Isoprostane-8 and GDF-15 as novel markers of post-PE syndrome: Relation with prothrombotic factors.

BACKGROUND: Post-pulmonary embolism (PE) syndrome occurs in up to 50% of PE patients. The pathophysiology of this syndrome is obscure. OBJECTIVE: We investigated whether enhanced oxidative stress and prothrombotic state may be involved in post-PE syndrome. METHODS: We studied 101 normotensive noncancer PE patients (aged 56.5 ± 13.9 years) on admission, after 5-7 days and after a 3-month anticoagulation, mostly with rivaroxaban. A marker of oxidative stress, 8-isoprostane, endogenous thrombin potential, fibrinolysis proteins, clot lysis time (CLT) and fibrin clot permeability (Ks ), along with PE biomarkers, were determined. RESULTS: Patients who developed the post-PE syndrome (n = 31, 30.7%) had at baseline 77.6% higher N-terminal brain natriuretic propeptide and 46.8% higher growth differentiation factor 15, along with 14.1% longer CLT associated with 34.4% higher plasminogen activator inhibitor-1 as compared to subjects without post-PE syndrome (all P < .05). After 5-7 days, only hypofibrinolysis was noted in post-PE syndrome patients. When measured at 3 months, prolonged CLT and reduced Ks were observed in post-PE syndrome patients, accompanied by 23.8% higher growth differentiation factor 15 and 35.8% higher plasminogen activator inhibitor-1 (all P < .05). 8-isoprostane levels ≥108 pg/ml (odds ratio=4.36; 95% confidence interval 1.63-12.27) and growth differentiation factor 15 ≥ 1529 pg/ml (odds ratio=3.89; 95% confidence interval 1.29-12.16) measured at 3 months were associated with higher risk of developing post-PE syndrome. CONCLUSIONS: Enhanced oxidative stress and prothrombotic fibrin clot properties could be involved in the pathogenesis of the post-PE syndrome. Elevated growth differentiation factor 15 assessed at 3 months might be a new biomarker of this syndrome.

Nanoantibiotics containing membrane-active human cathelicidin LL-37 or synthetic ceragenins attached to the surface of magnetic nanoparticles as novel and innovative therapeutic tools: current status and potential future applications.

Nanotechnology-based therapeutic approaches have attracted attention of scientists, in particular due to the special features of nanomaterials, such as adequate biocompatibility, ability to improve therapeutic efficiency of incorporated drugs and to limit their adverse effects. Among a variety of reported nanomaterials for biomedical applications, metal and metal oxide-based nanoparticles offer unique physicochemical properties allowing their use in combination with conventional antimicrobials and as magnetic field-controlled drug delivery nanocarriers. An ever-growing number of studies demonstrate that by combining magnetic nanoparticles with membrane-active, natural human cathelicidin-derived LL-37 peptide, and its synthetic mimics such as ceragenins, innovative nanoagents might be developed. Between others, they demonstrate high clinical potential as antimicrobial, anti-cancer, immunomodulatory and regenerative agents. Due to continuous research, knowledge on pleiotropic character of natural antibacterial peptides and their mimics is growing, and it is justifying to stay that the therapeutic potential of nanosystems containing membrane active compounds has not been exhausted yet.

Lead-related infective endocarditis: factors influencing the formation of large vegetations.

AIMS: The presence of intracardiac lead vegetations (ILV) is one of the important criteria for diagnosis of lead-related infective endocarditis (LRIE). The objective of the present study was to evaluate risk factors of ILV and their impact on vegetation size. METHODS AND RESULTS: Clinical data of 500 patients with LRIE undergoing transvenous lead extraction in 2006-15 were retrospectively analysed. The study population consisted of 352 patients with the presence of vegetations (giant, >3 cm; large, 2.0-2.9 cm; moderate-sized, 1.0-1.9 cm; and small, <1 cm) and 148 patients without ILV. We identified risk factors for vegetation occurrence and ILV size. Intracardiac lead vegetations were found more frequently in younger patients (P < 0.05), slightly more often in women (P = 0.084), and less commonly in patients with atrial fibrillation (P < 0.05). Intracardiac lead vegetation occurred significantly more frequently in patients with intracardiac lead abrasion (OR 2.373; 95% CI [1.497-3.765]; P < 0.001) and much less frequently in the concomitant presence of pocket infection (PI) (OR 0.127; 95% CI [0.074-0.218]; P < 0.00). Large vegetations were significantly more common in patients with renal failure (RF) (P < 0.001), heart failure (P < 0.001), implantable cardioverter defibrillator (P < 0.05), and loops of the leads (P < 0.001). CONCLUSION: Intracardiac lead abrasion is one of the most common factors influencing the occurrence of ILV. Metabolic disorders in patients with RF, heart failure, defibrillation leads, and loops of the leads were found to contribute to the formation of large vegetations. In LRIE patients, ILVs were less frequently detected in the presence of concomitant PI, indicating a different mechanism of LRIE development in patients with and without vegetations.

Adverse outcomes in patients with atrial fibrillation and peripheral arterial disease: a report from the EURObservational research programme pilot survey on atrial fibrillation.

AIMS: Peripheral arterial disease (PAD) is highly prevalent in general population. Data on the prevalence of symptomatic PAD in patients with atrial fibrillation (AF) are limited, and the impact of PAD on adverse outcomes in AF patients is controversial. Our aims were: (i) to define the prevalence of symptomatic PAD in European AF patients and describe its associated clinical risk factors and (ii) to establish the relationship of PAD to adverse events in AF, especially all-cause death. METHODS AND RESULTS: Atrial fibrillation patients enrolled in the EORP-AF Pilot study with data about PAD status were included in this analysis. Event rates were determined at 1-year follow-up. Peripheral arterial disease was recorded in 328 (11%) patients. Age (P < 0.0001), hypertension (P = 0.0059), diabetes mellitus (P = 0.0001), chronic heart failure (P < 0.0001), previous stroke/transient ischaemic attack (P = 0.0060), and antiplatelet drug treatment (P = 0.0001) were associated with the presence of PAD, while female gender was inversely associated (P = 0.0002). Peripheral arterial disease patients had higher absolute rates of both cardiovascular (CV) and all-cause death (both P < 0.0001). On Kaplan-Meier analysis, risk of all-cause death was higher in PAD patients compared with those without PAD (P < 0.0001), but PAD did not emerge as an independent risk factor for mortality on Cox regression analysis. A lower risk of all-cause death was associated with the prescription of statins (P = 0.0019), angiotensin-converting enzyme inhibitors (P = 0.0008), and calcium-channel blockers (P = 0.0071). CONCLUSION: Peripheral arterial disease is prevalent in 11% of AF patients and related to various atherosclerotic risk factors. Even if PAD is associated with higher risk of all-cause death on univariate analysis, this risk was significantly lowered and was no longer evident after adjusting for the use of CV prevention drugs.

[Modern pharmacotherapy in heart failure with reduced ejection fraction: is further improvement in prognosis possible?].

A growing number of patients with chronic heart failure (CHF) is a combined result of aging and, paradoxically, the progress in management of cardiovascular diseases. The modern pharmacotherapy of HF with reduced ejection fraction (HFrEF) is based on the understanding of excessive neurohormonal activation as a key point in the pathophysiology and progression of HFrEF. The introduction of neurohormonal modifiers decreased significantly the mortality, survival and acute cardiac death rate. However, the rate of hospitalization increased and the quality of life is still poor. There is a large body of evidence on disease progression and mechanical heart failure as a main cause of death. The improvement in survival and decreasing the hospitalization rate remain a real challenge. The risk of death is the highest in the first weeks following hospitalization due to HF. The maintenance of stable patient condition is the priority of management. Pharmacotherapy at discharge should be optimized according to the prognostic factors to modify the clinical course of disease. Data from registries suggest that target doses are not reached and dose titration is not performed in outpatient clinics as it should be done according to guidelines. Taken together, the system of complex management of patients with HF focused on the management on discharge and early post-discharge period seems to be the best solution to identify the HF progression factors (suboptimal therapy, lack of revascularization, arrhythmia, concomitant diseases) and to improve the prognosis and the quality of life and to decrease the hospitalization rate.

[Analysis of the incidence and causes of repeated surgical interventions in patients with early complications electrotherapy - 1 center experience from the period 2012-2015].

Baclground: Due to increasing number of patients treated by cardiac implantable electronic devices we observe increasing number of complications after these procedures Material and methods: We analysed causes of early surgical revision of implantable devices connected with 1673 procedures of implantation (871 procedures) or exchange (802 procedures) of pacing systems (PM), cardioverter-difibrillators (ICD) and resynchronisation systems (CRT) in one local centre of electrotherapy in years 2012 to 2015. We characterised risk factors and its influence on encountered complications. Results: In analysed period 72 reinterventions after implantations or exchanges of PM/ICD/CRT were performed. Main causes of early complications were: lead malfunction (2.5%), including the dislodgement of the leads in 1.9%, pocket hematoma (1.4%) and other abnormalities of the pocket (0.4 %), including pocket infections in 0.2%. The most important risk factors of early complications were often implantations of the leads with passive fixation and anticoagulation therapy in perioperative period. Conclusions: The knowledge of the early complications after implantations and exchanges of PM/ICD/CRT should improve the safety of procedures through more often used of the leads with active fixation and properly preparation of the patients requering the antithrombic therapy.

Lead-Dependent Infective Endocarditis: The Role of Factors Predisposing to Its Development in an Analysis of 414 Clinical Cases.

BACKGROUND: Lead-dependent infective endocarditis (LDIE) is a serious and insidious infective disease spreading along the leads to valve leaflets and endocardial surface. LDIE is still a lesser known disease with unclear risk factors, most often evaluated jointly for all infectious complications. METHODS: Clinical data from 414 patients with the diagnosis of LDIE according to the Modified Duke Leads Criteria were analyzed. Patients with LDIE were identified in a population of 1,426 subjects submitted to transvenous lead extraction (TLE) in the Reference Center on Lead Extraction in Lublin, Poland, between March 2006 and July 2013 due to infectious (619 patients-43.4%) and noninfectious (807-56.6% of patients) reasons. During the period of 2006-2011, the analysis was conducted retrospectively; from early 2012 on, patients were enrolled prospectively. The effect of potential risk factors on the development of the disease was evaluated in a comparative analysis of clinical data from the LDIE patients and from 807 subjects with noninfectious indications for TLE. Additionally, in order to identify the factors predisposing to the development of LDIE, the population of infectious patients was divided into three subgroups: with isolated LDIE (157 patients), with LDIE and pocket infection (PI; 257 patients), and with isolated PI (205 patients). The groups and subgroups were analyzed for the presence of patient-dependent risk factors (age, gender, accompanying diseases, anticoagulation, or antiplatelet therapy) and procedure-related risk factors (the number and lead dwell time, pacing system, prior procedures, lead loops, and intracardiac abrasion of the leads). Furthermore, microbes' identification was conducted. RESULTS: The LDIE patients were older (67.3 vs 62.3; P = 0.001) and were more frequently male (68.6% vs 55.0%; P = 0.001) as compared with patients submitted to TLE for noninfectious reasons, but not in comparison with subjects diagnosed with isolated LDIE. In univariate analysis, the independent prognostic factors of LDIE were: type 2 diabetes-increase of risk by 37.7% (hazard ratio [HR] = 1,377; 95% confidence interval [CI] [1,088-1,742]), elevated above 2 mg% creatinine level-increase of risk by 61.5% (HR = 1,615; 95% CI [1,96-2,182]), antiplatelet therapy (HR = 1,285; 95% CI [1,052-1,057]), number of intracardiac leads prior to TLE (HR = 1,199; 95% CI [1,075-1,337]), intracardiac device with implantable cardioverter defibrillator (ICD) lead (HR = 1,909; 95% CI [1,492-2,444]), intracardiac device with coronary sinus lead (HR = 1,411; 95% CI [1,099-1,810]), number of procedures prior to TLE (HR = 1,092; 95% CI [1,017-1,172]), and abrasion of intracardiac leads (HR = 1,350; 95% CI [1,097-1,662]). Multivariate logistic regression demonstrated that the independent risk factors of LDIE were: chronic renal failure (HR = 1,406; 95% CI [1,033-1,915]), number of intracardiac leads prior to TLE (HR = 1,152; 95% CI [1,017-1,305]), intracardiac devices with ICD leads (HR = 1,719; 95% CI [1,330-2,223]), and presence of abrasion of intracardiac leads (HR = 1,405; 95% CI [1,129-1,750]). Microbiological analysis showed the domination of coagulase-negative staphylococci with relative advantage of Staphylococcus epidermidis in pathogenesis of LDIE. CONCLUSIONS: The factors predisposing to LDIE are mainly related to procedures performed on the patients. LDIE develops more frequently in patients with multiple leads, especially ICD. An important, until now lesser known, risk factor for LDIE is intracardiac abrasion of the leads strongly connected with procedural agents and properties of specific kind of bacteries. A new concept of the pathogenesis of LDIE was proposed on the basis of present analysis.

[Acute myocardia infarction associated with pregnancy]. / Zawal serca u kobiet w ciazy.

Pregnancy-associated myocardial infarction is rare but potentially fatal. Clinical course is different from nonpregnant patients. As it is predominantly non-atherosclerotic in origin, optimal treatment is not unequivocally established. Common anterior wall involvement results in developing of heart failure and its complications. There is a high risk of coronary artery dissection during percutaneous interventions. Pharmacological treatment, beneficial for mother, may be harmful for fetus. Long term prognosis is unclear.

[Ventricular and supraventricular arrhythmias in women]. / Nadkomorowe i komorowe zaburzenia rytmu--skala problemu u kobiet.

There are few gender-related differences in electrophysiology regarding occurrence, clinical symptoms and prognosis of arrhythmias. Women tend to have higher incidence of sinus tachycardia and atrio-ventricular nodal re-entry tachycardia. Atrial fibrillation is more frequent among men, but women have worse prognosis as their mortality is higher, "rhythm control" strategy is less favorable and the thromboembolic risk is greater. Ventricular arrhythmias are less common in women and their significance is smaller. As women have longer QTc interval and torsade de pointes is typical women's arrhythmia, physicians must be very careful ordering QT-elongating drugs. Coronary heart disease (CHD) is seldom background for ventricular tachycardia and women with CHD and arrhythmias have better prognosis than men. Sex hormones play important role in women's electrophysiology. Pregnancy increase risk of supraventricular tachycardia and decrease occurrence of torsade de pointes.

[Transcatheter aortic valve implantation and its place in the contemporary treatment]. / Przezskórna implantacja zastawki aortalnej -- miejsce we wspólczesnej terapii.

Symptomatic stenosis of the aortic valve has recently been an important clinical issue. On one hand the number of patients who need surgical treatment of valve failure is increasing. On the other hand their general state of health and concomitant diseases determine that they are disqualified from surgery. The trasncutaneus technique of replacement of the aortic valve is for these patients a promising alternative. Therefore TAVI procedures have been developed and the number of performed transcatheter aortic valve replacements is still increasing. Although it would appear unlikely that TAVI could replace traditional surgery in the nearest future, it remains a possible treatment option for some of the high risk patients not suitable for surgery.

[Early invasive strategy in patients with myocardial infarction and intraventricular conduction disturbances and plasma B-type natriuretic peptide levels assessed 6 months after myocardial infarction]. / Wczesna strategia inwazyjna u chorych z zawalem serca i zaburzeniami przewodzenia sródkomorowego a stezenie peptydu natriuretycznego typu B w surowicy oceniany 6 miesiecy po zawale serca.

UNLABELLED: The aim of the study was to assess plasma B-type natriuretic peptide (BNP) levels in patients after myocardial infarction (MI) with intraventricular conduction defects (IVCD) and to define relationship between BNP level, treatment strategy and left ventricular performance. MATERIAL AND METHODS: Four types of IVCD were noted: left bundle branch block (LBBB), right bundle branch block (RBBB), left anterior hemiblock (LAH) and left posterior hemiblock (LPH). A total of 158 patients six months after MI treated either invasively or conservatively were included. Of them 126 had IVCD (group A): LBBB-31, RBBB-36, LAH-130, LPH-29, whereas 32 patients without IVCD served as controls (group B). Plasma BNP levels were measured using an immunoenzymatic method. All subjects underwent echocardiography to evaluate left ventricular function. RESULTS: In group A significantly lower plasma BNP levels (186.3 vs 355.3 pg/mL; p < 0.01) and significantly higher left ventricular ejection fraction (EF) (48.4 vs 42.4%; p < 0.05) were noted in favour of invasive treatment. In group B differences between plasma BNP level and echocardiographic parameters of left ventricle function were insignificant. In patients with LBBB plasma BNP levels were significantly lower in those treated invasively (163.9 vs 528.9; p < 0.01). Also, left ventricular EF and myocardial performance index (MPI) were comparable, whereas E/A value was lower as compared with patients treated conservatively (p < 0.05). There were no significant differences in BNP levels in groups with RBBB, LAH and LPH. Multifactorial regression analysis showed that BNP levels were most strongly correlated with magnitude of the ejection fraction EF (p < 0.001). Other parameters which affect significantly BNP level were MPI: OR 9.07 (95% CI 1.03-79.58; p < 0.05) and E/A: OR 6.58 (95% CI 1.01-42.76; p < 0.05). CONCLUSIONS: Invasive strategy in MI with IVCD, especially with LBBB, correlates with lower plasma BNP levels six months after index procedure. In patients with IVCD post MI plasma BNP level is better marker of dysfunction of the left ventricle than its ejection fraction.

[Sudden cardiac arrest in ventricular fibrillation mechanism as a first manifestation of primary mitral valve prolapse]. / Nagle zatrzymanie krazenia w mechanizmie migotania komór jako pierwsza manifestacja pierwotnego wypadania platka zastawki mitralnej.

We present the case of a 58 year-old patient with a primary mitral valve prolapse (MVP) at whose first manifestation of the disease was a sudden cardiac death (SCD) in ventricular fibrillation mechanism. In ECG paroxysmal atrial fibrillation was detected. The arrhythmia became persistent atrial fibrillation but in ECG sinus rhythm recording, QT dispersion occurred. In the echocardiography we found a classic MVP syndrome with large mitral regurgitation, preserved left ventricular systolic function and recent infective endocarditis features on posterior cusp of mitral valve. In the computed tomography of the head we found acute and recent history of stroke. The patient was qualified for implantable cardioverter-defibrillators (ICD) implantation as a secondary SCD preventive treatment. An artificial mitral valve was implanted. In the long-term observation (36 month) two adequate ICD interventions caused by ventricular tachycardia were recorded. General condition of the patient remains stable.

A female pattern of ischemic heart disease--a new look at an old problem.

Diseases of the circulatory system are the most common cause of death among women. It should be emphasized that this problem is still underestimated in daily practice. As women are less likely to have significant stenosis in coronary angiography than men, they are regarded to be at smaller risk. At the same time, numerous studies prove that the prognosis of women with ischemic heart disease is serious. Therefore, some researchers suggest distinguishing the so-called "female pattern" of ischemic heart disease, characterized by persistent, often atypical chest pain, positive results for noninvasive tests evaluating ischemia and no significant changes in coronary angiography. It is relevant in the diagnosis of women to assess the global risk, taking into consideration such parameters as inflammation indicators, endothelial dysfunction and microvascular reactivity. There is still no data on optimal treatment, but there seems to be a clear benefit from intensive modification and elimination of risk factors, as well as typical pharmacotherapy with angiotensin-converting enzyme inhibitors, beta-blockers and statins.

Altered plasma fibrin clot properties are associated with in-stent thrombosis.

OBJECTIVE: We sought to investigate whether patients with in-stent thrombosis (IST) display altered plasma fibrin clot properties. METHODS AND RESULTS: We studied 47 definite IST patients, including 15 with acute, 26 subacute and 6 late IST, and 48 controls matched for demographics, cardiovascular risk factors, concomitant treatment and angiographic/stent parameters. Plasma clot permeability (K(s)), which indicates a pore size, turbidity (lag phase, indicating the rate of fibrin clot formation, DeltaAbs(max), maximum absorbance of a fibrin gel, reflecting the fiber thickness), lysis time (t(50%)) and maximum rate of D-dimer release from clots (D-D(rate)) were determined 2 to 73 (median 14.7) months after IST. Patients with IST had 21% lower K(s), 14% higher DeltaAbs(max), 11% lower D-D(rate), 30% longer t(50%) (all P<0.0001) and 5% shorter lag phase compared to controls (P=0.042). There were no correlations between clot variables and the time of IST or that from IST to blood sampling. Multiple regression analysis showed that K(s) (odds ratio=0.36 per 0.1 microm(2), P<0.001), D-D(rate) (odds ratio=0.16 per 0.01 mg/L/min, P<0.001) and stent length (odds ratio=1.1 per 1 mm, P=0.043) were independent predictors of IST (R(2)=0.58, P<0.001). CONCLUSIONS: IST patients tend to form dense fibrin clots resistant to lysis, and altered plasma fibrin clot features might contribute to the occurrence of IST.

Late to early velocity index as a predictor of iatrogenic femoral artery pseudoaneurysm recurrence in patients treated with ultrasound-guided thrombin injection.

INTRODUCTION: Ultrasound-guided thrombin injection (UGTI) is the preferred treatment of pseudoaneurysms (psA). The potential risk of complications increases with the number of UGTI treatments needed for complete psA obliteration. Identification of risk factors for recurrent psA is needed. MATERIAL AND METHODS: In total, 508 patients with femoral artery psA underwent UGTI, followed by ultrasound examination repeated twice, at 1-week intervals, to assess UGTI effectiveness. In cases of psA recurrence, the procedure was repeated. Clinical and ultrasound data were prospectively collected. RESULTS: The psA recurrence occurred in 76 (15%) patients. UGTI was repeated twice in 49 (64%), three times in 15 (20%) and more than three times in 12 (16%) patients. The median thrombin dose was 150 IU (80-250 IU), and was lower in initial procedures than repeated UGTI (p = 0.025). The median psA volume was 2.26 ml (0.86-5.47 ml). The median length of the communicating channel was 4 mm (0-12 mm). A time interval between vessel catheterization and UGTI greater than 7 days (p < 0.001), a late to early velocity index (LEVI) of < 0.2 identified during the outflow phase (p < 0.001), a psA volume > 5 ml (p = 0.032), and a short communicating channel between the psA and the artery (p = 0.037) predicted psA recurrence. Antiplatelet and anticoagulant agents did not increase the risk. CONCLUSIONS: The LEVI and time interval between artery cannulation and UGTI treatment are strong parameters identifying patients at risk of psA recurrence. The psA volume and communicating channel length are less substantial risks, but still significant. Concomitant antiplatelet and anticoagulant therapy do not affect the success rate of UGTI.

Right ventricular echocardiographic parameters associated with prothrombotic abnormalities in normotensive patients with acute pulmonary embolism.

BACKGROUND: In acute pulmonary embolism (PE) right ventricular (RV) pressure overload negatively affects prognosis. Recently we have shown that RV dilatation is associated with a prothrombotic state in PE. We investigated which RV echocardiographic parameters best indicate prothrombotic alterations in acute PE. METHODS: In 121 normotensive, noncancer PE patients, markers of RV dilatation and dysfunction were evaluated on admission using transthoracic echocardiography, along with prothrombotic state markers, i.e. increased endogenous thrombin generation (ETP), low fibrin clot permeability (Ks, a measure of clot density), and prolonged clot lysis time (CLT). RESULTS: RV parasternal long axis (RVOT PLAX) >30 mm was associated with ETP (OR 3.86; 95% CI 1.55-9.62; p = 0.004) and CLT (OR 4.08; 95% CI 1.58-10.54; p = 0.004) in the top quartiles, but not with Ks. RV short parasternal axis (RVOT PSAX) >27 mm showed similar associations with higher ETP (OR 3.54; 95% CI 1.50-8.37; p = 0.004) and prolonged CLT (OR 2.78; 95% CI 1.17-6.62; p = 0.021). RV basal diameter >41 mm solely predicted prolonged CLT (OR 2.93; 95% CI 1.23-6.99; p = 0.016). The right atrium area, pulmonary trunk diameter, and tricuspid regurgitation maximum velocity were not related to prothrombotic markers, except for tricuspid annular plane systolic excursion weakly associated with ETP. Multivariable analysis showed that RVOT PSAX is independently associated with prolonged CLT (OR 1.16; 95% CI 1.04-1.30; p = 0.007), low Ks (OR 1.21; 95% CI 1.02-1.44; p = 0.029), and higher ETP (OR 1.14; 95% CI 1.03-1.26; p = 0.009). CONCLUSIONS: Among RV echocardiographic parameters, the RVOT dilatation measured in PSAX best predicts prothrombotic alterations in PE patients.

ROS-Mediated Apoptosis and Autophagy in Ovarian Cancer Cells Treated with Peanut-Shaped Gold Nanoparticles.

BACKGROUND: Even with considerable improvement in treatment of epithelial ovarian cancer achieved in recent years, an increasing chemotherapy resistance and disease 5-year relapse is recorded for a majority part of patients that encourages the search for better therapeutic options. Gold nanoparticles (Au NPs) due to plethora of unique physiochemical features are thoroughly tested as drug delivery, radiosensitizers, as well as photothermal and photodynamic therapy agents. Importantly, due to highly controlled synthesis, it is possible to obtain nanomaterials with directed size and shape. METHODS: In this work, we developed novel elongated-type gold nanoparticles in the shape of nanopeanuts (AuP NPs) and investigated their cytotoxic potential against ovarian cancer cells SKOV-3 using colorimetric and fluorimetric methods, Western blot, flow cytometry, and fluorescence microscopy. RESULTS: Peanut-shaped gold nanoparticles showed high anti-cancer activity in vitro against SKOV-3 cells at doses of 1-5 ng/mL upon 72 hours treatment. We demonstrate that AuP NPs decrease the viability and proliferation capability of ovarian cancer cells by triggering cell apoptosis and autophagy, as evidenced by flow cytometry and Western blot analyses. The overproduction of reactive oxygen species (ROS) was noted to be a critical mediator of AuP NPs-mediated cell death. CONCLUSION: These data indicate that gold nanopeanuts might be developed as nanotherapeutics against ovarian cancer.

Loose Fibrin Clot Structure and Increased Susceptibility to Lysis Characterize Patients with Central Acute Pulmonary Embolism: The Impact of Isolated Embolism.

BACKGROUND: Prothrombotic fibrin clot properties are associated with higher early mortality risk in acute pulmonary embolism (PE) patients. It is unknown whether different types of PE are associated with particular clot characteristics. METHODS: We assessed 126 normotensive, noncancer acute PE patients (median age: 59 [48-70] years; 52.4% males), who were categorized into central versus peripheral PE with or without concomitant deep vein thrombosis (DVT). Plasma fibrin clot permeability (K s), clot lysis time (CLT), thrombin generation, platelet-derived markers, and fibrinolytic parameters were measured on admission. Plasma fibrin clot morphology was assessed by scanning electron microscopy (SEM). RESULTS: Patients with central PE (n = 76; 60.3%) compared with peripheral PE (n = 50; 39.7%) had 17.8% higher K s and 14.3% shortened CLT (both p < 0.01 after adjustment for potential confounders including fibrinogen), with no differences between segmental and subsegmental PE. SEM analysis demonstrated larger fibrin fiber diameter and pore size in central PE compared with peripheral PE (both p < 0.01). For isolated PE, there was 23.3% higher K s in central PE than in peripheral PE (n = 24; 19%) with no differences in other variables. Central PE combined with DVT (n = 45; 35.7%), as compared with central isolated PE (n = 31; 24.6%), was associated with shortened CLT (all p < 0.05). CONCLUSION: Our findings suggest that looser fibrin networks composed of thicker fibers with increased susceptibility to lysis characterize patients with central PE, suggesting that fibrin clot phenotype affects the size of thrombi occluding the pulmonary arteries, highlighting the role of fibrin structures in thrombus formation and stability.

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study.

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).