The phenomenon of drug-coating embolism during lower extremity endovascular interventions with paclitaxel-coated balloon.

INTRODUCTION: There is a risk of distal embolization lower extremity endovascular interventions. Possibly a drug-coating embolism caused by coating detachment from intravascular devices. METHODS: This review focuses on providing updated information on distal embolism in endovascular revascularization of lower extremity arteries, including the use of drug-coated balloons. RESULTS: Drug-coating embolism is a special case of distal embolization during recanalization of the arteries of the lower extremities. Preclinical studies have demonstrated embolization of drug-coated balloons during angioplasty of lower extremity arteries. However, the clinical role of drug-coating embolism is not completely clear. A 2020 meta-analysis found an increased risk of major lower extremity amputation after drug-coated balloon angioplasty in patients with critical limb ischemia. But long-term research is emerging to support the safety of using these devices. Perhaps a more thorough assessment of the quality of life and the degree of compensation of lower limb ischemia with an intraoperative assessment of the frequency of peripheral embolizations using ultrasound emboli detection, as well as microcirculation with transcutaneous oximetry and laser Doppler flowmetry of the operated lower limb will allow a more detailed study of the phenomenon of drug-coating embolism and its impact on long-term clinical outcomes. CONCLUSION: According to the results of preclinical studies, the use of paclitaxel-coated balloons leads to an increase in the concentration of paclitaxel in distal skeletal muscles. However, paclitaxel concentration in skeletal muscle was significantly higher in first-generation DCBs. The non-target effects of drug-coating balloon are not fully understood and require further study. Understanding the phenomenon of drug-coating embolism can help physicians to better assess the patient risk and to minimize complications.

Ultraviolet light scattering scanning flow cytometry in the characterization of submicron microparticles.

Ultraviolet lasers are commonly used in flow cytometry to excite fluorochrome molecules with subsequent measurement of the specific fluorescence of individual cells. In this study, the performance of the ultraviolet light scattering (UVLS) in the analysis of individual particles with flow cytometry has been demonstrated for the first time. The main advantage of the UVLS relates to the improvement of the analysis of submicron particles due to the strong dependence of the scattering efficiency on the wavelength of the incident light. In this work, submicron particles were analyzed using a scanning flow cytometer (SFC) that allows measurements of light scattering in an angle-resolved regime. The measured light-scattering profiles of individual particles were utilized in solution of the inverse light-scattering problem to retrieve the particle characteristics using a global optimization. The standard polystyrene microspheres were successfully characterized from the analysis of UVLS which provided the size and refractive index (RI) of individual beads. We believe that the main application of UVLS relates to the analysis of microparticles in a serum, in particular in the analysis of chylomicrons (CMs). We have demonstrated the performance of the UVLS SFC in the analysis of CMs of a donor. The RI versus size scatterplot of CMs was successfully retrieved from the analysis. The current set-up of the SFC has allowed us to characterize individual CMs starting from the size of 160 nm that provides determination of the CM concentration in a serum with flow cytometry. This feature of the UVLS should help with the analysis of lipid metabolism measuring RI and size map evolution after lipase action.

A light scatter based model relating erythrocyte vesiculation to lifetime in circulation.

Methods for measuring erythrocyte age distribution are not available as a simple analytical tool. Most of them utilize the fluorescence or radioactive isotopes labeling to construct the age distribution and support physicians with aging indices of donor's erythrocytes. The age distribution of erythrocyte may be a useful snapshot of patient state over 120-days period of life. Previously, we introduced the enhanced assay of erythrocytes with measurement of 48 indices in four categories: concentration/content, morphology, aging and function (10.1002/cyto.a.24554). The aging category was formed by the indices based on the evaluation of the derived age of individual cells. The derived age does not exactly mean the real age of erythrocytes and its evaluation utilizes changes of cellular morphology during a lifespan. In this study, we are introducing the improved methodological approach that allows us to retrieve the derived age of individual erythrocytes, to construct the aging distribution, and to reform the aging category consisting of eight indices. The approach is based on the analysis of the erythrocyte vesiculation. The erythrocyte morphology is analyzed by scanning flow cytometry that measures the primary characteristics (diameter, thickness, and waist) of individual cells. The surface area (S) and sphericity index (SI) are calculated from the primary characteristics and the scattering diagram SI versus S is used in the evaluation of the derived age of each erythrocyte in a sample. We developed the algorithm to evaluate the derived age that provides eight indices in the aging category based on a model using light scatter features. The novel erythrocyte indices were measured for simulated cells and blood samples of 50 donors. We determined the first-ever reference intervals for these indices.

Erythrocyte lysis and angle-resolved light scattering measured by scanning flow cytometry result to 48 indices quantifying a gas exchange function of the human organism.

Molecular/cell level of gas exchange function assumes the accurate measurement of erythrocyte characteristics and rate constants concerning to molecules involved into the CO2 /O2 transport. Unfortunately, common hematology analyzers provide the measurement of eight indices of erythrocytes only and say little about erythrocyte morphology and nothing about rate constants of cellular function. The aim of this study is to demonstrate the ability of the Scanning Flow Cytometer (SFC) in the complete morphological analysis of mature erythrocytes and characterization of erythrocyte function via measurement of lysing kinetics. With this study we are introducing 48 erythrocyte indices. To provide the usability of application of the SFC in clinical diagnosis, we formed four categories of indices which are as follows: content/concentration (9 indices), morphology (26 indices), age (5 indices), and function (8 indices). The erythrocytes of 39 healthy volunteers were analyzed with the SFC to fix the first-ever reference intervals for the new indices introduced. The essential measurable reliability of the presented method is expressed in terms of errors of characteristics of single erythrocytes retrieved from the solution of the inverse light-scattering problem and errors of parameters retrieved from the fitting of the experimental kinetics by molecular-kinetics model of erythrocyte lysis.

Treatment of Long Femoropopliteal Occlusive Lesions With Self-expanding Interwoven Nitinol Stent: 24 Month Outcomes of the STELLA-SUPERA-SIBERIA Register Trial.

PURPOSE: The efficacy and safety of the Supera stent in superficial femoral artery (SFA) have been reported mostly in shorter lesions with relatively low proportion of occlusions. There are little data on the effectiveness of the Supera stent in long lesions. The aim of this study was to assess the clinical safety and efficiency of the Supera stent in the treatment of long femoropopliteal occlusive lesions (Trans-Atlantic Inter-Society Consensus [TASC] C/D) in patients with symptomatic peripheral artery disease. MATERIALS AND METHODS: The STELLA-SUPERA-SIBERIA is a prospective, single-center, single-arm study. Patients with symptomatic (Rutherford stages 3-6) de novo and TASC C/D occlusive lesions of the femoropopliteal segment were treated with Supera stent. The primary endpoint was the 12 month rate of primary sustained clinical improvement (upward shift on the Rutherford classification to a one level without the need for repeated target lesion revascularization (TLR) in surviving patients without the need for unplanned amputation). Secondary endpoints were the 24 month of primary sustained clinical improvement, MALE, limb salvage, the primary patency, the secondary patency, 24 month MACE. Follow-up included clinical examination, duplex scan, and biplane x-ray up to 24 months. RESULTS: Between April 2019 and January 2020, 52 symptomatic patients with 55 long femoropopliteal occlusive lesions (52.7% TASC D lesions and 47.3% TASC C lesions) were treated. The mean target lesion length was 205±72 mm. All patients had total occlusions. The mean lesion length of the implanted Supera stents was 198±82 mm. At 12 and 24 months, the primary sustained clinical improvement rate was 80.2% and 63.6%, respectively. The Rutherford category assessment was significantly improved at 24 months compared with baseline (p=0.02). The primary patency rate at 12 and 24 months was 78.1% and 60.0%, respectively. At 12 and 24 months, freedom from TLR was 83.5% and 81.8%, respectively. There were no stent fractures at 24 months. CONCLUSION: Supera Stent implantation for TASC C/D femoropopliteal lesions revascularization appears to be a safe and efficient implant given the complexity of the treated lesions. Head-to-head studies are mandatory to establish Supera Stent as an alternative tool to open surgery for long femoropopliteal lesions. CLINICAL IMPACT: Our study indicated, that using self-expanding interwoven nitinol stent for TASC C/D femoropopliteal lesions revascularization appears to be a safe and efficient implant given the complexity of the treated lesions. Although bypass grafting is recommended for prolonged femoropopliteal lesions, open surgery is more traumatic and is associated with greater risks than endovascular procedures. Our findings suggest that the use of interwoven nitinol stents can overcome the disadvantages of traditional stents in such cases, which may help to improve patients' outcomes and reduce the risk of adverse events.

One-Year Results of Long femoropopliteal Lesions Stenting with Fasciotomy Lamina Vastoadductoria.

BACKGROUND: Fasciotomy can increase the mobility of the superficial femoral artery and decrease the incidence of stent fractures. This study aimed to compare the long-term patency of drug-eluting nitinol stents with and without fasciotomy in patients with prolonged superficial femoral artery occlusions. METHODS: A randomized clinical trial was conducted in 60 (1:1) patients with long femoropopliteal steno-occlusive lesions >200 mm. Patients in group 1 (Zilver) underwent recanalization of femoropopliteal artery occlusion with stenting. In group 2 (ZilverFas), the femoropopliteal occlusion was recanalized with stenting and fasciotomy of Gunter's canal. The follow-up assessment of the patency took place after 6-12 months. RESULTS: Twelve-month primary patency in Zilver and ZilverFas groups was 51% and 80%, respectively (P = 0.02). The freedom from target lesion revascularization in the Zilver and ZilverFas groups was 50% and 76%, respectively (P = 0.04). At 1 year, primary-assisted patency and secondary patency for the ZilverFas and Zilver groups were 83% vs. 62% (P = 0.07) and 86% vs. 65% (P = 0.05), respectively. In the Zilver and ZilverFas groups, the number of stent fractures was 14 and 7, respectively (P = 0.05). The multivariable Cox regression indicated that the stent fracture and diabetes mellitus were independent predictors of restenosis and reocclusion. Fasciotomy reduced the risk of reocclusion and restenosis by 2.94 times. CONCLUSIONS: Our study has shown that decompressing the stented segment with fasciotomy significantly improves the patency of the femoropopliteal segment and significantly reduces the number and severity of stent fractures.

Activated Carbon-Enriched Electrospun-Produced Scaffolds for Drug Delivery/Release in Biological Systems.

To vectorize drug delivery from electrospun-produced scaffolds, we introduce a thin outer drug retention layer produced by electrospinning from activated carbon nanoparticles (ACNs)-enriched polycaprolacton (PCL) suspension. Homogeneous or coaxial fibers filled with ACNs were produced by electrospinning from different PCL-based suspensions. Stable ACN suspensions were selected by sorting through solvents, stabilizers and auxiliary components. The ACN-enriched scaffolds produced were characterized for fiber diameter, porosity, pore size and mechanical properties. The scaffold structure was analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy. It was found that ACNs were mainly coated with a polymer layer for both homogeneous and coaxial fibers. Drug binding and release from the scaffolds were tested using tritium-labeled sirolimus. We showed that the kinetics of sirolimus binding/release by ACN-enriched scaffolds was determined by the fiber composition and differed from that obtained with a free ACN. ACN-enriched scaffolds with coaxial and homogeneous fibers had a biocompatibility close to scaffold-free AC, as was shown by the cultivation of human gingival fibroblasts and umbilical vein cells on scaffolds. The data obtained demonstrated that ACN-enriched scaffolds had good physico-chemical properties and biocompatibility and, thus, could be used as a retaining layer for vectored drug delivery.

A prospective randomized trial on endovascular recanalization with stenting versus remote endarterectomy for the superficial femoral artery total occlusive lesions.

OBJECTIVE: The objective of this randomized study was to compare the short- and long-term safety and efficacy of endovascular recanalization with stenting (EI) and remote endarterectomy (RE) for patients with superficial femoral artery (SFA) total occlusive lesions (≥250 mm). METHODS: Between July 2013 and July 2017, eligible patients with SFA total occlusive lesions were randomized to EI or RE. The EI group underwent recanalization and stenting of long SFA atherosclerotic occlusive lesions. The RE group underwent semiclosed endarterectomy. Short- (30-day) and long-term (48-month) morbidity, mortality, and patency rates were compared between both groups. RESULTS: Of 400 patients assessed, 238 were ultimately randomized (119 EI and 119 RE). The cumulative primary patencies were 83% (EI) vs 82% (RE) at 12 months and 28% (EI) vs 46% (RE) at 48 months (P = .04). The limb salvage was 98% (EI) vs 95% (RE) at 12 months and 87% (EI) vs 92% (RE) at 48 months (P = .26). One-year and 4-year secondary patencies were 98% and 87% in the EI group and 100% and 90% in the RE group, respectively (P = .4). A total of 65 patients in the stenting group and 32 patients in the endarterectomy group underwent endovascular reintervention. Four-year patencies of endovascular reintervention subgroups were 37% and 60% (P = .04), respectively. CONCLUSIONS: RE shows significantly better results in the long term than primary stenting of SFA long lesions (TASC-II D lesions). In case of loss patency, a desobliterated artery can be successfully subjected to endovascular revascularization and stenting with good short- and long-term results.

Editor's Choice - Hybrid vs. Open Surgical Reconstruction for Iliofemoral Occlusive Disease: A Prospective Randomised Trial.

OBJECTIVE: The aim of this non-inferiority randomised trial was to compare the short and midterm safety and efficacy of hybrid repair (HR) and open reconstruction (OR) for patients with co-existing iliac and common femoral artery (CFA) occlusive disease. METHODS: The study was registered on the ClinicalTrials.gov register (identifier: NCT02580084). From 2015 to 2017, eligible patients presenting with combined iliac and CFA occlusive disease were randomised to either HR or OR. HR group patients underwent recanalisation and stenting of iliac arteries combined with CFA endarterectomy and patch angioplasty. The OR group underwent aortofemoral bypass with simultaneous CFA endarterectomy. Short (30 day) and midterm (36 month) outcomes including morbidity, mortality, and patency rates were compared between groups. RESULTS: Of 427 patients assessed, 202 were randomised (102 HR and 100 OR). The average hospital length of stay was shorter in the HR group (8.2 ± 4.2 days HR group vs. 15.7 ± 6.9 days OR group, p < .001); the 30 day peri-operative morbidity rate was 8.8% in the HR group vs. 21% in the OR group (p = .030). There was no significant difference in the 36 month mortality rate (p = .16). The cumulative primary patency rates were 93% (HR) vs. 93% (OR) at 12 months and 91% (HR) vs. 89% (OR) at 36 months (p = .38). The limb salvage rates were 99% (HR) vs. 99% (OR) at 12 months and 98% (HR) vs. 97% (OR) at 36 months (p = .49). CONCLUSION: The results of this first non-inferiority randomised study support the safety and midterm efficacy of hybrid procedures for patients with iliofemoral peripheral arterial disease. HR patients had a shorter length of stay with reduced peri-operative morbidity and similar medium term patency rates.

The effect of the stented iliac lesions TASC-II C, D on the femoropopliteal bypass patency: Propensity score-matched observational study.

INTRODUCTION: Concurrent stenting of complex iliac lesions during infrainguinal bypasses can increase the complexity of a case and impact outcomes. OBJECTIVE: Our aim was to evaluate the effect of inflow stenting of TASC-II C, D iliac lesions on femoropopliteal bypass patency. METHODS: A retrospective observational cohort study of patients who underwent femoropopliteal bypass with TASC-II C, D iliac artery stenting (hybrid group) or without inflow lesions (non-hybrid group) was conducted. After propensity score matching, 120 patients were included in the non-hybrid group and 60 patients in the hybrid one. The median follow-up was 432 (193; 1313) days in the hybrid group and 472 (196; 1376) days in the non-hybrid group (p = 0.94). RESULTS: No significant differences were found between the groups in 30-day morbidity and serious adverse events. At 3 years, primary and secondary bypass patency for the hybrid group and non-hybrid group were 62.2% versus 59.9% (p = 0.36) and 63.7% versus 64.3% (p = 0.077), respectively. The primary patency of the iliac stents in patients of the hybrid group was 95% at 3 years. The estimated hazard ratio for primary patency for hybrid versus non-hybrid was 0.77, with 90% CI: 0.50-1.21; the noninferiority upper bound being 1.31, which corresponds to a 10% additive noninferiority margin for probabilities. The 3 years of freedom from amputation in patients with chronic limb-threatening ischemia was 94.1% and 75.0% in the hybrid and non-hybrid groups, respectively (p = 0.09). CONCLUSION: The outcomes of the femoropopliteal bypass in hybrid surgery supplemented with stenting of TASC-II C, D iliac lesions was similar to femoropopliteal bypass with intact inflow arteries.

Comparative Analysis of Carotid Artery Stenting and Carotid Endarterectomy in Clinical Practice.

The objective of the study was to describe immediate and long-term results of carotid endarterectomy (CEA) versus carotid stenting (CAS) with embolic protection in patients with severe carotid artery stenosis in clinical practice. MATERIALS AND METHODS: This is a retrospective cohort study, conducted between 2009 and 2017. During the analyzed period, 2132 operations (2006 patients) were performed: 1215 (57%) CEA and 917 (43%) CAS. 278 patients (13.8% of 2006) were not contactable during the follow-up period (>30 days) leaving 1791 cases (1728 patients) for inclusion in the analysis. Propensity score matching was used to compare the treatment results of groups (561 cases were matched out of 1791). The results of 615 CEA (316 eversion, 299 "classic" with patch) and 615 CAS (using a variety of carotid stents) were compared. RESULTS: In the asymptomatic subgroup (n = 455), the 30-day rate of stroke was not significantly different between the CEA group and the CAS group (1.5% versus 2.4%, P = .48). The 5-year rate of stroke was not significantly higher for CAS than for CEA (4.6% versus 3.3%, P = .3). In the symptomatic subgroup (n = 160), the 30-day rate of stroke was significantly higher in the CAS group than in the CEA group (7.5% versus 2.5%, P = .04). The 5-year rate of stroke was 13% for CAS and 8.7% for CEA (P = .2). CONCLUSIONS: In the symptomatic subgroup, the 30-day rate of stroke was significantly higher in the CAS group than in the CEA group, therefore the use of CAS for symptomatic patients in routine practice should be limited. Our study demonstrates that the rates of stroke and survival after CEA and CAS in patients aged 80 years or younger with asymptomatic or symptomatic severe carotid stenosis did not differ significantly over a period of 5 years.

The roles of mechanotransduction, vascular wall cells, and blood cells in atheroma induction.

BACKGROUND: This paper describes and analyzes the cellular and molecular mechanisms underlying atherosclerosis development. In particular, the roles of monocytes/macrophages, smooth muscle cells, and vascular endothelium in the formation of stable/unstable atheromatous plaques, and the contributions of some processes to atheroma formation. METHODS AND RESULTS: In this study we analyzed endothelium: function, dysfunction, and involvement into atherogenesis; cell proteins mediating mechanotransduction; proatherogenic role of monocytes; the role of macrophages in the development of unstable atheromatous plaques and smooth muscle cell origin in atherosclerosis. Smooth muscle cell phenotypic switching; their functioning; the ability to retain cholesterol and lipoproteins as well as secretion of pro- and anti-inflammatory molecules and extracellular matrix proteins, their response to extracellular stimuli secreted by other cells, and the effect of smooth muscle cells on the cells surrounding atheromatous plaques are fundamentally important for the insight into atherosclerosis molecular basis. CONCLUSION: Atheromatous plaque transcriptome studies will be helpful in the identification of the key genes involved in atheroma transformation and development as well as discovery of the new targets for diagnosis and therapy.

Carotid Endarterectomy with Autoarterial Remodeling of Bifurcation of the Common Carotid Artery and Carotid Endarterectomy with Patch Closure: Comparison of Methods.

BACKGROUND: The objectives of our research were to identify whether the new method of carotid endarterectomy (CEA) with autoarterial remodeling of bifurcation of the common carotid artery (ARBCCA) influences daily parameters of blood pressure and heart rate (HR) while monitoring them on a daily basis and to assess the efficacy of the suggested method. MATERIALS AND METHODS: It is a prospective randomized comparative study. The first group (n = 100) included patients that underwent ARBCCA, the second group (n = 100) included patients that underwent "classic" CEA with xenopericardial patch closure. Diurnal Holter recording of blood pressure and (HR) was performed before and after the surgical treatment in both groups. RESULTS: Surgical treatment in both groups leads to an increase of HR, arterial hypertension time index by systolic blood pressure, and arterial hypertension time index by diastolic arterial blood pressure. The damage of carotid artery bulb increases sympathetic innervation and causes dysregulation of the baroreceptor mechanism. CONCLUSIONS: In our study, we did not reveal a significant difference in the incidence of postoperative hypertension and the dependence of HR on the choice of surgical technique. Thus, the proposed ARBCCA method does not lead to an increased risk of pre-existing arterial hypertension development. A significant difference is found out on the parameter of the clamping time of carotid arteries in favor to ARBCCA group. Another advantage of the suggested technique is the number of restenosis greater than 50% during the 2-year follow-up (4 [4%] cases (ARBCCA group) versus 12 [12%] cases ["classic" CEA], respectively, P = .037).

Mechanisms Underlying Atheroma Induction: The Roles of Mechanotransduction, Vascular Wall Cells, and Blood Cells.

BACKGROUND: The objective of this article is to review cellular mechanism of atherosclerosis (AS) development. The pathogenesis of AS comprises a sequence of biological events leading to build up of a dense or loose atheromatous plaque (AP). METHODS: In this review, we tried to attempt to analyze the cellular mechanisms underlying AS development, including the roles of monocytes/macrophages and smooth muscle cells in the formation of stable/unstable APs. RESULTS: As a rule, APs are formed in the regions with irregular blood flow; both mechanical perturbations of the vascular wall and several biological events contribute to plaque formation. Blood lipid/lipoprotein deposition, recruitment of monocytes/macrophages, foam cell formation, migration and proliferation of smooth muscle cells, secretion of extracellular matrix, and formation of the connective tissue in plaques are among the latter events. CONCLUSIONS: The review briefs the contributions of different processes to atheroma formation and describes the molecular mechanisms involved in AS development. AP transcriptome studies will be helpful in the identification of the key genes involved in atheroma transformation and development as well as discovery of the new targets for diagnosis and therapy.

Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) pathway activation in squamous cell carcinoma of the head and neck contributes to treatment resistance and disease progression. Buparlisib, a pan-PI3K inhibitor, has shown preclinical antitumour activity and objective responses in patients with epithelial malignancies. We assessed whether the addition of buparlisib to paclitaxel improves clinical outcomes compared with paclitaxel and placebo in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. METHODS: In this multicentre, randomised, double-blind, placebo-controlled phase 2 study (BERIL-1), we recruited patients aged 18 years and older with histologically or cytologically confirmed recurrent and metastatic squamous cell carcinoma of the head and neck after disease progression on or after one previous platinum-based chemotherapy regimen in the metastatic setting. Eligible patients were enrolled from 58 centres across 18 countries and randomly assigned (1:1) to receive second-line oral buparlisib (100 mg once daily) or placebo, plus intravenous paclitaxel (80 mg/m2 on days 1, 8, 15, and 22) in 28 day treatment cycles. Randomisation was done via a central patient screening and randomisation system with an interactive (voice and web) response system and stratification by number of previous lines of therapy in the recurrent and metastatic setting and study site. Patients and investigators (including local radiologists) were masked to treatment assignment from randomisation until the final overall survival analysis. The primary endpoint was progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in all randomly assigned patients. Efficacy analyses were done on the intention-to-treat population, whereas safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received. This trial is registered with ClinicalTrials.gov, number NCT01852292, and is ongoing but no longer enrolling patients. FINDINGS: Between Nov 5, 2013, and May 5, 2015, 158 patients were enrolled and randomly assigned to receive either buparlisib plus paclitaxel (n=79) or placebo plus paclitaxel (n=79). Median progression-free survival was 4·6 months (95% CI 3·5-5·3) in the buparlisib group and 3·5 months (2·2-3·7) in the placebo group (hazard ratio 0·65 [95% CI 0·45-0·95], nominal one-sided p=0·011). Grade 3-4 adverse events were reported in 62 (82%) of 76 patients in the buparlisib group and 56 (72%) of 78 patients in the placebo group. The most common grade 3-4 adverse events (occurring in ≥10% of patients in the buparlisib group vs the placebo group) were hyperglycaemia (17 [22%] of 76 vs two [3%] of 78), anaemia (14 [18%] vs nine [12%]), neutropenia (13 [17%] vs four [5%]), and fatigue (six [8%] vs eight [10%]). Serious adverse events (regardless of relation to study treatment) were reported for 43 (57%) of 76 patients in the buparlisib group and 37 (47%) of 78 in the placebo group. On-treatment deaths occurred in 15 (20%) of 76 patients in the buparlisib group and 17 (22%) of 78 patients in the placebo group; most were caused by disease progression and none were judged to be related to study treatment. INTERPRETATION: On the basis of the improved clinical efficacy with a manageable safety profile, the results of this randomised phase 2 study suggest that buparlisib in combination with paclitaxel could be an effective second-line treatment for patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck. Further phase 3 studies are warranted to confirm this phase 2 finding. FUNDING: Novartis Pharmaceuticals Corporation.

Systemic Thrombolytic Therapy and Catheter-Directed Fragmentation with Local Thrombolytic Therapy in Patients with Pulmonary Embolism.

BACKGROUND: The objective was to compare immediate and long-term results of systemic thrombolytic therapy (STT) and catheter-directed fragmentation (CDF) with local thrombolytic therapy (LTT) in patients with massive pulmonary embolism (PE). METHODS: About 209 patients with massive PE (the high risk of early death) were included in our study. From 2008 till 2010 in the first group (n = 102), STT was performed. From 2011 till 2013 in the second group (n = 107), CDF with LTT was carried out. Echocardiography and pulmonary arteriography were performed in all patients on admission to hospital and in 5 days after treatment. The patients of both groups were re-examined in 6 months, 1, 2, and 3 years after the operation. RESULTS: In the first group, there were 5 (4.9%) cases of in-hospital 30-day mortality. In the second group, there was 1 (0.9%) case of in-hospital 30-day mortality (P = 0.08). In the first group, a clinically significant bleeding was noted in 4 (3.9%) cases, but it caused mortality only in 1 case. In the second group, the clinically significant bleeding was not found (P = 0.038). Persistent postembolic pulmonary hypertension (PPPH) in 9.8% cases of patients in the first group and 2.9% cases of patients in the second group was determined (P = 0.048). CONCLUSIONS: CDF combined with LTT is an effective minimal invasive treatment (helped us to reduce significantly the number of bleeding and PPPH cases), at least in the midterm, in patients with massive PE.

The role of stump pressure and cerebral oximetry in predicting ischaemic brain damage during carotid endarterectomy.

Objective is to compare the predictive value of stump pressure (SP) and cerebral oximetry (rSO2) levels in the evaluation of ischaemic injury of the cerebrum during clamping of the carotid artery (CCA) without temporary shunt (TS). Methods We included 84 patients with an asymptomatic stenosis (>70%) of the internal carotid artery (ICA) who underwent carotid endarterectomy (CEA) under GA. Cerebral ischaemic tolerance (CIT) was determined on the basis of SP, rSO2 and ∆rSO2 (↓rSO2 from baseline) during CCA. The levels of S100 protein (S100) and neuron-specific enolase (NSE) were measured on each stage of the study. MRI was performed for all patients. Results There were no perioperative strokes and myocardial infarctions during the study. Temporary shutdown of blood flow in CAs during CEA is accompanied by a significant elevation of S100, NSE concentration with their subsequent restoration (three days after surgery). ROC analysis showed that none of the methods for CIT assessment (SP, rSO2 and ∆rSO2) was a valuable predictor of cerebral damage during CEA. Conclusion SP with a threshold value of ≤40 mmHg has an average quality of prediction (AUC = 63). ∆rSO2 of ≥20% and a threshold value of rSO2 ≤ 40% have an unsatisfactory quality of prediction (AUC < 60).

Endovascular Treatment of the Subclavian Artery Steno-Occlusive Disease.

OBJECTIVE: The aim of our study was to compare immediate and long-term results of endovascular interventions for the treatment of steno-occlusive disease of subclavian arteries (SAs) depending on the length of lesion. MATERIALS AND METHODS: Between 2010 and 2013, we performed 245 endovascular procedures to treat patients with atherosclerotic steno-occlusive disease of SAs. All patients were examined and subdivided according to the received results into 2 groups: 125 patients with stenosis of SA were included in the first group and 120 patients with occlusion of SA were included in the second group. The patients were then followed up at 6, 12, 24, 36, and 48 months after endovascular interventions. Follow-up visits contained symptomatic evaluation, clinical assessment with physical examination, complete neurological evaluation, and serial color Doppler ultrasonography. RESULT: Transitory ischemic attacks in the vertebrobasilar system were intraoperatively developed by 1 patient from the first group (.8%) and 3 patients from the second group (2.5%). Reinterventions in the long-term period were carried out in 9 (7.2%) cases in the first group and 12 (10%) cases in the second group (P = .43). The cumulative primary stent patency at 4 years was 89.8% in the first group and 87% in the second group (P = .4). CONCLUSIONS: In the case of SA occlusion on the first stage, it is expedient to carry out endovascular recanalization followed by stenting. Our study revealed an increased risk of stent thrombosis or in-stent restenosis in patients with stents >40 mm.

Hybrid Interventions in the Case of Combined Stenosis of the Carotid Bifurcations and Supra-Aortic Arteries.

OBJECTIVES: The purpose of our study is to describe the technique, safety, and efficacy of hybrid carotid revascularization for the treatment of combined occlusive lesions of the carotid bifurcations and supra-aortic arteries. MATERIALS AND METHODS: We monitored the results of hybrid surgical interventions including carotid endarterectomy (CEA) and stenting either the common carotid artery (CCA) or the brachiocephalic trunk (BCT) in 12 patients. Nine men and 3 women with occlusive atherosclerosis made up the cohort. All surgical interventions were performed with local anesthesia by means of standard operative access to the bifurcation of the carotid artery. After the correction of the proximal stenosis of the CCA or BCT with subsequent angiography, the CEA was performed. The mean follow-up was 33.5 months (range, 6-48). RESULT: Ten patients underwent left CCA stenting in combination with CEA. Among the 10 patients, CEA was performed using the eversion technique in 5 cases and patch angioplasty in the other 5 cases. In the remaining 2 cases, the patients underwent CEA with patch angioplasty of the right internal carotid artery in combination with stenting of the BCT critical stenosis. During the early postoperative period and follow-up to 48 months, a stroke was not registered. CONCLUSION: Hybrid interventions (CEA and stenting of the CCA or BCT) allow combination of the advantages of each method in the treatment of multilevel vascular disease. This study confirms the safety and efficacy of hybrid interventions in a small cohort of patients while emphasizing the need for future randomized controlled trials in larger populations.

The role of asymmetry and volume of thrombotic masses in the formation of local deformation of the aneurysmal-altered vascular wall: An in vivo study and mathematical modeling.

Currently, the primary factor indicating the necessity of an operation for an abdominal aortic aneurysm (AAA) is the diameter at its widest part. However, in practice, a large number of aneurysm ruptures occur before reaching a critical size. This means that the mechanics of aneurysm growth and remodeling have not been fully elucidated. This study presents a novel method for assessing the elastic properties of an aneurysm using an ultrasound technique based on tracking the oscillations of the vascular wall as well as the inner border of the thrombus. Twenty nine patients with AAA and eighteen healthy volunteers were considered. The study presents the stratification of a group of patients according to the elastic properties of the aneurysm, depending on the relative volume of intraluminal thrombus masses. Additionally, the neural network analysis of CT angiography images of these patients shows direct (r = 0.664271) correlation with thrombus volume according to ultrasound data, the reliability of the Spearman correlation is p = 0.000215. The use of finite element numerical analysis made it possible to reveal the mechanism of the negative impact on the AAA integrity of an asymmetrically located intraluminal thrombus. The aneurysm itself is considered as a complex structure consisting of a wall, intraluminal thrombus masses, and areas of calcification. When the thrombus occupies > 70% of the lumen of the aneurysm, the deformations of the outer and inner surfaces of the thrombus have different rates, leading to tensile stresses in the thrombus. This poses a risk of its detachment and subsequent thromboembolism or the rupture of the aneurysm wall. This study is the first to provide a mechanistic explanation for the effects of an asymmetrical intraluminal thrombus in an abdominal aortic aneurysm. The obtained results will help develop more accurate risk criteria for AAA rupture using non-invasive conventional diagnostic methods.