The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)

Endovascular Use of Cyanoacrylate-Lipiodol Mixture for Peripheral Embolization: Properties, Techniques, Pitfalls, and Applications

International audienceEndovascular embolization agents are particles and fluids that can be released into the bloodstream through a catheter to mechanically and/or biologically occlude a target vessel, either temporarily or permanently. Vascular embolization agents are available as solids, liquids, and suspensions. Although liquid adhesives (glues) have been used as embolic agents for decades, experience with them for peripheral applications is generally limited. Cyanoacrylates are the main liquid adhesives used for endovascular interventions and have a major role in managing vascular abnormalities, bleeding, and many vascular diseases. They can only be injected as a mixture with ethiodized oil, which provides radiopacity and modulates the polymerization rate. This review describes the characteristics, properties, mechanisms of action, modalities of use, and indications of the cyanoacrylate-Lipiodol® combination for peripheral embolization

Prostate Artery Embolization Using N-Butyl Cyanoacrylate Glue for Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: A Valid Alternative to Microparticles?

International audienceOur goal was to evaluate the feasibility, safety, and short-term outcomes of prostate artery embolization (PAE) with N-butyl cyanoacrylate (NBCA) glue as the only embolic agent in patients with benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTSs). A two-center retrospective study of 50 patients (mean age, 67.6 ± 7.4 years; range, 54–85 years) treated with NBCA between 2017 and 2020 was conducted. PAE was performed using a mixture of Glubran 2 glue and Lipiodol in a 1:8 ratio, under local anesthesia, on an outpatient basis, after cone-beam computed tomography vascular mapping. Mean total injected NBCA/Lipiodol volume was 0.9 ± 0.3 mL, total injection time was 21.9 ± 7.8 s, and total radiation dose was 18,458 ± 16,397 mGy·cm. Statistically significant improvements over time occurred for the International Prostate Symptoms Score (9.9 ± 6.8 versus 20.5 ± 6.7, p = 0.0001), quality-of-life score (2.2 ± 1.5 versus 4.9 ± 1.0, p = 0.0001), prostate-specific antigen level (4.6 ± 3.0 versus 6.4 ± 3.7, p = 0.0001), and prostate volume (77.3 ± 30.5 versus 98.3 ± 40.2, p = 0.0001) at a median of 3 months versus baseline. Minor adverse events developed in 11/50 (22%) patients, but no major complications occurred. The International Index of Erectile Function did not change significantly. PAE with NBCA is feasible, safe, fast, and effective for patients with BPH-related LUTSs. Prospective comparative studies with longer follow-ups are warranted

Packing Technique with or without Remodeling for Endovascular Coil Embolization of Renal Artery Aneurysms: Safety, Efficacy and Mid-Term Outcomes

International audienc

Selective Arterial Embolization of Renal Angiomyolipomas with a N-Butyl Cyanoacrylate-Lipiodol Mixture: Efficacy, Safety, Short- and Mid-Term Outcomes

International audienceSelective arterial embolization (SAE) for renal angiomyolipoma (rAML) is effective to treat or prevent bleeding. We report our experience using a cyanoacrylate–Lipiodol mixture. We performed a single-center retrospective review of all rAMLs embolized with cyanoacrylate glue between July 2014 and June 2020. Demographics, tuberous sclerosis complex (TSC) status, clinical presentation, angiography features, and follow-up data were recorded. Pre- and post-procedure rAML sizes and volumes were estimated from computed tomography (CT) or magnetic resonance imaging (MRI) studies. Kidney function was assessed before and after the procedure. We identified 24 patients (22 females and 2 males, mean age 51 years) treated for 27 AMLs, either prophylactically (n = 20) or as an emergency (n = 4). Technical success was achieved for 25/27 AMLs; two patients, each with a single AML, required nephrectomy and repeated embolization, respectively. Major complications occurred in three patients and minor complications such as postembolization syndrome in 15 patients. AML volume reduction after embolization was 55.1% after a mean follow-up of 15 months (range, 1–72 months). Factors associated with greater volume reduction were a smaller percentage of fat (p = 0.001), larger initial rAML volume (p = 0.014), and longer follow-up (p = 0.0001). The mean creatinine level did not change after SAE. Embolization of rAMLs with a mixture of cyanoacrylate and Lipiodol is feasible, safe, and effective in significantly decreasing tumor volume

Safety, Efficacy, and Outcomes of N-Butyl Cyanoacrylate Glue Injection through the Endoscopic or Radiologic Route for Variceal Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis

International audienceWe performed a systematic review and meta-analysis of published studies to assess the efficacy, safety, and outcomes of N-butyl cyanoacrylate (NBCA) injection for the treatment of variceal gastrointestinal bleeding (GIB). The MEDLINE/PubMed, EMBASE, and SCOPUS databases were searched for English-language studies published from January 1980 to December 2019 and including patients who had injection of NBCA for variceal GIB. Two independent reviewers extracted and evaluated the data from eligible studies. Exclusion criteria were sample size < 5, article reporting the use of NBCA with other embolic agents, no extractable data, and duplicate reports. NBCA was injected during endoscopy in 42 studies and through a direct percutaneous approach for stomal varices in 1 study. The study’s endpoints were: Technical success, 30-day rebleeding, and 30-day overall and major complications. The estimated overall rates were computed with 95% confidence intervals, based on each study rate, weighted by the number of patients involved in each study. In total, 43 studies with 3484 patients were included. The technical success rate was 94.1% (95% CI: 91.6–96.1%), the 30-day rebleeding rate was 24.2% (18.9–29.9%), and 30-day overall and major complications occurred in 15.9% (11.2–21.3%) and 5.3% (3.3–7.8%) of patients, respectively. For treating variceal GIB, NBCA injection is a safe and effective method that demonstrates high technical success rate and very low major complication rate

Selective Arterial Embolization with N-Butyl Cyanoacrylate Prior to CT-Guided Percutaneous Cryoablation of Kidney Malignancies: A Single-Center Experience

International audienceThe study’s purpose was to assess the safety, feasibility and efficiency of selective arterial embolization (SAE) using N-butyl cyanoacrylate (NBCA) glue before percutaneous cryoablation (PCA) of renal malignancies in patients whose tumor characteristics and/or comorbidities resulted in an unacceptable risk of bleeding. In this single-center retrospective study of 19 consecutive high-risk patients (median age, 74 years) with renal malignancies managed in 2017–2020 by SAE with NBCA followed by PCA, data about patients, tumor and procedures characteristics, complications, renal function and hemoglobin concentration before and after treatment, as well as recurrence were collected. Charlson comorbidity index was ≥4 in 89.5% of patients. Ten patients were treated by antiplatelet and/or anticoagulant therapy. Median tumor largest diameter was 3.75 cm (range, 1–6.5 cm) and R.E.N.A.L. nephrometry score was ≥7 in 80%, indicating substantial tumor complexity. No major complications were recorded and minor complications occurred in 7 patients. No residual tumor was found at 6-week imaging follow-up in 18/19 patients. Tumor recurrence was visible in 1/16 patients at 6-month imaging follow-up. No significant difference was found for renal function after treatment (p = 0.07), whereas significant decrease in hemoglobin concentration was noted (p = 0.00004), although it was relevant for only one patient who required only blood transfusion and no further intervention. SAE prior to PCA is safe and effective for managing renal malignancies in high-risk patients

Bleomycin for Percutaneous Sclerotherapy of Venous and Lymphatic Malformations: A Retrospective Study of Safety, Efficacy and Mid-Term Outcomes in 26 Patients

International audiencePercutaneous sclerotherapy is used to treat venous and lymphatic vascular malformations, which can cause significant discomfort and/or disfigurement. The purpose of this study is to describe the bleomycin sclerotherapy technique and to evaluate its clinical and radiological efficacy and safety. We retrospectively identified consecutive patients with venous malformations (VMs) and lymphatic malformations (LMs) who underwent bleomycin sclerotherapy in 2011–2020 at our institution. We collected the clinical and radiological success rates, complications and recurrences separately in the VM and LM groups. We identified 26 patients, 15 with VMs and 11 with LMs. The significant volume reductions obtained were 45% in the VM group and 76% in the LM group (p = 0.003 and p = 0.009, respectively). Significant reductions in discomfort/pain and in cosmetic disfigurement were obtained in both groups. An overall improvement was reported by 69% and 82% of patients in the VM and LM groups, respectively. No major complications occurred during the mean follow-up of 51 ± 34 months in the VM group and 29 ± 18 months in the LM group. A recurrence developed within 2 years in 23% of patients. Bleomycin is clinically and radiologically effective for the treatment of venous and lymphatic malformations, with a high level of patient safety

Efficacy, safety and outcomes of transcatheter arterial embolization with N-butyl cyanoacrylate glue for non-variceal gastrointestinal bleeding: A systematic review and meta-analysis

International audienc