Myocardial Surgical Revascularization in Patients with Reduced Left Ventricular Ejection Fraction.

Background: Myocardial surgical revascularization in patients with low left ventricular ejection fraction (LVEF) is accompanied by a high rate of morbidity and mortality. Objective: The aim of this study was to investigate and eliminate the reasons for the most common perioperative and postoperative complications. Methods: A total of 64 were analyzed. of patients during 2019 who underwent coronary artery bypass grafting (CABG), average age 61.29±9.12 years. Results: Out of the total number of operated patients, there were 16 women and 48 men. Patients were divided into two groups. The first group consisted of patients who underwent surgery with the use of cardiopulmonary bypass (cCABG-CPB) and the second group those who underwent surgery without the use of cardiopulmonary bypass (OPCAB). In 41 patients, myocardial infarction was previously recorded. Critical stenosis of the main trunk of the left coronary artery was present in 14 patients. The incidence of postoperative complications was higher in the cCABG-CPB 16/10 group (p0.030). Conclusion: In our study, we confirmed that myocardial revascularization is justified, especially in the case of multivessel coronary disease. In the long term, it significantly improves the systolic function of the left ventricle, and thus and quality and length of life.

Time Management of Tuzla University Clinical Center Health Managers.

INTRODUCTION: Time management is an important aspect of successful leadership and involves mastering your own work and time instead of allowing them to master you. Time management is a daily process that is applied in order to rationally use time, work schedules, lists of tasks, delegation of responsibilities and everything else that helps to efficiently use time. MATERIAL AND METHODS: This research was prospective, descriptive, analytical and controlled. There was 100 medical worker involved, who have managing jobs of different levels and 100 medical workers who do not have managing jobs, who represented the control group. The questionnaire on "time stealers" according to Sewert. Demographic data was gathered according to the questionnaire on self construction. RESULTS AND CONCLUSIONS: Based on conducted research, it was established that there were differences in frequencies of certain "time stealers" in managers of different levels of University Clinical Center Tuzla; the "time stealers" are more frequent among these with shorter length of service; These differences are significantly more frequent (p<0.05) for some questions e.g. being distracted by phone calls, meetings that are held just for the sake of having a meetings, insufficient, one-way or bad communication with superiors, and have negative effects on management of business hours.

Assessment of the Drug Interaction Potential of Unconjugated and GalNAc3-Conjugated 2'-MOE-ASOs.

Antisense oligonucleotides are metabolized by nucleases and drug interactions with small drug molecules at either the cytochrome P450 (CYP) enzyme or transporter levels have not been observed to date. Herein, a comprehensive in vitro assessment of the drug-drug interaction (DDI) potential was carried out with four 2'-O-(2-methoxyethyl)-modified antisense oligonucleotides (2'-MOE-ASOs), including a single triantennary N-acetyl galactosamine (GalNAc3)-conjugated ASO. Several investigations to describe the DDI potential of a 2'-MOE-ASO conjugated to a high-affinity ligand for hepatocyte-specific asialoglycoprotein receptors are explored. The inhibition on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 and induction on CYP1A2, CYP2B6, and CYP3A4 were investigated in cryopreserved hepatocytes using up to 100 µM of each ASO. No significant inhibition (half maximal inhibitory concentration [IC50] > 100 µM) or induction was observed based on either enzymatic phenotype or mRNA levels. In addition, transporter interaction studies were conducted with nine major transporters per recommendations from regulatory guidances and included three hepatic uptake transporters, organic cation transporter 1 (OCT1), organic anion transporting polypeptide 1B1 (OATP1B1), and OATP1B3; three renal uptake transporters, organic anion transporter 1 (OAT1), OAT3, and OCT2; and three efflux transporters, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and bile salt export pump (BSEP). None of the four ASOs (10 µM) were substrates of any of the nine transporters, with uptake <2-fold compared to controls, and efflux ratios were below 2.0 for BCRP and P-gp. Additionally, neither of the four ASOs showed meaningful inhibition on any of the nine transporters tested, with the mean percent inhibition ranging from -38.3% to 24.2% with 100 µM ASO. Based on these findings, the unconjugated and GalNAc3-conjugated 2'-MOE-ASOs would have no or minimal DDI with small drug molecules via any major CYP enzyme or drug transporters at clinically relevant exposures.

Lack of Interactions Between an Antisense Oligonucleotide with 2'-O-(2-Methoxyethyl) Modifications and Major Drug Transporters.

ISIS 141923 is a model compound of 2'-O-(2-methoxyethyl) (2'-MOE) modified antisense oligonucleotides (ASOs). The purpose of this study is to determine whether ISIS 141923 is a substrate or an inhibitor against a panel of nine major uptake or efflux drug transporters, namely breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)1, OCT2, organic anion transporting polypeptide 1B (OATP1B)1, OATP1B3, and bile salt export pump (BSEP), in vitro. The uptake test system for transporters in the solute carrier (SLC) family (OAT1, OAT3, OCT1, OCT2, OATP1B1, and OATP1B3) was studied in Madin-Darby canine kidney (MDCK)-II cells transfected to express the transporters of interest. BCRP was studied using carcinoma colon-2 (Caco-2) cells with endogenously expressed BCRP. P-gp transporter was studied in MDCK-multi-drug resistance 1 (MDR1) cells, while BSEP was studied using Spodoptera frugiperda 9 (Sf9) membrane vesicles containing human BSEP. The ISIS 141293 concentrations evaluated were 10 and 100 µM for the substrate and inhibition study, respectively. Cellular uptake of ISIS 141923 was analyzed using a high performance liquid chromatography-mass spectrometry method, while concentrations of known substrates (used as positive controls) of each transporters evaluated were determined by radiometric detection. At 10 µM ISIS 141923, there was no significant transporter-mediated uptake of ISIS 141923 (P > 0.05) in the SLC family, and the efflux ratios were not above 2.0 for either BCRP or P-gp. Therefore, no transporter-mediated uptake of ISIS 141923 was observed by any of the nine transporters studied. At 100 µM ISIS 141923, the % inhibition was in the range of -16.0% to 19.0% for the nine transporters evaluated. Therefore, ISIS 141923 is not considered as an inhibitor of the nine transporters studied. Overall, the results from this study suggest that it is unlikely that ISIS 141923 or similar 2'-MOE ASOs would interact with small molecule drugs either as a victim (substrate) or perpetrator (inhibitor) of major transporters in humans. The results from available clinical drug-drug interaction studies conducted with this class of compounds to date are also supportive of this conclusion.

Operative treatment of combined aortic stenosis and coronary artery disease.

INTRODUCTION: The aortic valve replacement is a standard operating procedure in patients with severe aortic stenosis. Structure of patients undergoing surgery ranges from young population with isolated mitral valvular disease to the elderly population, which is in addition to the underlying disease additionally burdened with comorbidity. One of the most commonly present factors that further complicate the surgery is coronary heart disease that occurs in, almost, one third of patients with aortic stenosis. The aim is to compare the results of surgery for aortic valve replacement with or without coronary artery bypass graft (CABG). PATIENTS AND METHODS: From August 2008 to January 2013 in our center operated on 120 patients for aortic stenosis. Of this number, 75 were men and 45 women. The average age was 63.37 years (16-78). Isolated aortic valve replacement was performed in 89 patients and in 31 patients underwent aortic valve replacement and coronary bypass surgery. Implanted 89 biological and 31 mechanical valves. RESULTS: Patients with associated aortic stenosis and coronary artery disease were more expressed symptomatic symptoms preoperatively to patients with isolated aortic stenosis who were on average younger age. Intra-hospital morbidity and mortality was more pronounced in the group of patients with concomitant aortic valve replacement and coronary bypass surgery. Morbidity was recorded in 17 patients (14.3%) in both groups, while the mortality rate in both groups was 12 patients (10.1%). CONCLUSION: Evaluation of preoperative risk factors and comorbidity in patients with aortic stenosis and coronary artery disease contributes to a significant reduction in intraoperative and postoperative complications. Also, early diagnosis of associated coronary artery disease and aortic stenosis contributes to timely decision for surgery thus avoiding subsequent ischaemic changes and myocardial damage.

Surgical revascularization in elderly patients with and without cardiopulmonary bypass.

UNLABELLED: The number of patients undergoing coronary artery bypass grafting (coronary artery bypass grafting-CABG) older than 70 years is increasing. Cardiac surgeons are investigate applicability of alternative and less invasive methods such as surgery without the use of cardiopulmonary bypass (CPB). The aim of this study was to compare the peri- and postoperative results of CABG in elderly patients operated with and without CPB. PATIENTS AND METHODS: The study included subjects older than 70 years, who underwent coronary bypass surgery at the BH Heart Center Tuzla in the period from August 2008 to August 2010, divided into two groups. Group A consisted of 50 patients operated without CPB, group B 50 patients operated with CPB, adjusted by sex, left ventricular ejection fraction values, EuroSCORE, and the number of bypass grafts was made. RESULTS: In the group treated without the use CPB there were significantly lower values of the time-duration of mechanical ventilation, length of stay in the Intensive Care Unit (ICU), the amount of postoperative bleeding and blood recovered, the length of hospital stay, levels of serum creatinine, C-reactive protein and creatine kinase MB fraction. CONCLUSION: CABG without the use of CPB has a number of advantages over the method with CPB in elderly patients, which is evident from the lower values of renal and inflammatory parameters and markers of myocardial lesion, less time spent on a ventilator, shorter length of stay in the ICU and total hospitalization time, less postoperative bleeding and blood transfusion.

Interactions of bilastine, a new oral H1 antihistamine, with human transporter systems.

Membrane transporters play a significant role in facilitating transmembrane drug movement. For new pharmacological agents, it is important to evaluate potential interactions (e.g., substrate specificity and/or inhibition) with human transporters that may affect their pharmacokinetics, efficacy, or toxicity. Bilastine is a new nonsedating H1 antihistamine indicated for the treatment of allergic rhinoconjunctivitis and urticaria. The in vitro inhibitory effects of bilastine were assessed on 12 human transporters: four efflux [multidrug resistance protein 1 (MDR1) or P-glycoprotein, breast cancer resistance protein (BCRP), multidrug resistance associated protein 2 (MRP2), and bile salt export pump) and eight uptake transporters (sodium taurocholate cotransporting polypeptide, organic cation transporter (OCT)1, organic anion transporter (OAT)1, OAT3, OCT2, OATP2B1, OATP1B1, and OATP1B3). Only mild inhibition was found for MDR1-, OCT1-, and OATP2B1-mediated transport of probe substrates at the highest bilastine concentration assayed (300 µM; half-maximal inhibitory concentration: ≥300 µM). Bilastine transport by MDR1, BCRP, OAT1, OAT3, and OCT2 was also investigated in vitro. Only MDR1 active transport of bilastine was relevant, whereas it did not appear to be a substrate of OCT2, OAT1, or OAT3, nor was it transported substantially by BCRP. Drug-drug interactions resulting from bilastine inhibition of drug transporters that would be generally regarded as clinically relevant are unlikely. Additionally, bilastine did not appear to be a substrate of human BCRP, OAT1, OAT3, or OCT2 and thus is not a potential victim of inhibitors of these transporters. On the other hand, based on in vitro evaluation, clinically relevant interactions with MDR1 inhibitors are anticipated.

Bloodless off pump coronary artery bypass grafting treatment of choice for Jehova's witness patients.

Jehovah's witnesses (JW) belong to a religious group refusing to accept blood transfusion Surgical treatment remains a challenge in this subset of patients. From 1945, JW introduced a ban on accepting blood transfusions, even in life-threatening situations while autologous blood must also be refused if it is predeposited-thus excluding preoperative autodonation. However, autologous blood is acceptable if it is not separated from the patients' circulation at any time. The invasive nature of coronary artery bypass grafting (CABG), the associated decrease of body temperature and the use of cardiopulmonary bypass (CPB) are major reasons for increased blood loss and high incidence for blood transfusions during and after this procedures. Allogenic blood transfusions are often given and considered necessary in such operations, in spite of increased mortality, morbidity and major adverse outcomes resulting from transfusion. Reduction in the use of blood products should therefore be a general desire for every patient due to the associated risk factors. The evolution of less invasive cardiac surgical approaches, such as CABG without CPB (OPCAB) may contribute to a further reduction of blood transfusion and although these minimally invasive techniques may benefit every patient, they might be particularly valuable for JW. In this report, we present our initial experience in JW patient undergoing OPCAB and the way to use patient blood management for improved surgical outcome in such patient.