Immunotherapy and Transarterial Radioembolization Combination Treatment for Advanced Hepatocellular Carcinoma.

INTRODUCTION: The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in preclinical and early-phase trials, but these were limited by small sample sizes. We sought to compare the efficacy of combined therapy and immunotherapy alone in patients with advanced hepatocellular carcinoma (HCC). METHODS: The National Cancer Database was used to identify patients with advanced HCC diagnosed between January 1, 2017, and December 31, 2019. We included patients who received combined therapy or immunotherapy alone as first-line treatment. Multivariable logistic regression was conducted to determine predictors of combined therapy. Kaplan-Meier and Cox regression approaches were used to identify predictors of overall survival and to compare hazards of mortality between the patients who received combined therapy and immunotherapy alone. RESULTS: Of 1,664 eligible patients with advanced-stage HCC, 142 received combined TARE/immunotherapy and 1,522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanic and Black individuals). The median overall survival was significantly higher in the combination group than in the immunotherapy alone group (19.8 vs 9.5 months). In multivariable analysis, combined therapy was independently associated with reduced mortality (adjusted hazard ratio 0.50, 95% confidence interval: 0.36-0.68, P < 0.001). Results were consistent across subgroups and in sensitivity analyses using propensity score matching and inverse probability of treatment weighting. DISCUSSION: The combination of TARE and immunotherapy was associated with improved survival compared with immunotherapy alone in patients with advanced-stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients.

Inferior Vena Cava Filters: When to Place and When to Remove.

Pulmonary embolism (PE) is a common and feared result of deep vein thrombosis. While anticoagulation is the mainstay of management, interruption of flow of thrombus from leg veins to the pulmonary circulation is frequently desired either in lieu of or in addition to anticoagulation. Inferior vena cava filters have become frequently used to prevent PE despite a paucity of evidence for efficacy and increasing concerns about the long-term complications of indwelling filters.

Amanita Mushroom Toxin Poisoning in Los Angeles County.

Mushroom (amatoxin) poisoning from ingestion is a rare but life-threatening medical emergency characterized by gastrointestinal symptoms before progression to multisystem organ failure in severe cases. Many therapies of amatoxin intoxication have been described, including supportive care, medical therapies, detoxification strategies, and liver transplant. The evidence supporting these therapies remains limited due to the rarity of amatoxin poisoning and challenge of a timely diagnosis. We report a case of amatoxin poisoning in Los Angeles causing severe liver injury without acute liver failure treated successfully using medical therapies, gallbladder drainage, and plasma exchange.

Correction to: Amanita Mushroom Toxin Poisoning in Los Angeles County.

[This corrects the article DOI: 10.14309/crj.0000000000001246.].

Long term recovery of right ventricular function after treatment of intermediate and high risk pulmonary emboli.

INTRODUCTION: Pulmonary embolism (PE) is a common and significant source of mortality and morbidity worldwide. A subset of patients with PE, particularly those who have intermediate and high risk events, are at increased risk for long-term right ventricular (RV) dysfunction; however, the impact of novel advanced therapies used for acute PE, including catheter-directed intervention, on long-term RV function remains uncertain. We sought to determine whether use of advanced therapies (catheter-directed intervention or systemic thrombolysis) is associated with improved long-term RV function. MATERIALS AND METHODS: Retrospective, single-center cohort study of adult (≥18 year old) patients admitted and discharged alive with a diagnosis of acute PE, who fell under the category of intermediate or high risk, with available follow-up echocardiograms at least 6 months after the index, seen at a single quaternary referral center in Los Angeles, CA between 2012 and 2021. RESULTS: There were 113 patients in this study (58 (51.3 %) treated with anticoagulation alone, 12 (10.6 %) treated with systemic thrombolysis, and 43 (38.1 %) treated with catheter-directed intervention), with approximately equal gender and racial distribution. Patients treated with advanced therapies were significantly more likely to have moderate-severe RV dysfunction (100 % for those treated with thrombolysis, 88.3 % for those treated with catheter-directed intervention, vs 55.2 % for those treated with anticoagulation alone; p < 0.001). At a follow-up of about 1.5 years, patients treated with advanced therapy (systemic thrombolysis or catheter-directed intervention) were more likely to have normalization of RV function (93-100 % vs 81 % for anticoagulation alone, p = 0.04). The subgroup of patients with intermediate-risk PE was significantly more likely to have normalization of RV function (95.6 % vs 80.4 % for anticoagulation alone, p = 0.03). Use of advanced therapy was not associated with substantial short-term adverse events among patients who survived to hospital discharge. CONCLUSION: Patients with intermediate and high risk PE were more likely to have recovery in RV function long-term if treated with catheter-directed intervention or systemic thrombolysis, as compared to anticoagulation alone, without substantial safety issues, despite having worse RV function at baseline. Further data is needed to verify this observation.

Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3.

Structural data of integrin alphaIIbbeta3 have been interpreted as supporting a model in which: 1) the receptor exists primarily in a "bent," low affinity conformation on unactivated platelets and 2) activation induces an extended, high affinity conformation prior to, or following, ligand binding. Previous studies found that "clasping" the alphaIIb head domain to the beta3 tail decreased fibrinogen binding. To study the role of alphaIIb extension about the genu, we introduced a disulfide "clamp" between the alphaIIb thigh and calf-1 domains. Clamped alphaIIbbeta3 had markedly reduced ability to bind the large soluble ligands fibrinogen and PAC-1 when activated with monoclonal antibody (mAb) PT25-2 but not when activated by Mn(2+) or by coexpressing the clamped alphaIIb with a beta3 subunit containing the activating mutation N339S. The clamp had little effect on the binding of the snake venom kistrin (M(r) 7,500) or alphaIIbbeta3-mediated adhesion to immobilized fibrinogen, but it did diminish the enhanced binding of mAb AP5 in the presence of kistrin. Collectively, our studies support a role for alphaIIb extension about the genu in the binding of ligands of 340,000 and 900,000 M(r) with mAb-induced activation but indicate that it is not an absolute requirement. Our data are consistent with alphaIIb extension resulting in increased access to the ligand-binding site and/or facilitating the conformational change(s) in beta3 that affect the intrinsic affinity of the binding pocket for ligand.

Milestones in magnetic resonance imaging and transcranial sonography of movement disorders.

Twenty-five years ago, when this journal was initiated, imaging of movement disorders was in its infancy. Since that time, magnetic resonance imaging has become a standard technique that is routinely performed in patients with movement disorders in order to exclude secondary causes and in some instances to provide specific information that aids in making the diagnosis of a neurodegenerative condition. Transcranial sonography is a more recent advance and is now widely employed to aid in the diagnosis of Parkinson's disease and possibly in detecting individuals in the premotor phases of the disease. Investigations are currently under way to evaluate the value of this technique in other movement disorders.

Effect of scheduling inferior vena cava filter removal during the placement encounter on filter removal rate.

OBJECTIVE: In the present study, we sought to determine whether early pre-emptive scheduling of inferior vena cava filter (IVCF) removal during the preoperative IVCF placement visit would affect the IVCF removal rate. METHODS: All electronically documented IVCF placements at a single institution were reviewed from April 2015 to July 2019. The baseline characteristics included age, the clinical indications for IVCF placement, inpatient/outpatient status, and type of IVCF placed. Statistical analysis was performed using the χ2 for discrete variables and the two-tailed paired t test for continuous variables. RESULTS: A total of 599 patients (mean age, 68 years; 273 women and 326 men) had undergone technically successful IVCF placement. During the preoperative consent process for placement, 232 patients had been scheduled for IVCF removal within 3 months after placement. However, 367 patients had not been scheduled for removal at the preoperative consent process. The indications for placement included failure of anticoagulation, a contraindication to anticoagulation (eg, bleeding), preoperative prophylaxis, and others. Of the 232 patients scheduled for IVCF removal during preoperative consent for IVCF placement, 103 (44%) had undergone successful IVCF removal (mean interval from placement, 107 ± 100 days). Of the 367 nonscheduled patients, 89 (24%) had undergone successful IVCF removal (mean time, 184 ± 215 days). We found a significant improvement in the IVCF removal rate between the scheduled and nonscheduled patients (P < .0001). Three patients (all from the scheduled group) had a clot burden within the IVCF, which meant they were inappropriate for removal. These patients were rescheduled and had eventually undergone uncomplicated removal. CONCLUSIONS: Scheduling IVCF removal during the placement encounter significantly increased the IVCF removal rate. This approach could be a viable option for institutions where clinic time and/or resources are limited or unavailable and for patients who have difficulty traveling for clinical evaluations.

Treatment of pulmonary arteriovenous malformations: clinical experience using different embolization strategies.

PURPOSE: To evaluate embolization efficacy of pulmonary arteriovenous malformations (PAVM) using Amplatzer vascular plugs (AVP) and coils. MATERIALS AND METHODS: Eighty-eight embolized simple PAVMs in 38 patients were retrospectively analyzed by follow-up CT. Mean age was 50.2 ± 15.6 years and 22 (57.9%) patients were females. Mean follow-up interval was 38.2 ± 28.4 months (median 29.9 months). Embolization devices included AVP I, AVP II, AVP 4, and coils. Technical success was defined as no visualization of an early draining vein at angiography after embolization. Treatment success was defined as complete disappearance or decrease in size of the venous aneurysm ≥ 70% at follow-up CT. RESULTS: Technical success rate was 100% and treatment success rate evaluated by CT for the various embolization strategies was 100% for AVP I (n = 6), 100% for AVP I + coils (n = 5), 83.3% for AVP II (n = 6), 40.0% for AVP II + coils (n = 5), 87.5% for AVP 4 (n = 8), 50.0% for AVP 4 + coils (n = 8), and 78.0% for coils alone (n = 50). No statistically significant difference in embolization efficacy was seen between different devices (P = 0.083). Although not statistically significant, combination use of coils with AVPs demonstrated lower rates of clinical embolization success (P = 0.053). CONCLUSION: Embolization of PAVMs demonstrated high technical and treatment success rates with available embolic devices. No significant statistical differences were demonstrated between AVPs. However, the need for both coils and AVPs may suggest a more complicated underlying lesion at risk for recurrence.

The Role of Inferior Vena Cava Filters in Pulmonary Embolism.

Pulmonary embolism (PE) is a cause of significant morbidity and mortality, with an estimated 600,000 cases of clinically significant PE in the United States annually, and roughly 200,000 deaths per annum directly attributable to PE. By far the most frequent cause of PE is deep vein thrombosis originating in the lower extremities, which travels to the pulmonary vasculature. The mainstay of treatment is anticoagulation, but multiple additional treatments exist for patients in whom anticoagulation is inadequate or contraindicated. The absolute indications for inferior vena cava (IVC) filtration are narrow, but many filters are placed in patients with relative indications. There is growing concern for overuse of IVC filters, with a relatively low rate of retrieval. It is essential for interventional radiologists to understand the appropriate and correct use and retrieval of IVC filters. Familiarity with placement techniques, protocols and techniques for retrieval, current and emerging technologies, and the clinical model for management of venous thromboembolism, will ensure that interventional radiologists remain an integral member of the care team for these often complex patients.

Needs-Based Innovation in Interventional Radiology: The Biodesign Process.

There are many possible mechanisms for innovation and bringing new technology into the marketplace. The Stanford Biodesign innovation process is based in a deep understanding of clinical unmet needs as the basis for focused ideation and development. By identifying and vetting a compelling unmet need, the aspiring innovator can "derisk" a project and maximize chances for successful development in an increasingly challenging regulatory and economic environment. As a specialty founded by tinkerers, with a history of disruptive innovation that has yielded countless new ways of delivering care with minimal invasiveness, lower morbidity, and lower cost, interventional radiologists are uniquely well positioned to identify unmet needs and develop novel solutions free of dogmatic convention.

Alternative Aortic Access: Translumbar, Transapical, Subclavian, Conduit, and Transvenous Access to the Aorta.

Large-caliber access to the arterial system is more frequently required in the age of thoracic endovascular aneurysm repair, endovascular aneurysm repair, and transaortic valve implantation. Frequently either anatomical or vessel size constraints preclude use of common access points such as the common femoral, radial, and brachial arteries. Alternative approaches include percutaneous access at alternate sites (subclavian, axillary, and carotid), open surgical access to the heart (left ventricular apex), open surgical access to large-caliber vessels (ascending aorta, subclavian, and axillary arteries, retroperitoneal access to the iliac artery or distal aorta), and novel percutaneous approaches (transvenous). Such approaches require additional skill sets, equipment, and, frequently, multidisciplinary teams to ensure safety and success. The techniques and approaches outlined in this article may allow expansion of endovascular treatments to greater patient populations and disease states than previously thought feasible.