Thrombosis in unvaccinated and Gam-COVID-Vac-vaccinated patients with COVID-19

Aim. To analyze the incidence of thrombotic events in unvaccinated and GamCOVID-Vac-vaccinated patients with coronavirus disease 2019 (COVID-19).Material and methods. This prospective study included 316 patients (group 1) vaccinated with two doses of Sputnik V (Gam-COVID-Vac) hospitalized between November 20, 2020 and June 1, 2021 for COVID-19. Group 2 included 754 unvaccinated patients with a positive polymerase chain reaction test for SARSCoV-2.Results. During inhospital period, deaths were recorded only in unvaccinated patients (group 1 — 0%; group 2 — 10,7% (n=87); p<0,0001). Among unvaccinated patients, the following thrombotic events were more common: upper- extremity deep vein thrombosis (group 1 — 0,63% (n=2); group 2 — 5,4% (n=41); p=0,0003), lower-extremity deep vein thrombosis (group 1 — 2,21% (n=7); group 2 — 11,4% (n=86); p<0,0001), pulmonary embolism (PE) (group 1 — 0%; group 2 — 3,4% (n=26); p=0,0008), lower limb arterial thrombosis followed by thrombectomy (group 1 — 0,31% (n=1); group 2 — 12% (n=91); p <0,0001), lower limb arterial retrombosis after retrombectomy (group 1 — 0,31% (n=1); group 2 — 8,7% (n=66); p<0,0001), lower limb amputation (group 1 — 0%; group 2 — 8,7% (n=66); p<0,0001), composite endpoint (group 1 — 3,8% (n=12); group 2 — 55,2% (n=416); p<0,0001). In the long-term follow-up period (125,5±26,5 days), recurrent COVID-19 developed significantly more often in unvaccinated patients (group 1 — 0,63% (n=2); group 2 — 3,6% (n=24); p=0,007). All arterial and venous thromboses, limb amputations were diagnosed only among unvaccinated patients.Conclusion. Vaccination with Sputnik V (Gam-COVID-Vak) prevents the severe COVID-19 with the development of deaths, pulmonary embolism, venous and arterial thrombosis

Три наиболее обсуждаемых вопроса каротидной хирургии. Обзор российских и зарубежных исследований последнего пятилетия

This literature review analyzes Russian and foreign publications over the past five years on the three most discussed issues related to carotid artery surgery: 1.Which is more effective: eversion carotid endarterectomy or conventional carotid endarterectomy with patch closure? 2. Which is better: carotid endarterectomy (CEE) or carotid angioplasty and stenting (CAS)? 3. How soon after the development of ischemic stroke should cerebral revascularization be performed?  The authors of the article came to the following conclusions: 1. According to the majority of large studies and meta-analyses, conventional CEE with patch closure is associated with a higher risk of internal carotid artery restenosis compared to eversion carotid endarterectomy. Single-center trials with small samples of patients do not find statistical differences between the outcomes of applying both surgical techniques. 2. Large multicenter randomized trials are required to address the effectiveness of CEA and CAS in symptomatic and asymptomatic patients. To date, there has been no consensus on this matter. 3. CEE and CAS can be equally effective and safe in the most acute and acute periods of ischemic stroke when performed in the presence of a mild neurological deficit and the ischemic brain lesion not exceeding 2.5 cm in diameter. Nevertheless, the choice of treatment strategy should be made strictly personalized by a multidisciplinary council based on the experience of the institution and current recommendations. В настоящем обзоре литературы проведен анализ российских и зарубежных публикаций за последние 5 лет по трем самым обсуждаемым вопросам, связанным с каротидной хирургией: 1. Что более эффективно: эверсионная или классическая техника операции с пластикой зоны реконструкции заплатой? 2. Что оптимальнее: каротидная эндартерэктомия (КЭЭ) или каротидная ангиопластика со стентированием (КАС)? 3. В какие сроки после развития ишемического инсульта следует выполнять реваскуляризацию головного мозга?Авторы статьи пришли к следующим заключениям: 1. По данным большинства крупных исследований и метаанализов классическая КЭЭ с пластикой зоны реконструкции заплатой сочетается с высоким риском развития рестеноза внутренней сонной артерии относительно эверсионной техники операции. Одноцентровые исследования с небольшими выборками больных статистических различий между результатами применения обоих методов операции не находят. 2. Требуется проведение крупных многоцентровых рандомизированных исследований для решения вопросов эффективности КЭЭ и КАС у симптомных и бессимптомных больных. На сегодняшний день единого мнения по этому поводу не выработано. 3. КЭЭ и КАС могут быть одинаково эффективны и безопасны в острейшем и остром периодах ишемического инсульта при реализации в условиях наличия легкого неврологического дефицита и ишемического очага в головном мозге, не превышающего 2,5 см в диаметре. Тем не менее, выбор стратегии лечения должен осуществляться строго персонифицированно мультидисциплинарным консилиумом на основе опыта учреждения и действующих рекомендаций

Long-term outcomes of combined coronary bypass surgery and carotid endarterectomy in patients with type 2 diabetes

At present, there are no studies on the analysis of the incidence of complications in patients with concomitant lesions of the coronary and internal carotid arteries (ICA) after combined operation of carotid endarterectomy (CE) and coronary artery bypass grafting (CABG) against the background of type 2 diabetes (T2D). However, there is no doubt that this condition can be a predictor of cardiovascular and wound complications during in-hospital and long-term postoperative periods.Aim. To study in-hospital and long-term outcomes of combined CABG+CE in patients with and without type 2 diabetes.Material and methods. This multicenter retrospective study for the period from January 2015 to December 2019 included 653 patients with concomitant atherosclerotic lesions of ICA and coronary arteries, who underwent combined CE+CABG. Depending on presence of type 2 diabetes, 2 groups were formed: group 1 (n=183) — patients with type 2 diabetes; group 2 (n=471) — patients without type 2 diabetes. The duration of postoperative follow-up was 37,8±14,9 months.Results. During hospitalization, significant differences in the incidence of death (group 1 =1,1%; group 2 =1,0%; p=0,97), myocardial infarction (MI) (group 1 =1,1%; group 2 =0,8%; p=0,76), bleeding events (group 1 =1,1%; group 2 =0,8%; p=0,76) were not detected. However, stroke (group 1 =3,8%; group 2 =0,4%; p=0,0008), sternal wound infection and mediastinitis (group 1 =3,3%; group 2 =0,2%; p=0,0006) were significantly more often developed in patients with type 2 diabetes.In the long-term follow-up period, death (group 1 =6,6%; group 2 =1,1%; p<0,0001), MI (group 1 =4,9%; group 2 =0,8%; p=0,0008), stroke (group 1 =7,7%; group 2 =1,5%; p<0,0001), ICA restenosis (group 1 =8,8%; group 2 =1,6%; p<0,0001), repeated emergency myocardial revascularization (group 1 =7,2%; group 2 =1,5%; p=0,0002), repeated emergency cerebral revascularization (group 1 =8,8%; group 2 =1,6%; p<0,0001) were significantly more often recorded in patients with type 2 diabetes.Kaplan-Meier curve analysis and its comparison using the log rank test revealed that the death, MI, and stroke were also significantly more often observed in patients with type 2 diabetes (p=0,0007, p=0,003, p<0,0001, respectively).Conclusion. Patients with type 2 diabetes who are referred for combined CE+CABG are at an increased risk of stroke, sternal wound infection and mediastinitis in the in-hospital postoperative period, as well as all adverse cardiovascular events in the long-term follow-up period

Predictors of rethrombosis and death in patients with COVID-19 after lower limb arterial thrombectomy for acute ischemia

Aim. To identify predictors of rethrombosis and death in patients with coronavirus disease (COVID-19) after thrombectomy for acute lower limb ischemia.Material and methods. For the period from April 2020 to January 2022, 189 pa tients with acute arterial lower limb thrombosis and acute lower limb ischemia were included in this study. In all cases, a positive polymerase chain reaction test for SARS-CoV-2 was obtained. According to chest multislice computed tomography, bilateral multisegmental pneumonia was identified as follows: 76 patients — grade 2 (25-50% of lung tissue involvement); 52 patients — grade 3 (50-75%); 61 patients — grade 4 (>75%). Breathing was carried out as follows: in 88 patients — spontaneous; in 42 — with oxygen administration by nasal cannula; 26 — non-invasive ventilation; 33 had artificial ventilation. All acute arterial thromboses developed within the hospital at 4,5±1,5 days after hospitalization. The time between the onset to diagnosis verification was 27,8±5,0 min. The revascularization strategy was established by a multidisciplinary team meeting. The interval between the development of acute ischemia symptoms and surgery was 45,9±6,3 minutes. Thrombectomy was performed according to the standard technique, under local and/or intravenous anesthesia, using 3F-7F Fogarty catheters.Results. Retrombosis developed in 80,4% of cases 6,4±5,1 hours after surgery. In 59,8% of cases, retrombectomy turned out to be ineffective and the patient underwent limb amputation. In 65,6% of patients, a death was established due to multiple organ dysfunction. Among them, limb amputation was performed in 103 patients. Binary logistic regression identified following predictors of retrombosis/ death: age over 70 years (odds ratio (OR), 30,73; 95% confidence interval (CI), 11,52-33,7), obesity (OR, 15,53; 95% CI, 6,41-78,19), diabetes (OR 14,21; 95% CI, 5,86-49,21), vasopressor support (OR 8,55; 95% CI, 4,94-17,93), mechanical ventilation (OR 7,39; 95% CI, 4,81-16,52).Conclusion. Predictors of retrombosis and death in patients with COVID-19 after lower limb arterial thrombectomy are age over 70 years, obesity, diabetes, vasopressor support, and mechanical ventilation

Carotid endarterectomy in Russia. What if current guidelines do not answer difficult questions?

This literature review covers the publications of Russian vascular surgeons in recent years and deals with debatable issues of carotid surgery, including: 1. What is the best technique for carotid endarterectomy (CEA)? 2. Why does restenosis of the internal carotid artery (ICA) develop and how to eliminate it? 3. How to operate on bilateral ICA stenosis? 4. Should carotid glomus be preserved? 5. Is CEA safe in the acute phase of cerebrovascular accident (CVA)? 6. Is CEA safe in elderly patients? 7. How to operate on patients with combined internal carotid and coronary artery involvement? The evidence presented in this publication makes it possible to draw the following conclusions: 1. When choosing a CEA technique, the classical technique with patch angioplasty should be avoided due to the high risk of ICA restenosis. 2. To eliminate ICA restenosis, carotid angioplasty with stenting (CAS) should be used. When performing primary CEA with ICA transposition over the hypoglossal nerve, reCEA can be used 3. In the absence of contraindications, bilateral ICA stenosis can be operated at the same time using CEA. 4. CEA with carotid glomus preservation is the operation of choice in the treatment of patients with hemodynamically significant ICA stenosis due to the elimination of the risks of postoperative hypertension and the formation of hemorrhagic transformation. 5. If there are indications for cerebral revascularization in the most acute period of stroke, CEA should be abandoned in favor of CAS. 6. In old age, CAS is the safest treatment strategy. 7. In the presence of a combined ICA and coronary involvement, the choice of treatment tactics should be carried out only by a multidisciplinary commission, taking into account the risk stratification of adverse cardiovascular events

Многоцентровое исследование по изучению течения резистентной артериальной гипертензии после классической и эверсионной каротидной эндартерэктомии

Aim of study. Analysis of the dynamics of resistant arterial hypertension (RAH) and the spectrum of adverse cardiovascular events in patients after classical carotid endarterectomy (CEE) with preservation of carotid body (CB) and eversion CEE with CB transection.Material and methods. This cohort, comparative, retrospective, open-label study from January 2014 to December 2020 included 761 patients with hemodynamically significant stenosis of the internal carotid arteries (ICA) and RH lasting more than 3 years. Depending on the implemented revascularization strategy, 2 groups were formed: Group 1: 38.0% (n=289) — classical CEE with plasty of the reconstruction zone with a patch (made of diepoxy-treated xenopericardium or synthetic); Group 2: 62% (n=472) — eversion CEE with CB transection. To study the dynamics of systolic blood pressure (SBP) in the preoperative period for 4 days, and in the postoperative period, blood pressure was measured for 10 days (during the period when the patient was in intensive care - according to daily monitoring of blood pressure; in the department - 10 times per day, daily). The average SBP figures for all patients were taken into account when constructing a graph of BP fluctuations.Results. In the postoperative period, the groups were comparable in the frequency of the following events: death (group 1: 0.34% (n=1), group 2: 0.63% (n=3); p=0.98; OR 0.54; 95% CI 0.05–5.21), myocardial infarction (group 1: 0.34% (n=1), group 2: 0.84% (n=4); p=0.71; OR 0, 40; 95% CI 0.04–3.65), ischemic stroke (group 1: 0.34% (n=1), group 2: 1.27% (n=6); p=0.36; OR 0.26; 95% CI 0.03–2.25), hemorrhagic transformation (group 1: 0%, group 2: 0.84% (n=4); p=0.29; OR 0.17; 95% CI 0.009–3.35). However, in terms of the number of all complications (death + myocardial infarction + ischemic stroke + hemorrhagic transformation) presented as a combined endpoint, patients after eversion CEE with CB transection were three times superior to classical surgery (group 1: 1.03% (n=3 ), group 2: 3.60% (n=17); p=0.05; OR 0.28; 95% CI 0.08–0.9).Conclusion. The choice of a revascularization strategy in patients with hemodynamically significant ICA stenosis should be personalized and based on the conclusion of a multidisciplinary consultation, and not only on the preferences of the operating surgeon. In patients with RH, it is more expedient to use classical CEE with plasty of the reconstruction zone with a patch in view of the preservation of the CB during this operation. The intersection of the latter with eversion CEE provokes labile hypertension, progression of RAH and a statistically significant increase in the number of all unfavorable cardiovascular events. Thus, the use of carotid body preserving CEE in patients with RAH confirms the therapeutic mechanism of this manipulation in achieving the target SBP level. Цель. Анализ динамики резистентной артериальной гипертензии (РАГ) и спектра неблагоприятных кардиоваскулярных событий у пациентов после классической каротидной эндартерэктомии (КЭЭ) с сохранением каротидного гломуса (КГ) и эверсионной КЭЭ с отсечением КГ.Материал и методы. В данное когортное сравнительное ретроспективное открытое исследование за период с января 2014 г. по декабрь 2020 г. вошел 761 пациент с гемодинамически значимыми стенозами внутренних сонных артерий (ВСА) и РАГ длительностью более 3 лет. В зависимости от реализованной стратегии реваскуляризации были сформированы две группы: 1-я группа: 38,0% (n=289) — классическая КЭЭ с пластикой зоны реконструкции заплатой (из диэпоксиобработанного ксеноперикарда или синтетическая); 2-я группа: 62% (n=472) — эверсионная КЭЭ с отсечением КГ. Для изучения динамики систолического артериального давления (САД) в дооперационном периоде в течение 4 суток, а в послеоперационном периоде в течение 10 суток измерялось артериальное давление — АД (в период нахождения пациента в реанимации — по данным суточного мониторинга АД; в отделении — 10 раз в сутки ежедневно). Средние цифры САД по всем больным учитывали при построении графика колебания АД.Результаты. В послеоперационном периоде группы оказались сопоставимы по частоте следующих событий: смерть (группа 1: 0,34% (n=1), группа 2: 0,63% (n=3); р=0,98; ОШ 0,54; 95% ДИ 0,05–5,21), инфаркт миокарда (группа 1: 0,34% (n=1), группа 2: 0,84% (n=4); р=0,71; ОШ 0,40; 95% ДИ 0,04–3,65), ишемический инсульт (группа 1: 0,34% (n=1), группа 2: 1,27% (n=6); р=0,36; ОШ 0,26; 95% ДИ 0,03– 2,25), геморрагическая трансформация (группа 1: 0%, группа 2: 0,84% (n=4); р=0,29; ОШ 0,17; 95% ДИ 0,009–3,35). Однако по числу всех осложнений (смерть + инфаркт миокарда + ишемический инсульт + геморрагическая трансформация), представленных в виде комбинированной конечной точки, пациенты после эверсионной КЭЭ с пересечением КГ превосходили классическую операцию в 3 раза (группа 1: 1,03% (n=3), группа 2: 3,60% (n=17); р=0,05; ОШ 0,28; 95% ДИ 0,08–0,9).Заключение. Выбор стратегии реваскуляризации у пациентов с гемодинамически значимым стенозом внутренних сонных артерий должен быть персонифицированным и основываться на заключении мультидисциплинарного консилиума, а не только на предпочтениях оперирующего хирурга. У пациентов с резистентной артериальной гипертензией более целесообразно применение классической каротидной эндартерэктомии с пластикой зоны реконструкции заплатой ввиду сохранения каротидного гломуса во время данной операции. Пересечение последнего при эверсионной каротидной эндартерэктомии провоцирует лабильную артериальную гипертензию, прогрессирование резистентной артериальной гипертензии и статистически значимое возрастание числа всех неблагоприятных кардиоваскулярных событий. Таким образом, применение гломус-сберегающей каротидной эндартерэктомии у пациентов с резистентной артериальной гипертензией подтверждает лечебный механизм данной манипуляции в достижении целевого уровня систолического артериального давления.

Results of thrombectomy in lower-extremity ischemia in patients with COVID-19 and respiratory failure of different severity

Aim. To analyze the results of thrombectomy in lower-extremity ischemia in patients with coronavirus disease 2019 (COVID-19) and respiratory failure of different severity.Material and methods. This retrospective, cohort, comparative study for the period from May 1, 2020 to March 1, 2022 included 305 patients with acute lower-extremity ischemia and COVID-19. Depending on the type of oxygen support, three groups of patients were formed: group 1 (n=168) — nasal oxygen insufflation; group 2 (n=92) — non-invasive ventilation (NIV); group 3 (n=45) — artificial ventilation (AV). Thrombectomy was carried out according to the standard technique using Fogarty catheters (3F-6F — depending on the vessel size). After the diagnosis was established before and after the start of surgical treatment, all patients received the following therapy: Unfractionated IV heparin infusion at an initial rate of 1000 U/r, adjusted to maintain the activated partial thromboplastin time at 2-3 times the normal value; 2. Oral acetylsalicylic acid 125 mg; 3. Analgesics.Results. Myocardial infarction and ischemic stroke were not detected in the total sample. The highest number of deaths (group 1: 5,3%, n=9; group 2: 72,8%, n=67; group 3: 100%, n=45; p<0,0001), retrombosis (group 1 : 18,4%, n=31; group 2: 69,5%, n=64; group 3: 91,1%, n=41; p<0,0001) and limb amputations (group 1: 9,5%, n=16; group 2: 56,5%, n=52; group 3: 91,1%, n=41; p<0,0001) was recorded in group 3 patients.Conclusion. In patients receiving mechanical ventilation, COVID-19 have more aggressive course, which is expressed in an increase in laboratory para- meters (C-reactive protein, ferritin, interleukin-6, D-dimer), the severity of pneumonia and location of thrombosis in the tibial arteries. Among patients with COVID-19 receiving mechanical ventilation, the greatest number of rethromboses (91,1%), limb amputations (91,1%), and deaths (100%) are noted, which suggests the expediency of abandoning open thrombectomy in favor of anticoagulant/antiplatelet therapy in this cohort of patients. The development of arterial thrombosis in patients with COVID-19 receiving mechanical ventilation is an indicator of a high risk of death. Open thrombectomy in combination with anticoagulant/antiplatelet therapy is most effective in patients on nasal oxygen insufflation or NIV

Results of different kinds of carotid endarterectomy in patients with and without type 2 diabetes mellitus

BACKGROUND: Type 2 diabetes mellitus (DM) is one of the important markers for the development of adverse cardiovascular events after carotid endarterectomy (CEE). However, studies on this issue are based on small sample of patients and do not take into account the type of surgery as an additional factor of potentially negative impact on the course of the postoperative period.AIM: Analysis of hospital and long-term results of eversion and classical CEE with plastic surgery of the reconstruction zone with a biological patch in patients with type 2 diabetes and without it.MATERIALS AND METHODS: In this multicenter retrospective study from January 2010 to December 2020. included 5731 patients. Depending on the presence / absence of type 2 diabetes and the type of implemented CEE, 4 groups were formed: group 1 — 12.2% (n = 702) — patients with type 2 diabetes and eversion CEE; Group 2 — 55.0% (n = 3153) patients without type 2 diabetes and eversion CEE; Group 3 — 8.5% (n = 484) patients with type 2 diabetes and classical CEE; Group 4 — 24.3% (n = 1392) patients without type 2 diabetes and classical CEE. The duration of postoperative follow-up was 78.6 ± 39.2 months.RESULTS: At the long-term follow-up stage, patients with type 2 diabetes after the classical surgical technique demonstrated the highest rates of all types of complications: death (p <0.0001), MI (p = 0.011), ischemic stroke (p <0.0001), restenosis / occlusion of the ICA (p <0.0001), combined end point (p <0.0001). At the same time, the group of eversion CEE with impaired carbohydrate metabolism took the second position in terms of the prevalence of adverse events. These circumstances demonstrate that patch implantation is accompanied by an increased risk of developing not only myocardial infarction, but also restenosis of the reconstruction zone, as well as the associated ischemic stroke, which was demonstrated by our results.CONCLUSION: Patients with type 2 diabetes and a history of CEE are at increased risk of ischemic stroke at the hospital stage of observation and all unfavorable cardiovascular conditions (death, myocardial infarction, ischemic stroke, restenosis or ICA occlusion in the reconstruction zone) in the long-term postoperative period

‘Multi-Epitope-Targeted’ Immune-Specific Therapy for a Multiple Sclerosis-Like Disease via Engineered Multi-Epitope Protein Is Superior to Peptides

Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS) yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and “epitope spread”, have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such “multi-epitope-targeting” approach in murine experimental autoimmune encephalomyelitis (EAE) associated with a single (“classical”) or multiple (“complex”) anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc) encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as “multi-epitope-targeting” agents. Y-MSPc was superior to peptide(s) in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells). Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of “classical” or “complex EAE” or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a “multi-epitope-targeting” strategy is required for effective immune-specific therapy of organ-specific autoimmune diseases associated with complex and dynamic pathogenic autoimmunity, such as MS; our data further demonstrate that the “multi-epitope-targeting” approach to therapy is optimized through specifically designed multi-epitope-proteins, rather than myelin peptide cocktails, as “multi-epitope-targeting” agents. Such artificial multi-epitope proteins can be tailored to other organ-specific autoimmune diseases