Specific features of reperfusion therapy for vertebrobasilar ischemic stroke

Ischemic stroke in the vertebrobasilar system (VBS) is characterized by the high rates of death and disability; reperfusion therapy in patients with a lesion focus in the VBS is safe and effective beyond the 4.5-hour therapeutic window. Actively developed current methods for the endovascular treatment of acute ischemic stroke enable one to increase recanalization rates and hence to improve the degree of functional recovery in this group of patients. Considering that there are no significant differences in the outcomes of systemic and selective thrombolytic therapy in patients with occlusion of the basilar arteries, the urgent problem is to increase the time from the onset of the disease to reperfusion therapy, therefore combined reperfusion therapy may be an optimal option. This approach would make it possible to initiate the therapy in a shorter period of time and to use the advantages of both reperfusion techniques. Intravenous thrombolysis as the rapidest and technically simplest method may be performed in the first step of therapy in the clinics unequipped with an X-ray surgical service, with the patient being further transported to a specialized endovascular center if the intravenous injection of a thrombolytic agent has no effect. Taking into account the fact that reperfusion therapy may be performed in patients with vertebrobasilar stroke in the wider therapeutic window, a similar organizational chart with multistep therapy for this disease might become the treatment of choice

In-vitro Optimization of Nanoparticle-Cell Labeling Protocols for In-vivo Cell Tracking Applications.

Recent advances in theranostic nanomedicine can promote stem cell and immune cell-based therapy. Gold nanoparticles (GNPs) have been shown to be promising agents for in-vivo cell-tracking in cell-based therapy applications. Yet a crucial challenge is to develop a reliable protocol for cell upload with, on the one hand, sufficient nanoparticles to achieve maximum visibility of cells, while on the other hand, assuring minimal effect of particles on cell function and viability. Previous studies have demonstrated that the physicochemical parameters of GNPs have a critical impact on their efficient uptake by cells. In the current study we have examined possible variations in GNP uptake, resulting from different incubation period and concentrations in different cell-lines. We have found that GNPs effectively labeled three different cell-lines - stem, immune and cancer cells, with minimal impairment to cell viability and functionality. We further found that uptake efficiency of GNPs into cells stabilized after a short period of time, while GNP concentration had a significant impact on cellular uptake, revealing cell-dependent differences. Our results suggest that while heeding the slight variations within cell lines, modifying the loading time and concentration of GNPs, can promote cell visibility in various nanoparticle-dependent in-vivo cell tracking and imaging applications.Israel Cancer Research Fund (ICRF), Israel Science Foundation (grant #749/14), Christians for Israel Chair in Medical Researc

A systematic review of clinical trials of pharmacological interventions for acute ischaemic stroke (1955-2008) that were completed, but not published in full

<p>Abstract</p> <p>Background</p> <p>We assessed the prevalence, and potential impact of, trials of pharmacological agents for acute stroke that were completed but not published in full. Failure to publish trial data is to be deprecated as it sets aside the altruism of participants' consent to be exposed to the risks of experimental interventions, potentially biases the assessment of the effects of therapies, and may lead to premature discontinuation of research into promising treatments.</p> <p>Methods</p> <p>We searched the Cochrane Stroke Group's Specialised Register of Trials in June 2008 for completed trials of pharmacological interventions for acute ischaemic stroke, and searched MEDLINE and EMBASE (January 2007 - March 2009) for references to recent full publications. We assessed trial completion status from trial reports, online trials registers and correspondence with experts.</p> <p>Results</p> <p>We identified 940 trials. Of these, 125 (19.6%, 95% confidence interval 16.5-22.6) were completed but not published in full by the point prevalence date. They included 16,058 participants (16 trials had over 300 participants each) and tested 89 different interventions. Twenty-two trials with a total of 4,251 participants reported the number of deaths. In these trials, 636/4251 (15.0%) died.</p> <p>Conclusions</p> <p>Our data suggest that, at the point prevalence date, a substantial body of evidence that was of relevance both to clinical practice in acute stroke and future research in the field was not published in full. Over 16,000 patients had given informed consent and were exposed to the risks of therapy. Responsibility for non-publication lies with investigators, but pharmaceutical companies, research ethics committees, journals and governments can all encourage the timely publication of trial data.</p

Хронические нарушения сознания: клинические рекомендации Общероссийской общественной организации «Федерация анестезиологов и реаниматологов»

Хронические нарушения сознания (ХНС) представляют собой синдромы тяжелого поражения центральной нервной системы, приводящие к длительной грубой инвалидизации и требующие значительных усилий по лечению и реабилитации, которые ложатся на медицинские учреждения и на плечи близких пациентов. ХНС развиваются у пациентов после комы и характеризуются наличием бодрствования при полном или практически полном отсутствии признаков осознанного поведения. К ХНС относятся вегетативное состояние (ВС) и состояние минимального сознания (СМС). Также для описания начальных стадий этих состояний используется термин «продленное нарушение сознания» (ПНС). Отдельно выделяют выход из СМС — состояние, которое формируется по мере восстановления когнитивных функций. Диагностика ХНС основывается на многократном структурированном клиническом осмотре с применением специализированных шкал при условии исключения обратимых причин нарушения сознания. Лечение пациентов с ХНС включает в себя поддержание жизненно важных функций, обеспечение оптимального питания и борьбу с типичными осложнениями и сопутствующими состояниями (пролежни, спастичность, боль, пароксизмальная симпатическая гиперактивность и др.). У пациентов с ХНС должна проводиться реабилитация с участием мультидисциплинарной реабилитационной команды в объеме, который определяется проблемами и возможностями конкретного пациента. Наиболее эффективной реабилитация является при условии ее раннего начала. На данный момент однозначных доказательств эффективности каких-либо специфических методов, направленных на восстановление сознания, не получено; изучается ряд соответствующих фармакологических и нефармакологических вмешательств, обязательным условием применения которых является максимально возможная коррекция соматических проблем пациента. Важную роль в ведении пациентов с ХНС играет вовлечение близких пациента, которые, в свою очередь, нуждаются в получении объективной практической информации о состоянии своего родственника и о направлениях реабилитации, а также в психологической помощи

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Factors influencing the efficiency and safety of systemic thrombolysis in patients with ischemic stroke

Systemic thrombolysis using recombinant tissue plasminogen activator is the most effective and safe therapy option for ischemic stroke (IS) in the first 4.5 hours after onset of the disease. The safety and efficiency (or inefficiency) of perfusion therapy in patients with IS may be affected by a multitude of factors associated with the time of the therapy, patient age, the presence and size of a brain region with potentially reversible changes, the location of a cerebral lesion region, the specific features of systemic and local hemodynamics, and the degree of blood-brain barrier impairment. The hemorrhagic transformation of a brain lesion focus in IS is a serious complication of thrombolytic therapy (TT). The analysis and detection of predictors for hemorrhagic complications, TT in terms of the clinical and pathogenetic features of the disease, the location of a lesion focus and the degree of early neuroimaging signs, and data of additional studies will contribute to the safer and more effectiveuse of this treatment in patients with IS

Thrombolytic therapy in patients with ischemic stroke in the vertebrobasilar system

The paper shows the efficiency and safety of increasing the therapeutic window for systemic thrombolysis in verified ischemic stroke in the vertebrobasilar system (VBS), as well as the possibility of effective reperfusion in patients with stenotic occlusive lesions of the basilar artery and clinical signs of severe truncal stroke. Thrombolytic therapy (TLT) over 4.5 hours and in a neurological deficit of &gt;25 scores according to the National Institute of Health (NIHSS) Scale should be performed only within the framework of clinical trials. TLT for stroke in the VBS may substantially alter the approach to rendering care in this pathology and contribute to an increase in the number of patients with a good functional outcome

Endovascular treatment results in patients with large cerebral artery occlusions in a metropolis. Moscow Stroke Registry data over 2019

Objective: to assess results from the Stroke Network created on the basis of the Infarction Network in the metropolis Moscow for endovascular treatment in patients with occlusion of the large cerebral artery (the internal carotid artery, the M1 and M2 segments of the middle cerebral artery, and the main artery).Patients and methods. A total of 742 thromboextractions were performed in patients with ischemic stroke in Moscow Stroke Network hospitals in 2019. The final analysis included 729 patients aged 25 to 97 years (mean age, 71 years); of them there were 370 (50.8%) men and 359 (49.2%) women. The selection criteria for endovascular treatment for ischemic stroke were consistent with those set out in the 2015 American Heart Association/American Stroke Association (AHA/ASA) guidelines, which included a pre-stroke modified Rankin Scale (MRS) score of 0–1; ≥18 years of age; a National Institutes of Health Stroke Scale (NIHSS) score of ≥6; and an Alberta Stroke Programme Early CT score (ASPECTS) ≥6. The angiographic results were assessed using the Thrombolysis in Cerebral Infarction (TICI) scale. The clinical outcomes were measured with the NIHSS and the MRS.Results and discussion. Successful recanalization (TICI 2b/3) was achieved in 547 (75%) patients. The predominant technique for thromboextraction was thromboaspiration that was used in 376 (51.6%) patients. Combined procedures (the co-use of an aspiration catheter and a stent retriever) were the second most commonly used – in 231 (31.7%) patients. By the end of the 20th day, good functional recovery (MSR 0–2 scores) was observed in 213 (29.2%) patients. The 20-day mortality rate was 31.8%.Conclusion. The successfully functioning Infarction Network in Moscow was used to create the Stroke Network for treatment in patients with ischemic stroke and large cerebral artery occlusion, the clinical results of which are comparable to large European registry studies

Resolution of the International meeting of experts on the exchange of scientific experience in the use of anticoagulants in patients with COVID-19

С целью получения экспертного мнения по вопросам, связанным с актуальностью, протоколами и режимами антитромботической терапии у пациентов с COVID-19 на госпитальном и амбулаторном этапах лечения 25 июля 2020г была проведена Международная он-лайн встреча экспертов по научному обмену опытом.Группа экспертов различных специальностей (кардиологи, неврологи, эндокринологи, анестезиологи-реаниматологи), имеющих клинический опыт лечения пациентов с COVID-19, ответила на вопросы, касающиеся использования антикоагулянтов на различных этапах оказания помощи при COVID-19. Учитывая недостаточное количество структурированной научной информации, отсутствие рандомизированных контролируемых исследований в области использования антикоагулянтов у пациентов с COVID-19, наличие различных мнений в профессиональных медицинских сообществах было принято решение провести голосование с использованием Дельфийского метода экспертных оценок и прогнозирования. На первом этапе для экспертов формировались вопросы, которые касались нескольких областей терапии: тактика ведения больных, постоянно принимавших антикоагулянты до заболевания COVID-19, назначение антикоагулянтной терапии больным по поводу COVID-19 и особенности назначения антикоагулянтной терапии у больных с высоким риском венозной тромбоэмболии при COVID-19. После утверждения списка вопросов проводилось анонимное анкетирование экспертов вне очной встречи и затем обрабатывались полученные результаты, определяя обычное большинство при голосовании по каждому вопросу