Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

ORGANIZATIONAL ISSUES OF CARDIOREHABILITATION SERVICE IN RUSSIA. THE RESULTS OF PILOT PROJECT “DEVELOPMENT OF REHABILITATION SYSTEM OF CARDIOVASCULAR PATIENTS IN MEDICAL INSTITUTIONS OF RUSSIAN FEDERATION ENTITIES”

Aim. To analyze,  how is, under  the  framework of the  Pilot Project, organized and being conducted  the improvement of work of the known departments in exact medical institutions (MI) of RF for rehabilitation of cardiovascular  diseases (CVD) patients  at the  three  steps  under  the current “Order of medical care and medical rehabilitation”, and how do the scientifically proven and types and methods  of cardiorehabilitation (CR) being implemented,  and to try to elaborate  on an exact algorithm for patients course.Material and methods. Into the Pilot Project, 17 MI included, from 13 entities of RF. For the analysis of effectiveness of organizational models of CR in MI the unified charts were developed making to assess the equality to the  Order  of the  rehabilitation care  provided to patients  with CVD, of multidisciplinary team  involved in care,  the staff list and MI equipment. Specific charts included the units assessing the efficacy of work on three stages of CR: I stage — in resuscitation and intensive care unit or specialized cardiology department, II — in in-patient department, III — in polyclinics. The article presents data from CR analysis of Jan 2013 to Dec 2015. Results. The CR was organized at the stage I in 10 MI, stage II in 10 MI and stage III in 7 MI. By the year 2015, almost in all MI the multidisciplinary teams   were  shaped,   including  cardiologist,  cardiorehabilitologist, exercise specialist, clinical psychologist, physiotherapist; the rooms for exercise were equipped, as the halls for education of patients. The start of rehabilitation process  from ICU made it to decrease the remaining of patient on the bedside for 0,7 days in average (2013-2015) and for 1 day in cardiovascular department. About 67% myocardial infarction patients in average  were transferred  to the stage  II of CR. In all MI there  were educational  Schools  organized,  and  the  explanatory  talks  with the relatives were done as well. By now, the project is on its way. Conclusion. The analysis of three-staged CR system  for myocardial infarction  patients   according   to  current   laws,  showed  significant improvement  of  rehabilitational  activeness   of  the  newly  created multidisciplinary teams  at all stages  of CR, increase  of the number of methods  of CR and  better  fulfillment of those,  as  demonstrated the safety of proposed  principals of physical rehabilitation according to the Russian  clinical guidelines  “Myocardial infarction with ST elevation: rehabilitation and  secondary  prevention” under  the framework of the organizational model of CR

International register “Dynamics analysis of comorbidities in SARS-CoV-2 survivors” (AKTIV SARS-CoV-2): analysis of 1,000 patients

COVID-19 is a severe infection with high mortality. The concept of the disease has been shaped to a greater extent on the basis of large registers from the USA, Spain, Italy, and China. However, there is no information on the disease characteristics in Caucasian patients.Therefore, we created an international register with the estimated capacity of 5,000 patients — Dynamics Analysis of Comorbidities in SARS-CoV-2 Survivors (AKTIV SARS-CoV-2), which brought together professionals from the Russian Federation, Republic of Armenia, Republic of Kazakhstan, and Kyrgyz Republic. The article presents the first analysis of the register involving 1,003 patients. It was shown that the most significant difference of the Caucasian population was the higher effect of multimorbidity on the mortality risk vs other registers. More pronounced effect on mortality of such diseases as diabetes, obesity, hypertension, chronic kidney disease, and age over 60 years was also revealed