Clinical presentation and treatment of 26 spinal epidural arteriovenous fistulas: a single-center experience.

BACKGROUND: Spinal epidural arteriovenous fistulas (SEDAVFs) are rarely diagnosed vascular malformations that can cause spinal cord compression and congestive myelopathy. METHODS: This is a single-center, retrospective case series of patients with SEDAVFs who underwent observation or treatment at UCLA medical center between 1993 and 2023. RESULTS: Between 1993 and 2023 a total of 26 patients at UCLA were found to have a SEDAVF. The median age at treatment was 59 years (range 4 months to 91 years). Compared with sacral, lumbar, and thoracic SEDAVFs, patients with cervical SEDAVF were younger (41 years vs 63 years, P=0.016) and more likely to be female (66.7% vs 14.3%, P=0.006). Possible triggers for development of SEDAVFs may be prior spinal surgery or trauma (n=4), turning the neck (n=1), lifting a heavy box (n=1), a prolonged period of bending over (n=1), and neurofibromatosis type 1 (n=1). Of the 22 patients treated endovascularly, 18 (82%) were angiographically cured on the first attempt without complications. One patient underwent surgical treatment alone and had a failed surgery on the first attempt, and developed a surgical site infection after the second successful attempt at treatment. Of the 16 patients with adequate clinical follow-up, 11 (69%) demonstrated early improved clinical outcome (eg, improved strength on examination, absent bruit). CONCLUSIONS: SEDAVFs are a rarely diagnosed disease that can be treated effectively and safely with endovascular embolization in most cases. Patients with sacral, lumbar, and thoracic SEDAVFs were older and more often male compared to patients with cervical SEDAVFs.

Expansion of CD4+ cytotoxic T lymphocytes with specific gene expression patterns may contribute to suppression of tumor immunity in oral squamous cell carcinoma: single-cell analysis and in vitro experiments.

Background: Cancer immunotherapy targeting CD8+ T cells has made remarkable progress, even for oral squamous cell carcinoma (OSCC), a heterogeneous epithelial tumor without a substantial increase in the overall survival rate over the past decade. However, the therapeutic effects remain limited due to therapy resistance. Thus, a more comprehensive understanding of the roles of CD4+ T cells and B cells is crucial for more robust development of cancer immunotherapy. Methods: In this study, we examined immune responses and effector functions of CD4+ T cells, CD8+ T cells and B cells infiltrating in OSCC lesions using single-cell RNA sequencing analysis, T cell receptor (TCR) and B cell receptor (BCR) repertoire sequencing analysis, and multi-color immunofluorescence staining. Finally, two Kaplan-Meier curves and several Cox proportional hazards models were constructed for the survival analysis. Results: We observed expansion of CD4+ cytotoxic T lymphocytes (CTLs) expressing granzymes, which are reported to induce cell apoptosis, with a unique gene expression patterns. CD4+ CTLs also expressed CXCL13, which is a B cell chemoattractant. Cell-cell communication analysis and multi-color immunofluorescence staining demonstrated potential interactions between CD4+ CTLs and B cells, particularly IgD- CD27- double negative (DN) B cells. Expansion of CD4+ CTLs, DN B cells, and their contacts has been reported in T and B cell-activated diseases, including IgG4-related disease and COVID-19. Notably, we observed upregulation of several inhibitory receptor genes including CTLA-4 in CD4+ CTLs, which possibly dampened T and B cell activity. We next demonstrated comprehensive delineation of the potential for CD8+ T cell differentiation towards dysfunctional states. Furthermore, prognostic analysis revealed unfavorable outcomes of patients with a high proportion of CD4+ CTLs in OSCC lesions. Conclusion: Our study provides a dynamic landscape of lymphocytes and demonstrates a systemic investigation of CD4+ CTL effects infiltrating into OSCC lesions, which may share some pathogenesis reported in severe T and B cell-activated diseases such as autoimmune and infectious diseases.

Hemostatic patch with ultra-strengthened mechanical properties for efficient adhesion to wet surfaces.

Controlling traumatic bleeding from damaged internal organs while effectively sealing the wound is critical for saving the lives of patients. Existing bioadhesives suffer from blood incompatibility, insufficient adhesion to wet surfaces, weak mechanical properties, and complex application procedures. Here, we engineered a ready-to-use hemostatic bioadhesive with ultra-strengthened mechanical properties and fatigue resistance, robust adhesion to wet tissues within a few seconds of gentle pressing, deformability to accommodate physiological function and action, and the ability to stop bleeding efficiently. The engineered hydrogel, which demonstrated high elasticity (>900%) and toughness (>4600 kJ/m3), was formed by fine-tuning a series of molecular interactions and crosslinking mechanisms involving N-hydroxysuccinimide (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe3+ ions. Dual adhesive moieties including mussel-inspired pyrogallol/catechol and NHS synergistically enhanced wet tissue adhesion (>400 kPa in a wound closure test). In conjunction with physical sealing, the high affinity of TA/Fe3+ for blood could further augment hemostasis. The engineered bioadhesive demonstrated excellent in vitro and in vivo biocompatibility as well as improved hemostatic efficacy as compared to commercial Surgicel®. Overall, the hydrogel design strategy described herein holds great promise for overcoming existing obstacles impeding clinical translation of engineered hemostatic bioadhesives.

Robotic Diagnostic Cerebral Angiography: A Multicenter Experience of 113 Patients.

BACKGROUND: Neurointerventional robotic systems have potential to reduce occupational radiation, improve procedural precision, and allow for future remote teleoperation. A limited number of single institution case reports and series have been published outlining the safety and feasibility of robot-assisted diagnostic cerebral angiography. METHODS: This is a multicenter, retrospective case series of patients undergoing diagnostic cerebral angiography at three separate institutions - University of California, Davis (UCD); University of California, Los Angeles (UCLA); and University of California, San Francisco (UCSF). The equipment used was the CorPath GRX Robotic System (Corindus, Waltham, MA). RESULTS: A total of 113 cases were analyzed who underwent robot-assisted diagnostic cerebral angiography from September 28, 2020 to October 27, 2022. There were no significant complications related to use of the robotic system including stroke, arterial dissection, bleeding, or pseudoaneurysm formation at the access site. Using the robotic system, 88 of 113 (77.9%) cases were completed successfully without unplanned manual conversion. The principal causes for unplanned manual conversion included challenging anatomy, technical difficulty with the bedside robotic cassette, and hubbing out of the robotic system due to limited working length. For robotic operation, average fluoroscopy time was 13.2 min (interquartile range (IQR), 9.3 to 16.8 min) and average cumulative air kerma was 975.8 mGY (IQR, 350.8 to 1073.5 mGy). CONCLUSIONS: Robotic cerebral angiography with the CorPath GRX Robotic System is safe and easily learned by novice users without much prior manual experience. However, there are technical limitations such as a short working length and an inability to support 0.035" wires which may limit its widespread adoption in clinical practice.

Extrafollicular IgD-CD27-CXCR5-CD11c- DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19.

Although therapeutic B cell depletion dramatically resolves inflammation in many diseases in which antibodies appear not to play a central role, distinct extrafollicular pathogenic B cell subsets that accumulate in disease lesions have hitherto not been identified. The circulating immunoglobulin D (IgD)-CD27-CXCR5-CD11c+ DN2 B cell subset has been previously studied in some autoimmune diseases. A distinct IgD-CD27-CXCR5-CD11c- DN3 B cell subset accumulates in the blood both in IgG4-related disease, an autoimmune disease in which inflammation and fibrosis can be reversed by B cell depletion, and in severe COVID-19. These DN3 B cells prominently accumulate in the end organs of IgG4-related disease and in lung lesions in COVID-19, and double-negative B cells prominently cluster with CD4+ T cells in these lesions. Extrafollicular DN3 B cells may participate in tissue inflammation and fibrosis in autoimmune fibrotic diseases, as well as in COVID-19.

Effect of Arginine Vasopressin on Intraoperative Hypotension Caused by Oral Administration of 5-Aminolevulinic Acid.

5-Aminolevulinic acid (5-ALA) is used for the photodynamic diagnosis of malignant tumors and has been effectively utilized to improve the complete resection rate and reduce the risk of tumor recurrence. However, intraoperative hypotension is a common adverse effect of oral 5-ALA, and it occasionally progresses to severe prolonged hypotension requiring high-dose catecholamine administration. We report a case of intraoperative hypotension due to oral 5-ALA in which arginine vasopressin (AVP) administration was effective for increasing the blood pressure. A 77-year-old man scheduled for a craniotomy for glioma was administered 5-ALA orally before surgery. After the induction of anesthesia, his blood pressure decreased substantially. Although we administered various vasopressor agents, hypotension was prolonged. However, after starting a continuous administration of AVP, the systolic blood pressure increased, and the hemodynamic parameters remained stable during the remainder of the operation. 5-ALA administration may lower blood pressure by inducing nitric oxide production, and AVP inhibits inducible nitric oxide synthase messenger RNA expression and interleukin-1ß-stimulated nitric oxide production. In light of these mechanisms, AVP may be a reasonable treatment agent for hypotension induced by 5-ALA.

Impact of ARUBA trial on trends and outcomes in symptomatic non-ruptured brain AVMs: A national sample analysis.

INTRODUCTION: The real-world evolution of management and outcomes of patients with unruptured brain arteriovenous malformations (AVMs) has not been well-delineated following the ARUBA trial findings of no general advantage of initial interventional (surgical/endovascular/radiotherapy) vs. initial conservative medical therapy. METHODS: We analyzed the National Inpatient Sample from 2009-2018, capturing 20% of all admissions in the U.S. Validated ICD-9 and -10 codes defined brain AVMs, comorbidities, and the use of interventional modalities. Analyses were performed by year and for the dichotomized periods of pre-ARUBA (2009-2013) vs. post-ARUBA (2014-2018). RESULTS: Among the national projected 88,037 AVM admissions, 72,812 (82.7%) were unruptured AVMs and 15,225 (17.3%) were ruptured AVMs. Among uAVMs, 51.4% admitted pre-ARUBA and 48.6% in post-ARUBA period. The post-ARUBA patients were mildly older (median age 53.3 vs. 51.8 (p = 0.001) and had more comorbidities including hypertension, diabetes, obesity, renal impairment, and smoking. Before the first platform report of ARUBA (2009-2012), rates of use of interventional treatments during uAVM admissions trended up from 31.8% to 35.4%. Thereafter, they declined significantly to 26.4% in 2018 (p = 0.02). The decline was driven by a reduction in the frequency of endovascular treatment from 18.8% to 13.9% and inpatient stereotactic radiosurgery from 0.5% to 0.1%. No change occurred in the frequency of microsurgery or combined endovascular and surgical approaches. Adjusted multivariable model of uAVMs showed increased odds of discharge to a long-term inpatient facility or in-hospital death [OR 1.14 (1.02-1.28), p = 0.020] in post-ARUBA. A significantly increased proportion of ruptured AVMs from 17.0% to 23.3% was observed consistently in post-ARUBA. CONCLUSION: Nationwide practice in the management of unruptured AVMs changed substantially with the publication of the ARUBA trial in a durable and increasing manner. Fewer admissions with the interventional treatment of unruptured AVMs occurred, and a corresponding increase in admission for ruptured AVMs transpired, as expected with a strategy of watchful waiting and treatment only after an index bleeding event. Further studies are needed to determine whether these trends can be considered to be ARUBA trial effect or are merely coincidental.

Interventional compared with medical management of symptomatic carotid web: A systematic review.

BACKGROUND: Carotid web (CaW) is non-atheromatous, shelf-like intraluminal projection, generally affecting the posterolateral wall of the proximal internal carotid artery, and associated with embolic stroke, particularly in younger patients without traditional stroke risk factors. Treatment options for symptomatic CaWs include interventional therapy with carotid endarterectomy or carotid stenting versus medical therapy with antiplatelet or anticoagulants. As safety and efficacy of these approaches have been incompletely delineated in small-to-moderate case series, we performed a systematic review of outcomes with interventional and medical management. METHODS: Systematic literature search was conducted and data analyzed per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) from January 2000 to October 2021 using the search strategy: "Carotid web" OR "Carotid shelf" OR "Web vessels" OR "Intraluminal web". Patient-level demographics, stroke risk factors, technical procedure details, medical and interventional management strategies were abstracted across 15 series. All data were analyzed using descriptive statistics. RESULTS: Among a total of symptomatic 282 CaW patients across 14 series, age was 49.5 (44-55.7) years, 61.7% were women, and 76.6% were black. Traditional stroke risk factors were less frequent than the other stroke causes, including hypertension in 28.6%, hyperlipidemia 14.6%, DM 7.0%, and smoking 19.8%. Thrombus adherent to CaW was detected on initial imaging in 16.2%. Among 289 symptomatic CaWs across 15 series, interventional management was pursued in 151 (52.2%), carotid artery stenting in 87, and carotid endarterectomy in 64; medical management was pursued in 138 (47.8%), including antiplatelet therapy in 80.4% and anticoagulants in 11.6%. Interventional and medical patients were similar in baseline characteristics. The reported time from index stroke to carotid revascularization was median 14 days (IQR 9.5-44). In the interventional group, no periprocedural mortality was noted, major periprocedural complications occurred in 1/151 (0.5%), and no recurrent ischemic events were observed over follow-up range of 3-60 months. In the medical group, over a follow-up of 2-55 months, the recurrence cerebral ischemia rate was 26.8%. CONCLUSION: Cumulative evidence from multiple series suggests that carotid revascularization is a safe and effective option for preventing recurrent ischemic events in patients with symptomatic carotid webs.

Distinct disease-specific Tfh cell populations in 2 different fibrotic diseases: IgG4-related disease and Kimura disease.

BACKGROUND: How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T-cell-dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs in patients with elevated tissue expression levels of IgE (Kimura disease, KD) and those of IgG4 (IgG4-related disease, IgG4-RD) can provide important insights regarding cytokine expression by Tfh cells. OBJECTIVE: We sought to identify disease-specific Tfh cell subsets in secondary and tertiary lymphoid organs expressing IL-10 or IL-13 and thus identify different cellular drivers of class switching in 2 distinct types of fibrotic disorders: allergic fibrosis (driven by type 2 immune cells) and inflammatory fibrosis (driven by cytotoxic T lymphocytes). METHODS: Single-cell RNA sequencing, in situ sequencing, and multicolor immunofluorescence analysis were used to investigate B cells, Tfh cells, and infiltrating type 2 cells in lesion tissues from patients with KD or IgG4-RD. RESULTS: Infiltrating Tfh cells in tertiary lymphoid organs from IgG4-RD were divided into 6 main clusters. We encountered abundant infiltrating IL-10-expressing LAG3+ Tfh cells in patients with IgG4-RD. Furthermore, we found that infiltrating AICDA+CD19+ B cells expressing IL-4, IL-10, and IL-21 receptors correlated with IgG4 expression. In contrast, we found that infiltrating IL-13-expressing Tfh cells were abundant in affected tissues from patients with KD. Moreover, we observed few infiltrating IL-13-expressing Tfh cells in tissues from patients with IgG4-RD, despite high serum levels of IgE (but low IgE in the disease lesions). Cytotoxic T cells were abundant in IgG4-RD; in contrast, type 2 immune cells were abundant in KD. CONCLUSIONS: Our analysis revealed a novel subset of IL-10+LAG3+ Tfh cells infiltrating the affected organs of IgG4-RD patients. In contrast, IL-13+ Tfh cells and type 2 immune cells infiltrated those of KD patients.

The "Bright Falx" Sign-Midline Embolic Penetration Is Associated With Faster Resolution of Chronic Subdural Hematoma After Middle Meningeal Artery Embolization: A Case Series.

BACKGROUND: Chronic subdural hematomas (CSDHs) are common in the elderly population and patients taking antiplatelet/anticoagulation medications. Middle meningeal artery (MMA) embolization has become an adjunctive treatment to observation and surgery. Despite many embolization techniques, best practices for optimal CSDH resolution remain unknown. OBJECTIVE: To report a retrospective case series of MMA embolization for CSDHs regarding rate of hematoma improvement and the significance of distal embolic penetration into the falx. METHODS: Retrospective chart review was performed on all patients who underwent MMA embolization for CSDHs between January 2017 and June 2021. Patient demographics, clinical presentation, anticoagulant use, and radiographic features were collected. Pre-embolization and postembolization computed tomography scans were analyzed for volumetric changes and assessed for midline penetration of embolic material in the falx. RESULTS: MMA embolization was performed in 37 patients and 53 hemispheres. Older patients took longer to obtain complete resolution of CSDHs (r = 0.47, P = .03). Patients with larger pre-embolization (r = 0.57, P = .007) and postembolization (r = 0.56, P = .008) CSDH volumes took longer to completely resolve. Patients who had n-butyl cyanoacrylate embolization with midline penetration, as evidenced by the "bright falx" sign, had faster improvement rates than those who did not (5.64 cm 3 /d vs 1.2 cm 3 /d, P = .02). CONCLUSION: Distal penetration of embolic material, particularly n-butyl cyanoacrylate, into the falx may lead to more rapid improvement of CSDH.