Prescribed Versus Taken Polypharmacy and Drug-Drug Interactions in Older Cardiovascular Patients during the COVID-19 Pandemic: Observational Cross-Sectional Analytical Study.

The study aimed to assess clinical pharmacology patterns of prescribed and taken medications in older cardiovascular patients using electronic health records (EHRs) (n = 704) (2019-2022). Medscape Drug Interaction Checker was used to identify pairwise drug-drug interactions (DDIs). Prevalence rates of DDIs were 73.5% and 68.5% among taken and prescribed drugs, respectively. However, the total number of DDIs was significantly higher among the prescribed medications (p < 0.05). Serious DDIs comprised 16% and 7% of all DDIs among the prescribed and taken medications, respectively (p < 0.05). Median numbers of DDIs between the prescribed vs. taken medications were Me = 2, IQR 0-7 vs. Me = 3, IQR 0-7 per record, respectively. Prevalence of polypharmacy was significantly higher among the prescribed medications compared with that among the taken drugs (p < 0.05). Women were taking significantly more drugs and had higher prevalence of polypharmacy and DDIs (p < 0.05). No sex-related differences were observed in the list of prescribed medications. ICD code U07.1 (COVID-19, virus identified) was associated with the highest median DDI number per record. Further research is warranted to improve EHR structure, implement patient engagement in reporting adverse drug reactions, and provide genetic profiling of patients to avoid potentially serious DDIs.

KATP channels are regulators of programmed cell death and targets for the creation of novel drugs against ischemia/reperfusion cardiac injury.

BACKGROUND: The use of percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is associated with a mortality rate of 5%-7%. It is clear that there is an urgent need to develop new drugs that can effectively prevent cardiac reperfusion injury. ATP-sensitive K+ (KATP ) channel openers (KCOs) can be classified as such drugs. RESULTS: KCOs prevent irreversible ischemia and reperfusion injury of the heart. KATP channel opening promotes inhibition of apoptosis, necroptosis, pyroptosis, and stimulation of autophagy. KCOs prevent the development of cardiac adverse remodeling and improve cardiac contractility in reperfusion. KCOs exhibit antiarrhythmic properties and prevent the appearance of the no-reflow phenomenon in animals with coronary artery occlusion and reperfusion. Diabetes mellitus and a cholesterol-enriched diet abolish the cardioprotective effect of KCOs. Nicorandil, a KCO, attenuates major adverse cardiovascular event and the no-reflow phenomenon, reduces infarct size, and decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction. CONCLUSION: The cardioprotective effect of KCOs is mediated by the opening of mitochondrial KATP (mitoKATP ) and sarcolemmal KATP (sarcKATP ) channels, triggered free radicals' production, and kinase activation.

Isolated Atrial Fibrillation, Inflammation and Efficacy of Radiofrequency Ablation: Preliminary Insights Based on a Single-Center Endomyocardial Biopsy Study.

The aim of the study was to evaluate the inflammatory changes in the myocardium, based on endomyocardial biopsy (EMB) data in patients undergoing radiofrequency ablation (RFA) for idiopathic atrial fibrillation (AF). A total of 67 patients with idiopathic AF were enrolled in the study. Patients underwent the intracardiac examination, RFA of AF, and EMB with histological and immunohistochemical studies. The catheter-treatment effectiveness, and occurrence of early and late recurrences of atrial tachyarrhythmias, were assessed depending on the identified histological changes. Nine patients (13.4%) did not have any histological changes in the myocardium according to EMB. Fibrotic changes were detected in 26 cases (38.8%). Inflammatory changes according to the Dallas criteria were observed in 32 patients (47.8%). The follow-up period for patients averaged 19.3 ± 3.7 months. The effectiveness rates of primary RFA were 88.9% in patients with the intact myocardium, 46.2% in patients with fibrotic changes of varying severity, and 34.4% in patients with the presence of criteria for myocarditis. No early recurrence of arrhythmias was observed in patients with unchanged myocardia. The presence of inflammatory and fibrotic changes in the myocardium increased the rates of early and late arrhythmia recurrences and accordingly halved the effectiveness RFA of AF.

Pharmacological Approaches to Limit Ischemic and Reperfusion Injuries of the Heart: Analysis of Experimental and Clinical Data on P2Y12 Receptor Antagonists.

Ischemic and reperfusion injuries of the heart underlie the pathogenesis of acute myocardial infarction (AMI) and sudden cardiac death. The mortality rate is still high and is 5-7% in patients with ST-segment elevation myocardial infarction. The review is devoted to pharmacological approaches to limitation of ischemic and reperfusion injuries of the heart. The article analyzes experimental evidence and the clinical data on the effects of P2Y12 receptor antagonists on the heart's tolerance to ischemia/reperfusion in animals with coronary artery occlusion and reperfusion and also in patients with AMI. Chronic administration of ticagrelor prevented adverse remodeling of the heart. There is evidence that sphingosine-1-phosphate is the molecule that mediates the infarct-reducing effect of P2Y12 receptor antagonists. It was discussed a role of adenosine in the cardioprotective effect of ticagrelor.

Existing and Emerging Approaches to Risk Assessment in Patients with Ascending Thoracic Aortic Dilatation.

Ascending thoracic aortic aneurysm is a life-threatening disease, which is difficult to detect prior to the occurrence of a catastrophe. Epidemiology patterns of ascending thoracic aortic dilations/aneurysms remain understudied, whereas the risk assessment of it may be improved. The electronic databases PubMed/Medline 1966-2022, Web of Science 1975-2022, Scopus 1975-2022, and RSCI 1994-2022 were searched. The current guidelines recommend a purely aortic diameter-based assessment of the thoracic aortic aneurysm risk, but over 80% of the ascending aorta dissections occur at a size that is lower than the recommended threshold of 55 mm. Moreover, a 55 mm diameter criterion could exclude a vast majority (up to 99%) of the patients from preventive surgery. The authors review several visualization-based and alternative approaches which are proposed to better predict the risk of dissection in patients with borderline dilated thoracic aorta. The imaging-based assessments of the biomechanical aortic properties, the Young's elastic modulus, the Windkessel function, compliance, distensibility, wall shear stress, pulse wave velocity, and some other parameters have been proposed to improve the risk assessment in patients with ascending thoracic aortic aneurysm. While the authors do not argue for shifting the diameter threshold to the left, they emphasize the need for more personalized solutions that integrate the imaging data with the patient's genotypes and phenotypes in this heterogeneous pathology.

The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury.

In the last 10 years, mortality from acute myocardial infarction (AMI) has not significantly decreased. This situation is associated with the absence in clinical practice of highly effective drugs capable of preventing the occurrence of reperfusion injury of the heart. Necroptosis inhibitors may become prototypes for the creation of highly effective drugs that increase cardiac tolerance to ischemic/reperfusion (I/R) and reduce the mortality rate in patients with AMI. Necroptosis is involved in I/R cardiac injury and inhibition of RIPK1 or RIPK3 contributes to an increase in cardiac tolerance to I/R. Necroptosis could also be involved in the development of adverse remodeling of the heart. It is unclear whether pre- and postconditioning could inhibit necroptosis of cardiomyocytes and endothelial cells. The role of necroptosis in coronary microvascular obstruction and the no-reflow phenomenon also needs to be studied. MicroRNAs and LncRNAs can regulate necroptotic cell death. Ca2+ overload and reactive oxygen species could be the triggers of necroptosis. Activation of kinases (p38, JNK1, Akt, and mTOR) could promote necroptotic cell death. The interaction of necroptosis, apoptosis, autophagy, ferroptosis, and pyroptosis is discussed. The water-soluble necroptosis inhibitors may be highly effective drugs for treatment of AMI or stroke. It is possible that microRNAs may become the basis for creating drugs for treatment of diseases triggered by I/R of organs.

Cardiac Strangulation in Children: Asymptomatic Complication of Epicardial Pacing.

Cardiac strangulation is a rare but potentially life-threatening mechanical complication associated with epicardial pacemaker implantation in growing children. This article presents 2 case reports of left ventricular strangulation in 4- and 3-year-old children who had an epicardial pacemaker system implanted at an early age. (Level of Difficulty: Advanced.).

Urethral leiomyoma: A rare neoplasm.

Extrauterine leiomyoma is a rare benign tumor, originating from smooth muscle cells, most often localized in the uterus. Extrauterine localization of leiomyoma is extremely rare. The presence of a neoplasm near the urethra always poses a challenge for differential diagnosis. Variety of pathologies sharing similar clinical findings requires further diagnostic testing and doctor alertness. We present the clinical case of urethral leiomyoma in a female patient aged 42 years complaining of frequent urination and vulval mass. The patient underwent neoplasm removal with further histologic examination revealing urethral leiomyoma. The article features the diagnosis and treatment of this rare pathology.

Cystic Prostatic Carcinoma - A Clinical Case and Literature Review.

Cystic formations in the prostate are quite common, but the vast majority are benign. The cystic form of prostate adenocarcinoma can present unexpected symptoms, and management can be difficult because of the local advanced stage of the disease. A unique feature of this case is the surgical local cancer treatment. In this clinical case, we describe the literature surrounding this rare form of neoplasm. We present a clinical case of a rare form of prostate cancer in a 71-year-old male who was admitted to ER with acute urinary retention. A huge obstructing prostatic cyst was revealed. After successful trial-without-catheter, the patient underwent transperineal cyst draining and this restored urination. PSAt was increased up to 55 ng/mL. The cystic wall biopsy revealed adenocarcinoma with a Gleason score of 8 (4+4) (Gleason Group IV), and distant metastasis was noticed with PSMA PET/CT. The patient started androgen deprivation therapy (ADT) with excellent PSA dynamics in three months. Because of lower urinary tract symptoms, he needed local treatment and underwent radical prostatectomy. A three-month follow-up demonstrated a common post-operative period, mild stress incontinence, and PSAt 0.004 ng/mL. Cystic prostatic carcinoma can manifest as urinary retention and be mistakenly taken for a benign obstructing prostate cyst. Despite the locally advanced tumor, it can be successfully treated locally in highly selected patients.

Trends and concerns of potentially inappropriate medication use in patients with cardiovascular diseases.

Introduction: The use of potentially inappropriate medications (PIM) is an alarming social risk factor in cardiovascular patients. PIM administration may result in iatrogenic disorders and adverse consequences may be attenuated by limiting PIM intake.Areas covered: The goal of this review article is to discuss the trends, risks, and concerns regarding PIM administration with focus on cardiovascular patients. To find data, we searched literature using electronic databases (Pubmed/Medline 1966-2021 and Web of Science 1975-2021). The data search terms were cardiovascular diseases, potentially inappropriate medication, potentially harmful drug-drug combination, potentially harmful drug-disease combination, drug interaction, deprescribing, and electronic health record.Expert opinion: Drugs for heart diseases are the most commonly prescribed medications in older individuals. Despite the availability of explicit and implicit PIM criteria, the incidence of PIM use in cardiovascular patients remains high ranging from 7 to 85% in different patient categories. Physician-induced disorders often occur when PIM is administered and adverse effects may be reduced by limiting PIM intake. Main strategies promising for addressing PIM use include deprescribing, implementation of systematic electronic records, pharmacist medication review, and collaboration among cardiologists, internists, geriatricians, clinical pharmacologists, pharmacists, and other healthcare professionals as basis of multidisciplinary assessment teams.

Mechanical properties of the pectin hydrogels and inflammation response to their subcutaneous implantation.

We studied the influence of the mechanical properties of pectin hydrogels on acute inflammation and tissue repair after subcutaneous implantation. We used hard and soft pectin hydrogels. The results of histology and the analysis of serum-level cytokines demonstrated that the intensity of acute inflammation increased with increasing hardness of the pectin hydrogels. We also showed that the pectin hydrogels did not inhibit tissue repair. The results of the morphometric and texture analysis of the pectin hydrogels showed that the in vivo biodegradation kinetics of hard hydrogels were greater than those of soft pectin hydrogels. We also observed that on the surface of the hard and soft pectin hydrogels, a network of collagen fibers was formed. The surface of the pectin hydrogel was shown to prevent the adhesion of infiltrating inflammatory cells. The results of the in vitro experiments demonstrated that pectin hydrogels inhibited the functional activity of macrophages and minimally activated the complement system. Therefore, we showed that soft pectin hydrogels have low proinflammatory potential and can be used in surgery as a barrier material as prevention of adhesions in the abdominal cavity. The hard pectin hydrogel can be used in tissue engineering. The hard pectin hydrogels can be used in the reconstruction of skin because are overpopulated with collagen fibers and contribute to the formation of new connective tissue, their elasticity is comparable to the skin and can be adjusted. They are biodegradable, and no additional manipulation is required to remove them.

A Review of Humoral Factors in Remote Preconditioning of the Heart.

A humoral mechanism of cardioprotection by remote ischemic preconditioning (RIP) has been clearly demonstrated in various models of ischemia-reperfusion including upper and lower extremities, liver, and the mesenteric and renal arteries. A wide range of humoral factors for RIP have been proposed including hydrophobic peptides, opioid peptides, adenosine, prostanoids, endovanilloids, endocannabinoids, calcitonin gene-related peptide, leukotrienes, noradrenaline, adrenomedullin, erythropoietin, apolipoprotein, A-I glucagon-like peptide-1, interleukin 10, stromal cell-derived factor 1, and microRNAs. Virtually, all of the components of ischemic preconditioning's signaling pathway such as nitric oxide synthase, protein kinase C, redox signaling, PI3-kinase/Akt, glycogen synthase kinase ß, ERK1/2, mitoKATP channels, Connexin 43, and STAT were all found to play a role. The signaling pattern also depends on which remote vascular bed was subjected to ischemia and on the time between applying the rip and myocardial ischemia occurs. Because there is convincing evidence for many seemingly diverse humoral components in RIP, the most likely explanation is that the overall mechanism is complex like that seen in ischemic preconditioning where multiple components are both in series and in parallel and interact with each other. Inhibition of any single component in the right circumstance may block the resulting protective effect, and selectively activating that component may trigger the protection. Identifying the humoral factors responsible for RIP might be useful in developing drugs that confer RIP's protection in a more comfortable and reliable manner.

The Possibility of Preventive and Therapeutic Use of Green Tea Catechins in Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most frequent types of cancer. Despite the existence of various treatment strategies, treatment of prostate cancer still presents serious difficulties (especially in advanced stages). Polyphenols have been extensively assessed in terms of their potential use for prostate cancer treatment and prevention. Catechins are among the most well-known polyphenols in this respect. OBJECTIVE: In this review, we summarize clinical study results concerning catechin applications with regard to prostate cancer treatment and prevention. We discuss some of the main mechanisms of the anticarcinogenic action of catechins. CONCLUSION: The main mechanisms of the anticarcinogenic action of catechins are subdivided into two major types: (i) direct action on cancer cells and (ii) indirect effect based on catechins's impact on the microenvironment of cancer cells, particularly in relation to the immune system. At this level catechins might reduce tumor-associated inflammation and immune tolerance.

Trigger, Signaling Mechanism and End Effector of Cardioprotective Effect of Remote Postconditioning of Heart.

The hypothetical trigger of remote postconditioning (RPost) of the heart is the highmolecular weight hydrophobic peptide(s). Nitric oxide and adenosine serve as intermediaries between the peptide and intracellular structures. The role of the autonomic nervous system in RPost requires further study. In signaling mechanism RPost, kinases are involved: protein kinase C, PI3, Akt, JAK. The hypothetical end effector of RPost is aldehyde dehydrogenase-2, the transcription factors STAT, Nrf2, and also the BKCa channel.

Mechanical properties, structure, bioadhesion, and biocompatibility of pectin hydrogels.

The surface structure, biocompatibility, textural, and adhesive properties of calcium hydrogels derived from 1, 2, and 4% solutions of apple pectin were examined in this study. An increase in the pectin concentration in hydrogels was shown to improve their stability toward elastic and plastic deformation. The elasticity of pectin hydrogels, measured as Young's modulus, ranged from 6 to 100 kPa. The mechanical properties of the pectin hydrogels were shown to correspond to those of soft tissues. The characterization of surface roughness in terms of the roughness profile (Ra) and the root-mean-square deviation of the roughness profile (Rq) indicated an increased roughness profile for hydrogels depending on their pectin concentration. The adhesion of AU2% and AU4% hydrogels to the serosa abdominal wall, liver, and colon was higher than that of the AU1% hydrogel. The adhesion of macrophages and the non-specific adsorption of blood plasma proteins were found to increase as the pectin concentration in the hydrogels increased. The rate of degradation of all hydrogels was higher in phosphate buffered saline (PBS) than that in DMEM and a fibroblast cell monolayer. The pectin hydrogel was also found to have a low cytotoxicity. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2572-2581, 2017.

Macrophage activation and polarization in post-infarction cardiac remodeling.

Adverse cardiac remodeling leads to impaired ventricular function and heart failure, remaining a major cause of mortality and morbidity in patients with acute myocardial infarction. It have been shown that, even if all the recommended therapies for ST-segment elevation myocardial infarction are performed, one third of patients undergoes progressive cardiac remodeling that represents morphological basis for following heart failure. The need to extend our knowledge about factors leading to different clinical scenarios of myocardial infarction and following complications has resulted in a research of immuno-inflammatory pathways and molecular activities as the basis for post-infarction remodeling. Recently, macrophages (cells of the innate immune system) have become a subject of scientific interest under both normal and pathological conditions. Macrophages, besides their role in host protection and tissue homeostasis, play an important role in pathophysiological processes induced by myocardial infarction. In this article we summarize data about the function of monocytes and macrophages plasticity in myocardial infarction and outline potential role of these cells as effective targets to control processes of inflammation, cardiac remodeling and healing following acute coronary event.

Assessment of radiological techniques application possibility for non-invasive diagnostics of latent inflammatory processes in myocardium in patients with atrial fibrillation.

OBJECTIVE: Aim was to study the performance of single-photon emission computed tomography (SPECT) with 99mTc-pyrophosphate (99mTc-PYP) in diagnostics of chronic latent inflammation in myocardium of patients with atrial fibrillation (AF). METHODS: The research included 70 patients (the average age of 49.3 ± 10.2 years) with persistent form of idiopathic AF. All patients underwent myocardium SPECT with 99mTc-PYP and cardiac magnetic resonance imaging (CMR) before the ablation. During the ablation endomyocardium sampling for histological and immunohistochemical verification of myocarditis was performed. RESULTS: Sensitivity of SPECT with 99mTc-PYP in diagnoses of chronic latent myocarditis in patients with AF in relation to endomyocardial biopsy was 80 %, specificity-83 % and diagnostic accuracy-82 %. Sensitivity, specificity and diagnostic accuracy of myocardium perfusion scintigraphy for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 30, 50 and 50 % correspondingly. Also the close correlation between the size of the perfusion defect and the severity of myocardial fibrosis in patients with AF was revealed. Specificity of the Lake Louise criteria for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 77.6 %, sensitivity-60 % and diagnostic accuracy-74.5 %. For only LGE specificity was 16 %, sensitivity-90 % and diagnostic accuracy-28 %. CONCLUSIONS: The study showed the possibility of successful application of radionuclide methods for diagnoses of chronic latent myocarditis at AF. Taking into account high informative values the results of scintigraphy can be also considered as a promising additional criteria for selecting patients with AF of unexplained etiology for non-invasive endomyocardial biopsy procedure.

Pectic polysaccharides of the fresh plum Prunus domestica L. isolated with a simulated gastric fluid and their anti-inflammatory and antioxidant activities.

A pectic polysaccharide, designated as PD, was extracted from fresh plums (Prunus domestica L.) with a simulated gastric fluid. Galacturonan, which was partially substituted with methyl and O-acetyl ester groups, and rhamnogalacturonan were the main constituents of the linear regions of the sugar chains of PD. The ramified region contained mainly 1,4-linked ß-d-galactopyranose residues and, to a lesser extent, 1,5-linked α-l-arabinofuranose residues. The separation of PD, by DEAE-cellulose column chromatography, yielded two pectic fractions: PD-1 and PD-2, eluted with 0.1 and 0.2 M NaCl, respectively. Enzymatic digestion of PD with 1,4-α-d-polygalacturonase yielded the fraction PD-E. The parent pectin PD and the PD-1 fraction were found to diminish the adhesion of peritoneal leukocytes at the concentrations of 0.05-1.0mg/ml. However, the PD-E fraction failed to have an effect on cell adhesion at the concentrations of 0.05-0.1mg/ml. PD, PD-1 and PD-E were found to inhibit the production of superoxide anion radicals by reducing xanthine oxidase activity by 38%, 97% and 47%, respectively. Therefore, the PD-1 fraction appeared to be an active fragment of pectic macromolecule isolated from fresh plum with a simulated gastric fluid.

Radiofrequency ablation of drug-refractory arrhythmias in small children younger than 1 year of age: single-center experience.

The use of radiofrequency ablation (RFA) for the management of supraventricular tachycardia (SVT) in infants and small children remains controversial. The aim of this study was to evaluate the safety and efficacy of RFA in critically ill small children (<1 year of age) with drug-resistant tachycardia accompanied by arrhythmogenic cardiomyopathy and heart failure. The study included 15 patients age 5.3 ± 3.7 months. Wolff-Parkinson-White syndrome and atrial tachycardia were detected in eight (53.3 %) and seven (46.7 %) of patients, respectively. Patients with structural heart pathology, including congenital heart diseases and laboratory-confirmed myocarditis, were excluded from the study. Indications for RFA included drag-refractory SVT accompanied by arrhythmogenic cardiomyopathy and heart failure. Unsuccessful ablation was observed in two 1-month-old patients who underwent successful ablation 3 months later. The follow-up period ranged from 0.5 to 8 years (average 3.9). Only one patient (6.7 %) had tachycardia recurrence 1 month after RFA. The short- and long-term RFA success rates were 86.7 and 93.3 %, respectively. The study did not show any procedure-related complications. Heart failure disappeared within 5-7 days. Complete normalization of heart chamber sizes was documented within 1 month after effective RFA. A three-dimensional CARTO system (Biosense Webster, Inc., USA) was used in three patients with body weight >7 kg. The use of the CARTO system resulted in a remarkable decrease of the fluoroscopy time without vascular injury or other procedure-related complications in all cases. Our study suggests that RFA may be considered the method of choice for SVT treatment in small children when drug therapy is ineffective and arrhythmogenic cardiomyopathy progresses.

Abrogation of the oral tolerance to ovalbumin in mice by citrus pectin.

OBJECTIVE: We studied the effects of dietary pectins (citrus pectin [CP] and apple pectin) on oral tolerance in mice. METHODS: Pectins (1 mg/d) were administered orally for 2 wk. Tolerance was induced with 20 mg of ovalbumin (OVA). Levels of serum antibodies (immunoglobulin [Ig] G, IgG1, IgG2a, IgE) and delayed type hypersensitivity response determined in footpad tests were measured after subcutaneous injection of OVA with complete Freund's adjuvant. Concentrations of immunoreactive OVA in blood were measured by enzyme-linked immunosorbent assay after feeding the animals 20 mg of OVA. Adhesion and cytokine production (tumor necrosis factor-alpha, interferon-gamma) were measured in peritoneal macrophages. RESULTS: Oral administration of CP was found to prevent the induction of immune hyporesponsiveness induced by OVA feeding. Animals fed OVA and CP were found to produce similar titers of antigen-specific serum IgG and levels of delayed type hypersensitivity response as those animals not fed OVA. CP increased levels of serum IgG1 and IgE. CP was found to enhance the penetration of immunogenic OVA into the serum. CP (1 mg/d) administered orally for 1 wk was also observed to enhance the adhesion and production of cytokines (tumor necrosis factor-alpha, interferon-gamma) in peritoneal macrophages. CONCLUSION: CP administered orally was shown to inhibit oral tolerance. Enhancement of protein antigen penetration to the blood and activation of macrophages were found to precede the inhibitory effect and appeared to mediate it.