Ethical Considerations and Adverse Events in Cyanoacrylate Embolization for Non-Saphenous Veins: A Case Report.

The cyanoacrylate embolization (CAE) technique for chronic venous disease treatment is less painful and leads to a faster recovery than conventional endovenous thermal treatment. According to the instructions for use (IFU) of the VenaSeal closure system (Medtronic), a representative CAE product, it has only been approved for treating saphenous veins, not non-saphenous veins. Here, we report a case of ignoring the VenaSeal IFU for treating testicular pain using CAE for non-saphenous veins within the abdominal wall, which is a baseless and non-scientific approach nearing malpractice. Hence, it is imperative for physicians to rigorously adhere to the IFU and abstain from experimenting with new treatment methods solely based on personal experience.

In Vivo Animal Study of a Highly Viscous N-butyl Cyanoacrylate Medical Adhesive for Intravenous Embolization.

N-butyl cyanoacrylate (NBCA) is a liquid monomer that undergoes an exothermic polymerization reaction to form a solid upon initiation with hydroxyl anions. Recently, EGpresto, a highly viscous NBCA-based adhesive, has been developed for vascular-occlusion purposes. In this study, we investigated the heat of polymerization of EGpresto and compared the results with those of a low-viscosity NBCA glue. Results show that EGpresto exhibited a lower heat of polymerization (64 ± 7 °C vs. 34 ± 1 °C). This was due to its high viscosity, which resulted in a delayed polymerization time. To investigate the efficacy and safety of EGpresto for intravenous embolization, a 14 d in vivo animal test was conducted using three pigs. Five cc of EGpresto was injected into the epigastric vein of each animal. Complete postoperative vein occlusion was confirmed at 7 and 14 d by ultrasonographic visualization. After the animals were sacrificed, the operated and unoperated veins were exposed, and the injected adhesive was found without migration. During the histology, the injected adhesive was not found in the inner or outer vein walls, and the immune reactions seemed to be the only foreign-body reaction, showing that EGpresto is a non-toxic and safe intravascular embolic agent.

Human Saphenous Vein Histopathology 2 Years After Cyanoacrylate Closure Using the VenaSeal™ System.

There are few long-term histological studies of changes that occur after the treatment of chronic venous disease with cyanoacrylate. In the present study, a histological examination was performed in a 71-year-old man 2 years after he was treated with a VenaSeal™ system. After 2 years, most endothelial cells were destroyed; however, most of the media layer was viable. Moreover, we identified multinucleated giant cells distributed throughout the media layer but found no adventitial infiltration.

Comparison of Short-Term Outcomes Between Endovenous 1,940-nm Laser Ablation and Radiofrequency Ablation for Incompetent Saphenous Veins.

Background: Radiofrequency ablation (RFA) has shown faster recovery and lower pain scores compared to Endovenous laser ablation (EVLA) for treatment of varicose veins. However, a comparison of 1,940-nm EVLA and RFA has not been reported. This study compared short-term outcomes using 1,940-nm EVLA and RFA for varicose veins. Methods: Between April 2018 and June 2018, 43 patients (83 incompetent saphenous veins) were treated with 1,940-nm EVLA and 37 patients (64 incompetent saphenous veins) with RFA. Follow-up duplex was checked at 1 month and 3 months. Results: Baseline characteristics showed no significant differences between both groups except for age. Pain scores at 6 h, and at 1, 10, and 30 days after treatment showed no differences. Complications and time to return to normal activity showed no differences. The 100% closure rate was checked in both groups at 1 month and 3 months follow-up. Conclusion: Short-term outcomes showed no significant differences between 1,940-nm EVLA and RFA treatment.

Automatic Sclerosant Injection Technique of Mechanochemical Ablation with ClariVein Using a Syringe Pump for the Treatment of Varicose Veins.

Mechanochemical ablation (MOCA) is a non-thermal, non-tumescent technique for the treatment of incompetent saphenous vein. It is sometimes difficult to maintain consistency when simultaneously implementing wire rotation, sclerosant injection, and wire pullback. Here, we report a simple technique for achieving constant injection during MOCA with the help of a syringe pump; thus, the operator can focus on wire pullback only with convenience and consistency.

Photocatalytic degradation of 1,4-dioxane using liquid phase plasma on visible light photocatalysts.

The compound 1,4-dioxane (DO) irritates the eyes, skin, and mucous membrane and is classified as a carcinogen. In this study, the decomposition of DO by photocatalytic reaction using liquid phase plasma (LPP) with photocatalyst was suggested. Plasma was directly discharged as an aqueous DO solution to enhance photocatalytic decomposition activity. To increase the decomposition efficiency of DO by plasma, bismuth ferrite (BFO) prepared by a sol-gel method was introduced as a visible-light photocatalyst. In the application of LPP and BFO photocatalyst, the decomposition of DO by photocatalytic reaction was evaluated. BFO showed UV-vis diffusion reflectance spectroscopy results of absorption of UV and visible light over 600 nm, with a bandgap of approximately 2.2 eV. BFO showed visible light photochemical reaction characteristics to decompose particulate matter (PM) in the irradiation of 6 W visible light LED lamps. It seems that the narrow bandgap of BFO led to the photocatalytic activity in the visible light. In the decomposition reaction of DO with a photocatalyst and LPP, BFO showed better decomposition efficiency than TiO2. BFO can cause photocatalytic reactions in both UV and visible light in the case of LPP irradiation, which emits strong ultraviolet and visible light.

Correlation Between the Immediate Remnant Stump Length and Vein Diameter After Cyanoacrylate Closure Using the VenaSeal System During Treatment of an Incompetent Great Saphenous Vein.

OBJECTIVES: Cyanoacrylate glue is injected for incompetent great saphenous vein (GSV) treatment 5 cm distal to the saphenofemoral junction (SFJ). Although a few reports have investigated the postprocedural remnant stump length, none have focused on the factors affecting glue extension length and the consequent remnant stump length. METHODS: Seventy-nine patients undergoing cyanoacrylate closure using the VenaSeal system at our clinic between August 2018 and November 2018 were investigated. The GSV diameter was measured just before treatment in the supine position 3 cm distal to the SFJ. Cyanoacrylate glue was injected 5 cm distal to the SFJ. RESULTS: The mean glue extension length was 1.13 ± 1.12 cm. The GSV diameter and glue extension length exhibited a significant inversely proportional relationship (P < .001). More specifically, patients with a GSV diameter ≥0.7 cm had a longer remnant stump length than those with a smaller GSV diameter (P < .001). CONCLUSIONS: An increased GSV diameter is likely associated with a decreased glue extension length and, consequently, a longer remnant stump.

Heterogeneous photocatalytic degradation and hydrogen evolution from ethanolamine nuclear wastewater by a liquid phase plasma process.

Ethanolamine in a wastewater which is released from nuclear power plant was decomposed using a plasma discharged into the solution directly. Ni-TiO2 supported on mesoporous materials were employed as a photocatalyst. The photocatalytic reaction using the liquid phase plasma led to a degradation of ethanolamine with hydrogen evolution, simultaneously. The ethanolamine in the wastewater was degraded over 90% on the photocatalytic decomposition reaction by irradiation of liquid phase plasma. The rate of hydrogen evolution increased significantly with Ni incorporation on TiO2 because the bandgap was reduced with Ni incorporation on TiO2. Incorporating Ni on TiO2 nanocrystallites brought out an improvement of the ethanolamine degradation with hydrogen generation. The rate of hydrogen evolution in the ethanolamine-containing aqueous solution was increased in comparison with that in pure water. Additional hydrogen evolution by the photodecomposition of ethanolamine was attributed to the increasing H2 production.

Role of stem cell mobilization in the treatment of ischemic diseases.

Stem cell mobilization plays important roles in the treatment of severe ischemic diseases, including myocardial infarction, limb ischemia, ischemic stroke, and acute kidney injury. Stem cell mobilization refers to the egress of heterogeneous stem cells residing in the bone marrow into the peripheral blood. In the clinic, granulocyte colony-stimulating factor (G-CSF) is the drug most commonly used to induce stem cell mobilization. Plerixafor, a direct antagonist of CXCR4, is also frequently used alone or in combination with G-CSF to mobilize stem cells. The molecular mechanisms by which G-CSF induces stem cell mobilization are well characterized. Briefly, G-CSF activates neutrophils in the bone marrow, which then release proteolytic enzymes, such as neutrophil elastase, cathepsin G, and matrix metalloproteinase 9, which cleave a variety of molecules responsible for stem cell retention in the bone marrow, including CXCL12, VCAM-1, and SCF. Subsequently, stem cells are released from the bone marrow into the peripheral blood. The released stem cells can be collected and used in autologous or allogeneic transplantation. To identify better conditions for stem cell mobilization in the treatment of acute and chronic ischemic diseases, several preclinical and clinical studies have been conducted over the past decade on various mobilizing agents. In this paper, we are going to review methods that induce mobilization of stem cells from the bone marrow and introduce the application of stem cell mobilization to therapy of ischemic diseases.

Characterization of hidden rules linking symptoms and selection of acupoint using an artificial neural network model.

Comprehension of the medical diagnoses of doctors and treatment of diseases is important to understand the underlying principle in selecting appropriate acupoints. The pattern recognition process that pertains to symptoms and diseases and informs acupuncture treatment in a clinical setting was explored. A total of 232 clinical records were collected using a Charting Language program. The relationship between symptom information and selected acupoints was trained using an artificial neural network (ANN). A total of 11 hidden nodes with the highest average precision score were selected through a tenfold cross-validation. Our ANN model could predict the selected acupoints based on symptom and disease information with an average precision score of 0.865 (precision, 0.911; recall, 0.811). This model is a useful tool for diagnostic classification or pattern recognition and for the prediction and modeling of acupuncture treatment based on clinical data obtained in a real-world setting. The relationship between symptoms and selected acupoints could be systematically characterized through knowledge discovery processes, such as pattern identification.

Clinical Features and Management of "Phlebitis-like Abnormal Reaction" After Cyanoacrylate Closure for the Treatment of Incompetent Saphenous Veins.

BACKGROUND: Cyanoacrylate closure for the treatment of incompetent saphenous veins does not cause thermal damage and demonstrates satisfactory outcomes with rapid recovery. However, the characteristics of phlebitis-like abnormal reaction (PLAR), the most common adverse event after cyanoacrylate closure, have not been clarified. Moreover, it differs from typical phlebitis after thermal ablation. The objective of our study is to investigate the clinical features of PLAR after cyanoacrylate closure and to report its management. METHODS: A total of 160 patients with 271 incompetent saphenous veins (great saphenous veins, 201; small saphenous veins, 70) underwent cyanoacrylate closure with the VenaSeal™ system. We defined PLAR as any unusual skin condition that develops suddenly, such as erythema, itching, swelling, and pain/tenderness, over the treated veins several days after cyanoacrylate closure. Oral antihistamines and intravenous dexamethasone were administered to manage PLAR. RESULTS: Of the 271 treated veins, 69 experienced PLAR (25.4%). The mean time of occurrence was 13.6 ± 4.6 days after treatment. The rate of occurrence of erythema, itching, swelling, and pain/tenderness were 92.2%, 91.2%, 66.2%, and 48.5%, respectively. The occurrence of PLAR was significantly higher for great saphenous veins than for small saphenous veins (P < 0.001). Occurrences were more frequent in cases with a suprafascial great saphenous vein of length >10 cm than in cases with a subfascial great saphenous vein (P = 0.001). The proportion of patients who reported swelling decreased by more than half after the administration of oral antihistamine. The pain score on the 10th day also decreased significantly after the administration of antihistamine (P = 0.006). CONCLUSIONS: PLAR must be distinguished from classic phlebitis. We believe that PLAR is a type IV hypersensitivity reaction due to a foreign body, and in our experience, antihistamines or steroids are effective for the prevention and management of PLAR.

Initial outcomes of endovenous laser ablation with 1940 nm diode laser in the treatment of incompetent saphenous veins.

OBJECTIVES: To investigate the initial outcomes of 1940 nm diode laser in the treatment of incompetent saphenous veins. METHODS: This was a prospective observational study. We treated 89 patients with 160 incompetent saphenous veins using a 1940 nm diode laser and bare fiber. The laser's power was set to 4.5 W with a mean linear endovenous energy density of 50.4 J/cm. RESULTS: The one-month closure rate was 100%. The post-procedural pain score at 6 h, 1 day, 10 days, and 1 month was 0.85 ± 1.04, 0.65 ± 1.01, 0.82 ± 1.25, and 0.47 ± 0.82, respectively. Complications encountered included paresthesia (3.8%) and thrombophlebitis (4.4%), whereas no cases of endovenous heat-induced thrombosis were observed. CONCLUSION: The 1940 nm laser and bare fiber at 50.4 J/cm showed satisfactory initial outcomes with less pain and fewer complications, in the treatment of incompetent saphenous veins.

Facile Preparation of Ni-Co Bimetallic Oxide/Activated Carbon Composites Using the Plasma in Liquid Process for Supercapacitor Electrode Applications.

In this study, a plasma in a liquid process (PiLP) was used to facilely precipitate bimetallic nanoparticles composed of Ni and Co elements on the surface of activated carbon. The physicochemical and electrochemical properties of the fabricated composites were evaluated to examine the potential of supercapacitors as electrode materials. Nickel and cobalt ions in the aqueous reactant solution were uniformly precipitated on the AC surface as spherical nanoparticles with a size of about 100 nm by PiLP reaction. The composition of nanoparticles was determined by the molar ratio of nickel and cobalt precursors and precipitated in the form of bimetallic oxide. The electrical conductivity and specific capacitance were increased by Ni-Co bimetallic oxide nanoparticles precipitated on the AC surface. In addition, the electrochemical performance was improved by stable cycling stability and resistance reduction and showed the best performance when the molar ratios of Ni and Co precursors were the same.

Successful use of VenaSeal system for the treatment of large great saphenous vein of 2.84-cm diameter.

Cyanoacrylate closure, VenaSeal system, for the treatment of incompetent saphenous vein is a new technique. We report a successful case with a large great saphenous vein of 2.84 cm in diameter.

Initial Outcomes of Cyanoacrylate Closure, VenaSeal System, for the Treatment of the Incompetent Great and Small Saphenous Veins.

PURPOSE: Cyanoacrylate closure of the saphenous vein with the VenaSeal system is a new technique just approved on December 2016 in Korea. Therefore, there are seldom reports about postprocedural outcomes of VenaSeal system in Asian countries. We report the initial outcomes of VenaSeal system for the treatment of great saphenous veins (GSVs) and small saphenous veins (SSVs) as a first report in Korea. METHODS: Thirty-four patients with incompetent saphenous veins (47 GSVs and 16 SSVs) were treated at a single session. Concomitant phlebectomy was performed in 15 (44.1%) of 34 patients. All procedures were started with local anesthesia with music therapy and switched to intravenous sedation if patient requested. Patients revisited the clinic on 10 days, 1 month, and 3 months after surgery. Postprocedural evaluations including numerical pain rating score, revised Venous Clinical Severity Scores (rVCSS), and Aberdeen Varicose Vein Questionnaires were checked. Duplex ultrasound was performed on 10 days, 1 month, and 3 months. RESULTS: All treated veins (47 GSVs and 16 SSVs; 100%) had complete closure by duplex ultrasound during the follow-up period. Mean numerical pain rating scale of 6 hours after procedure was 2.7. The rVCSS was improved during the follow-up period. Phlebitis-like "abnormal skin reaction" in the treatment area was occurred in 8 (23.5%) of 34 patients and recovered fully in 2 weeks. CONCLUSIONS: Cyanoacrylate closure, VenaSeal system, is safe and effective for the treatment of incompetent saphenous veins.

Generation, Diversity Determination, and Application to Antibody Selection of a Human Naïve Fab Library.

We constructed a large naïve human Fab library (3 × 1010 colonies) from the lymphocytes of 809 human donors, assessed available diversities of the heavy-chain variable (VH) and κ light-chain variable (VK) domain repertoires, and validated the library by selecting Fabs against 10 therapeutically relevant antigens by phage display. We obtained a database of unique 7,373 VH and 41,804 VK sequences by 454 pyrosequencing, and analyzed the repertoires. The distribution of VH and VK subfamilies and germline genes in our antibody repertoires slightly differed from those in earlier published natural antibody libraries. The frequency of somatic hypermutations (SHMs) in heavy-chain complementarity determining region (HCDR)1 and HCDR2 are higher compared with the natural IgM repertoire. Analysis of position-specific SHMs in CDRs indicates that asparagine, threonine, arginine, aspartate and phenylalanine are the most frequent non-germline residues on the antibody-antigen interface and are converted mostly from the germline residues, which are highly represented in germline SHM hotspots. The amino acid composition and length-dependent changes in amino acid frequencies of HCDR3 are similar to those in previous reports, except that frequencies of aspartate and phenylalanine are a little higher in our repertoire. Taken together, the results show that this antibody library shares common features of natural antibody repertoires and also has unique features. The antibody library will be useful in the generation of human antibodies against diverse antigens, and the information about the diversity of natural antibody repertoires will be valuable in the future design of synthetic human antibody libraries with high functional diversity.

Generation, characterization and preclinical studies of a human anti-L1CAM monoclonal antibody that cross-reacts with rodent L1CAM.

L1 cell adhesion molecule (L1CAM) is aberrantly expressed in malignant tumors and plays important roles in tumor progression. Thus, L1CAM could serve as a therapeutic target and anti-L1CAM antibodies may have potential as anticancer agents. However, L1CAM is expressed in neural cells and the druggability of anti-L1AM antibody must be validated at the earliest stages of preclinical study. Here, we generated a human monoclonal antibody that is cross-reactive with mouse L1CAM and evaluated its pharmacokinetic properties and anti-tumor efficacy in rodent models. First, we selected an antibody (Ab4) that binds human and mouse L1CAM from the human naïve Fab library using phage display, then increased its affinity 45-fold through mutation of 3 residues in the complementarity-determining regions (CDRs) to generate Ab4M. Next, the affinity of Ab4M was increased 1.8-fold by yeast display of single-chain variable fragment containing randomly mutated light chain CDR3 to generate Ab417. The affinities (KD) of Ab417 for human and mouse L1CAM were 0.24 nM and 79.16 pM, respectively. Ab417 specifically bound the Ig5 domain of L1CAM and did not exhibit off-target activity, but bound to the peripheral nerves embedded in normal human tissues as expected in immunohistochemical analysis. In a pharmacokinetics study, the mean half-life of Ab417 was 114.49 h when a single dose (10 mg/kg) was intravenously injected into SD rats. Ab417 significantly inhibited tumor growth in a human cholangiocarcinoma xenograft nude mouse model and did not induce any adverse effect in in vivo studies. Thus, Ab417 may have potential as an anticancer agent.

RNA recognition by a human antibody against brain cytoplasmic 200 RNA.

Diverse functional RNAs participate in a wide range of cellular processes. The RNA structure is critical for function, either on its own or as a complex form with proteins and other ligands. Therefore, analysis of the RNA conformation in cells is essential for understanding their functional mechanisms. However, no appropriate methods have been established as yet. Here, we developed an efficient strategy for panning and affinity maturation of anti-RNA human monoclonal antibodies from a naïve antigen binding fragment (Fab) combinatorial phage library. Brain cytoplasmic 200 (BC200) RNA, which is also highly expressed in some tumors, was used as an RNA antigen. We identified MabBC200-A3 as the optimal binding antibody. Mutagenesis and SELEX experiments showed that the antibody recognized a domain of BC200 in a structure- and sequence-dependent manner. Various breast cancer cell lines were further examined for BC200 RNA expression using conventional hybridization and immunoanalysis with MabBC200-A3 to see whether the antibody specifically recognizes BC200 RNA among the total purified RNAs. The amounts of antibody-recognizable BC200 RNA were consistent with hybridization signals among the cell lines. Furthermore, the antibody was able to discriminate BC200 RNA from other RNAs, supporting the utility of this antibody as a specific RNA structure-recognizing probe. Intriguingly, however, when permeabilized cells were subjected to immunoanalysis instead of purified total RNA, the amount of antibody-recognizable RNA was not correlated with the cellular level of BC200 RNA, indicating that BC200 RNA exists as two distinct forms (antibody-recognizable and nonrecognizable) in breast cancer cells and that their distribution depends on the cell type. Our results clearly demonstrate that anti-RNA antibodies provide an effective novel tool for detecting and analyzing RNA conformation.