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The article discusses a case study of an 80-year-old Japanese woman with rheumatoid arthritis who tested positive for SARS-CoV-2 and experienced prolonged shedding of the virus while on methotrexate (MTX) treatment. The patient's antigen levels fluctuated, and the virus isolated was identified as Omicron BA-5. The study suggests that MTX treatment may have delayed the clearance of SARS-CoV-2, emphasizing the need for clinicians to carefully balance the risks and benefits of DMARD therapy in infected patients. The patient's COVID-19 symptoms did not worsen despite the prolonged shedding of the virus. [Extracted from the article]

This study aimed to investigate in detail the efficacy of switching from etanercept reference product (RP) to etanercept biosimilar in patients with rheumatoid arthritis (RA) under real-world clinical conditions using clinical indices and musculoskeletal ultrasound (MSUS). This interventional, multicenter, open-label, single-arm clinical trial involved 24- or 52-week follow-up. This study enrolled patients with RA who had been treated with etanercept-RP for ≥ 24 weeks, achieved clinical low disease activity (LDA) or remission, and switched from etanercept-RP to etanercept biosimilar. This study included 20 patients. Of the 17 patients, 16 (94.1%; 95% confidence interval [CI]: 71.3-99.9) remained in LDA/remission on DAS28-ESR at 24 weeks. The dose of 50 mg/week was reduced to 25 mg/week at 24 weeks, and LDA/remission was sustained until 52 weeks in 9 (81.8%, 95% CI: 48.2-97.7] of 11 participants. DAS28-ESR, DAS28-CRP, SDAI, and CDAI scores showed no apparent worsening. The median total PD score remained 0. The switch from etanercept-RP to etanercept biosimilar and subsequent dose reduction demonstrated favorable outcomes, including MSUS evaluation.

Brain arteriovenous malformations (bAVMs) are a notable cause of intracranial hemorrhage, strongly associated with severe morbidity and mortality. Contemporary treatment options include surgery, stereotactic radiosurgery, and endovascular embolization, each of which has limitations. Hence, development of pharmacological interventions is urgently needed. The recent discovery of the presence of activating Kirsten rat sarcoma ( KRAS ) viral oncogene homologue mutations in most sporadic bAVMs has opened the door for a more comprehensive understanding of the pathogenesis of bAVMs and has pointed to entirely novel possible therapeutic targets. Herein, we review the status quo of genetics, animal models, and therapeutic approaches in bAVMs., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To evaluate the preoperative risk factors for early intravesical recurrence after radical nephroureterectomy (RNU) in patients with upper urinary tract carcinoma (UTUC) according to the history of non-muscle invasive bladder cancer (NMIBC)., Methods: We retrospectively evaluated patients who underwent RNU for UTUC between 2012 and 2022 at 14 hospitals. Early recurrence was defined as intravesical pathologically confirmed recurrence within 1 year after RNU. Patients who received single-dose immediate intravesical instillation (IVI) as prevention for intravesical recurrence were excluded. Using preoperative factors, we examined the risk factors for early intravesical recurrences in patients with and without a history of NMIBC. Death from any cause within 1 year after RNU was regarded as a competitive risk., Results: We included 504 UTUC patients who were treated with RNU. Among these patients, 126 (25.0%) had a history of NMIBC, whereas 378 (75%) did not. According to multivariate analysis, the presence of macrohematuria, positive cytology in self-voided urine, and performing diagnostic ureteroscopy prior to RNU were risk factors in patients without a history of NMIBC. On the other hand, an NMIBC diagnosis within 1 year prior to RNU and an extravesical approach for bladder cuff management were risk factors in RNU-treated patients with a history of NMIBC., Conclusions: Early intravesical recurrence risk factors differ between UTUC patients with and without a history of NMIBC. Different stratification may be needed to predict intravesical recurrence risk in these two types of UTUC patients., (© 2025 The Japanese Urological Association.)

Purpose: Geriatric nutritional related index (GNRI) is a simple and well-established screening method of nutritional status. We aimed to develop and validate a scoring system including GNRI to predict long-term outcomes in patients with chronic limb-threatening ischemia (CLTI) undergoing endovascular treatment (EVT)., Materials and Methods: Patients undergoing EVT for symptomatic LEAD from August 2015 to August 2016 were enrolled into the I-PAD NAGANO registry, a prospective, multicenter, observational registry. We identified predictors of amputation-free survival (AFS) at 5 years using Cox proportional hazards regression and developed a risk scoring system. The predictive performance of the risk score was assessed., Results: A total of 126 patients with CLTI were analyzed. Cox multivariate analysis revealed GNRI score <92 points, ≥72 years of age, hemodialysis, heart failure, and anemia to be significant predictors. We developed a 5-item risk score (I-PAD CLTI score) assigning points to each factor based on the magnitude of association with AFS at 5 years. The I-PAD CLTI score showed a c-index of 0.80 for 5-year AFS. Patients with high score (≥7 points, n=50) had an increased risk of AFS at 5 years compared with those with low score (<7 points, n=68) (26.5% vs 72.1%, p<0.001)., Conclusion: A simple 5-item risk score including nutritional status showed reasonable discriminative and prognostic ability for long-term AFS among patients with CLTI., Clinical Impact: The I-PAD CLTI score, a simple five-item risk score including nutritional status determined by geriatric nutritional related index, showed reasonable discriminative and prognostic ability for long-term amputation free survival among patients with chronic limb-threatening ischemia. This risk score may be useful for clinicians to accurately predict patient's prognosis and thus identify high-risk patients who may derive the greater clinical benefit from more intensive risk modification. Further research is required to test the clinical utility of risk-score-based treatment approach to improve the prognosis of patients with chronic limb-threatening ischemia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Sealing of the aneurysm neck with a Woven EndoBridge (WEB) device is recommended for disrupting the blood flow inside the aneurysm. This study investigates the relationship between WEB neck apposition and aneurysm occlusion rates., Methods: Aneurysms treated with a WEB from March 2017 to May 2022 at a single center were included. WEB neck apposition (poor/good) and WEB protrusion (yes/no) were evaluated on post-detachment high resolution cone beam CT images. Angiographic occlusion was assessed with the Bicêtre Occlusion Scale score (BOSS). Univariate and multivariable analysis tested the association between neck apposition and occlusion rates., Results: The study included 159 aneurysms in 141 patients (mean age 55.8±11.2 years; 64.2% women). Good neck apposition and protrusion were noted in 123 (77.4%) and 30 (18.9%) cases, respectively. Inter-rater agreements were good for neck apposition (κ=0.75) and protrusion (κ=0.78). Complete and adequate occlusion was achieved in 104 (65%) and 130 (82%) cases, respectively (median follow-up 18 months). Good neck apposition was a strong independent predictor for both adequate (adjusted OR (aOR)=5.9, 95% CI 2.4 to 14.9; P<0.001) and complete occlusion (aOR=7.1, 95% CI 3.0 to 18.1; P<0.001). Protrusion was more frequent in the adequate occlusion group versus the aneurysm recurrence group without reaching statistical significance (P=0.06), but was associated with more thromboembolic complications (9/30 (30%) vs 12/129 (9%); P<0.01). WEB shape modification was significantly greater in poor apposition cases (P=0.03)., Conclusions: Achieving good neck apposition of the WEB strongly predicts aneurysm occlusion during follow-up. WEB protrusion should be minimized due to the increase in thromboembolic risk with limited impact on aneurysm occlusion., Competing Interests: Competing interests: JCo received an educational grant from Medtronic, Phenox, and Microvention, and received honoraria for lectures from Balt. DFK received research support from Cerenovus, Sensome, Neurogami Medical, Insera Therapeutics, Medtronic, Microvention, Balt, Monarch Biosciences, Brainomix, MiVi, Stryker, and National Institutes of Health; royalties from Medtronic; is on the data safety monitoring board of NoNO and Vesalio; and is a stockholder of Nested Knowledge, Superior Medical Experts, Marblehead Medical, and Conway Medical. JCa received honoraria from Balt, Cerenovus, and Medtronic for lectures. LS is a consultant for Microvention, Balt, Phenox, Stryker, and Medtronic; data safety monitoring board or advisory board for CHOICE Study, INSPIRE Study, CLEVER study, and COATING study; and grant or contract from Philips with institution., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The New Zealand rabbit elastase-induced arterial aneurysm of the right common carotid artery remains a widely used model for assessing the effectiveness and safety of new neuroendovascular devices.1 This model offers a simple and reliable platform for pre-clinical in vivo investigations, crucial for comprehending the biological processes underlying aneurysm healing after endovascular treatment.2 Notably, the induced aneurysm exhibits morphological, hemodynamic, and histological characteristics similar to human intracranial aneurysms. The creation of the aneurysm is performed using open and endovascular techniques. Each step of the procedure requires a meticulous and controlled gesture to ensure reproducibility of the aneurysm and minimize animal misuse. In video 1 we present a step-by-step procedural guide for aneurysm creation and follow-up. We hope this resource will help in promoting this model and provide useful guidance for researchers in the field.neurintsurg;jnis-2024-021912v2/V1F1V1Video 1Surgical procedure of creating elastase-induced aneurysms in rabbits., Competing Interests: Competing interests: JC received an educational grant from Balt, Medtronic, Phenox, Microvention, all unrelated to this work. WB received research support from Cerenovus, Sensome and Brainomix and is a stockholder in Piraeus, Serenity, MomEase and Nested Knowledge, all unrelated to this work. RK received research support from Cerenovus, Sensome, Neurogami Medical, Insera Therapeutics, Medtronic, Monarch Biosciences, MiVi, Stryker, Piraeus Medical, Bionaut Labs, NSF and NIH, all unrelated to this work. DFK received research support from Cerenovus, Sensome, Neurogami Medical, Insera Therapeutics, Medtronic, Microvention, Balt, Monarch Biosciences, Brainomix, MiVi, Stryker and NIH; royalties from Medtronic; is on the DSMB of NoNO Inc and Vesalio; and is a stockholder in Nested Knowledge, Superior Medical Experts, Marblehead Medical, and Conway Medical, all unrelated to this work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and serum cytokine and chemokine profiles as predictors of clinical outcomes in rheumatoid arthritis (RA)., Patients and Methods: We included 200 patients with RA treated with biological and targeted synthetic disease-modifying antirheumatic drugs in a prospective multicentre ultrasound cohort study. Their serum levels of multiple cytokines and chemokines, rheumatoid factors, and serum autoantibodies (anti-cyclic citrullinated peptide-2 (anti-CCP2) and anti-carbamylated protein antibodies) were measured at baseline, 3 months and 12 months., Results: Dimensionality reduction using 38 cytokines and chemokines demonstrated four distinct clusters that differed significantly regarding the frequencies of remission defined by clinical composite measures and ultrasound evaluations. Prominent differences in IL-1β, IL-5, IL-7, IL-10, IFNγ, GRO, IP-10, MCP-1 and MIP-1β characterised the between-cluster differences. Two distinct groups made of four clusters showed a significant difference in IgM-anti-CCP2 positivity. The least absolute shrinkage and selection operator regression of 38 cytokines and chemokines for Clinical Disease Activity Index (CDAI) remission at 12 months resulted in the selection of MIP-1β. Logistic regression using baseline levels of anti-citrullinated protein antibody, IgM-anti-CCP2 positivity, the CDAI, the total power Doppler score, the cluster by cytokines and chemokines, MIP-1β, methotrexate dose and mechanisms of action revealed that cluster by cytokines and chemokines was the sole significant factor for CDAI remission at 12 months., Conclusions: Specific patterns of cytokines and chemokines-no other clinical factors and autoantibody profiles-were important to distinguish patients with RA achieving remission at 12 months., Trial Registration Number: UMIN000012524., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Nivolumab paved a new way in the treatment of patients with recurrent or metastatic (RM) head and neck squamous cell carcinoma (RM-HNSCC). However, the limited rates of long-term survivors (< 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and provides a biological clue to develop effective therapies for a majority of non-survivors., Methods: Pre-treatment plasmas ( N = 104) of RM-HNSCC patients were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment-naïve tumor and plasma samples ( N = 20) were assayed to elucidate biological implications of the PEX mRNA signature., Results: Assays for pre-treatment blood samples ( N = 104) demonstrated that a combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely distinguished non-survivors from >2-year survivors (2-year OS; 0% vs 57.7%; P = 0.000124) with a high hazard ratio of 2.878 (95% CI 1.639-5.055; P = 0.0002348). Parallel biological assays demonstrated that in the paired treatment-naïve HNSCC tumor and plasma samples ( N = 20), PEX HLA-E mRNA (a non-survivor-predicting marker) was positively corelated with overexpression of HLA-E protein ( P = 0.0191) and the dense population of tumor-infiltrating NK cells ( P = 0.024) in the corresponding tumor, suggesting that the HLA-E-NKG2A immune checkpoint may inhibit the antitumor effect of PD-1blockade., Conclusion: The PEX mRNA signature could be useful as a companion diagnostic of nivolumab. The combination of an anti-NKG2A antibody (i.e., monalizumab) and nivolumab may serve as a treatment option for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Sato, Toh, Murakami, Nakano, Hongo, Matsuo, Hashimoto, Sugasawa, Yamazaki, Ueki, Nakashima, Uryu, Ono, Umeno, Ueda, Kano, Tsukahara, Watanabe, Ota, Monden, Iwae, Maruo, Asada, Hanai, Sano, Ozawa, Asakage, Fukusumi and Masuda.)

Background and Purpose: A single-aspiration maneuver using a large-volume syringe is a common and effective technique for aspiration thrombectomy. Multiple aspiration cycles using large aspiration syringes have been proposed as a means to improve the efficacy over single aspiration. In this study, we sought to investigate the efficacy of a "triple aspiration technique" in which a large-volume syringe is cycled 3 times before catheter retraction during aspiration thrombectomy., Materials and Methods: A 3D-printed adult vasculature was used as a benchtop thrombectomy platform. Fibrin-rich and red blood cell-rich clots were prepared in centrifuge tubes using human plasma, red blood cells, and calcium chloride. Next, clots were placed in the carotid terminus of the model, and the performances of 3 different aspiration techniques-triple syringe, single syringe, and continuous pump aspiration-were compared in a randomized manner (1:1:1). Outcomes of interest included first-pass efficacy (FPE), complete clot removal (final modified TICI 2c/3), the number of thrombectomy attempts to achieve modified TICI 2c/3, vacuum pressure, and distal embolization. The distal emboli were detected using a 70-μm cell strainer placed at the outflow of the model and quantified using an image-processing algorithm. The vacuum pressures were measured using a pressure transducer., Results: A total of 102 replicates were performed, 34 for each technique. The triple-aspiration technique provided a significantly higher rate of FPE than the syringe and pump aspiration techniques (67.6% versus 41.1%, P = .02). Additionally, the triple-aspiration technique achieved complete clot removal with a significantly lower mean number of thrombectomy attempts compared with single-syringe aspiration (1.2 [SD, 0.5] versus 1.8 [SD, 0.8], P = .005). The triple-aspiration technique generated significantly higher mean vacuum pressure than both the single-syringe and vacuum pump aspiration (28.3 [SD, 0.2] versus 27.2 [SD, 0.3], P = .002 and 26.2 [SD, 0.4], P = .001, respectively). The differences in complete clot removal and distal embolization parameters were not statistically significantly different across the groups., Conclusions: Our findings suggest that the triple aspiration technique can improve FPE rates and vacuum pressure in aspiration thrombectomy. Further studies are needed to examine the safety and efficacy of triple aspiration in the clinical setting., (© 2025 by American Journal of Neuroradiology.)

Relapsing epiglottitis has rarely been reported, and its etiology is not well established. A 44-year-old previously healthy Japanese man presented with a quickly progressing choking sensation. He had been experiencing refractory and relapsing laryngeal edema and probably acute epiglottitis (three episodes within 2 weeks), with rash and elevated pancreatic amylase. The patient required immediate intubation. After the initial extubation, he required reintubation and a subsequent tracheostomy. Antibiotics, glucocorticoid, and antihistamines were administered, and he finally recovered with the tracheostomy's closure. Potential causes of this patient's relapsing epiglottitis are as follows: persistent right swollen tonsil; a positive result on a Mycoplasma pneumoniae antigen test and a particle agglutination (PA) test, implicating chronic tonsillitis; and/or Mycoplasma infection. This is the first case report of refractory and relapsing epiglottitis requiring reintubation possibly concurrent with chronic tonsillitis and Mycoplasma infection., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2025 Yutaka Tsukamoto et al. Case Reports in Medicine published by John Wiley & Sons Ltd.)

We herein report a case of Systemic Capillary Leak Syndrome (SCLS) attributed to coronavirus disease (COVID-19) that emerged in 2019. A 56-year-old woman presented with a COVID-19 infection 7 days prior to the visit with upper respiratory symptoms, fatigue, and decreased appetite. Secondary SCLS due to COVID-19 was diagnosed, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated as mechanical support, and intravenous immunoglobulin was administered, marking the transition to the recovery phase with the initiation of fluid resuscitation. This case is noteworthy for successfully employing VA-ECMO in treating secondary SCLS due to COVID-19, mimicking the course of fulminant myocarditis.

We present two patients with a history of paroxysmal atrial fibrillation who developed pulmonary vein stenosis (PVS) following atrial fibrillation (AF) ablation. Case 1 involved a female patient in her 50s who was asymptomatic for pulmonary symptoms but was found to have a high degree of left superior PVS 15 months after AF ablation. This was demonstrated using contrast-enhanced computed tomography (CE-CT) and supported by findings of perfusion defects on ventilation-perfusion (V/Q) scan. Case 2 was a male patient in his 60s who developed progressive left superior PVS nine months after AF ablation, evidenced by serial CE-CT and V/Q scans. PVS is a rare but well-known complication of pulmonary vein ablation for the treatment of AF that can lead to severe complications if left untreated. V/Q scans effectively assess the functional significance of PVS by detecting abnormal blood flow segments. Although a V/Q mismatch characterized by reduced perfusion defects is more commonly used in evaluating pulmonary embolism, PVS should not be disregarded as a differential diagnosis. Few studies emphasize the utility of V/Q scans in managing PVS and highlight V/Q mismatch as a notable finding. This case report aimed to highlight their significance., (© 2025 mums.ac.ir All rights reserved.)