Hajime Isomoto

Background/Objectives: Accurate assessment of the glomerular filtration rate (GFR) is essential for managing chronic kidney disease (CKD). Although creatinine-based estimated GFR (eGFRcr) may be affected by reduced muscle mass, the contribution of muscle characteristics beyond muscle mass remains unclear. This study investigated whether phase angle (PhA), a bioelectrical impedance analysis-derived indicator associated with muscle quality, provides complementary information beyond appendicular skeletal muscle mass (ASM) regarding discordance between eGFRcr and a creatinine clearance (CCr)-based reference estimate. Methods: We enrolled 86 adults with CKD not receiving maintenance dialysis. CCr was calculated from 24 h urine collections, indexed to a standard body surface area (BSA) of 1.73 m², and multiplied by 0.715. KOI was calculated as eGFRcr divided by (BSA-indexed CCr × 0.715). A KOI > 1.2 was used as an exploratory threshold for clinically significant discordance. Results: KOI > 1.2 was observed in 24.4% of patients. KOI was negatively correlated with ASM (r = −0.301, p = 0.005) and PhA (r = −0.451, p < 0.001). Adding PhA to a multivariable linear regression model including ASM improved model performance (adjusted R², 0.060–0.200). Multivariable logistic regression, including ASM and PhA as explanatory variables, showed that only PhA remained independently associated with KOI > 1.2 (odds ratio, 0.258; 95% CI, 0.113–0.585; p = 0.001). Conclusions: PhA may provide complementary information beyond skeletal muscle mass for identifying patients with greater discordance between eGFRcr and corrected, BSA-indexed CCr. Further studies using measured GFR are needed to validate these findings.

Background/Objectives: Distinguishing glomerulonephritis (GN) from diabetic kidney disease (DKD) and nephrosclerosis (NS) is clinically important. Urinary uromodulin (uUMOD), a biomarker of renal tubular integrity, may help discriminate among these chronic kidney disease (CKD) etiologies. We evaluated the diagnostic utility of uUMOD for differentiating GN from DKD and NS. Methods: This retrospective single-center study included 90 patients with biopsy-proven GN (n = 30), DKD (n = 25), or NS (n = 35). First-morning spot urine samples obtained before biopsy were analyzed for uUMOD concentration and normalized to urinary creatinine levels (uUMOD/Cr). Results: The uUMOD/Cr ratio was significantly higher in GN (21.2 mg/gCr [10.3–31.3]) than in DKD (5.5 [3.6–12.3], p < 0.001) or NS (10.7 [6.4–19.9], p = 0.021). In multivariate analyses adjusted for age, sex, estimated glomerular filtration rate, interstitial fibrosis, and urinary protein, the uUMOD/Cr ratio was independently associated with GN (p = 0.003) and this correlation remained statistically significant after additional adjustment for diabetes mellitus. Receiver operating characteristic curve analysis showed an area under the curve value of 0.833 for GN versus DKD, 0.714 for GN versus NS, and 0.764 for GN versus DKD and NS combined. A cutoff value of 16.5 mg/gCr yielded 72.8% sensitivity and 70.0% specificity for identifying GN. Conclusions: uUMOD secretion is preserved in GN compared to DKD or NS and shows moderate diagnostic utility for differentiating between these biopsy-proven CKD etiologies. uUMOD may serve as a simple, noninvasive biomarker when biopsy is difficult or clinical findings are inconclusive.

Objectives: Simulation‐based colonoscopy training may support early acquisition of insertion skills, but its clinical effect remains uncertain. We evaluated whether a self‐directed curriculum using the mikoto colonoscopy simulator improved insertion performance in gastroenterology trainees. Methods: In this multicenter cluster‐randomized trial, 12 gastroenterology trainees from 11 institutions in Japan and Taiwan were assigned 1:1 to mikoto simulator training or standard training, with the trainee as the unit of randomization. Each trainee performed 35 colonoscopies; intervention‐arm trainees additionally completed 100 self‐directed simulator sessions over 2 weeks. The primary endpoint was post‐training cecal intubation rate (CIR), compared using mixed‐effects logistic regression with trainee as a random intercept and pre‐training CIR as a covariate. Results: A total of 420 colonoscopies were analyzed. Post‐training CIR was 80.0% (72/90) in the mikoto group versus 77.8% (70/90) in controls (adjusted OR, 1.34; 95% confidence interval, 0.37–4.84; p = 0.606). Within the mikoto group, CIR increased from 60.0% to 80.0% ( p = 0.003) and cecal intubation time decreased, but the group‐by‐period interaction was not significant. Detection outcomes were unchanged. Conclusions: Although the between‐group difference in post‐training CIR did not reach statistical significance, self‐directed mikoto simulator training produced a significant within‐group improvement in CIR and a parallel reduction in cecal intubation time, supporting it as a feasible and educationally meaningful adjunct to conventional colonoscopy training for gastroenterology trainees. Trial Registration: UMIN Clinical Trials Registry: UMIN000054647

Background/Objectives: Ultra-high-magnification endoscopy (Endocyto) visualizes microscopic mucosal structures and has been proposed as a tool for assessing mucosal inflammation. We previously developed an endocytoscopic classification system (EC-A to EC-D) for grading the severity of inflammation. In this study, we investigated the relationship between endocytoscopic classification and microRNA (miRNA) expression in 36 patients with ulcerative colitis (UC). Methods: This cross-sectional study was conducted in two phases at two institutions. In the first phase, microarray analysis was performed on biopsy samples from patients with UC and healthy controls enrolled at Nagasaki University Hospital. In the second phase, 36 patients with UC who underwent total colonoscopy via Endocyto at Tottori University Hospital were included, and selected miRNAs were analyzed via quantitative polymerase chain reaction. Results: Differentially expressed miRNAs were identified, and four (miR-141-5p, miR-192-5p, miR-194-5p, and miR-215-5p) were downregulated in inflammatory areas. Notably, miR-192-5p expression was markedly lower in the EC-B and EC-C+D groups than in the EC-A group. Furthermore, expression of CXC motif ligand 2 (CXCL2), a pro-inflammatory chemokine, was upregulated in inflammatory tissues and negatively correlated with miR-192-5p expression. Conclusions: These results indicate that reduced miR-192-5p expression is inversely associated with CXCL2 expression and that, among the miRNAs examined, miR-192-5p downregulation most consistently corresponded to the endocytoscopic classification. Our findings suggest that Endocyto may serve as a real-time, in vivo adjunct for a histology-like assessment of mucosal inflammation; its clinical utility requires prospective validation.

Three technical refinements facilitated effective septotomy and diverticular reduction in Zenker's diverticulum, resulting in a safe procedure and favorable clinical outcome.

Background: Endoscopic resection has become a standard curative treatment for superficial esophageal cancer. However, limited data are available regarding long-term outcomes and causes of death after curative endoscopic treatment, particularly deaths unrelated to the primary esophageal cancer. This study aimed to clarify post-treatment prognosis and to identify factors associated with mortality in patients with superficial esophageal cancer who underwent curative endoscopic resection. Methods: We conducted a multicenter cohort study in Japan to evaluate survival outcomes, causes of death, and prognostic factors in patients with superficial esophageal cancer who achieved curative resection by endoscopic treatment. Patients were stratified according to endoscopic treatment indication categories (absolute, relative, and beyond indication). Five-year overall survival and disease-specific survival were analyzed, along with risk factors for all-cause and cause-specific mortality. Results: No disease-specific deaths were observed in patients with absolute or relative indication lesions, whereas the disease-specific 5-year survival rate was 81% in patients with beyond-indication lesions. When overall mortality, including deaths from other diseases and other malignancies, was evaluated, the 5-year survival rates were 92% for absolute indication cases, 85% for relative indication cases, and 69% for beyond-indication cases. Multivariate analysis identified low body mass index (BMI) and advanced age as independent risk factors for mortality. Notably, low BMI was significantly associated with non-cancer-related death. Conclusions: Even among patients who achieve curative endoscopic treatment for superficial esophageal cancer, long-term survival is limited by deaths from other malignancies and non-cancer-related causes. Low BMI represents a clinically important prognostic factor, underscoring the need for comprehensive post-treatment surveillance and supportive care beyond cancer control.

Background: Peroral endoscopic myotomy (POEM) is an effective treatment for achalasia; however, accurately identifying the distal extent of myotomy remains a technical challenge. Indocyanine green with infrared imaging (ICG‐IRI) may facilitate the intraoperative visualization of the esophagogastric junction. Methods: We evaluated 39 patients who underwent POEM using ICG‐IRI. The primary outcome was the success rate of ICG‐IRI, defined as a clear endoscopic visualization of fluorescence at the distal myotomy endpoint. The secondary outcomes included technical success, changes in integrated relaxation pressure, and Eckardt scores before and after treatment. Results: The technical success rate was 100%, and ICG‐IRI was successful in 94.9% of the cases (37/39). The median integrated relaxation pressure decreased from 26.9 to 10.8 mmHg, and the median Eckardt score improved from 5.0 to 1.0 (both p < 0.01). No adverse events were attributed to the ICG‐IRI. Conclusions: The ICG‐IRI method is a reliable visual aid for identifying distal myotomy endpoints during POEM. This technique may enhance the procedural accuracy and improve clinical outcomes.

Hyperuricemia has been increasingly recognized as a modifiable contributor to chronic kidney disease (CKD) progression. Although the traditional classification of hyperuricemia distinguished between renal underexcretion and renal overload types, recent studies suggest that hyperuricemia in patients with CKD can result from heterogeneous excretory defects, including glomerular under-filtration and tubular over-reabsorption. These distinct phenotypes may drive divergent renal injury mechanisms. Experimental and clinical data reveal that monosodium urate crystals and soluble uric acid independently induce renal damage through oxidative stress, inflammasome activation, and endothelial dysfunction. Furthermore, clinical investigations showed inconsistent associations between serum uric acid levels and renal outcomes, suggesting that serum levels alone may not fully reflect urate-related renal risk. This has prompted increasing interest in uricosuric agents, particularly the selective urate reabsorption inhibitors (SURIs), which target tubular urate handling. Urate transporter 1 inhibitors have shown promise in enhancing urinary uric acid excretion and potentially preserving kidney function, especially in patients with CKD. In this review, we summarize the current evidence linking the emerging pathophysiological classification of hyperuricemia, mechanisms or urate-induced kidney injury, and therapeutic interventions. These insights may inform individualized approaches to urate-lowering therapy in CKD and support future research into phenotype-guided treatment strategies.

Background/Objectives: Muscle quality reflects functional characteristics beyond muscle mass and may offer prognostic insights in patients with chronic kidney disease (CKD). This study investigated whether muscle quality predicts sarcopenia and renal outcomes in non-dialysis CKD patients. Methods: We prospectively recruited 93 patients with CKD (stage G1–5). Muscle quality was evaluated using phase angle (PhA) derived from bioelectrical impedance analysis. Sarcopenia was diagnosed based on criteria from the Asian Working Group for Sarcopenia. The primary renal outcome was defined as a > 30% decline in eGFR or the initiation of dialysis. Logistic regression identified factors associated with sarcopenia. Kaplan–Meier and Cox regression analyses were used to assess predictors of renal outcomes. Results: Lower PhA (odds ratio [OR] 0.044, p = 0.002) and BMI (OR 0.648, p = 0.015) were independently associated with sarcopenia. Sex-specific PhA cutoffs of 4.50° for men and 4.00° for women yielded high diagnostic accuracy for sarcopenia (AUC: 0.878 and 0.969, respectively). Over a median observation period of 574 days, patients with lower PhA values showed a significantly higher risk of poor renal outcomes, independent of confounding factors (hazard ratio [HR] 4.540, p = 0.011), even after adjustment for age, sex, BMI, systolic blood pressure, diastolic blood pressure, eGFR, and albumin. However, muscle mass was not significantly associated with renal prognosis. Conclusions: PhA is a non-invasive marker that may reflect muscle quality and is associated with sarcopenia and renal outcomes in CKD. It may help inform risk stratification in clinical practice.