We report a fatal case of a 40-year-old man who developed rhino-orbito-cerebral mucormycosis complicated by central retinal artery occlusion, cavernous sinus thrombosis, and internal carotid artery occlusion. Mechanical...We report a fatal case of a 40-year-old man who developed rhino-orbito-cerebral mucormycosis complicated by central retinal artery occlusion, cavernous sinus thrombosis, and internal carotid artery occlusion. Mechanical thrombectomy was performed for the internal carotid artery occlusion, with subsequent Sanger sequencing of the fungal components within the retrieved thrombus to identify Rhizopus arrhizus. To the best of our knowledge, this is the first report establishing the species-level identification of R. arrhizus in mucormycosis-associated large-vessel occlusion. These findings provide direct histopathological evidence of angioinvasive mucormycosis attributable to R. arrhizus.
A 76-year-old man presented with headache, progressive left-sided visual loss, and cranial neuropathy. Initial MRI and cerebrospinal fluid findings mimicked those of hypertrophic pachymeningitis. Corticosteroid therapy p...A 76-year-old man presented with headache, progressive left-sided visual loss, and cranial neuropathy. Initial MRI and cerebrospinal fluid findings mimicked those of hypertrophic pachymeningitis. Corticosteroid therapy provided only a transient improvement before clinical deterioration, including right-eye blindness. A re-evaluation revealed destructive sphenoid sinus disease, and surgical decompression confirmed invasive Aspergillus sinusitis. The course was complicated by a ruptured infectious internal carotid artery aneurysm, which required emergency endovascular embolization. Despite the catastrophic subarachnoid hemorrhage, the patient survived with intensive multidisciplinary treatment. This case highlights the diagnostic pitfalls of invasive fungal sinusitis and the catastrophic risks of empirical corticosteroid administration for suspected inflammatory diseases without excluding a fungal etiology.
A previously healthy 23-year-old man developed acute-onset fever, headache, and a rapidly deteriorating altered mental status, occurring 11 days after the resolution of self-limiting respiratory symptoms. The cerebrospin...A previously healthy 23-year-old man developed acute-onset fever, headache, and a rapidly deteriorating altered mental status, occurring 11 days after the resolution of self-limiting respiratory symptoms. The cerebrospinal fluid and brain MRI findings were consistent with meningoencephalitis. A recent M. pneumoniae infection was confirmed using nasopharyngeal PCR and serological testing. Despite appropriate antimicrobial therapy, his neurological deterioration progressed. The addition of steroids and intravenous immunoglobulin resulted in a rapid and complete neurological recovery. This case underscores the immune-mediated pathogenesis of M. pneumoniae-associated meningoencephalitis, particularly in cases with a delayed neurological onset following respiratory prodromes. Clinicians should therefore consider early immunotherapy in conjunction with antibiotics, even in adult populations.
Objectives To describe the tyrosine kinase inhibitor (TKI) treatment patterns in patients with BCR::ABL-positive chronic myeloid leukemia (CML) in Japan. The secondary objective was to describe healthcare resource utiliz...Objectives To describe the tyrosine kinase inhibitor (TKI) treatment patterns in patients with BCR::ABL-positive chronic myeloid leukemia (CML) in Japan. The secondary objective was to describe healthcare resource utilization and any adverse events of interest. Methods This retrospective observational study was conducted using the Medical Data Vision insurance claims database in Japan. All patients in the database who received at least one prescription of any TKI for the treatment of CML between 2011 and 2019 were included. Patients were followed up for at least 12 months (or until death or loss from the database). All healthcare resource consumption during the follow-up period was recorded. Treatment persistence with TKIs was determined using the Kaplan-Meier survival analysis. Adverse events of interest that occurred during treatment were documented. Results Overall, the most frequently used TKI was dasatinib (411 patients, 54.5%). The median duration of persistence on first-line TKI was 30.6 months; 174 (23.1%) patients moved to a second-line treatment, 46 (6.1%) to a third-line treatment, and 14 (0.2%) to a fourth-line treatment. The most common adverse events were vascular diseases (≥64% of patients, depending on the TKI). The median annual per capita cost of CML management was ¥2,105,000, with the acquisition of TKIs being the main cost driver (median: ¥2,026,000 per patient annually). Overall, treatment persistence with TKIs, especially in the later treatment lines, remains relatively short, and patients still experience adverse events during treatment. Conclusion Our results suggest that there is still room for improvement in CML treatment, particularly with regard to new, effective drugs that are better tolerated.
Background LGI1 antibody is one of the most important antibodies associated with autoimmune encephalitis. A biological biomarker for assessing disease severity in LGI1 antibody-associated encephalitis has not yet been es...Background LGI1 antibody is one of the most important antibodies associated with autoimmune encephalitis. A biological biomarker for assessing disease severity in LGI1 antibody-associated encephalitis has not yet been established. In this study, we used serum and cerebrospinal fluid (CSF) from patients with LGI1 antibody-positive encephalitis to immunoprecipitate antigens from mouse brain tissue, and the immunoprecipitation (IP) products were subsequently analyzed using mass spectrometry (IP-shotgun proteomics). Methods Five patients with LGI1 antibody-positive cases were included in the patient group. The control group comprised healthy individuals, those with idiopathic normal pressure hydrocephalus, and NMDAR antibody-positive cases. IP-shotgun proteomics was performed for each sample, and specific amino acid sequences identified in the immunoprecipitated products were quantified as peptide spectrum match (PSM) values. We analyzed the PSM values of LGI1 and its binding partners, ADAM22, ADAM23, and DLG4. Results The PSM values of LGI1, ADAM22, and ADAM23 were significantly higher in IP products using sera and CSF from patients with AE with LGI1 antibody than in those from the control group. The most severe case showed the highest PSM values for LGI1, ADAM22, ADAM23, and DLG4 in both serum and CSF, and the mildest case showed the lowest PSM values for these proteins. Conclusion In LGI1 antibody-positive cases, the PSM values of LGI1, ADAM22, ADAM23, and DLG4, which form a complex with LGI1, were higher than those in the control group. Further studies are required to determine whether these PSM values have diagnostic utility and can thus serve as biomarkers of disease severity.
Isolated thyroid-stimulating hormone (TSH) deficiency is a rare form of central hypothyroidism that requires long-term levothyroxine replacement therapy. We report a rare case of isolated TSH deficiency in which Graves'...Isolated thyroid-stimulating hormone (TSH) deficiency is a rare form of central hypothyroidism that requires long-term levothyroxine replacement therapy. We report a rare case of isolated TSH deficiency in which Graves' disease developed after long-term thyroid hormone replacement therapy, followed by a recovery of the TSH secretory capacity. A 46-year-old woman with isolated TSH deficiency developed thyrotoxicosis with positive TSH receptor antibody levels and a preserved thyroid uptake on scintigraphy. After radioactive iodine therapy (I, 13 mCi), her thyroid function stabilized, and a TRH stimulation test demonstrated a recovery of TSH secretion. This case suggests the potential plasticity of the hypothalamic-pituitary-thyroid axis.
A 76-year-old woman was admitted to our hospital due to a relapse of eosinophilic granulomatosis with polyangiitis (EGPA). On day 4 of hospitalization, the patient developed hypotension and anemia. Contrast-enhanced comp...A 76-year-old woman was admitted to our hospital due to a relapse of eosinophilic granulomatosis with polyangiitis (EGPA). On day 4 of hospitalization, the patient developed hypotension and anemia. Contrast-enhanced computed tomography (CT) revealed an intra-abdominal hematoma with contrast extravasation near the right gastroepiploic artery. The patient died despite receiving emergency embolization and intensive care. An autopsy revealed eosinophilic necrotizing vasculitis widely distributed in multiple organs. No vasculitis was found in the gastroepiploic artery, suggesting that vasa vasorum involvement may have contributed to the arterial rupture. This case report describes a rare instance of a fatal hemorrhage associated with EGPA.
Evans syndrome is characterized by the coexistence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Corticosteroids are the first-line therapy. However, many patients become steroid-dependent or e...Evans syndrome is characterized by the coexistence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Corticosteroids are the first-line therapy. However, many patients become steroid-dependent or experience significant adverse effects. An 80-year-old man with a 33-year history of ITP was admitted with laboratory findings suggestive of hemolytic anemia and he was diagnosed with Evans syndrome. High-dose corticosteroids achieved hematologic control, but they also caused delirium, necessitating dose reduction. Rituximab produced a limited response. Efgartigimod was initiated for chronic ITP with the expectation of a concurrent benefit for AIHA. Following treatment, the platelet counts improved, hemolysis stabilized, and corticosteroids were successfully tapered without relapse. This case suggests that efgartigimod may be effective in IgG-mediated autoimmune cytopenias, such as Evans syndrome, and it may serve as a steroid-sparing therapeutic option.
Modern medicine has struggled to cope with the pathologies induced by sedentary lifestyles and excess calories. As hibernating bears are remarkably resilient to such complications, this review compares the pathophysiolog...Modern medicine has struggled to cope with the pathologies induced by sedentary lifestyles and excess calories. As hibernating bears are remarkably resilient to such complications, this review compares the pathophysiology of the two across three critical domains. While humans experience inflammatory adipose hypertrophy, bears control obesity by utilizing immunomodulatory lipids and the hyperplastic expansion of adipose tissue. Unlike catabolism and nitrogenous waste accumulation, which are typical of human muscles, bears employ a gut microbiota-based urea recycling system to preserve proteostatic integrity. Finally, bears bypass stasis-induced thromboembolism and disuse-induced osteoporosis through targeted molecular reprogramming, including the suppression of heat shock protein 47 and balanced bone remodeling. An analysis of these divergent responses helped identify the mechanisms underlying adaptive resilience in bears, which serves as a blueprint for hibernation-inspired medicine. The translation of these evolutionary strategies, -from target-specific antithrombotics to metabolic toggling, -offers tremendous potential for treating metabolic failure, sarcopenia, and the degenerative diseases associated with chronic immobility in humans.
Ketosis-prone diabetes (KPD) is characterized by episodes of diabetic ketosis or diabetic ketoacidosis (DKA) requiring insulin therapy, followed by periods during which insulin treatment may be discontinued. We herein re...Ketosis-prone diabetes (KPD) is characterized by episodes of diabetic ketosis or diabetic ketoacidosis (DKA) requiring insulin therapy, followed by periods during which insulin treatment may be discontinued. We herein report a case of a young obese male with clinical features consistent with KPD. He developed diabetic ketosis at the age of 16 years but recovered insulin secretion soon after undergoing intensive therapy, allowing for insulin withdrawal. At 25 years of age, he developed severe DKA again, but was able to discontinue insulin therapy after two months. Whole-exome sequencing identified a rare heterozygous missense variant (p.R51Q) in ARRB1. The ARRB1 variant may be a genetic contributor to KPD.
A 75-year-old man presented with a subcutaneous hemorrhage, swelling, and pain in the right lower limb. Computed tomography revealed a pseudoaneurysm of the right common femoral artery. Laboratory findings showed marked...A 75-year-old man presented with a subcutaneous hemorrhage, swelling, and pain in the right lower limb. Computed tomography revealed a pseudoaneurysm of the right common femoral artery. Laboratory findings showed marked hyperfibrinolysis and thrombocytopenia, and he was diagnosed with disseminated intravascular coagulation (DIC) secondary to the pseudoaneurysm. We speculated that the pseudoaneurysm may have resulted from chronic mechanical interference caused by the total hip arthroplasty device that had been implanted five years previously. When DIC of unknown etiology occurs in patients with a history of orthopedic surgery, clinicians should therefore consider late complications of joint arthroplasty as potential underlying causes.
Nakaya Y, Hashimoto K, Fukushima K
… +14 more, Fatimah M, Matsumoto Y, Funauchi A, Tsukaguchi A, Yamauchi K, Miyazaki A, Iwahashi Y, Tone M, Naito M, Shiroyama T, Hirata H, Takeda Y, Nakamura S, Kumanogoh A
A 73-year-old woman with a history of tracheostomy for tracheomalacia and bronchiectasis developed a worsening productive cough with progressive nodular/bronchocentric opacities on computed tomography. She was diagnosed...A 73-year-old woman with a history of tracheostomy for tracheomalacia and bronchiectasis developed a worsening productive cough with progressive nodular/bronchocentric opacities on computed tomography. She was diagnosed with Mycobacterium brisbanense pulmonary disease based on repeated sputum culture results. Antimicrobial susceptibility testing revealed a low minimum inhibitory concentration for clarithromycin, and whole-genome sequencing confirmed the absence of the erm gene. Owing to repeated smear positivity and clinical progression, macrolide-based multidrug therapy was initiated, resulting in both clinical and radiographic improvements. To our knowledge, this is the first reported case of M. brisbanense pulmonary disease in Japan, thus highlighting its potential pathogenicity.
A 38-year-old woman with a five-year history of ulcerative colitis (UC) treated with 5-aminosalicylic acid presented with an acute flare of UC. The patient was treated with azathioprine (AZA) as maintenance therapy follo...A 38-year-old woman with a five-year history of ulcerative colitis (UC) treated with 5-aminosalicylic acid presented with an acute flare of UC. The patient was treated with azathioprine (AZA) as maintenance therapy following budesonide rectal foam and developed AZA-induced sialadenitis and pancreatitis. To the best of our knowledge, this is the first reported case of concomitant azathioprine-induced sialadenitis and pancreatitis, highlighting the possibility of a shared immunologically mediated hypersensitivity mechanism. This case highlights the impact of idiosyncratic hypersensitivity reactions in thiopurine toxicity and provides clinically relevant insights into the safe application of AZA for inflammatory bowel disease management.
A 28-year-old woman, previously diagnosed with seronegative rheumatoid arthritis, was admitted with fever, vomiting, and diarrhea. She developed septic shock with disseminated intravascular coagulation and was treated wi...A 28-year-old woman, previously diagnosed with seronegative rheumatoid arthritis, was admitted with fever, vomiting, and diarrhea. She developed septic shock with disseminated intravascular coagulation and was treated with antibiotics, noradrenaline, prednisolone, and thrombomodulin. On day 3, a rash appeared, and polymerase chain reaction detected Orientia tsutsugamushi deoxyribonucleic acid, thus confirming the diagnosis of scrub typhus. Her symptoms resolved after minocycline treatment. After tapering the prednisolone, fever, rash, and arthralgia recurred. Laboratory tests revealed elevated ferritin and interleukin-18 levels. After excluding other causes, adult-onset Still's disease (AOSD) was diagnosed in this patient. The patient exhibited a rapid improvement following tocilizumab treatment. Scrub typhus and AOSD share overlapping features that complicate diagnosis.
Objective Anti-mitochondrial antibodies (AMA) are primarily used as serological markers for primary biliary cholangitis, but they have also been implicated in cardiac dysfunction and arrhythmias. This study aimed to inve...Objective Anti-mitochondrial antibodies (AMA) are primarily used as serological markers for primary biliary cholangitis, but they have also been implicated in cardiac dysfunction and arrhythmias. This study aimed to investigate the association between AMA positivity, the right atrial low-voltage area (RA-LVA), and sick sinus syndrome (SSS) in patients with isolated cardiac involvement. Methods We retrospectively analyzed patients who underwent AMA testing at the Ogaki Municipal Hospital between 2008 and 2024. Clinical, electrocardiographic, and echocardiographic data were reviewed at the time of AMA testing. RA-LVA was assessed using data from cardiac implantable electronic device implantation or three-dimensional electroanatomic mapping during catheter ablation. The factors associated with AMA positivity and SSS were evaluated using a univariate logistic regression analysis. Patients Among 5,901 patients who underwent AMA testing, 50 patients with isolated cardiac involvement were included after excluding those with primary biliary cholangitis, mitochondrial myositis, or no cardiac involvement. Five patients were AMA-positive, and 45 were AMA-negative. Results AMA positivity was significantly more frequent in patients with RA-LVA than in those without RA-LVA (100% vs. 4.3%, p <0.001), and similarly in those with SSS (75.0% vs. 4.3%, p = 0.002), indicating a consistent association across RA-LVA and SSS. In the univariate analysis, AMA positivity was strongly associated with SSS (odds ratio 66.0; 95% confidence interval 4.57-953.0; p = 0.002). Conclusion AMA positivity is strongly associated with RA-LVA and SSS in patients with isolated cardiac involvement, suggesting a potential pathogenic role for AMA in right atrial and sinoatrial node dysfunction.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized because of improved diagnostic modalities and disease-modifying therapy. We report the first Japanese case of hereditary ATTR-CM (ATTRv-CM) caused...Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized because of improved diagnostic modalities and disease-modifying therapy. We report the first Japanese case of hereditary ATTR-CM (ATTRv-CM) caused by the Ile68Leu variant, which has been previously described in European cohorts. A man in his 40s presented with heart failure and typical imaging findings of transthyretin amyloid cardiomyopathy (ATTR-CM). Genetic testing identified the Ile68Leu variant, which was absent in East Asian population databases. This case expands the genetic spectrum of ATTRv-CM in Japan and suggests that cardiac-predominant non-Val30Met TTR variants may occur in Japanese patients, with implications for the diagnosis, family counseling, and cascade screening in the future.
Objective Among cardiometabolic risk factors (CMRs), the relative contribution of obesity-related indices, particularly the body mass index (BMI) and waist circumference, to the development of metabolic dysfunction-assoc...Objective Among cardiometabolic risk factors (CMRs), the relative contribution of obesity-related indices, particularly the body mass index (BMI) and waist circumference, to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. We assessed the impact of these indices on incident MASLD compared with other CMRs and determined the threshold of weight gain associated with an increased risk. Methods This retrospective cohort study included 7,687 individuals without steatotic liver disease at baseline who underwent health screening. The baseline risk factors and 5-year weight changes were assessed to evaluate their associations with incident MASLD. The participants were stratified according to the presence or absence of CMRs. Results Multivariable logistic regression analyses showed that baseline obesity was the strongest factor associated with incident MASLD (odds ratio (OR), 2.75; 95% confidence intervals (CI), 2.33-3.24), followed by a history of weight gain of ≥10 kg since 20 years of age (OR, 2.23; 95% CI, 1.90-2.63). A dose-response relationship was observed between the 5-year weight gain and MASLD incidence. The risk of MASLD increased from a 3-5% weight gain in participants with baseline CMRs (OR = 2.39; 95% CI = 1.92-2.99), whereas a higher threshold of 7-10% was required in those without CMRs (OR = 3.92; 95% CI = 2.05-7.47). Conclusions Among CMRs, obesity-related indices were the most influential factors for incident MASLD. The threshold for weight gain differed according to the baseline CMR status, highlighting the importance of individualized weight management strategies. These findings provide clinically relevant thresholds for weight management in the prevention of MASLD.
Atypical hemolytic uremic syndrome (aHUS) is a rare cause of thrombotic microangiopathy (TMA). When aHUS cannot be excluded, diagnostic treatment with anti-C5 antibody agents should be considered. We report a patient wit...Atypical hemolytic uremic syndrome (aHUS) is a rare cause of thrombotic microangiopathy (TMA). When aHUS cannot be excluded, diagnostic treatment with anti-C5 antibody agents should be considered. We report a patient with a novel heterozygous complement factor H (CFH) variant, p.Glu1198Asp (c.3594A>T), who received ravulizumab three months after disease onset. Ravulizumab was administered for relapse prevention in the chronic phase, and no recurrence of thrombotic microangiopathy was observed during the follow-up.