Endovascular retrieval of a migrated covered stent from the pulmonary artery.

Stent migration is a rare but significant complication following endovascular procedures. Techniques for managing dislodged stents have included surgical, endovascular, and conservative approaches. This case details a patient who had a covered stent placed within the left renal vein which later migrated to the pulmonary artery causing damage to the tricuspid valve. The migrated stent was successfully removed using a percutaneous endovascular approach utilizing fluoroscopy and transesophageal echocardiogram guidance.

A1-reprogrammed mesenchymal stromal cells prime potent antitumoral responses.

Mesenchymal stromal cells (MSCs) have been modified via genetic or pharmacological engineering into potent antigen-presenting cells-like capable of priming responding CD8 T cells. In this study, our screening of a variant library of Accum molecule revealed a molecule (A1) capable of eliciting antigen cross-presentation properties in MSCs. A1-reprogrammed MSCs (ARM) exhibited improved soluble antigen uptake and processing. Our comprehensive analysis, encompassing cross-presentation assays and molecular profiling, among other cellular investigations, elucidated A1's impact on endosomal escape, reactive oxygen species production, and cytokine secretion. By evaluating ARM-based cellular vaccine in mouse models of lymphoma and melanoma, we observe significant therapeutic potency, particularly in allogeneic setting and in combination with anti-PD-1 immune checkpoint inhibitor. Overall, this study introduces a strong target for developing an antigen-adaptable vaccination platform, capable of synergizing with immune checkpoint blockers to trigger tumor regression, supporting further investigation of ARMs as an effective and versatile anti-cancer vaccine.

An engineered Accum-E7 protein-based vaccine with dual anti-cervical cancer activity.

Worldwide prevalence of cervical cancer decreased significantly with the use of human papilloma virus (HPV)-targeted prophylactic vaccines. However, these multivalent antiviral vaccines are inert against established tumors, which leave patients with surgical ablative options possibly resulting in long-term reproductive complications and morbidity. In an attempt to bypass this unmet medical need, we designed a new E7 protein-based vaccine formulation using Accum™, a technology platform designed to promote endosome-to-cytosol escape as a means to enhance protein accumulation in target cells. Prophylactic vaccination of immunocompetent mice using the Accum-E7 vaccine (aE7) leads to complete protection from cervical cancer despite multiple challenges conducted with ascending C3.43 cellular doses (0.5-, 1.0-, and 2.0 × 106 cells). Moreover, the humoral response induced by aE7 was higher in magnitude compared with naked E7 protein vaccination and displayed potent inhibitory effects on C3.43 proliferation in vitro. When administered therapeutically to animals with pre-established C3.43 or Tal3 tumors, the vaccine-induced response synergized with multiple immune checkpoint blockers (anti-PD-1, anti-CTLA4, and anti-CD47) to effectively control tumor growth. Mechanistically, the observed therapeutic effect requires cross-presenting dendritic cells as well as CD8 T cells predominantly, with a non-negligible role played by both CD4+ and CD19+ lymphocytes. good laboratory practice (GLP) studies revealed that aE7 is immunogenic and well tolerated by immunocompetent mice with no observed adverse effects despite the use of a fourfold exceeding dose. In a nutshell, aE7 represents an ideal vaccine candidate for further clinical development as it uses a single engineered protein capable of exhibiting both prophylactic and therapeutic activity.

Interventional Radiology Approaches for Managing Postpancreatic Transplant Complications and Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-secreting beta cells in the pancreas, resulting in metabolic disturbances and long-term complications. While subcutaneous insulin remains the primary approach for achieving normoglycemia, pancreatic transplantation has emerged as an effective intervention for long-standing T1DM, providing insulin independence and normalized glycosylated hemoglobin levels. However, complications associated with pancreatic transplantation are frequent, necessitating thorough evaluation using diverse imaging modalities. This manuscript presents an overview of complications encountered with pancreatic transplantation, including vascular complications such as arterial and venous graft thrombosis, vessel stenosis, pseudoaneurysm, arterio-enteric fistula, and arteriovenous malformations. Additionally, the manuscript discusses other associated complications such as pancreatitis, pseudocyst formation, fistulas, pseudo-thrombosis of the iliac vein, post-transplantation lymphoproliferative disorder, and fluid collections. The integration of various imaging modalities plays a crucial role in diagnosing and managing these complications, with interventional radiologists assuming a vital role in employing image-guided procedures. Moreover, the manuscript explores pancreatic islet cell transplantation as a promising cellular-based therapy for T1DM, offering stable long-term glycemic control and decreased reliance on exogenous insulin in a significant proportion of recipients. This minimally invasive procedure involves the image-guided transcatheter infusion of islet cells obtained from deceased donors into the recipient's liver. The importance of interventional radiologists in managing complications related to pancreatic transplantation is underscored, with endovascular or image-guided approaches being utilized to address the diverse spectrum of encountered complications. Furthermore, the potential of islet cell transplantation as a minimally invasive alternative to traditional pancreatic transplantation is emphasized, as it offers the prospect of preventing many associated complications.

Transplant Hepatic Artery Complications.

Hepatic artery complications can be divided into 2 different categories, nonocclusive and steno-occlusive disease. Steno-occlusive disease is a collective term that encompasses hepatic artery thrombosis, hepatic artery stenosis, and hepatic arterial kinks, while nonocclusive arterial disease encompasses less than 5% of complications and is a collective term used to describe arteriovenous fistulae, pseudoaneurysms, arterial rupture and nonocclusive hepatic artery hypoperfusion syndrome. This article details the angiographic techniques and definitions needed to accurately diagnose arterial transplant complications and describes the technical aspects and results of endoluminal management of these arterial complications. In addition, this article discusses the presentation, etiology and indications for treatment, including surgical management of these various complications.

Persistent Bleeding after Coil Embolization of a Pancreatic Transplant Pseudoaneurysm: Should Covered Stents Be the Primary Management?

Life-threatening arterial complications after pancreatic transplantation can be dire. Pseudoaneurysms can be challenging to treat. There are multiple strategies to treat such complications. We present a case of pancreatic pseudoaneurysm which was initially treated by coiling followed by subsequent covered stent placement for a more durable outcome. We advocate for a "stent first" approach to these lesions if feasible.

CD146 Defines a Mesenchymal Stromal Cell Subpopulation with Enhanced Suppressive Properties.

Mesenchymal stromal cells (MSCs) are largely known for their immune-suppressive capacity, hence, their common use in the control of unwanted inflammation. However, novel concepts related to their biology, combined with the urgent need to identify MSC subpopulations with enhanced suppressive properties, drive the search for isolation protocols optimized for clinical applications. We show, in this study, that MSCs expressing high CD146 levels exhibit altered surface expression profiles of CD44 and secrete elevated levels of interleukin (IL)-6, amongst other factors. In addition, CD146hi MSCs surpass the polyclonal parental populations in inhibiting alloreactive T cells in vitro, in both a soluble- and cell-contact-dependent manner. Despite the lack of CD146hi MSC-mediated activation of peritoneal macrophages to release the suppressive factor IL-10 in vitro, their administration in animals with graft-versus-host disease alleviates inflammation and leads to 40% survival rate up to 7 weeks post-transplantation. This pronounced inhibitory property is driven by CD146-mediated in situ efferocytosis by myeloid cells. Altogether, this study provides the impetus to adopt an isolation protocol for MSCs based on a CD146 expression profile before their therapeutic use and suggests a major role played by CD146 as a novel "eat-me" signal, capable of enhancing MSC uptake by competent phagocytes.

LSD1 Inhibition Enhances the Immunogenicity of Mesenchymal Stromal Cells by Eliciting a dsRNA Stress Response.

Mesenchymal stromal cells (MSCs) are commonly known for their immune-suppressive abilities. However, our group provided evidence that it is possible to convert MSCs into potent antigen presenting cells (APCs) using either genetic engineering or pharmacological means. Given the capacity of UM171a to trigger APC-like function in MSCs, and the recent finding that this drug may modulate the epigenome by inhibiting the lysine-specific demethylase 1 (LSD1), we explored whether the direct pharmacological inhibition of LSD1 could instill APC-like functions in MSCs akin to UM171a. The treatment of MSCs with the LSD1 inhibitor tranylcypromine (TC) elicits a double-stranded (ds)RNA stress response along with its associated responsive elements, including pattern recognition receptors (PRRs), Type-I interferon (IFN), and IFN-stimulated genes (ISGs). The net outcome culminates in the enhanced expression of H2-Kb, and an increased stability of the cell surface peptide: MHCI complexes. As a result, TC-treated MSCs stimulate CD8 T-cell activation efficiently, and elicit potent anti-tumoral responses against the EG.7 T-cell lymphoma in the context of prophylactic vaccination. Altogether, our findings reveal a new pharmacological protocol whereby targeting LSD1 in MSCs elicits APC-like capabilities that could be easily exploited in the design of future MSC-based anti-cancer vaccines.

UM171A-induced ROS promote antigen cross-presentation of immunogenic peptides by bone marrow-derived mesenchymal stromal cells.

BACKGROUND: Mesenchymal stromal cells (MSCs) have been extensively used in the clinic due to their exquisite tissue repair capacity. However, they also hold promise in the field of cellular vaccination as they can behave as conditional antigen presenting cells in response to interferon (IFN)-gamma treatment under a specific treatment regimen. This suggests that the immune function of MSCs can be pharmacologically modulated. Given the capacity of the agonist pyrimido-indole derivative UM171a to trigger the expression of various antigen presentation-related genes in human hematopoietic progenitor cells, we explored the potential use of UM171a as a means to pharmacologically instill and/or promote antigen presentation by MSCs. METHODS: Besides completing a series of flow-cytometry-based phenotypic analyses, several functional antigen presentation assays were conducted using the SIINFEKL-specific T-cell clone B3Z. Anti-oxidants and electron transport chain inhibitors were also used to decipher UM171a's mode of action in MSCs. Finally, the potency of UM171a-treated MSCs was evaluated in the context of therapeutic vaccination using immunocompetent C57BL/6 mice with pre-established syngeneic EG.7T-cell lymphoma. RESULTS: Treatment of MSCs with UM171a triggered potent increase in H2-Kb cell surface levels along with the acquisition of antigen cross-presentation abilities. Mechanistically, such effects occurred in response to UM171a-mediated production of mitochondrial-derived reactive oxygen species as their neutralization using anti-oxidants or Antimycin-A mitigated MSCs' ability to cross-present antigens. Processing and presentation of the immunogenic ovalbumin-derived SIINFEKL peptide was caused by de novo expression of the Psmb8 gene in response to UM171a-triggered oxidative stress. When evaluated for their anti-tumoral properties in the context of therapeutic vaccination, UM171a-treated MSC administration to immunocompetent mice with pre-established T-cell lymphoma controlled tumor growth resulting in 40% survival without the need of additional supportive therapy and/or standard-of-care. CONCLUSIONS: Altogether, our findings reveal a new immune-related function for UM171a and clearly allude to a direct link between UM171a-mediated ROS induction and antigen cross-presentation by MSCs. The fact that UM171a treatment modulates MSCs to become antigen-presenting cells without the use of IFN-gamma opens-up a new line of investigation to search for additional agents capable of converting immune-suppressive MSCs to a cellular tool easily adaptable to vaccination.

Academic Radiology in the United States: Defining Gender Disparities in Faculty Leadership and Academic Rank.

RATIONALE AND OBJECTIVES: Female physicians in academic medicine have faced barriers that potentially affect representation in different fields and delay promotion. Little is known about gender representation differences in United States academic radiology departments, particularly within the most pursued subspecialties. PURPOSE: To determine whether gender differences exist in United States academic radiology departments across seven subspecialties with respect to academic ranks, departmental leadership positions, experience, and scholarly metrics. MATERIALS AND METHODS: In this cross-sectional study from November 2018 to June 2020, a database of United States academic radiologists at 129 academic departments in seven subspecialties was created. Each radiologist's academic rank, departmental leadership position (executive-level - Chair, Director, Chief, and Department or Division Head vs vice-level - vice, assistant, or associate positions of executive level), self-identified gender, years in practice, and measures of scholarly productivity (number of publications, citations, and h-index) were compiled from institutional websites, Doximity, LinkedIn, Scopus, and official NPI profiles. The primary outcome, gender composition differences in these cohorts, was analyzed using Chi2 while continuous data were analyzed using Kruskal-Wallis rank sum test. The adjusted gender difference for all factors was determined using a multivariate logistic regression model. RESULTS: Overall, 5086 academic radiologists (34.7% women) with a median 14 years of practice (YOP) were identified and indexed. There were 919 full professors (26.1% women, p < 0.01) and 1055 executive-level leadership faculty (30.6% women, p < 0.01). Within all subspecialties except breast imaging, women were in the minority (35.4% abdominal, 79.1% breast, 12.1% interventional, 27.5% musculoskeletal, 22.8% neuroradiology, 45.1% pediatric, and 19.5% nuclear; p < 0.01). Relative to subspecialty gender composition, women full professors were underrepresented in abdominal, pediatric, and nuclear radiology (p < 0.05) and women in any executive-level leadership were underrepresented in abdominal and nuclear radiology (p < 0.05). However, after adjusting for h-index and YOP, gender did not influence rates of professorship or executive leadership. The strongest single predictors for professorship or executive leadership were h-index and YOP. CONCLUSION: Women academic radiologists in the United States are underrepresented among senior faculty members despite having similar levels of experience as men. Gender disparities regarding the expected number of women senior faculty members relative to individual subspecialty gender composition were more pronounced in abdominal and nuclear radiology, and less pronounced in breast and neuroradiology. Overall, h-index and YOP were the strongest predictors for full-professorship and executive leadership among faculty. KEY RESULTS: ● Though women comprise 34.7% of all academic radiologists, women are underrepresented among senior faculty members (26.1% of full professors and 30.6% of executive leadership) ● Women in junior faculty positions had higher median years of practice than their male counterparts (10 vs 8 for assistant professors, 21 vs 13 for vice leadership) ● Years of practice and h-index were the strongest predictors for full professorship and executive leadership.

Perspective on the New IR Residency Selection Process: 4-year Experience at a Large, Collaborative Training Program.

Interventional Radiology (IR) was officially approved by the American Board of Medical Specialties in 2012 and the Accreditation Council of Graduate Medical Education as a unique, integrated residency in 2014. Its establishment and distinction from diagnostic radiology was compelled by the increasing emphasis on clinical care delivery by IRs. The shift in the IR training paradigm, as exemplified in the Integrated IR residency programs, appeals to a distinct cohort of applicants, prompting the need to re-evaluate the recruitment and selection process. This article discusses selection criteria for identifying ideal candidates for the new IR training model (focusing on Integrated IR residency training), highlights the importance of collaboration between the IR and DR selection committees, and illustrates the changes made at a single institution over the course of 4 selection cycles prior to the COVID-19 pandemic as well as significant changes in the current climate of the global pandemic.

Issues Most Pressing to Early-Career Interventional Radiologists: Results of a Descriptive Survey.

PURPOSE: To determine demographics, practice patterns, needs from Society of Interventional Radiology (SIR), and preferences of interventional radiologists (IRs) early in their careers. METHODS: A 28-question descriptive survey was used to identify demographic and practice composition, practice issues, and needs of early career IRs. The survey was distributed to SIR members in the United States (US) (n = 859) within the first 8 years of practice, with 213 respondents (25%). RESULTS: Respondents were primarily male (n = 181, 87%), less than 40 years old (n = 156, 73%), in practice for 6 years or less (n = 167, 79%), and satisfied with IR as a career (n = 183, 92.4%). The majority were in academic practice (n = 89, 43.2%) or large private practice group (n = 67, 32.5%). Most respondents read diagnostic imaging daily or weekly (n = 130, 61%). The majority of respondents perform complex procedures regularly including transarterial tumor therapy, percutaneous tumor ablation, peripheral arterial interventions, and biliary interventions monthly. Many respondents (n = 49, 23%) have changed jobs at least once citing career advancement, practice issues/disagreements, or compensation as reason. Most respondents would serve as mentors (n = 170, 80%) for trainees and were satisfied with their career mentorship (n = 166, 78%). Respondents felt that mentorship, identification of barriers facing early career IRs, and networking should be the most important functions of the Early Career Section (ECS)of the SIR. CONCLUSION: As nearly all survey respondents indicated that early career IRs have different needs and priorities than established physicians, they felt that mentorship, identification of barriers facing early career IRs, and networking should be the most important functions of the ECS. Additionally, this same group of IRs report low comfort with the business side of medicine and may benefit from directed content provided by the SIR ECS.

AGA Clinical Practice Update on Management of Bleeding Gastric Varices: Expert Review.

Management of bleeding gastric varices (GV) presents a unique challenge for patients with portal hypertension. Despite over thirty years of diagnostic and treatment advances standardized practices for bleeding GV are lacking and unsupported by adequate evidence. There are no definitive natural history studies to help with risk assessment or prospective clinical trials to guide clinical decision making. Available literature on the natural history and management of gastric varices consists of case series, restricted cohort studies, and a few small randomized trials, all of which have significant selection biases. This review summarizes the available data and recommendations based on expert opinion on how best to diagnose and manage bleeding from gastric varices. Table 1 summarizes our recommendations.

Lymphatic Anatomy and Physiology.

Lymphatics have long been overshadowed by the remainder of the circulatory system. Historically, lymphatics were difficult to study because of their small and indistinct vessels, colorless fluid contents, and limited effective interventions. However, the past several decades have brought increased funding, advanced imaging technologies, and novel interventional techniques to the field. Understanding the history of lymphatic anatomy and physiology is vital to further realize the role lymphatics play in most major disease pathologies and innovate interventional solutions for them.

Traumatic Chylothorax: Approach and Outcomes.

Traumatic chylothorax occurs more often now than in historic reports. In part, this is due to the increased ability to perform more advanced and aggressive thoracic resections and cardiovascular surgeries as well as the improved mortality of cancer patients. If untreated, chylothorax can result in significant morbidity and mortality, particularly in patients with underlying malignancy. Thoracic duct embolization for chylothorax was the first successful lymphatic intervention and has been performed for over 20 years. An overview of the clinical and technical approach to thoracic duct embolization for traumatic chylothorax is presented in addition to a review of outcomes.

Smartphone Augmented Reality CT-Based Platform for Needle Insertion Guidance: A Phantom Study.

OBJECTIVE: To develop and assess the accuracy of an augmented reality (AR) needle guidance smartphone application. METHODS: A needle guidance AR smartphone application was developed using Unity and Vuforia SDK platforms, enabling real-time displays of planned and actual needle trajectories. To assess the application's accuracy in a phantom, eleven operators (including interventional radiologists, non-interventional radiology physicians, and non-physicians) performed single-pass needle insertions using AR guidance (n = 8) and CT-guided freehand (n = 8). Placement errors were measured on post-placement CT scans. Two interventional radiologists then used AR guidance (n = 3) and CT-guided freehand (n = 3) to navigate needles to within 5 mm of targets with intermediate CT scans permitted to mimic clinical use. The total time and number of intermediate CT scans required for successful navigation were recorded. RESULTS: In the first experiment, the average operator insertion error for AR-guided needles was 78% less than that for CT-guided freehand (2.69 ± 2.61 mm vs. 12.51 ± 8.39 mm, respectively, p < 0.001). In the task-based experiment, interventional radiologists achieved successful needle insertions on each first attempt when using AR guidance, thereby eliminating the need for intraoperative CT scans. This contrasted with 2 ± 0.9 intermediate CT scans when using CT-guided freehand. Additionally, average procedural times were reduced from 13.1 ± 6.6 min with CT-guided freehand to 4.5 ± 1.3 min with AR guidance, reflecting a 66% reduction. CONCLUSIONS: All operators exhibited superior needle insertion accuracy when using the smartphone-based AR guidance application compared to CT-guided freehand. This AR platform can potentially facilitate percutaneous biopsies and ablations by improving needle insertion accuracy, expediting procedural times, and reducing radiation exposures.

Transvenous Biopsy in the Diagnosis of Intravascular or Perivascular Neoplasm: A Single-Center Retrospective Analysis of 36 Patients.

Between September 2008 and August 2017, 36 patients (mean age 56 y; range, 30-89 y) underwent transvenous biopsy of suspected tumor thrombus or perivascular tumor. Intravascular biopsy was pursued because of inaccessible percutaneous access in 9 patients (25%) and as part of a planned revascularization procedure in 27 patients (75%). Histopathologic results showed malignancy in 26 patients (72%) and benign etiologies in 10 patients (28%). No patients required repeat biopsy. There were no complications related to the biopsy procedure. The present series suggests that transvenous biopsy is a safe and accurate method of intravascular and perivascular mass tissue sampling.

Establishing a Surgical Preliminary Year in the IR Residency: Keys to Success.

The training paradigm of the interventional radiologist has quickly evolved with the approval of the integrated interventional radiology (IR) residency by the American Board of Medical Specialties and the Accreditation Council of Graduate Medical Education. Prior to appointment in an integrated IR program, a resident must complete a preliminary clinical year, which may be surgical, medical, or transitional. The unique procedural- and clinical-based skillset required of the IR resident is best aligned with a surgical preliminary year. The following is a review of the steps to successful creation of a surgical preliminary year based on a single institution's experience.