabolic risk marker; however, its dynamic behavior during glucose-lowering therapy remains incompletely understood. We compared UA responses to a modified traditional Japanese diet (MJDD) and the DPP-4 inhibitor alogliptin in patients with early-stage type 2 diabetes mellitus (T2DM). In this prospective observational study, drug-naïve patients received MJDD (n=58) or alogliptin (n=52) monotherapy for 3 months. Changes (Δ) in serum UA were analyzed in relation to glycemic control, insulin resistance, adipose tissue insulin resistance (adipo-IR), and beta-cell function. Both interventions significantly reduced fasting blood glucose and HbA1c while paradoxically increasing serum UA and HOMA-B. Baseline UA was the primary determinant of ΔUA in both cohorts. MJDD significantly reduced body mass index, insulin, free fatty acids, HOMA-R, and adipo-IR, with effects most pronounced in subjects with baseline BMI >25. In contrast, alogliptin selectively reduced adipo-IR in leaner subjects (BMI <25). Across both treatments, ΔUA correlated positively with ΔHOMA-B and inversely with ΔHbA1c. Notably, during MJDD, ΔUA showed a paradoxical negative correlation with ΔBMI and ΔFBG, and a positive correlation with ΔFFA. Patients exhibiting the greatest UA increases demonstrated the most marked improvements in beta-cell function and, with MJDD, the greatest weight loss. These findings indicate that MJDD and alogliptin exert distinct metabolic effects in early T2DM, yet both link rising UA to enhanced beta-cell function, suggesting that UA may serve as a dynamic pharmacometabolic biomarker reflecting therapy-specific metabolic adaptation rather than metabolic deterioration.

BackgroundNudge strategies are well-established in behavioral economics as effective approaches for promoting desirable behaviors. However, the potential benefits of integrating nudge-based strategies into pharmacist-led patient education have not yet been demonstrated. Here, we present a study protocol for an interventional trial to address this issue.MethodsThe PHARM-NUDGE study is a multicenter, randomized, parallel-group, single-blind, controlled trial prospectively designed to evaluate whether nudge-based pharmacist-led education can promote patients’ preventive behaviors against skin toxicities associated with cancer chemotherapy. The key inclusion criteria are as follows: (1) patients who are men or women and aged 18 years or older and (2) patients scheduled to receive a chemotherapy regimen containing capecitabine, liposomal doxorubicin, lenvatinib, cetuximab, or panitumumab in outpatient chemotherapy units or during hospitalization. The enrolled patients are randomly assigned in a 2:1 ratio to the nudge-based education or standard education groups. Pharmacists responsible for patient education utilize special educational tools that incorporate nudge strategies and provide skincare education to patients assigned to the nudge-based education group. Patients assigned to the standard education group receive skincare education with equivalent content but without nudges. The primary endpoint is the proportion of patients in each group who achieve four or more of the five predefined behavioral criteria.ConclusionsThe PHARM-NUDGE study is the first randomized controlled trial to evaluate the potential benefits of integrating nudge strategies into pharmacist-led skincare education for patients undergoing cancer chemotherapy with a high risk of skin toxicity, with patient enrollment initiated on October 15, 2025. Completion of the trial and acquisition of the final results are eagerly anticipated.Trial registrationThis trial was registeredwith the Japan Registry of Clinical Trials (clinical trial number: jRCT1040250089, registration date: September 3, 2025).Supplementary InformationThe online version contains supplementary material available at 10.1186/s40780-026-00556-4.

Tumor budding (TB) in colorectal cancer (CRC) has been associated with poor prognosis. TB has been considered a form of epithelial–mesenchymal transition (EMT). Additional discovery of proteins involved in TB can help suppress the aggressiveness of CRC. This study focused on examining whether S100A10, which has been implicated in TB and EMT, qualifies as a biomarker for TB. Formalin-fixed, paraffin-embedded tissue sections from 339 low-grade adenocarcinomas were used. TB was assessed using the recommended hotspot method. Immunohistochemical analysis focused on S100A10 expression on both the tumor buds at the hotspot and tumor glands (TGs), which serve as the direct background for TB, with the stroma-facing membrane (SFM) being the target for the evaluation. Among the 339 patients analyzed, 190 (56.0%) were confirmed to have TB. S100A10 positivity in the tumor buds was detected in 153 patients (80.5%) and was significantly correlated with high-grade TB and high S100A10 positivity in background TGs. S100A10 positivity in background TGs was significantly correlated with high-grade TB, node metastasis, and poor pStage. S100A10 positivity in TGs was often observed in the portions having an irregular border with the stroma, especially ones protruding toward the stroma. In CRC, S100A10 expression at the SFMs of the TGs likely promotes TB from its earliest stage and remains active during TB. The increase in the number of S100A10-expressing tumor cells was associated with poor biological behavior in CRC. Overall, our findings suggest that S100A10 could be a potential biomarker for TB of CRC.

Patients with chronic kidney disease (CKD) who develop sepsis experience worse prognoses; however, the impact of CKD on the incidence of sepsis has not been systematically investigated. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Medical Literature Analysis and Retrieval System Online, Web of Science, the Cochrane Register of Controlled Trials, and ClinicalTrials.gov was performed for literature published prior to May 22, 2025, comparing the onset of sepsis in patients with or without CKD. The risk of bias was determined using the Risk of Bias in Nonrandomized Studies of Interventions tool. This study was registered with the International Prospective Register of Systematic Reviews (CRD42023465075). A total of 14 studies met the inclusion criteria for the systematic review. Of these, 5 examined community-acquired sepsis, 2 focused on intensive care unit-acquired sepsis, and the rest investigated surgery-acquired sepsis. Most studies enrolled populations aged over 65 years; 2 assessed age-related sepsis risk. One study evaluated sepsis occurrence in patients with end-stage CKD, while 3 studies stratified this association by estimated glomerular filtration rate (eGFR). Nearly all studies demonstrated an increased risk of sepsis among patients with CKD, with the risk progressively increasing as eGFR declined. Additionally, 2 studies reported that CKD elevated the risk of sepsis regardless of age, and all included studies indicated a low risk of bias. We indicate that patients with CKD may have a higher risk of developing sepsis than individuals without CKD.

To summarize descriptively health-related quality of life (HRQOL) and physical activity (PA) evaluated with a mobile application and wearable device among patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 -) advanced breast cancer (ABC) treated with first- or second-line palbociclib plus endocrine therapy (ET) or ET alone. HRQOL was assessed with the EORTC QLQ-C30 at baseline and Day 15 of 6 treatment cycles (~ 24weeks). PA metrics were averaged on a weekly basis for 24weeks. Co-primary endpoints were mean change from baseline in Global Health Status (GHS) and sedentary time. Ninety-nine patients were enrolled; 78 received palbociclib plus ET (mean age: 57.2years; 75.6% initiated first-line treatment) and 21 received ET alone (mean age: 56.3years; 90.5% initiated first-line treatment). Baseline mean GHS score was 60.9 in the palbociclib plus ET group and 64.3 in the ET alone group; mean changes from baseline to Day 15 of Cycle 6 were +4.8 and +2.9, respectively, and not deteriorated beyond the 10-point clinically significant threshold in either treatment group. Baseline mean sedentary time was 581min/day in the palbociclib plus ET group and 513min/day in the ET alone group; mean changes from baseline to Week 24 were -22 and -102min/day, respectively. In this real-world study of women with HR+/HER2- ABC in Japan, neither palbociclib plus ET nor ET alone had any substantial detrimental impacts on HRQOL, according to patients' assessments recorded in a smartphone-based mobile application, and PA, as measured by a wearable device. ClinicalTrials.gov NCT04736576; registered, February 3, 2021.

We used the sodium-glucose cotransporter 2 inhibitor, luseogliflozin in two patients with diabetes mellitus with Child-Pugh classification B cirrhosis and cirrhotic ascites. In each case, luseogliflozin was safely used for over three years and was also considered effective in reducing ascites. In one of the patients in particular, when luseogliflozin was discontinued and switched to insulin treatment before colorectal cancer surgery, ascites accumulation was observed within two weeks, which subsequently decreased rapidly when luseogliflozin was restarted. In this case, the effect of luseogliflozin on ascites was evident by the clear increase and decrease in ascites over a short period of time, as evaluated using body weight, abdominal circumference and CT scan, without changing her other diuretic medication. Although sodium-glucose cotransporter 2 inhibitors need to be used with caution, they might be an option for the treatment of diabetes in patients with cirrhosis. Luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, is effective for glycemic control and safe in patients with cirrhosis. Luseogliflozin administration reduced ascites in patients with diabetes mellitus. Caution is warranted, as discontinuation of sodium-glucose cotransporter 2 inhibitors might lead to an increase in ascites.

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are salivary gland tumors with biphasic differentiation, composed of luminal ductal cells and abluminal basal cells with a high nuclear-to-cytoplasmic ratio. While BCA is a relatively common benign tumor, BCAC is a rare malignancy, and its genetic context and relationship with BCA remain unclear. We investigated 93 BCA and 36 BCAC cases to further characterize these two tumor entities from histological and molecular perspectives. BCA/BCAC proliferated in a mixture of tubular, trabecular, solid, cribriform, and membranous patterns. A jigsaw puzzle pattern, peripheral palisading, S100-positive stroma, cystic change, and sclerosis were observed in approximately 50% of the cases. BCAC demonstrated the following malignant features: infiltration to surrounding tissue, tumor necrosis, and increased mitotic activity (81%, 22%, and 22%, respectively). The nuclear expression of β-catenin was frequently observed in both BCA and BCAC (89% and 60%), and CTNNB1 hotspot mutations were detected in 46% and 48% of BCA and BCAC cases, respectively. Tubular patterns of growth, jigsaw puzzle patterns, peripheral palisading, S100-positive stroma, and cystic changes were more common in β-catenin-positive BCA/BCAC than in β-catenin-negative BCA/BCAC. Among the β-catenin-negative BCA/BCAC cases, one case each harbored PLAG1 and MYB rearrangements. We concluded that β-catenin-positive BCA and BCAC share common histologic and molecular features, and BCAC is considered a malignant counterpart of BCA. β-Catenin-negative BCA/BCAC might include morphological mimickers, which can be genetically classified into other tumor types, including pleomorphic adenoma and adenoid cystic carcinoma.