Sarcoidosis is a multisystemic disease that causes organ dysfunction through the formation of non-caseating granulomas. Cardiac sarcoidosis (CS) is a phenotype associated with a poor prognosis and benefits from timely diagnosis and management. A nonspecific clinical presentation and the lack of a reliable diagnostic gold standard make obtaining a definitive diagnosis challenging. Advanced cardiac imaging techniques, such as cardiac magnetic resonance imaging (CMR) and 18F-labeled fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET), play an essential role in CS assessment and have been incorporated into several diagnostic guidelines. These modalities have significantly improved our knowledge and understanding of CS by contributing to risk stratification and the assessment of inflammatory and therapeutic response monitoring. The integration of hybrid imaging techniques, such as PET/CMR and PET/computed tomography (PET/CT), has also demonstrated potential in enhancing diagnostic accuracy and disease staging. Each modality offers complementary insights, and their integration through multimodal and hybrid imaging improves diagnostic confidence, disease staging, and therapy monitoring. This review synthesizes current evidence and illustrative cases to highlight the clinical utility of multimodal imaging in CS and discusses limitations and emerging tools guiding future directions. J. Med. Invest. 72 : 225-234, August, 2025

Intestinal organoids are three-dimensional cell culture models that replicate the structure and function of the intestine, and have drawn significant attention in recent years for their potential in research and medical applications. Organoid culture technology enables the reconstruction of miniature tissues with intestinal structures, often referred to as “mini-organs”, from adult stem cells or induced pluripotent stem cells. This technology allows for the faithful replication of intestinal functions and pathologies that are challenging to reproduce using conventional two-dimensional culture systems. As a result, organoid culture has emerged as a vital platform that is widely utilized in developmental biology, disease modeling, drug screening, and personalized medicine. This article focuses on the clinical applications of organoid culture technology, particularly with respect to the gastrointestinal tract, and provides an overview of its advancements and clinical potential. J. Med. Invest. 72 : 235-240, August, 2025

The local renal renin-angiotensin system (RAS) is regulated independently of the systemic RAS. The renal RAS not only regulates blood pressure and hemodynamics but also plays an important role in the kidney disease development. Many studies have shown that the of angiotensinogen urinary excretion rate is a specific index of the intrarenal RAS activation. Moreover, urinary angiotensinogen (AGT) levels reflect the intrarenal RAS status associated with hypertension, chronic kidney disease, and diabetic nephropathy. In addition, urinary AGT is a novel biomarker of intrarenal RAS activation during neonatal kidney development. Furthermore, angiotensin-converting enzyme 2 and the (pro)renin receptor have recently been identified as new components of the RAS that have novel functions in kidney diseases and development. This review summarizes the current knowledge on intrarenal RAS activation in the context of pathological and physiological processes in children. J. Med. Invest. 72 : 241-244, August, 2025

Background:The number of elderly patients with frailty who require hepatectomy is increasing. This study aimed to investigate the effect of Ninjin’yoeito (NYT) on the post-hepatectomy state in naturally aged frailty model mice. Methods:Seventy-two-week-old mice were subjected to 70% partial hepatectomy and then divided into an NYT-treated group and a control group. Mice were sacrificed immediately (0 hours) or 24 or 48 hours after hepatectomy. Body weight, grip strength, endurance, and survival duration were investigated. Furthermore, liver function was assessed, and mRNA expression was measured using reverse-transcription PCR. Results:The body weight tended to be higher in the NYT group than in the control group 24 hours after hepatectomy (p=0.09). The grip strength was significantly stronger in the NYT group before and 48 hours after hepatectomy (p<0.05). Although survival time was slightly prolonged in the NYT group, there was no significant difference between the two groups. HMGB1 mRNA expression in the liver was significantly suppressed in the NYT group compared with that in the control group at 24 and 48 hours after hepatectomy (p<0.05). Conclusions:NYT may affect the postoperative state, including body weight and motor function, in aged model mice. Suppression of HMGB1 might affect postoperative survival. J. Med. Invest. 72 : 245-251, August, 2025

Objective;In order to maintain a patient’s adequate nutritional status, it is important to accurately assess energy expenditure and to provide nutritional administration commensurate with that expenditure. In this study, we have assessed the resting energy expenditures (REE) in patients with esophageal and head and neck cancer, and association between REE, metabolites, nutritional intake, and body composition. Methods;Patients included in the study had to be diagnosed with esophageal and head and neck cancer, and hospitalized and receiving chemotherapy. REE was measured using indirect calorimetry with a mask and calculated using 3 different equations. Result;Patients with esophageal and head and neck cancer (67.1±8.5 years old, n=52, all patients were male) were enrolled. The average of REE measured by indirect calorimetry were 22.1kcal/kg/day. REE was positively correlated with muscle mass, body cell mass, and lean body mass. REE was higher in group with oral intake of more than 72%. Blood levels of lactate, pyruvate, and amino acids were higher in cancer patients with esophageal and head and neck cancer compared to healthy subjects. Conclusion:REE measured by indirect calorimetry correlated with the estimated BEE. There was an association between energy expenditure and muscle mass and nutritional intake. J. Med. Invest. 72 : 252-259, August, 2025

Fungi are one of the main sources of microbial contamination in food and residential environments. There has been reported that fungi are more resistant to drugs than are viruses and bacteria, so efficient sterilization methods are still required. In this study, we examined the effectiveness of ultraviolet (UV) sterilization against mold by focusing on the wavelength and radiant flux dependence of UV. UVC or UVA irradiation inactivated the mold species Cladosporium sphaerospermum in a dose-dependent manner. The energy required to obtain the same inactivation differed significantly between UVC irradiation and UVA irradiation. UVC irradiation induced the formation of substantial amounts of cyclobutane pyrimidine dimers, whereas UVA irradiation did not show any significant difference from the unirradiated group. Furthermore, UVC irradiation induced morphological changes that could be observed by electron microscopy. On the other hand, UVA irradiation suppressed the growth rate. These results suggest that UVC and UVA irradiation have different effects on fungi. The results suggest that both UVC and UVA irradiation may help control fungal contamination. Since the effect of UV differs depending on the wavelength of irradiation, it will be necessary to understand the wavelength-specific effect and use it to control fungal contamination in the living environment. J. Med. Invest. 72 : 260-265, August, 2025

Background:Detailed depiction of bony structures on conventional magnetic resonance imaging (MRI) is difficult and the modality is inferior to computerized tomography (CT) for showing bony injuries, ossification and calcification. Novel sequences such as zero-echo time (ZTE) and fast field echo resembling a CT using restricted echo-spacing (FRACTURE) may overcome the weak points of conventional MRI. The objective of this study was to determine the usefulness of these sequences on 3.0-T MRI for imaging the cervical spine. Methods:ZTE and FRACTURE images were obtained from 3.0-T scans for three representative cases of ossification of the posterior longitudinal ligament, retro-odontoid pseudotumor, and fracture in the cervical spine and compared with CT. Results:FRACTURE images were superior to ZTE images in both of 2D images and 3D images reconstructed from 2D images. But, both ZTE and FRACTURE images from 3.0-T scans could take the place of CT and fused images reconstructed from 2D images and MR angiography could be used instead of CT angiography. Conclusion:High-resolution MRI sequences may completely replace CT and appear very useful when surgical strategies are considered for patients with allergies to contrast agents or renal failure for whom use of contrast agents is contraindicated. J. Med. Invest. 72 : 266-271, August, 2025

Background:Early detection of sarcopenia is critical in countries with rapidly aging populations. In this study, we investigated the diagnostic accuracy of Kihon Checklist (KCL) in screening sarcopenia among older adults. Methods:This retrospective, cross-sectional study included 442 community-dwelling. A baseline questionnaire and KCL were administered to the participants, and their physical function and body composition were measured. Sarcopenia was defined according to Asian Working Group for Sarcopenia 2019 guidelines. Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic accuracy of KCL for sarcopenia. In addition, a novel approach using KCL along with patient age was considered. Results:Among the subjects (72.1% women;average age, 76.7 years), 34 (7.6%) had sarcopenia. The ROC-based diagnostic accuracy for sarcopenia was as follows:Area under the ROC curve (AUC) = 0.805 (95% confidence interval [CI] = 0.735–0.874) for KCL, 0.865 (95% CI = 0.811–0.920) for KCL 5 items model, 0.892 (95% CI = 0.851–0.934) for KCL plus age, and 0.922 (95% CI = 0.886–0.957) for KCL 5 items model plus age. Conclusion:KCL showed good diagnostic accuracy as a screening tool for predicting sarcopenia, suggesting utility in population-based approaches for sarcopenia detection. J. Med. Invest. 72 : 272-280, August, 2025

Background/Objectives:Although dietary intake has been shown to affect various diseases, the effect of dietary intake on body composition remains unclear. Therefore, this study aimed to assess the effects of dietary intake on body composition. Methods:A total of 51 Japanese dietetic students (11 men and 40 women;average age:20.9±2.8) participated in this study. We assessed their body composition (i.e., muscle mass, body fat, and total body water) using the Physion MD® system. The subjects also completed an FFQg that was used to analyze dietary intake. Results:The mean body mass index was 21.09±3.28 kg/m2, the mean percentage of body muscle was 35.9±6.2%, and the mean percentage of body fat was 21.1±6.7%. The body fat percentage was negatively correlated with vegetable intake (r=-0.5872, p<0.0001) and positively correlated with snack intake (r=0.6853, p<0.0001). Conclusions:Daily dietary intake, especially intake of vegetables and snacks, was independently associated with body fat percentage in healthy subjects. This suggests that intake of vegetables and snacks has a direct impact on body composition. J. Med. Invest. 72 : 281-285, August, 2025

The onset age of amyotrophic lateral sclerosis (ALS) has been increasing, but recent trends remain unclear. This study examined changes in ALS onset age over the past decade. We analyzed 233 ALS patients diagnosed from 2011 to 2020 at Tokushima University Hospital. The Jonckheere–Terpstra test assessed the trend in onset age. We compared onset age between 2011–2015 (Group A) and 2016–2020 (Group B) using the Mann–Whitney U test. We also analyzed the annual proportion of patients with onset age ≥80 using Spearman’s rank correlation. In Tokushima Prefecture, we evaluated annual increase rates of individuals aged ≥80 and ALS patients with onset age ≥80, using 2011 as baseline. Regression slopes were compared using a t test. Onset age showed a significant positive trend (p=0.04), and Group B had older onset age than Group A (p=0.048). The proportion of patients with onset age ≥80 increased significantly (ρ=0.69, p=0.03). No significant difference was found between regression slopes for the general elderly population and ALS patients with onset age ≥80 (p=0.49). These findings suggest that the onset age of ALS at Tokushima University Hospital has increased over the past decade. J. Med. Invest. 72 : 286-289, August, 2025

Background and aim:The associations between follicle-stimulating hormone (FSH) levels and lipid profiles have been controversial. The aim of this study was to examine the associations between FSH levels and lipid profiles before and during hormone replacement therapy (HRT) in Japanese women. Subjects and methods:We recruited 117 women who were receiving HRT and examined serum levels of FSH, LH, estradiol, triglycerides (TG), LDL-C and HDL-C. In addition, the associations of reduction rate of FSH and increase in estradiol level with changes in lipid parameters before and during HRT were examined. Results:FSH showed a significant negative correlation with TG and LDL-C and a significant positive correlation with LH and HDL-C. In women receiving oral estrogen, the rate of increase in HDL-C and TG was significantly greater in the group with a large decrease in FSH. In women receiving oral estrogen, LDL-C was significantly decreased and TG was significantly increased in the group with a large increase in estradiol. Conclusion:We demonstrated associations between FSH level and favorable lipid profiles in this study. During HRT, the action of reduction of FSH on lipid parameters did not exceed the direct action of estrogen. J. Med. Invest. 72 : 290-297, August, 2025

Background:Interstitial lung disease (ILD) associated with connective tissue diseases (CTD-ILD) remains to be a major cause of mortality. Different from idiopathic form, CTD-ILD involves more immune dysregulation along with aberrant fibroblast activation. Therefore, therapy targeting both profibrotic and proinflammatory molecules could be ideal for CTD-ILD. Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals. The purpose of this study is to reveal the anti-fibrotic potential of JAK inhibitors (JAKis). Methods:The anti-fibrotic effect of a JAKi with a particular focus on baricitinib was examined using a human lung fibroblast cell line and a bleomycin (BLM)-induced pulmonary fibrosis model in mice. Results:Baricitinib, a selective JAK1, 2 inhibitor suppressed transforming growth factor-β (TGF-β)-induced phosphorylation of JAK2 in human lung fibroblasts. Baricitinib also strongly suppressed the TGF-β-induced collagen1 and α-smooth muscle actin (α-SMA) expression in fibroblasts. Moreover, baricitinib ameliorated lung fibrosis in BLM-treated mice, particularly when administered in the late phase. The number of α-SMA or collagen triple helix repeat containing 1 (CTHRC1) positive fibroblasts in BLM-treated lungs was reduced by administration of baricitinib. Conclusions:Our data suggest that baricitinib may improve pulmonary fibrosis by directly inhibiting fibroblast activation via JAK2 blockade. J. Med. Invest. 72 : 298-307, August, 2025

Physiological studies on the amount and duration of vitamin D intake are limited. Noninvasive biomarkers for vitamin D status also need to be explored. Thus, we conducted a dietary challenge study to assess vitamin D metabolism. This crossover study included 21 healthy Japanese individuals, with each test lasting 6 consecutive days. Participants consumed test meals during the study period for 5 days. The main dish was either fish (FD) or meat (MD), and the FD group was provided with at least 18 μg of vitamin D per day. Fasting blood samples and 24 h urine samples were collected on the first and last days. The mean serum 25(OH)D3 level were low before the intervention and changed only slightly after intervention, with higher levels in the FD group. Serum 25(OH)D3 demonstrated a strong positive correlation with serum 24,25(OH)2D3 but showed no correlation with urinary 25(OH)D3. Surprisingly, it had a relatively strong positive correlation with urinary 24,25(OH)2D3. In conclusion, in healthy Japanese, adequate intake of vitamin D from fish failed to increase serum 25(OH)D3 concentrations. On the other hand, noninvasive urinary24,25(OH)2D3 excretion may be used instead of serum 25(OH)D3 levels to assess vitamin D status. J. Med. Invest. 72 : 308-315, August, 2025

Polycystic ovary syndrome (PCOS) is an endocrine disorder that causes infertility as well as obesity. Oxytocin (OT), a neuropeptide involved in appetite and fat metabolism, may be therapeutically beneficial for PCOS. Kamikihito (KKT), a traditional Japanese herbal medicine of Chinese origin, has been shown to up-regulate the expression of OT in the hypothalamus and exert various physiological effects. The present study investigated the anti-obesity effects of KKT in relation to OT using a PCOS model rat. Female rats were implanted with dihydrotestosterone to induce PCOS and divided into a normal food group (NF group) and food containing KKT group (KF group). After surgery, rats were fed normal food for four weeks, followed by food containing 3% KKT for another four weeks. The anti-obesity effects and impact on the ovarian morphology of KKT in PCOS were examined. KKT supplementation reduced food intake, the size of visceral adipocytes, and ovarian weight. The KF group showed increased mRNA expression levels of OT receptors (OTR) and leptin in visceral fat and slightly increased serum levels of OT and leptin. These results suggest the potential of KKT as a therapeutic agent for PCOS, potentially through effects on OT and leptin signaling pathways. J. Med. Invest. 72 : 316-323, August, 2025

The number of bedridden elderly is substantially increasing in our aging society. Bedridden patients experience muscle atrophy due to prolonged inactivity. We are concerned about whether the antioxidative flavonoid quercetin can prevent disuse muscle atrophy in elderly people considering that oxidative stress plays a role in this condition. This study explored the links between quercetin intake, oxidative stress, and muscle preservation in bedridden individuals. Onion was selected and a dose of 5 g of onion powder, which contains 99.7 mg of quercetin aglycone equivalent, was given to patients who were bedridden for 30 days. Plasma quercetin concentration was significantly increased in the onion powder group, with regular intake of quercetin meals maintaining high plasma levels (n=9). Higher plasma quercetin levels were linked to lower plasma oxidized low-density lipoprotein (ox-LDL) and urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) content. No correlation was identified in the indexes of muscle maintenance (volume of the quadriceps femoris muscle) and the minimum necessary activities of daily living (ADL). In conclusion, our small-scale pilot study involving bedridden individuals did not demonstrate a positive effect of continuous quercetin intake on the prevention of muscle atrophy. However, efficient dietary quercetin consumption can mitigate the elevation of in vivo oxidative stress. J. Med. Invest. 72 : 324-329, August, 2025

Background:Coronary artery disease (CAD) is a leading cause of mortality worldwide. Coronary artery calcification (CAC) is a key indicator of CAD, reflecting plaque burden. Pericoronary adipose tissue (PCAT) promotes vascular inflammation and contributes to plaque development, making it a promising imaging biomarker. This study aimed to create a radiomics-based model using cardiac CT features of PCAT around the left main coronary artery (LMCA) to predict CAC. Methods:Imaging from forty patients who underwent ECG-gated cardiac CT was retrospectively analyzed and grouped by CAC presence. Manual segmentation was performed using 3D Slicer to delineate PCAT surrounding the LMCA. Minimum Redundancy Maximum Relevance (mRMR) and Least Absolute Shrinkage and Selection Operator (LASSO) regression were utilized for feature selection. Random Forest and support vector machine (SVM) models were trained and compared. Results:From the 1,037 features extracted, two features with non-zero coefficients were retained at the optimal LASSO parameter (log α = 0.0128). The Random Forest model achieved 92% accuracy and an area under the curve (AUC) of 0.9143, outperforming SVM. Conclusion:Radiomic features of PCAT on cardiac CT can accurately predict CAC, showing its potential as an imaging-based biomarker for CAD risk assessment. J. Med. Invest. 72 : 330-336, August, 2025

Introduction:Vitamin D may reduce inflammation by affecting cytokine production, potentially alleviating chronic anemia. Iron deficiency can impair vitamin D absorption, yet the interaction between these deficiencies remains unclear. This study aimed to evaluate the effectiveness of combined vitamin D and iron supplementation in treating iron deficiency anemia (IDA) in children. Methods:An open-label, randomized controlled trial was conducted at four outpatient clinics and Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia. Of 250 assessed patients, 67 met the inclusion criteria. Participants were randomized into two groups:Group A received iron supplementation (3 mg/kg BW/day), while Group B received iron combined with vitamin D (400 IU). Treatment lasted 4 weeks, and iron status was evaluated pre- and post-treatment. Results:No significant changes were observed in complete blood count, serum iron, and ferritin levels after 4 weeks in either group (p>0.05). However, the mean change in serum ferritin levels was significantly greater in the combined group (p=0.039). Conclusion:Both iron alone and iron with vitamin D improved hematological parameters in children with iron deficiency anemia. Combined iron and vitamin D therapy showed a significant ferritin increase, suggesting that adding vitamin D may support better iron storage. J. Med. Invest. 72 : 337-342, August, 2025

The aim of this study was to determine the association between total soy product intake and metabolic syndrome (MetS) in Japanese workers. The cross-sectional study included 698 participants aged over 40 years, and the longitudinal study included 527 participants aged over 40 years in 2012 who participated at least once from 2013 to 2018. Dietary intake of total soy products was summed based on the total amount of 12 kinds of soy products assessed using a food frequency questionnaire. Participants were diagnosed as having MetS if they had abdominal obesity and at least one of the following conditions:hypertriglyceridemia, high blood pressure, and hyperglycemia. To calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for MetS according to tertile of total soy product intake, multivariable logistic regression was performed for the cross-sectional analysis, and generalized estimating equations were used for the longitudinal analysis. Cross-sectional analysis showed that there was an inverse association between total soy product intake and MetS, and the OR of tertile 3 was significantly higher than that of tertile 1. However, the inverse association disappeared in the longitudinal analysis. Further long-term studies are needed to determine the association between total soy product intake and MetS. J. Med. Invest. 72 : 343-353, August, 2025

BACKGROUND:Tumor-infiltrating CD8+ T cells express many immune checkpoint proteins and are currently the focus of therapeutic targeting, although dramatic results have not yet been achieved in hepatocellular carcinoma (HCC). In this study, we performed a statistical analysis of immune checkpoint proteins and prognosis in HCC to evaluate its utility as a biomarker for predicting prognosis. METHODS:We analyzed 474 HCC patients with two comprehensive miRNA profiling datasets (GSE76427:n=115 and TCGA:n=359) with clinical and transcriptomic data to examine associations between mRNA levels of CD8, TIM3, and PD-1/PD-L1. Each gene was divided into low- and high-expression groups using the tertiles of RNA expression. RESULTS:CD8 and TIM3 expression were associated with overall survival (OS) (P=0.021 and P=0.025, respectively), while PD-1/PD-L1 levels were not associated with OS (P=0.306 and P=0.318, respectively) in TCGA dataset. Among patients with high CD8 expression, low TIM3 expression was associated with better OS (TCGA:P=0.009, Whole patient cohort (TCGA+GSE dataset):P=0.008). CONCLUSIONS:The combination of CD8 and TIM3 expression which indicates T cell exhaustion was useful biomarker for predicting HCC prognosis than PD-1/PD-L1, suggesting that TIM3 may be a future target for immune checkpoint inhibition. J. Med. Invest. 72 : 354-360, August, 2025

Background:Positive-pressure ventilation (PPV) before extubation may improve oxygenation and reduce complications after extubation. However, no study has quantitatively evaluated the effects of extubation on breathing and lung volume. Methods:A crossover randomized study was performed on 16 patients who received mechanical ventilation and planned to undergo extubation in the intensive-care unit. We used the automatic tube compensation (ATC) mode to simulate extubation. We used electrical impedance tomography and an esophageal balloon catheter to evaluate the work of breathing and lung volume after simulated extubation. We compared the work of breathing and lung volume with and without PPV before simulated extubation. Result:There were no differences in the changes in end-expiratory lung impedance (-7.4 [-18.2–2.3] vs. -11.2 [-16.6–1.1] arbitrary units, p=0.53), anterior-to-posterior ventilation ratio (0.60 [0.49–0.74] vs. 0.60 [0.52–0.79], p=0.75), esophageal pressure swing (4.9 [2.1–8.7] vs. 5.4 [1.9–6.6] cmH2O, p=0.61), dynamic transpulmonary pressure (7.2 [6.7–9.9] vs. 7.6 [6.6–9.7] cmH2O, p=0.93), and pressure time product (2.4 [1.4–4.2] vs. 3.1 [1.0–4.3] cmH2O*s, p=0.84) with and without PPV before simulated extubation. Conclusion:PPV before extubation did not affect breathing work or lung volume after extubation. Therefore, it may delay extubation and increase patient stress. J. Med. Invest. 72 : 361-366, August, 2025

Objectives:Malignant peripheral nerve sheath tumors (MPNSTs) are rare neoplasms requiring differentiation from benign neurogenic tumors on diagnostic imaging. We evaluated the diagnostic utility of texture analysis (TA) in distinguishing seven pathologically confirmed MPNSTs from eight schwannomas using magnetic resonance imaging (MRI), including T1- (T1WI) and T2-weighted imaging (T2WI), and apparent diffusion coefficient (ADC) maps. TA’s performance was compared with that of conventional approaches using ADC values alone. Methods:Tumors were segmented, and 90 texture features were extracted using LIFEx software. Significantly different features (p < 0.05) were identified using the Mann–Whitney U test and evaluated through receiver operating characteristic (ROC) analysis. ADC maps were used to measure the minimum, mean, and maximum ADC values, followed by ROC analysis. Results:Two T2WI-based texture features (neighborhood grey-tone difference matrix Contrast and grey-level size zone matrix Grey Level Variance) demonstrated the highest diagnostic performance (area under the curve = 0.911 [95% confidence interval (CI):0.755–1.000]), comparable to the minimum and mean ADC values (area under the curve = 0.898 [95% CI:0.691–1.000]). Conclusions:TA may help differentiate MPNSTs from schwannomas. T2WI-based TA offers a viable alternative when ADC maps are limited by magnetic susceptibility artifacts. J. Med. Invest. 72 : 367-374, August, 2025

Metabolic dysfunction–associated steatohepatitis (MASH) exhibits inflammation and fibrosis in addition to lipid accumulation in the liver, which may progress to cirrhosis and liver failure. This study investigated whether the serum lipoprotein subfraction reflects fibrosis severity in a MASH mouse model. Nine-week-old male A/J and C57BL6/J mice were fed a high-fat/cholesterol/cholate-based diet to induce fibrotic MASH. To generate fibrosis of varying severity, mice were fed two diets with different cholesterol concentrations (1.25% and 2.5%). After 9 weeks of feeding, serum cholesterol and triglyceride levels of each lipoprotein were comprehensively analyzed, including chylomicron, very-large low-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein (HDL), with 20 subclasses according to particle size. Serum levels of very-large HDL-cholesterol, very-small HDL-cholesterol, very-small HDL-triglycerides, and very-small LDL-cholesterol were significantly higher in the stage 2 fibrosis group than the stage 1 fibrosis group. Serum very-small LDL-cholesterol levels were correlated with histological severity of MASH, which reportedly increases with the progression of MASH in humans. In conclusion, the serum lipoprotein subfraction reflects liver fibrosis severity even in early phase, independent of the severity of other MASH lesions in MASH model mice. Fractionating HDL, which have been measured in clinical practice, may help establish noninvasive markers of liver fibrosis. J. Med. Invest. 72 : 375-384, August, 2025

Purpose:Type 1 Modic change (MC) is associated with chronic low back pain and attributed to segmental instability. However, the relationship between type 1 MC and segmental instability is unclear. This study sought to clarify the role of mechanical abnormalities in type 1 MC. Method:Review of magnetic resonance images obtained for 727 patients over a 1-year period at our institution revealed 161 cases of type 1 MC. In 86 of these, the following indicators of mechanical abnormality could be evaluated on dynamic radiographs:segmental scoliosis (>5°), forward slippage (>1%), and posterior disc opening in flexion. Patients with one or more of these abnormalities were allocated to a mechanical group (n=62, 70%) and those with no abnormality to a non-mechanical group (n=26, 30%). The Pfirrmann grade of disc degeneration at the affected level was compared between the groups. Results:Segmental scoliosis, slippage, and posterior opening was observed in 34, 21 and 37 cases, respectively. Severe disc degeneration (grade IV or V) was present in 43 cases (69%) in the mechanical group and in 12 cases (46%) in the non-mechanical group;the difference was statistically significant (p=0.04). Conclusion:We propose that there are mechanical and non-mechanical variants of type 1 MC. J. Med. Invest. 72 : 385-389, August, 2025

We investigated mid-term outcomes after aortic valve replacement (AVR) with INSPIRIS RESILIA (IR) aortic bioprosthesis for severe aortic stenosis (AS). A total of 60 patients with a mean age of 73.2±6.2 years underwent AVR with IR bioprosthesis for severe AS. We prospectively followed up on 59 survivors and collected transthoracic echocardiographic data at 3-6 months, and annually thereafter. The mean follow-up period was 3.0±1.5 years, with a 100% follow-up rate. The preoperative mean pressure gradient (PG) and the effective orifice area were 52.5±18.2 mmHg, and 0.73±0.23 cm2, respectively, which improved to 10.3±3.5 mmHg (P<0.001), and 1.85±0.48 cm2 (P<0.001) at discharge. The mean PG at 5 years was 10.2±2.7 mmHg, which was similar to one at discharge (P=0.307). Left ventricular mass index decreased from 119.6±33.1 g/m2 before AVR to 104.0±32.5 g/m2 (P<0.001) at discharge, and further decreased to 78.5±22.2 g/m2 at 5 years compared with postoperative one (P=0.011). Survival rate at 5 years was 97.4±2.6%. Freedom from valve-related events at 5 years was 91.4±5.5%. Incidental cerebral infarction (n=2) and heart failure (n=1) were noted. IR bioprosthesis demonstrated a stable hemodynamic performance and few valve-related events. J. Med. Invest. 72 : 390-395, August, 2025

Background:The proportion of elderly patients within the gastric cancer (GC)-affected population has been increasing. Accordingly, there is a pressing need for reliable methods to stratify surgical risk in geriatric GC cases. Psoas muscle density (PMD), a parameter indicative of sarcopenia, is readily assessable using standard radiological techniques and has been recognized as a prognostic marker in various malignancies. However, its clinical significance in GC, particularly among elderly patients, remains inadequately defined. Methods:We retrospectively reviewed 110 patients aged ≥75 years who underwent R0 gastrectomy for GC. The prognostic value of preoperative PMD, along with other nutritional indices, was assessed using Cox proportional hazards models. Results:Lower PMD was significantly associated with diffuse-type histology and higher incidence of postoperative complications. On univariate Cox regression analysis, PMD was significantly associated with overall survival. Multivariate analysis confirmed PMD as an independent predictor of overall survival (hazard ratio:0.57;95% confidence interval:0.35–0.91 per 10-Hounsfield unit increase), along with other nutritional parameters. Conclusion:Preoperative PMD was significantly associated with postoperative morbidity and independently predicted overall survival in elderly GC patients. Incorporating PMD assessment into preoperative evaluation may enhance risk stratification and guide perioperative management in this vulnerable population. J. Med. Invest. 72 : 396-400, August, 2025

In this study, we aimed to investigate the impact of the COVID-19 pandemic on the number of pediatric inpatients and outpatients visiting medical institutions in Tokushima Prefecture, Japan. We evaluated medical claims data of individuals aged <15 years insured by the National Health Insurance. We calculated the mean and 95% confidence interval (CI) of the monthly number of inpatient and outpatient medical claims per 1,000 children for fiscal year 2019 (FY2019), the pre-pandemic period, and fiscal year 2020 (FY2020), the pandemic period. The mean monthly number of inpatients aged <15 years (per 1,000 children) was 27.6 (95% CI:24.7–30.4) in FY2019 and 16.9 (95% CI:14.9–18.9) in FY2020. For outpatients, the corresponding numbers were 638.1 (95% CI:610.6–665.6) in FY2019 and 501.1 (95% CI:471.0–531.0) in FY2020. We applied multivariable negative binomial regression to calculate incident rate ratios (IRRs). The inpatient IRR was 0.58 (95% CI:0.42–0.80), showing a significant decrease, while the outpatient IRR was 0.79 (95% CI:0.57–1.09), showing no significant difference from FY2019. These results suggest that pediatric inpatient and outpatient visits decreased during the COVID-19 pandemic, with a larger impact observed for inpatients. The pandemic likely influenced healthcare-seeking behavior and medical service utilization among children. J. Med. Invest. 72 : 401-407, August, 2025

Objective:We investigated the relationship between neutrophil-to-lymphocyte ratio (NLR) and symptom severity, clinical and socio-demographic variables in patients with schizophrenia. Methods:One hundred and ten patients with schizophrenia were compared with 110 healthy subjects matched by gender, age, body mass index, and smoking status. The NLR was determined after obtaining full blood counts by calculating the ratio of absolute neutrophil count and the absolute lymphocyte count. The Positive and Negative Syndrome Scale (PANSS) was used to determine the severity of symptoms in patients. Results:In patients with schizophrenia, neutrophil count and NLR were significantly higher (p<0.001), while lymphocyte count (p=0.035) was significantly lower compared to healthy controls. A significant positive correlation was found between NLR and the PANSS negative, general psychopathology, and total scores (all p<0.05). The NLR was also positively correlated with PANSS negative, cognitive, excitement, and depression factor scores (all p<0.05). Regression analysis revealed that NLR was a predictor for the clinical symptoms. No significant correlations were found between NLR and clinical and demographic characteristics in patients. Conclusion:Increased NLR is associated with the severity of symptoms in patients with schizophrenia, and may be a state marker in schizophrenia. J. Med. Invest. 72 : 408-418, August, 2025

This study aimed to propose a measurement protocol for visualizing nurses’ empathic communication competencies using gaze-tracking, voice-analysis, and digital video. This study was conducted at University A from June to November 2019 and two nursing students in their 20s. The scenario simulated nurses’ empathic listening to patients discuss their health. Data were collected using a gaze analysis device (Tobii Eye Tracker 4C), a voice analysis device (WavePad FFT), and a digital video camera. Gaze data were categorized into 16 facial and upper-body regions and visualized on the horizontal and vertical axes using scatter plots. Verbal communication lasted 4 min 59 s, with 24,222 valid data points recorded from the subjects’ gazes within the effective range. Subjects’ “focus of gaze” was more frequently on the lower right face (36.51%), upper right face (33.93%), lower left face (13.01%), and upper left face (8.31%), 94% of the gaze was directed at the other person’s face. Voice analysis revealed initial sound pressure levels between -18 to -12 dB, increasing beyond -6 dB with laughter and frequent utterances. The proposed measurement protocol allowed the visual and numerical identification of nurses’ expressed empathy and emotions toward the patient by voice, gaze, and digital video recorded data. J. Med. Invest. 72 : 419-424, August, 2025

Background:Women account for 23.6% of physicians in Japan yet account for only 5% of orthopedic surgeons and <1% of board-certified spine surgeons. We identified points along the training pathway where women perceive barriers to pursuing spine surgery. Methods:In this sequential explanatory mixed-methods study, we surveyed all 5th- and 6th-year medical students at our institution and postgraduate year-1–2 residents and received responses from 62 trainees (29 women, 33 men). Counts, percentages, and χ2 or Fisher exact tests were used to compare the groups. We thematically analyzed the semi-structured e-mail interviews conducted with 10 female orthopedic trainees (4 residents, 1 non-spine surgeon, and 5 spine fellows). Results:Interest in orthopedics was reported by 45% of women and 64% of men (p=0.22);within that subgroup interest in spine surgery was similar (31% vs. 33%;p=1.00). From the interviews, four categories of barriers to choosing spine surgery as a subspecialty emerged:(1) physical limitations, (2) radiation exposure, (3) demanding working hours/on‑call, and (4) a gender‑imbalanced environment. Conclusions:Many early-career women already express interest in orthopedics. However, translating that interest into careers as spine surgeons will require sustained mentorship plus the adoption of assistive technologies, ergonomic instruments, and team-based shift schedules—interventions that could benefit the entire surgical workforce. J. Med. Invest. 72 : 425-429, August, 2025

Background:Adenosine deaminase 2 (ADA2) deficiency is a rare autosomal recessive autoinflammatory disorder characterized by systemic vasculitis, recurrent stroke, and immunodeficiency. This results from the biallelic loss-of-function variants of ADA2, leading to enzymatic dysfunction and endothelial impairment. Although it is commonly diagnosed during childhood, adult-onset cases with milder phenotypes have also been reported. Objective:We report a case of adult-onset ADA2 deficiency that presented with recurrent juvenile stroke and systemic vasculitis. Case:A 42-year-old female with recurrent juvenile stroke and systemic vasculitis symptoms was diagnosed with ADA2 deficiency by genetic testing. The patient had a known pathogenic variant, c.139G>C (p.Gly47Arg), in a homozygous state. Given the mild phenotype and stable condition, the patient continued long-term aspirin therapy without additional immunosuppressive treatment. Conclusion:This case highlights the importance of considering ADA2 deficiency in patients with unexplained stroke and recurrent vasculitis, particularly those with a history of parental consanguinity. Measurement of serum ADA activity may serve as a potential screening tool for ADA2 deficiency, especially in settings in which genetic testing is not readily available. J. Med. Invest. 72 : 430-433, August, 2025

Background:Pneumonia caused by Legionella pneumophila and other Legionella spp. is associated with high hospitalization and mortality rates. We herein report a case of severe cardiogenic shock triggered by Legionella pneumonia that was successfully treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). Case presentation:A 59-year-old man was admitted to the emergency department with a fever and consciousness disturbance. He was diagnosed with Legionella pneumonia based on urinary antigen test results. Despite receiving supplemental oxygen, the patient’s oxygenation worsened, necessitating immediate tracheal intubation. Mechanical ventilation and vasopressor therapy were initiated;however, tachycardia due to atrial fibrillation, along with a reduced ejection fraction of only 15%, led to the development of cardiogenic shock. On day 1 in the intensive care unit (ICU), VA-ECMO and intra-aortic balloon pumping (IABP) were introduced. By day 3, his tachycardia and myocardial dysfunction had improved, leading to the withdrawal of VA-ECMO on day 4. His respiratory function improved and he was extubated on day 7. He was discharged from the ICU on day 9. Conclusions:VA-ECMO is a valuable treatment modality for refractory cardiogenic and septic shock. Considering the induction of VA-ECMO as a therapeutic option at an appropriate time is important in such cases. J. Med. Invest. 72 : 434-437, August, 2025

A 10-year-old Japanese female was referred to our hospital for a rapidly growing and easily bleeding nodule on her right temple. A physical examination revealed a red ulcerated nodule on her right temple. Our clinical diagnosis was pyogenic granuloma (PG), and cryotherapy was performed several times. However, this did not remove the tumor;therefore, we excised it under local anesthesia. A histopathological examination of the removed tumor showed vascular proliferations arranged in discrete lobules in the dermis. Based on these findings, we confirmed the diagnosis of PG. About 4 months after the surgery, small nodules gradually developed around the surgical scar. The patient returned to our hospital 1 year after the surgery. A physical examination showed multiple, small, red papules scattered around the surgical scar. Based on the clinical findings of this case, we made a diagnosis of the recurrence of PG with satellitosis (RPGS). The lesions disappeared after 6 months of topical steroid and liquid nitrogen therapy. RPGS is a rare phenomenon, but its diagnosis and management can be problematic. It is important for physicians to recognize this phenomenon and inform patients of the possibility of recurrence and the development of satellite lesions after PG is resected. J. Med. Invest. 72 : 440-442, August, 2025

Background:Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder (UCD) and may lead to life-threatening hyperammonemia. Refractory cases require prompt and aggressive treatment, including renal replacement therapy (RRT), to prevent irreversible neurological damage. Case presentation:We encountered a 14-year-old girl with OTC deficiency who presented with severe hyperammonemia (649 µg/dL;382 µmol/L). Pharmacological therapy and emergency intermittent hemodialysis (IHD) were followed by continuous hemodiafiltration (CHDF), resulting in rapid ammonia clearance. However, a 4-h interruption of CHDF due to catheter replacement led to rebound hyperammonemia (>500 µg/dL;>294 µmol/L), requiring resumption of RRT on day 4. OTC deficiency was subsequently diagnosed based on plasma amino acid and urine organic acid analyses on day 12. After intensifying the pharmacological therapy and achieving stable ammonia levels, RRT was discontinued on day 17. The patient recovered without apparent neurological sequelae and was discharged from the intensive-care unit. Conclusions:This case highlights the importance of uninterrupted RRT in managing acute hyperammonemia and suggests that even short pauses in CHDF can provoke clinically significant rebound. Early initiation of RRT, continuous monitoring of ammonia levels, and individualized treatment strategies are critical for optimizing patient outcomes. J. Med. Invest. 72 : 443-446, August, 2025

This study focused on ventilatory management during robot-assisted laparoscopic rectal resection in an obese patient, using electrical impedance tomography (EIT) to evaluate lung conditions. The case involved a 40s male with a history of smoking, obesity (BMI:31), and iodine allergy. General anesthesia was induced, and EIT was employed to assess positive end expiratory pressure (PEEP) during different surgical positions. The study found that the PEEP for supine positioning was 10-12 cmH2O for ventilatory conditions in which the anterior and posterior impedance changes were equal in patients, but during pneumoperitoneum and head lowering, a higher PEEP of 20 cmH2O was necessary to prevent lung collapse. This differed from conventional recommendations. Oxygenation was maintained, and the patient had no major complications. The study suggests that EIT may offer a noninvasive and bedside approach to evaluating ventilator settings, potentially changing perspectives on intraoperative ventilator management. J. Med. Invest. 72 : 447-450, August, 2025

Non-ST-elevation myocardial infarction (NSTEMI) showing biphasic or deep negative T waves in lead V2-3 suggests the presence of a severe stenotic lesion in the proximal left anterior descending artery, called Wellens’ syndrome. We report a case of NSTEMI with a positive T wave in lead aVR and widespread negative T waves in the precordial and inferior leads, presumed to be Wellens’ syndrome, resulting in three-vessel severe coronary artery disease. This report highlights the importance of identifying a positive T wave in lead aVR to avoid overlooking severe organic stenosis of the coronary arteries. J. Med. Invest. 72 : 451-454, August, 2025

Esophageal foreign body impaction is a common clinical issue, particularly among individuals with psychiatric disorders. Although most cases are managed successfully with endoscopic intervention, sharp or large foreign bodies can lead to serious complications. We present the case of a middle-aged man with schizophrenia who accidentally ingested a large chicken bone, resulting in esophageal impaction that required extraction under general anesthesia. This case underscores the importance of heightened clinical awareness regarding altered pain perception and disordered eating behaviors in patients with schizophrenia. J. Med. Invest. 72 : 455-458, August, 2025

Background:Shoulder injury related to vaccine administration (SIRVA) has been discussed as a complication of incorrect intramuscular vaccination technique, resulting in subacromial/subdeltoid bursitis or injury of the anterior branch of the axillary or radial nerve. Case presentation:We have encountered two cases of frozen shoulder following COVID-19 vaccination. In both cases, arthroscopic capsular release was performed after failure of conservative treatment. Arthroscopy revealed severe synovitis in the glenohumeral joint characteristic of idiopathic frozen shoulder. Conclusions:In these two cases, the synovial inflammation was predominantly intra-articular, suggesting that the pathology of frozen shoulder secondary to SIRVA was different from that reported previously. Although the postoperative course was favorable in these two cases, early diagnosis and prompt therapeutic intervention are essential to prevent development of frozen shoulder after COVID-19 vaccination. J. Med. Invest. 72 : 459-462, August, 2025

Photon-counting detector computed tomography (PCD-CT) allows for attainment of images with excellent spatial resolution at reduced radiation doses. However, practical utility of this diagnostic modality in neurosurgery is still not defined well. Herein, the authors report their initial experience with the use of postoperative PCD-CT (helical pitch, 0.85;gantry rotation time, 0.5 s;tube voltage, 120 kV) in a single-acquisition high-resolution mode with the iterative metal artifact reduction and attainment of the reconstructed images with slice thickness of 0.2 mm for assessment of the shunt valve pressure adjustment system and endovascular flow-diverting stent. In both cases, intracranially implanted neurosurgical devices were effectively visualized. J. Med. Invest. 72 : 463-466, August, 2025