Effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. There are a number of choices available to the vascular surgeon. Open or endovascular revascularization is the treatment of choice when applicable. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression. Therefore, new methods of treatment are needed. We conducted a phase 2b/3 multicenter randomized controlled clinical trial of the intramuscular transfer of a plasmid DNA encoding vascular endothelial growth factor (VEGF) 165 with cytomegalovirus promotor (CMV) in patients with atherosclerotic lower limb ischemia. A total of 100 patients were enrolled in the study, that is, 75 patients were randomized into the test group and received 2 intramuscular injections of 1.2 mg of pCMV-vegf165, 14 days apart together with standard pharmacological treatment. In all, 25 patients were randomized into the control group and received standard treatment only. The following end points were evaluated within the first 6 months of the study and during a 1.5-year additional follow-up period: pain-free walking distance (PWD), ankle–brachial index (ABI), and blood flow velocity (BFV). The pCMV-vegf165 therapy appeared to be significantly more effective than standard treatment. The PWD increased in the test group by 110.4%, 167.2%, and 190.8% at 6 months, 1 year, and 2 years after treatment, respectively. The pCMV-vegf165 intramuscular transfer caused a statistically significant increase in ABI and BFV. There were no positive results in the control group. Thus, pCMV-vegf165 intramuscular gene transfer is an effective method of treatment of moderate to severe claudication due to chronic lower limb ischemia.

Background: The effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression, and new treatment methods are needed. In 2011, a plasmid VEGF65-gene therapy drug was approved in Russia for the treatment of chronic lower limb ischemia ( ClinicalTrials.gov identifier: NCT03068585). The objective of this follow-up study was to evaluate the long-term safety and efficacy of gene therapy in patients with limb ischemia of atherosclerotic genesis. Aims: To evaluate the long-term safety and efficacy of the therapeutic angiogenesis, 36 patients in the treatment group (pl- VEGF165) and 12 patients in the control group participated in a 5-year follow-up study. Planned examinations were carried out annually for 5 years after pl- VEGF165 administration. Results: Differences in the frequency of major cardiovascular events (pl- VEGF165 5/36 versus control 2/12; p = 0.85), malignancies (pl- VEGF165 1/36 versus control 0/12; p = 0.38) and impaired vision (there was none in either group) over the 5-year follow-up period did not achieve statistical significance. The target limb salvage was 95% ( n = 36) and 67% ( n = 12) in the pl- VEGF165 and control groups, respectively. The pain-free walking distance value increased by 288% from 105.7 ± 16.5 m to 384 ± 39 m in the treatment group by the end of the fifth year, with a peak of 410.6 ± 86.1 m achieved by the end of the third year. The ankle-brachial index (ABI) increased from 0.47 ± 0.01 to 0.56 ± 0.02 by the end of the first year, with a subsequent slight decrease to 0.51 ± 0.02 by the fifth year. The maximum increment of transcutaneous oximetry test (tcoO₂) by 36%, from 66.6 ± 3.7 mm Hg to 90.7 ± 4.9 mm Hg, was observed by the end of the second year. Conclusion: The therapeutic effect of angiogenesis induction by gene therapy persists for 5 years.

Aim. To study and compare cytotoxicity of the main types of synthetic prostheses used in arterial reconstructive surgery, including polytetrafluoroethylene (PTFE) and polyethylene-terephthalate (Dacron). Materials and Methods. On the culture of human umbilical vein endothelial cells (HUVEC) of the 3rd passage, MTS test was conducted that is used in laboratory examinations with attraction of cellular technologies to study cytotoxicity of medical drugs and medical products. The test implies use of MTS reagent that is 3-(4,5-dimethylthiazol-2-il)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; additionally phenazine methosulfate (PMS) was used that plays the role of electron-binding reagent. In the experiment, cells were incubated with PTFE and Dacron within 24 hours at 37ᵒC with 5% CO2. For control, HUVEC cultured in the standard growth medium, were used. In the presence of PMS, MTS was reduced by mitochondrial dehydrogenases of endothelial cells to formazan staining blue. Supernatant of cell cultures was evaluated by photocolorimetric method on Stat Fax 3200 analyzer (microplate reader) of Awareness technology Inc. Palm City Fl. (USA). Results. The lowest mean values were noted in Dacron group 0.21 (0.20-0.22) optical density units, the highest values were noted in the control group 0.36 (0.35-0.38); parameters in PTFE group were 0.35 (0.33-0.36). In comparison of the groups statistically significant differences were found between the control group and Dacron group (р0.001), control and PTFE group (р=0.037), Dacron and PTFE (р0.001). Incubation with Dacron led to suppression of metabolic activity of cells by 41.7% as compared to the control group (р0.001). Metabolic activity of cells exposed to PTFE, approached that of the control group, that is, it corresponded to the optimal conditions of culturing of endothelial cells in vitro. Conclusion. In comparison with polyethylene-terephthalate (Dacron), polytetrafluoro-ethylene (PTFE) showed the least suppression of metabolic activity of endothelial cells in vitro.

Roman E. Kalinin, Igor A. Suchkov, Nina D. Mzhavanadze, Olga N. Zhurina, Emma A. Klimentova, and Vladislav O. Povarov. Vasc Specialist Int 2021;37:. https://doi.org/10.5758/vsi.210010

Introduction: As with many other surgical interventions, the implantation of a pacemaker may be associated with adverse outcomes in the immediate or distant period. The search for probable risk factors of adverse outcomes may promote the development of effective and safe management methods of patients with pacemaker postoperatively. One of the important directions in this field is the investigation of the effect of pacemaker implantation on the hemostasis system of these patients. Aim: To evaluate the effect of the implantation of dual-chamber pacemaker on the hemostasis system of patients with different kinds of bradyarrhythmias and to determine probable risk factors for unfavorable outcomes in this groupof patients. Materials and methods: The study was performed with the financial support of the Russian Foundation for Basic Research within the Scientific Project No. 19-315-90109. The prospective study (ClinicalTrials.gov ID, NCT04499612) enrolled 61 patients (men, 45.9%) with a mean age of 71.5 8.8 years. The groupwho received surgical treatment included 23 patients with atrioventricular (AV) block and 25 patients with sick sinus syndrome (SSS), and the groupwith conservative treatment included 13 patients with AV blocks and SSS, but without indications for pacemaker implantation. Anticoagulant therapy was given to one patient with AV block, 12 patients with SSS, and five patients with conservative therapy. All the remaining patients received antiplatelet therapy. The surgical groupunderwent ultrasound examination of the veins of the upper and lower extremities and sampling of peripheral venous blood before and 7 days after pacemaker implantation to determine the level of fibrinogen (FI) and activity of blood coagulation factors VIII (FVIII) and IX (FIX), antithrombin III (AT III), and protein C. In the conservative group, a similar examination was conducted only on inclusion in the study. Results: In patients with AV block, a significant increase in blood fibrinogen was noted at 7 days after surgery (р=0.042). In the intergroupcomparison, the activity of AT III after the implantation was higher in the surgical groupthan in the conservative group(р=0.018 and р=0.006, respectively). After surgery, the activity of FVIII and FIX was lower in patients with SSS on anticoagulant therapy than in patients with antiplatelet therapy (р=0.048 and р=0.015, respectively). Based on the receiver operating characteristics analysis, the risk factors for lethal outcomes were reduced activity of AT III in patients with AV block and increased activity of FIX in patients with SSS. Conclusions: The balance of the hemostasis system in patients with AV blocks on antiplatelet therapy was shifted toward hypercoagulation within at least 7 days after pacemaker implantation. The use of anticoagulants in patients with SSS caused a shift toward hypocoagulation. The reduced activity of AT III in patients with AV block and increased activity of FIX in patients with SSS are prognostic factors for lethal outcomes.

ЦЕЛЬ ИССЛЕДОВАНИЯ Провести анализ частоты, структуры, особенностей течения и исходов венозных тромбоэмболических осложнений (ВТЭО) у пациентов с новой коронавирусной инфекцией (COVID-19) во время первой и второй волны пандемии COVID-19, выявить и оценить особенности лабораторных показателей. МАТЕРИАЛ И МЕТОДЫ Проведена оценка инструментальных и лабораторных данных пациентов с COVID-19 в период первой (1839 больных) и второй (840 больных) волн пандемии. Выполнен анализ летальности, локализации тромбозов, вариантов антикоагулянтной терапии, лабораторных показателей (уровень лейкоцитов, С-реактивного белка, фибриногена, ферритина). РЕЗУЛЬТАТЫ ВТЭО были зарегистрированы в 27 (1,5%) и 13 (1,5%) случаях у пациентов с новой коронавирусной инфекцией во время первой и второй волны пандемии соответственно. Структура ВТЭО у пациентов первой волны новой коронавирусной инфекции была представлена следующим образом: тромбоз глубоких вен (ТГВ) — 16 (59%) случаев, тромбоэмболия легочной артерии (ТЭЛА) — 6 (22%), ТГВ+ТЭЛА — 2 (8%), тромбофлебит подкожных вен — 3 (11%) случая. Во время второй волны COVID-19 ТГВ выявили у 5 (38,5%) больных, ТГВ+ТЭЛА — у 5 (38,5%), ТЭЛА без ТГВ — у 2 (15,4%), тромбоз правой почечной вены — у 1 (7,6%) пациента. Средние величины лабораторных показателей у пациентов с ВТЭО во время первой волны COVID-19 были следующими: лейкоциты крови — 9,2∙10⁹/л (6,9—14,3); С-реактивный белок — 77,5 мг/л (26—159); фибриноген — 593,5 мг/мл (500—700); ферритин — 1132,6 мкг/л (165—1753). Для пациентов с ВТЭО во время второй волны пандемии были характерны: умеренный лейкоцитоз — 12,2∙10⁹/л (7—19), повышение уровня фибриногена — 544 мг/дл (405—781), а также высокие уровни С-реактивного белка — 102,75 мг/мл (80—163) и ферритина — 510 мкг/л (230—566). ЗАКЛЮЧЕНИЕ У пациентов с новой коронавирусной инфекцией при развитии ВТЭО отмечена высокая летальность. Во время второй волны пандемии летальность среди пациентов с ВТЭО увеличилась, что может быть связано как с тромботическими осложнениями, так и с сопутствующей сердечно-сосудистой патологией.