Atsushi Kawaguchi

Background/Objectives: Chronic pain in osteoarthritis alters large-scale brain networks, including the insular cortex and default mode network. While total hip arthroplasty (THA) provides substantial relief, the early postoperative reorganization of functional connectivity (FC) remains unclear. This longitudinal fMRI study exploratively investigated how early improvements in pain intensity and catastrophizing are associated with insular FC alterations following THA. Methods: In this exploratory, longitudinal observational study, 10 female patients with hip osteoarthritis underwent resting-state fMRI and clinical assessments—Pain Visual Analogue Scale (VAS), Pain Catastrophizing Scale (PCS), and Japanese Orthopaedic Association (JOA) hip score—preoperatively and two weeks post-THA Whole-brain seed-to-voxel FC analyses were conducted using the bilateral anterior insular cortex as the seed. Changes in FC (ΔFC) were correlated with preoperative scores and postoperative clinical changes (ΔVAS, ΔPCS). Results: Following THA, VAS and PCS scores decreased significantly, while JOA scores improved. rs-fMRI analysis revealed that FC between the left anterior insula and major DMN regions as well as the right anterior cingulate cortex (ACC) increased significantly overall. Correlation analysis showed that greater reductions in pain intensity (ΔVAS) were significantly associated with increased ΔFC across these regions. Conversely, greater reductions in pain catastrophizing (ΔPCS) were associated with a suppression of these FC increases. Conclusions: Given the preliminary nature of this study, these findings suggest that the alleviation of pain catastrophizing following THA may be associated with the initial reorganization of the aIC network, rather than establishing a definitive causal relationship. Further large-scale longitudinal studies are required to confirm these potential neural signatures.

Background/Objectives: Postprandial hyperglycemia is a risk factor for diabetes and cardiovascular diseases, even in healthy individuals. Kanzaki mulberry leaf and water chestnut tea (MW tea), a blend of mulberry (Morus alba) leaves and water chestnut (Trapa japonica) leaves and husks, is rich in polyphenols and 1-deoxynojirimycin (DNJ) and may suppress postprandial glucose spikes, but evidence regarding its short-term daily intake is limited. This study aimed to evaluate the postprandial glycemic response and safety of two-week MW tea consumption using continuous glucose monitoring (CGM). Methods: We conducted a randomized, double-blind, placebo-controlled, two-period crossover trial involving 31 participants. Each intervention period lasted two weeks, separated by a one-week washout. Participants consumed either MW tea or a placebo before meals. Interstitial glucose levels were measured every 15 min using CGM. Postprandial glucose responses were recorded every 15 min for 180 min after a standardized meal on the first day of each period. The primary outcome was the coefficient of variation (CV) in glucose levels, calculated using data from the central 10 days of each intervention period. Safety was assessed using CGM-derived hypoglycemia metrics and blood test results. Results: The CV of glucose levels during the MW tea period was significantly lower than during the placebo period (mean difference: 0.02, p = 0.0006). A significant reduction in 1 h postprandial glucose area under the curve was also observed. No significant differences were found in hypoglycemia occurrence, liver/renal/inflammatory markers, or self-reported adverse symptoms. Notably, 1,5-anhydroglucitol (1,5-AG) levels significantly increased during MW tea intake, suggesting improved glycemic control. Conclusions: Short-term consumption of Kanzaki MW tea effectively suppressed postprandial glucose variability without safety concerns. These findings support MW tea as a promising natural supplement for glycemic management and the prevention of diabetes.

The neuropathological diagnosis of Alzheimer’s disease (AD) relies on amyloid beta (Aβ) deposition in brain tissues. To study the relationship between Aβ deposition and brain structure, as determined using ¹¹C-Pittsburgh compound B (PiB) and magnetic resonance imaging (MRI), respectively, we developed a regression model with PiB and MRI data as the predictor and response variables, respectively, and proposed a regression method for studying the association between them based on a supervised sparse multivariate analysis with dimension reduction based on a composite paired basis function. By applying this method to imaging data of 61 patients with AD (age: 55–85), the first component showed the strongest correlation with the composite score, owing to the supervised feature. The spatial pattern included the hippocampal and parahippocampal regions for MRI. The peak value was observed in the posterior cingulate and precuneus for PiB. The differences in PiB scores among the diagnosis groups 12 months after PiB imaging were significant between the normal and AD groups (p = 0.0284), but not between the normal and mild cognitive impairment (MCI) groups or the MCI and AD groups (p = 0.3508). Our method may facilitate the development of a dementia biomarker from brain imaging data. Scoring imaging data allows for visualization and the application of traditional analysis, facilitating clinical analysis for better interpretation of results.

Background: The degree of exercise-induced oxygen desaturation and outcomes following antifibrotic drug therapy in asymptomatic patients with fibrosing interstitial lung disease (FILD) remain unclear. Methods: We compared clinical data, incidence of annual FILD progression, overall survival, and tolerability after initiating nintedanib between 58 patients with dyspnea and 18 patients without. Annual FILD progression was defined as >10% decrease in forced vital capacity (FVC), >15% decrease in diffusing capacity of the lungs for carbon monoxide (D_LCO), developing acute exacerbations, or FILD-related death within 1 year of starting nintedanib. Outcomes between the two groups were adjusted for covariates, including age, gender, FVC, D_LCO, and diagnosis of idiopathic pulmonary fibrosis, all known prognostic factors for FILD. Results: In 6-min walk test, incidence of decrease to 4% decreases showed no significant difference (71% vs. 89%, p = 0.11) The incidence of annual progression was significantly lower in non-dyspnea than in dyspnea group (17% vs. 53%, adjusted p = 0.026). The relative change in D_LCO was significantly slower in non-dyspnea group (adjusted p = 0.036), but FVC was not (adjusted p = 0.067). Overall survival was longer in non-dyspnea group (adjusted p = 0.0089). The discontinuation rate and therapeutic period of nintedanib were not significantly different between the groups. Conclusions: Asymptomatic patients with FILD have severe exercise-induced oxygen desaturation and better outcomes after nintedanib therapy than symptomatic patients. Antifibrotic drug therapy should not be avoided solely because of a lack of symptoms.

Introduction Non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated steatotic liver disease (MASLD), is a phenotype of the metabolic syndrome in the liver and is clearly associated with metabolic abnormalities such as hyperglycaemia and dyslipidaemia. Although the prevalence of MASLD is increasing worldwide, there is currently no consensus on the efficacy and safety of the drugs used to treat MASLD/metabolic dysfunction-associated steatohepatitis (MASH). Pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was designed to have higher peroxisome proliferator-activated receptor alfa (PPARα) agonist activity and selectivity than existing PPARα agonists, and in development trials, without increasing creatinine levels, lipid parameters and alanine aminotransferase (ALT) were significantly improved. Thus, pemafibrate may effectively ameliorate the pathogenesis and metabolic abnormalities in MASLD/MASH. In this trial, we evaluated the efficacy and safety of pemafibrate in patients with MASLD/MASH. Methods and analysis This trial was designed as an open-label, three-arm, randomised controlled study. After obtaining informed consent, patients aged 20–80 years who met the selection criteria were enrolled. Patients were randomised to receive pemafibrate 0.4 mg/day, 0.2 mg/day or fenofibrate (n=120 per group). The duration of treatment was 48 weeks. The primary endpoint was a change in ALT levels after 24 weeks of administration. Secondary endpoints included changes from baseline in liver fibrosis markers (fibrosis-4 index, type IV collagen 7s, enhanced liver fibrosis and Mac-2 binding protein glycosylation isomer) at 48 weeks as well as changes in liver fat mass and liver stiffness measured by MRI and ultrasound (US) at centres equipped with MRI and US capabilities. Ethics and dissemination Ethical approval was obtained from the Yokohama City University Certified Institutional Review Board before participant enrolment (CRB20-014). The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences. Participants wishing to understand the results of this study will be contacted directly on data publication. Trial registration number This trial was registered in the Japan Registry of Clinical Trials (number: jRCTs031200280). Protocol version V.1.9, 23 November 2023

Purpose: The purpose of this study was to find useful imaging features on non-contrast-enhanced magnetic resonance imaging (MRI) that can divide patients with thymic epithelial tumor (TET) into clinical stage I-II and III-IV groups under assumption that contrast media are contraindicated. Materials and methods: This retrospective study included 106 patients (median age, 60 years; range, 27–82 years; 62 women) with surgically resected TET who underwent MRI between August 1986 and July 2015. All cases were classified according to the 2015 WHO classification and staged using the eighth edition of the TNM system. Two radiologists independently evaluated 14 categories of MRI findings; the findings in patients with stage I-II were compared with those of patients with stage III-IV using a logistic regression model. Disease-specific survival associated with significant findings was calculated using the Kaplan–Meier method. Results: Univariate analysis showed that stage III-IV patients were more likely to have tumors with an irregular contour, heterogeneity on T1WI, low-signal intensity on T2WI, irregular border with lung, findings of great vessel invasion (GVI) (hereafter, GVI sign), pericardial thickening/nodule, and lymphadenopathy (all, P < 0.01). On multivariable analysis, only two findings, irregular border between tumor and lung (odds ratio [OR], 272.8; 95% CI 26.6–2794.1; P < 0.001) and positive GVI sign (OR, 49.3; 95% CI 4.5–539.8; P = 0.001) remained statistically significant. Patients with one or both features had significantly worse survival (log-rank test, P < 0.001). Conclusion: For patients with TET who are unable to receive contrast for preoperative staging, the two image findings of an irregular border between tumor and lung and the positive GVI sign on non-contrast-enhanced MRI could be helpful in determining stage III-IV disease which is associated with a worse survival.

There is an association between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis, but the genetic risk of atherosclerosis in NAFLD remains unclear. Here, a single-nucleotide polymorphism (SNP) of the heat shock 70 kDa protein 8 (HSPA8) gene was analyzed in 123 NAFLD patients who had been diagnosed using a liver biopsy, and the NAFLD phenotype including the maximum intima–media thickness (Max-IMT) of the carotid artery was investigated. Patients with the minor allele (A/G or G/G) of rs2236659 showed a lower serum heat shock cognate 71 kDa protein concentration than those with the major A/A allele. Compared with the patients with the major allele, those with the minor allele showed a higher prevalence of hypertension and higher Max-IMT in men. No significant associations between the HSPA8 genotype and hepatic pathological findings were identified. In decision-tree analysis, age, sex, liver fibrosis, and HSPA8 genotype were individually associated with severe carotid artery atherosclerosis (Max-IMT ≥ 1.5 mm). Noncirrhotic men aged ≥ 65 years were most significantly affected by the minor allele of HSPA8. To predict the risk of atherosclerosis and cardiovascular disease, HSPA8 SNP genotyping might be useful, particularly for older male NAFLD patients.

Certain biomarkers predict death due to acute respiratory distress syndrome in COVID-19 patients. We retrospectively analyzed biomarkers associated with time to mechanical ventilation for respiratory failure due to COVID-19 (time-to-mechanical ventilation) in 135 consecutive patients in our hospital. We analyzed biomarkers that were elevated immediately (at admission) and later (3 days after admission) using Cox proportional hazards regression analysis. Independent biomarkers of time-to-mechanical ventilation were high C-reactive protein (CRP), interleukin (IL)-6, and Krebs von den Lungen-6 (KL-6) concentrations at admission and elevated CRP, high-mobility group box-1 protein (HMGB-1), and d-dimer levels and low platelets 3 days after admission. Receiver operating characteristic analysis for detecting the association between independent biomarkers associated with time-to-event in multivariate analyses and the start of mechanical ventilation revealed that these biomarkers had area under the curve values higher than 0.700. The present study suggests that CRP was the only biomarker associated with time-to-mechanical ventilation both at admission and 3 days after admission. Moreover, IL-6 (an inflammatory cytokine), HMGB-1 (a late inflammatory mediator), and KL-6 (reflecting injury and/or remodeling of type II pneumocytes) were associated with outcomes in COVID-19 as reported previously. In conclusion, increased CRP, IL-6, KL-6, HMGB-1, and d-dimer levels and decreased platelet counts were associated with the start of mechanical ventilation due to COVID-19.