Objective There are no comparative studies on provoked coronary microvascular spasm (CMS) in patients undergoing both acetylcholine (ACh) and ergonovine (EM) vasoreactivity testing. We investigated the incidence of provoked CMS in patients with ischemia with nonobstructive coronary artery disease (INOCA) undergoing ACh and EM vasoreactivity testing.

Methods We recruited 494 INOCA patients who underwent both ACh and EM vasoreactivity testing. ACh was injected at incremental doses of 20/50/100/200 μg into the left coronary artery (LCA) and 20/50/80 μg into the right coronary artery (RCA), whereas 40 μg of EM was administered into the RCA and 64 μg into the LCA. Positive CMS was defined as <75% transient coronary constriction, accompanied by typical chest symptoms or ischemic ECG changes.

Results Among the 494 patients, CMS was observed in 23 (4.7%) patients. Eighteen patients had CMS alone, and 5 patients had coexisting epicardial spasm. The ACh test alone, EM test alone, and both tests provoked CMSs in 12 patients, 7 patients, and 4 patients, respectively. There were no marked differences in incidence between ACh- and EM-induced CMS (70% vs. 48%, p=0.2307).

Conclusion Differences were observed between ACh-induced CMS and EM-induced CMS. The complementary use of vasoreactivity testing is essential for accurately documenting the presence of CMS in real-world settings.

Objective Long-term uric acid exposure as an independent risk factor for cardiovascular disease remains unclear. This study investigated whether or not the running average serum uric acid (Ra-SUA) value measured after percutaneous coronary intervention (PCI) could be associated with the occurrence of subsequent cardiovascular events.

Methods The clinical records of 1,761 patients who underwent successful PCI were retrospectively examined. The Ra-SUA values were calculated by adding consecutive SUA values and dividing them by the number of measurements. Based on the Ra-SUA value during an observation period of up to 10 years after PCI, the patients were divided into 3 groups based on the Ra-SUA: >7.0, 5.5-7.0, and ≤5.5 mg/dL. Among these groups, the incidence of major adverse cardiac events (MACEs) was investigated. Furthermore, patients with Ra-SUA ≤5.5 mg/dL were further classified into 3 groups according to Ra-SUA values to investigate the association with the incidence of MACEs. MACEs were defined as coronary-related death, nonfatal myocardial infarction, and new coronary stenosis of non-culprit lesions.

Results A Kaplan-Meier analysis demonstrated that the incidence of MACEs was significantly higher in patients with Ra-SUA >7.0 mg/dL than in the other groups. A multivariate analysis indicated that the Ra-SUA value was significantly correlated with the incidence of MACEs. However, patients with Ra-SUA <4.0 mg/dL had an increased incidence of MACEs compared with patients with Ra-SUA 4.0-5.0 mg/dL.

Conclusion High Ra-SUA values may be a predictor of increased recurrence of cardiovascular disease after PCI. There may also be a J-curve association between the incidence of MACEs and Ra-SUA values.

Objective This study aimed to develop a clinical model in which the C-peptide index (CPI) under non-fasting conditions can predict future insulin therapy in patients with type 2 diabetes mellitus (T2DM).

Methods This was a single-center retrospective study. We analyzed the correlation between non-fasting CPI and future insulin therapy in 464 patients who T2DM not receive insulin therapy who attended our clinic and were evaluated for non-fasting CPI on an outpatient basis. We used machine learning as an adjunct method to create a clinical model to predict future insulin therapy.

Results At the end of the observation period, 22 participants remained on insulin therapy (continuous insulin therapy group: CIG), and 442 were not on insulin therapy (without insulin therapy group: WIG). HbA1c and serum creatinine (Cre) were significantly higher in the CIG than in the WIG (p<0.001 and p=0.045, respectively). The non-fasting CPI was lower in the CIG than in the WIG (p<0.001). The cutoff value of non-fasting CPI to predict the need of future insulin therapy was 1.62 (sensitivity 40.9%, specificity 90.7%), and the cutoff value to indicate the low possibility of future insulin therapy was 3.11 (sensitivity 90.1%, specificity 48.9%). A clinical model was created to predict future insulin therapy by machine learning using the Easy Ensemble Classifier method with non-fasting CPI, HbA1c, and Cre as features (accuracy, 78.5%; area under the ROC curve 0.86, false positive rate, 18.2%; false negative rate, 22.2%).

Conclusion CPI under non-fasting conditions can predict the likelihood of future insulin therapy in outpatients with T2DM.

Objective The global prevalence of multiple sclerosis (MS) is increasing worldwide. Although many disease-modifying therapies (DMTs) have been approved, they can cause serious adverse events, including infections. Dimethyl fumarate (DMF), an immunomodulator, has a favorable safety profile. In this era of personalized therapy, it is important to select an appropriate DMT for individual patients. This study evaluated DMF treatment outcomes in Japanese patients with MS.

Methods The medical records of Japanese patients with MS treated with DMF at a single institution between January 6, 2013, and October 31, 2022, were reviewed retrospectively. The reasons for discontinuation of DMF, switching from other DMTs to DMF, transition of DMF to other medications, absolute lymphocyte count, disease activity assessment, comparison of DMF continuation versus discontinuation, and factors associated with the annualized relapse rate during DMF use were assessed.

Results Of the 116 DMF-treated patients, DMF treatment was continued to prevent relapse recurrence in 54.7% of RRMS (n=86) and 23.3% of SPMS (n=30) patients. The main reasons for not continuing DMF treatment included failure to prevent relapse or disease progression (63% of patients who did not continue DMF). A lower annual recurrence rate prior to DMF initiation, lower Expanded Disability Status Scale score, shorter duration from disease onset to DMF initiation, fewer relapse recurrences during DMF therapy, and diagnosis of RRMS were associated with DMF continuation.

Conclusion Continuous monitoring is essential after initiating DMF treatment because patients may require transition to other therapies. Overall, 47% of the MS patients were effectively managed with DMF, with favorable outcomes observed in 54.7% of the RRMS patients.

Objective We herein report our experience with medically treated patients presenting with dropped head syndrome (DHS) due to isolated neck extensor myopathy (INEM) or primary hyperparathyroidism (PHPT)-related myopathy, focusing on the treatment response and the correlation between muscle pathology and INEM outcomes.

Methods This single-center retrospective observational study reviewed 20 consecutive patients who presented with DHS as their primary complaint between March 2021 and June 2025. Sixteen patients were included in this study: 13 with INEM who received immunotherapy as the primary medical treatment and 3 with PHPT-related myopathy who received oral evocalcet. The severity of DHS and treatment response were graded semi-quantitatively. Muscle biopsy findings were analyzed in one patient with INEM. We conducted a literature review of biopsy-proven INEM cases.

Results INEM was the most common cause of DHS (13/20). Patients with INEM with a shorter disease duration experienced dramatic improvement, whereas those with a longer disease duration showed only partial improvement. Relapse occurred in six patients with INEM. All three patients with PHPT-related myopathy achieved complete remission of DHS with oral evocalcet. Although our single biopsy case showed no pathological inflammation and responded well to immunotherapy, a literature review revealed that inflammatory infiltrates were present in 38% of the 56 INEM cases and correlated with a significantly better immunotherapy response.

Conclusion INEM is the predominant etiology of DHS at initial presentation, and immunotherapy is an effective management strategy, especially with early intervention. PHPT-related myopathy represents another important etiology of DHS, with a favorable response to medical therapy with evocalcet.

A woman in her 20s from Vietnam, an asymptomatic hepatitis B virus (HBV) carrier with a high viral load, was initiated on tenofovir disoproxil fumarate (TDF) at 31 weeks of gestation. TDF was discontinued after delivery; however, at eight weeks postpartum, she developed an acute exacerbation of hepatitis, characterized by elevated ALT levels and HBV DNA rebound. Although the risk of hepatitis flares following TDF discontinuation is generally considered low, this case highlights the potential for severe postpartum exacerbation and underscores the importance of considering continued antiviral therapy in the postpartum period.

Granular cell tumors and schwannomas rarely occur in cystic ducts. We herein report a case of a hybrid tumor consisting of a cystic duct-originating granular cell tumor and schwannoma. A 48-year-old woman was referred to our hospital with the chief complaint of occasional postprandial abdominal pain after an enlarged gallbladder was found on ultrasonography. The cause was identified as a mass measuring approximately 7 mm in diameter in the cystic duct, and the patient underwent extrahepatic cholangiectomy. An examination of the surgical specimen revealed that the mass originated from the cystic duct and narrowed the duct lumen. Histopathologically, both granular cell tumors and schwannoma components were detected. To our knowledge, this is the first report of a hybrid peripheral nerve sheath tumor with a mixture of granuloma cell tumors and schwannomas.

A 40-year-old woman presented with intermittent limb weakness, edema, and persistent hypokalemia. She had a history of recurrent urinary tract infections, but no diuretic or laxative use. Laboratory findings revealed metabolic alkalosis with elevated plasma renin activity and aldosterone levels. The urinary electrolyte response to fluid administration suggested pseudo-Bartter syndrome due to the volume depletion. Abdominal imaging revealed renal scarring, suggesting focal renin release from the ischemic regions. This case highlights the importance of recognizing secondary systemic renin-angiotensin-aldosterone system (RAAS) activation driven by focal renin release in renal scarring. This also illustrates a paradox in which salt and water restriction may worsen RAAS-driven hypokalemia.

A 67-year-old man was diagnosed with Hashimoto's thyroiditis, and replacement therapy with levothyroxine was initiated. Ten years later, although the patient was euthyroid, ultrasonography showed an increase in goiter size and a significant decrease in overall echogenicity with scattered high-echo areas. Computed tomography revealed diffuse low-density areas with no contrast effect in the thyroid parenchyma and partial high-density areas, indicating possible malignancy. However, a core needle biopsy revealed an amyloid light-chain (AL) κ-type amyloid goiter. Because serum immunoprecipitation electrophoresis showed IgG κ-type M-protein, the diagnosis was secondary amyloidosis. It is important to consider amyloid goiter with imaging findings, as in this case.

The effectiveness of selpercatinib against RET-fusion-positive non-small cell lung cancer (NSCLC) in geriatric patients is underreported. We report the case of an 84-year-old woman in whom reduced-dose selpercatinib elicited a significant tumor response in KIF5B-RET fusion-positive NSCLC. However, she developed acalculous cholecystitis, which led to the discontinuation of the drug. This is the first reported case of selpercatinib-induced acalculous cholecystitis in a patient. The report highlighted the potential efficacy of selpercatinib in elderly patients while underscoring the risk of severe adverse events and emphasizing monitoring and personalized dose management.

Myelofibrosis (MF) is a myeloproliferative neoplasm frequently complicated by splenomegaly, with vascular abnormalities, such as splenic artery aneurysm (SAA), rarely reported. We herein report a 74-year-old woman with secondary MF harboring a JAK2 V617F mutation who developed SAA requiring intervention because of its potential risk of rupture. Ruxolitinib therapy markedly reduced splenomegaly and improved constitutional symptoms, thereby optimizing hemodynamic conditions and overall status for safe spleen-preserving coil embolization. This case highlights the potential relationship between MF and aneurysm formation while demonstrating that concomitant Janus kinase inhibitor therapy may facilitate safe endovascular treatment in select patients.

Spinocerebellar ataxia type 3 (SCA3) is a hereditary neurodegenerative disorder characterized by cerebellar ataxia, whereas amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease. We herein report a 62-year-old man with genetically confirmed SCA3 who subsequently developed rapidly progressive asymmetric muscle weakness, atrophy, and fasciculations. Clinical features, including preserved tendon reflexes and widespread denervation observed on electromyography, support the diagnosis of concomitant sporadic ALS. Our literature review revealed only a few similar cases, suggesting the under-recognition of this rare combination. This case underscores the importance of considering coexisting ALS in patients with SCA3 to enable a timely diagnosis and management.

We herein report two cases of anti-contactin-associated protein-like 2 (CASPR2) autoimmune encephalitis in men in their 70s. Both patients presented with seizures and psychiatric symptoms that required sedation and mechanical ventilation. The treatment included high-dose intravenous methylprednisolone, plasma exchange, and rituximab. One patient fully recovered (modified Rankin Scale [mRS] score 0), whereas the other remained severely disabled (mRS score 5). This difference in outcome may be attributed to the time from symptom onset to treatment initiation. These cases highlight the importance of an early diagnosis and timely immunotherapy for anti-CASPR2 autoimmune encephalitis.

The diagnosis of cancer-associated stroke can be challenging, particularly when occult malignancy is not detected by standard evaluations. We report two patients with anticoagulation-resistant recurrent cryptogenic stroke in whom ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) successfully identified the underlying cancer after conventional tests were inconclusive. These cases highlight the value of FDG-PET/CT in uncovering malignancy-related stroke mechanisms and emphasize its role the timely diagnosis of cancer and targeted treatment in patients with cryptogenic stroke, as well as features suggestive of occult malignancy.

We report the case of a 49-year-old man with hereditary neuropathy with liability to pressure palsies unmasked by polatuzumab vedotin-containing chemotherapy. Neuropathic symptoms were predominant in areas surrounding the right and left ulnar nerves after the first course of chemotherapy. However, they progressed in a stepwise manner, involving other limb regions, after the second and third courses. Nerve conduction studies revealed demyelinating neuropathy conspicuous at the compression sites, and fluorescence in situ hybridization showed deletion of the PMP22 gene. This case underscores the importance of considering the development or exacerbation of hereditary neuropathies including hereditary neuropathy with liability to pressure palsies in patients receiving polatuzumab vedotin.

A 44-year-old man with spinal and bulbar muscular atrophy (SBMA) and an anterior mediastinal tumor presented with ptosis and diplopia with diurnal variation. Dysarthria, dysphagia, and limb weakness deteriorated acutely, and developed respiratory failure. Repetitive nerve stimulation resulted in a decremental response. Ice pack and edrophonium tests were positive. Myasthenia gravis (MG) was diagnosed based on the presence of anti-acetylcholine receptor (AChR) antibodies. Immunotherapy improved the myasthenic symptoms. Although a few cases of SBMA exhibiting myasthenic symptoms have been reported, none of these patients had anti-AChR antibodies. This is the first report of seropositive MG with comorbid SBMA.

We report the case of a man in his 60s, who was previously diagnosed with Alzheimer's disease and presented with acute respiratory failure. Investigations revealed severe hypercapnia and central sleep apnea. Imaging revealed a tortuous right vertebral artery compressing the ventral medulla. Cerebrospinal fluid analysis showed a normal amyloid-β 1-42/1-40 ratio, and he exhibited pyramidal and autonomic signs of brainstem involvement. Despite microvascular decompression, the patient remained ventilator dependent. This case illustrates that medullary compression can cause central hypoventilation that mimics a neurodegenerative disorder, with cognitive decline driven by chronic hypoxia rather than by Alzheimer's pathology.

Sporadic late-onset nemaline myopathy (SLONM) is a rare, acquired myopathy that is frequently associated with monoclonal gammopathy, most commonly monoclonal gammopathy of undetermined significance (MGUS). However, its association with overt multiple myeloma (MM) has been rarely reported. We present a case of SLONM associated with MM in which chemotherapy targeting the underlying MM led to mild-to-moderate improvement in muscle symptoms. This case underscores the potential pathogenic role of MM in SLONM and highlights the importance of treating underlying hematologic malignancies.