Background and Aims Covert hepatic encephalopathy (CHE) worsens the quality of life and the prognosis of patients with chronic liver disease (CLD). CHE can be caused by various factors, including age and the etiology of...Background and Aims Covert hepatic encephalopathy (CHE) worsens the quality of life and the prognosis of patients with chronic liver disease (CLD). CHE can be caused by various factors, including age and the etiology of CLD, such as metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to investigate factors associated with CHE in patients with CLD. Methods This retrospective study included 195 patients with CLD. CHE was diagnosed using Stroop test. Hyperammonemia was defined as a plasma ammonia level ≥80 μg/dL. The factors associated with CHE were evaluated using logistic regression, decision trees, and random forest analyses. Results The prevalence of CHE was 36.4%. According to a multivariate analysis, age (<65 years), hepatocellular carcinoma (HCC), and MASLD were identified as independent factors for CHE, whereas hyperammonemia was not (age: OR 4.36, p<0.0001; HCC: OR 4.07, p=0.0070; MASLD: OR 1.94, p=0.0500). A decision tree analysis identified age as the initial classifier; CHE prevalence was 62.5% in patients aged <65 years and 25.9% in those aged ≥65 years. Among the patients aged <65 years, MASLD was the next most significant classifier with a CHE prevalence of 90.5%. A random forest analysis confirmed that age was the highest-ranking factor associated with CHE, followed by MASLD score. Conclusion Age <65 years is the most important factor associated with CHE. Among these patients, MASLD was the second most significant factor. Accordingly, non-elderly age and MASLD may be the main pathogenic drivers of CHE in this era of steatotic liver disease.
Objective Malnutrition and sarcopenia are associated with poor clinical outcomes in patients with cirrhosis. While the Phase angle (PhA) is a promising marker, validated ethnicity-specific cutoff values for Asian populat...Objective Malnutrition and sarcopenia are associated with poor clinical outcomes in patients with cirrhosis. While the Phase angle (PhA) is a promising marker, validated ethnicity-specific cutoff values for Asian populations, who often show different body composition profiles, are lacking. This study aimed to establish and validate PhA cutoff values for diagnosing malnutrition and sarcopenia in a Japanese cohort. Methods We retrospectively analyzed 337 Japanese patients with liver cirrhosis who were randomly assigned to training (n=235) and validation (n=102) groups. Optimal sex-specific PhA cutoff values were then determined to identify malnutrition and sarcopenia. Overall survival was compared to assess the prognostic value of PhA. Results PhA was positively correlated with the body mass index, albumin level, and other nutritional indices (all p<0.05). A lower PhA was associated with a poorer hepatic reserve, as indicated by the Child-Pugh and mALBI grades (p<0.001). A multivariate analysis identified the PhA as an independent predictor of malnutrition and sarcopenia (p<0.01). Patients in the low PhA group had a shorter overall survival (p=0.024). The optimal PhA cut-off values for malnutrition and sarcopenia were 4.8 for males and 4.2 for females (AUROCs:0.70-0.76). In the validation cohort, the PhA cutoff values showed good sensitivity (76.7%) and a negative predictive value (75.0%) for malnutrition. Conclusion We established and validated the first sex-specific PhA cutoff values for malnutrition in Japanese patients with cirrhosis, which were lower than those in Western populations. PhA independently predicts malnutrition, sarcopenia, and overall survival, thereby offering clinicians a simple, noninvasive screening tool to enhance nutritional assessment in routine practice.
AL amyloidosis of the mesentery is rare and it has been associated with an extremely poor prognosis. We herein report a case of AL amyloidosis with diffuse calcifications (>13 cm) throughout the mesentery. After treatmen...AL amyloidosis of the mesentery is rare and it has been associated with an extremely poor prognosis. We herein report a case of AL amyloidosis with diffuse calcifications (>13 cm) throughout the mesentery. After treatment with daratumumab, bortezomib, and dexamethasone, the patient achieved a very good partial response (VGPR). However, even after continuing the treatment for over 14 months while maintaining VGPR and achieving a kidney organ response, diffuse calcifications remained throughout the mesentery. Although rare, AL amyloidosis should be considered in the differential diagnosis of mesenteric calcification.
The coexistence of warm-type autoimmune hemolytic anemia (wAIHA) and primary hyperparathyroidism (PHPT) in autoimmune polyendocrine syndrome type 3C (APS-3C) is rare. A 73-year-old female with Hashimoto thyroiditis was h...The coexistence of warm-type autoimmune hemolytic anemia (wAIHA) and primary hyperparathyroidism (PHPT) in autoimmune polyendocrine syndrome type 3C (APS-3C) is rare. A 73-year-old female with Hashimoto thyroiditis was hospitalized with progressive anemia. The direct Coombs test results were positive. The cold agglutinin test results were negative, consistent with wAIHA. Imaging revealed splenomegaly on CT. Biochemical tests showed hypercalcemia and hypophosphatemia with markedly elevated levels of unmodified parathyroid hormone (PTH), suggesting PHPT. The anemia improved with the administration of prednisolone. Parathyroidectomy was performed, and the calcium and PTH levels were normalized. The coexistence of APS-3C, wAIHA, and PHPT has not been reported previously, thereby underscoring the novelty of this case.
Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis is frequently complicated by rapidly progressive interstitial lung disease, whereas anti-aminoacyl-tRNA synthetase (ARS) antibody-p...Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis is frequently complicated by rapidly progressive interstitial lung disease, whereas anti-aminoacyl-tRNA synthetase (ARS) antibody-positive interstitial lung disease typically follows a subacute or chronic course and responds to immunosuppressive therapy. The coexistence of anti-MDA5 and anti-ARS antibodies, particularly anti-OJ antibodies, is very rare. We report the case of a 58-year-old man who was double positive for anti-MDA5 and anti-OJ antibodies and developed rapidly progressive interstitial lung disease. The disease continued to progress with triple immunosuppressive therapy; however, the introduction of plasma exchange led to marked clinical and radiological improvements. This case highlights the importance of recognizing the coexistence of antibodies and integrating serological, radiological, and clinical findings to guide timely and appropriate treatment.
Kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD) can cause symptoms of abdominal compression and nutritional deterioration. Renal transcatheter arterial embolization (TAE) is typically performed...Kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD) can cause symptoms of abdominal compression and nutritional deterioration. Renal transcatheter arterial embolization (TAE) is typically performed bilaterally for kidney volume reduction in patients with ADPKD undergoing hemodialysis. We report the case of a 61-year-old woman with ADPKD who developed abdominal distension and poor appetite after initiating peritoneal dialysis (PD). Unilateral renal TAE was performed to relieve compression symptoms and preserve the renal function, resulting in a 60% reduction in the left kidney volume, symptom relief, an improved nutritional status, and the continuation of PD. Unilateral renal TAE may be an effective therapeutic option in patients with ADPKD who have selected PD.
Okubo S, Nagasako Y, Nakamoto FK
… +12 more, Saito R, Suzuki R, Sugiyama Y, Yamada M, Bannai T, Seki T, Kawada M, Uchibori A, Funakoshi K, Fukami Y, Katsuno M, Shiio Y
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous immune-mediated neuropathy with up to 30% of such patients refractory to standard treatments. Rituximab, a B-cell-depleting monoclonal a...Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous immune-mediated neuropathy with up to 30% of such patients refractory to standard treatments. Rituximab, a B-cell-depleting monoclonal antibody, has shown promising efficacy in antibody-positive autoimmune diseases, but its efficacy in seronegative CIDP remains uncertain. We report the case of a 46-year-old man with severe refractory seronegative CIDP who experienced a rapid deterioration two weeks after rituximab initiation, while developing tetraplegia and respiratory failure that required mechanical ventilation. The patient subsequently achieved a full recovery and sustained remission for over 2.5 years. This highlights the therapeutic potential of rituximab in seronegative refractory CIDP, warranting further studies to identify the responsive subtypes and underlying mechanisms.
An 83-year-old male patient with pulmonary asbestosis was admitted to our hospital with a subacute onset of arthromyalgia affecting the shoulder girdles. He had a history of moderate asbestos exposure in the earlier part...An 83-year-old male patient with pulmonary asbestosis was admitted to our hospital with a subacute onset of arthromyalgia affecting the shoulder girdles. He had a history of moderate asbestos exposure in the earlier part of his occupation and was diagnosed with pulmonary asbestosis at 65 years of age. The patient exhibited recent-onset stiffness and myalgia of the shoulder and finger joints. Joint ultrasound findings showed bilateral long head biceps, resulting in a diagnosis of polymyalgia rheumatica (PMR) according to the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for PMR. Steroid treatment resolved the musculoskeletal symptoms.
We present the case of a 66-year-old man who underwent upper gastrointestinal (GI) endoscopy and developed significant gastric residue after treatment with a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA)...We present the case of a 66-year-old man who underwent upper gastrointestinal (GI) endoscopy and developed significant gastric residue after treatment with a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA) for type 2 diabetes. Despite prolonged fasting, large volumes of gastric residue persisted, thus impairing mucosal visualization. Instead of discontinuing GLP-1RA therapy, mosapride citrate was introduced as a gastroprokinetic agent. Three days before endoscopy, the patient received mosapride, which resulted in complete gastric clearance and optimal endoscopic visualization. This case suggests that mosapride may be an effective pre-endoscopic preparation to counteract GLP-1RA-induced delayed gastric emptying.
Among endocrine organoids, pancreatic β-cell organoids attract significant research attention. Nevertheless, various organoids have differentiated into the thyroid, parathyroid, adrenal gland, gonads, and kidney. In this...Among endocrine organoids, pancreatic β-cell organoids attract significant research attention. Nevertheless, various organoids have differentiated into the thyroid, parathyroid, adrenal gland, gonads, and kidney. In this manuscript, we outline the concept of recapitulating fetal development in vitro, using hypothalamus-pituitary organoids as a representative model. Within a single organoid, the hypothalamus and pituitary gland co-develop, undergo maturation, and establish functional interactions. This system readily serves as a disease model, and with further technological advancements, it holds significant potential for applications in regenerative medicine. Looking ahead, we aim to develop more complex and diverse hypothalamus-pituitary organoids encompassing wider anatomical regions, thereby consolidating the mechanisms governing systemic homeostasis into a single integrated structure.
A 75-year-old woman presented with left pleural effusion and pleural nodules. A computed tomography-guided percutaneous biopsy suggested rhabdomyoblastic differentiation; however, a definitive diagnosis could not be esta...A 75-year-old woman presented with left pleural effusion and pleural nodules. A computed tomography-guided percutaneous biopsy suggested rhabdomyoblastic differentiation; however, a definitive diagnosis could not be established. A subsequent thoracoscopic biopsy revealed combined small cell lung carcinoma (C-SCLC) with a rhabdomyosarcomatous component. Small cell carcinoma cells were positive for pancytokeratin, chromogranin A, and synaptophysin, whereas rhabdomyosarcomatous cells were positive for desmin and myogenin. Chemoimmunotherapy with carboplatin, etoposide, and atezolizumab resulted in a remarkable tumor response. This is an extremely rare case of C-SCLC with rhabdomyosarcomatous differentiation that was diagnosed using a thoracoscopic biopsy and was treated with chemoimmunotherapy.
Abe A, Ohyama H, Asahina Y
… +16 more, Nagasaka K, Tohyama S, Amano H, Takaoka S, Imai Y, Hirose S, Asakawa Y, Yokouchi R, Sato N, Hasegawa Y, Takano A, Iimuro Y, Kojima Y, Mochizuki H, Kato J, Omata M
Objective Pancreatic cancer (PC) is one of the most refractory malignancies with a poor prognosis. However, improvements in the PC prognosis over time have not yet been thoroughly evaluated.We herein present a retrospect...Objective Pancreatic cancer (PC) is one of the most refractory malignancies with a poor prognosis. However, improvements in the PC prognosis over time have not yet been thoroughly evaluated.We herein present a retrospective analysis of a prospectively maintained hospital-based cancer registry over 14 years. Methods The patients were prospectively enrolled in a Japanese government study. The period from 2007 to 2020 was divided into two seven-year periods to assess a prognostic improvement. The most recent censorship date is December 2024. Prognostic trends were compared across three treatment modalities: surgery, chemotherapy, and best supportive care (BSC). Results A total of 26,379 patients with all cancer types were prospectively enrolled over 14 years. Among these, 711 (2.7%) were enrolled for PC. Dichotomizing the period into the first and second halves, both the surgery group (18.7 months vs. 48.5 months, HR 0.45, P <0.001) and the chemotherapy group (9.1 months vs. 12.0 months, HR 0.58, P <0.001) had significantly better outcomes in the second half than in the first half. In the surgery group, the tumors were significantly smaller (P = 0.001) and detected earlier in the second half than in the first half (P = 0.007). In the chemotherapy group, the first-line treatment shifted from gemcitabine to gemcitabine plus nab-paclitaxel (GnP) in the second half (P <0.001). No significant improvement in the prognosis was observed in the BSC group (P = 0.597). Conclusions Prospective real-world data from 2007 to 2020 revealed that improvements in the early detection and adoption of GnP were temporally associated with an improved survival in patients with PC.
Objective To compare the effectiveness of initial metronidazole (MNZ) and vancomycin (VCM) for moderate Clostridioides difficile infection (CDI), as defined by the Japanese MN criteria. Methods: A single-center retrospec...Objective To compare the effectiveness of initial metronidazole (MNZ) and vancomycin (VCM) for moderate Clostridioides difficile infection (CDI), as defined by the Japanese MN criteria. Methods: A single-center retrospective cohort study (2011-2025). Adult inpatients with an initial episode of moderate CDI who received oral MNZ or VCM were identified. Propensity score matching (1:1; caliper 0.2) balanced the demographics, severity indicators, comorbidities, and concomitant medications. Patients After exclusion, 376 eligible patients (MNZ, n=260; VCM, n=116) were identified and 98 matched pairs were analyzed. Results In the matched cohort, a clinical cure occurred in 59/98 (60.2%) MNZ and 63/98 (64.3%) VCM [odds ratio (OR), 0.84; 95% confidence interval (CI) 0.47-1.50; p=0.556]. Global cure occurred in 53/98 (54.1%) and 51/98 (52.0%), respectively (OR 0.921; 95% CI 0.53-1.61; p=0.775). Recurrence within two months was similar [23/98 (23.5%) vs 20/98 (20.4%); OR 0.836; 95% CI 0.42-1.65; p=0.605]. Kaplan-Meier curves for time-to-recurrence overlapped (log-rank p=0.539). Treatment switching due to worsening symptoms was uncommon (6.1% vs. 3.1%; p=0.306). Conclusion For moderate CDI classified according to the MN criteria, no statistically significant differences were observed between initial MNZ and VCM with respect to the clinical cure, global cure, or recurrence. Within the limitations of this retrospective observational study, these findings suggest that MNZ may remain a treatment option for moderate CDI in Japan, which is commonly used in clinical practice.
Myelodysplastic syndrome (MDS) is frequently accompanied by systemic inflammatory disorders, including vasculitis. However, histopathologically confirmed pulmonary vasculitis is rare. We herein report the case of a man i...Myelodysplastic syndrome (MDS) is frequently accompanied by systemic inflammatory disorders, including vasculitis. However, histopathologically confirmed pulmonary vasculitis is rare. We herein report the case of a man in his 50s with MDS, who presented with fever, pulmonary infiltrates, and persistent inflammation that was unresponsive to antibiotics. Transbronchial lung biopsy (TBLB) revealed leukocytoclastic vasculitis of the small pulmonary vessels, thus confirming the diagnosis. The pulmonary lesions resolved spontaneously without corticosteroid therapy. This case suggests that pulmonary vasculitis may contribute to the development of noninfectious pulmonary complications in MDS and that TBLB, despite its limitations, can occasionally provide histopathological confirmation.
Edwardsiella tarda is an opportunistic aquatic pathogen that rarely causes human bacteremia, but it carries high mortality, particularly in immunocompromised hosts. We report the fatal case of a 74-year-old man with refr...Edwardsiella tarda is an opportunistic aquatic pathogen that rarely causes human bacteremia, but it carries high mortality, particularly in immunocompromised hosts. We report the fatal case of a 74-year-old man with refractory multiple myeloma (MM) and profound iatrogenic immunodeficiency who developed septic shock shortly after acquiring tropical fish. Despite the isolate's susceptibility to administered broad-spectrum antibiotics, including meropenem, the patient died within 72 hours of admission. This report highlights the lethal synergy between modern anti-myeloma therapies, specifically the cumulative immunosuppression from proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies, and the virulence factors of E. tarda. We provide a detailed clinical course and comparative discussion of hematological cases in Japan. This case underscores the critical need for thorough environmental history-taking and specific counseling for profoundly immunocompromised patients regarding the risks of exotic pet ownership.