The predictive value of multiple electrode platelet aggregometry for postoperative bleeding complications in patients undergoing coronary artery bypass graft surgery.

INTRODUCTION: Postoperative bleeding is one of the most serious complications of cardiac surgery and requires transfusion of blood or blood products. Acetylsalicylic acid (ASA) and clopidogrel (CLO) are the two most commonly used antiplatelet agents; when used in combination (i.e., as dual antiplatelet therapy [DAPT]), they exert a synergistic effect. Dual antiplatelet therapy, however, significantly increases the risk of postoperative bleeding. The effect of antiplatelet therapy can be monitored by platelet aggregation testing. One of the most commonly methods used for assessing platelet reactivity is multiple electrode aggregometry (MEA) which can be performed with the use of Multiplate analyzer. Although the method has long been used in interventional cardiology to assess the effect of antiplatelet therapy, it is not available at cardiac surgery departments as a standard diagnostic procedure. The aim of the study was to establish the frequency of bleeding complications following coronary artery bypass graft (CABG) surgery in patients on single antiplatelet therapy (SAPT) and patients on DAPT and to determine the usefulness of routine measurement of platelet responsiveness before CABG surgery in patients receiving antiplatelet therapy. MATERIAL AND METHODS: A consecutive cohort of 200 patients referred for elective surgical treatment of stable coronary artery disease was enrolled (100 consecutive patients on SAPT [ASA 75 mg/day] and 100 consecutive patients on DAPT [ASA 75 mg/day + CLO 75 mg/day]). All subjects continued their antiplatelet therapy until the day before surgery. For each subject, platelet aggregation testing in the form of an ASPI test and an ADP test was performed on the Multiplate analyzer. Each subject underwent coronary artery bypass grafting surgery. For the primary and secondary endpoints in our study we adopted the definition provided in 'Standardised Bleeding Definitions for Cardiovascular Clinical Trials: A Consensus Report from the Bleeding Academic Research Consortium' ('Circulation', 2011) for BARC type 4 bleeding (i.e. CABG-related bleeding). RESULTS: An ROC curve was constructed for the ASPI test and ADP test for a total of 200 patients. No significant correlations were demonstrated between the ASPI test results and either the primary endpoint or the secondary endpoints. A correlation was found between the ADP test results and the composite primary endpoint and each of the secondary endpoints. The primary endpoint of major postoperative bleeding occurred in 16 subjects. From the ROC curve, we established the optimal cut-off value for the ADP test of 26 U at sensitivity of 72%, specificity of 69%, positive predictive value of 69.90%, and negative predictive value of 71.13%. CONCLUSIONS: In patients on antiplatelet therapy, an ADP test result of < 26 U is strongly predictive of serious bleeding complications after CABG surgery. The MEA ADP test allows to identify the group of patients at an increased risk of postoperative bleeding.

Understanding the purpose of treatment and expectations in patients with inoperable lung cancer treated with palliative chemotherapy.

AIM OF THE STUDY: Informing cancer patients about various types of treatment and their adverse effects and communicating negative information is an important element of diagnostic and therapeutic procedures. Understanding the purpose of treatment and expectations, and socio-demographic factors in patients undergoing palliative chemotherapy because of lung cancer. MATERIAL AND METHODS: The study included 100 patients with lung cancer at the age of 40-80 years (mean 63.1) in the Oncology Center in Bydgoszcz in 2013-2014. The diagnostic survey method with the author's questionnaire was used. RESULTS: Forty-one percent of patients were convinced that the purpose of chemotherapy is to cure the disease. Both inhabitants of small towns (population below 50 thousand) and large villages (p = 0.09) were similarly convinced about the effectiveness of chemotherapy. Seventy-three percent of inhabitants of small towns and 79% of country dwellers (p = 0.005) thought that chemotherapy is aimed at improving the quality of life. Patients with very good economic conditions responded that chemotherapy is designed to improve the quality of life more often than those with good and bad economic conditions, 90%, 88% and 60%, respectively (p = 0.001). With the increase in population the number of people who claimed that palliative chemotherapy prolongs their life increased, 71%, 77% and 90%, respectively (p = 0.03). CONCLUSIONS: The knowledge of patients with lung cancer about palliative chemotherapy is insufficient. Almost half of them do not understand the purpose of treatment and hope that chemotherapy will cure them of the disease. Most patients know that the aim of chemotherapy is to alleviate symptoms and improve quality of life and prolong their life. Half of the patients want to obtain information on treatment and half of them about life expectancy. Almost half of the patients feel stress and anxiety towards chemotherapy. Most patients do not use the help of a psychologist and do not feel such a need.

Chemical synthesis of the 5-taurinomethyl(-2-thio)uridine modified anticodon arm of the human mitochondrial tRNA(Leu(UUR)) and tRNA(Lys).

5-Taurinomethyluridine (τm(5)U) and 5-taurinomethyl-2-thiouridine (τm(5)s(2)U) are located at the wobble position of human mitochondrial (hmt) tRNA(Leu(UUR)) and tRNA(Lys), respectively. Both hypermodified units restrict decoding of the third codon letter to A and G. Pathogenic mutations in the genes encoding hmt-tRNA(Leu(UUR)) and hmt-tRNA(Lys) are responsible for the loss of the discussed modifications and, as a consequence, for the occurrence of severe mitochondrial dysfunctions (MELAS, MERRF). Synthetic oligoribonucleotides bearing modified nucleosides are a versatile tool for studying mechanisms of genetic message translation and accompanying pathologies at nucleoside resolution. In this paper, we present site-specific chemical incorporation of τm(5)U and τm(5)s(2)U into 17-mers related to the sequence of the anticodon arms hmt-tRNA(Leu(UUR)) and hmt-tRNA(Lys), respectively employing phosphoramidite chemistry on CPG support. Selected protecting groups for the sulfonic acid (4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutyl) and the exoamine function (-C(O)CF3) are compatible with the blockage of the canonical monomeric units. The synthesis of τm(5)s(2)U-modified RNA fragment was performed under conditions eliminating the formation of side products of 2-thiocarbonyl group oxidation and/or oxidative desulphurization. The structure of the final oligomers was confirmed by mass spectroscopy and enzymatic cleavage data.

Site-selected incorporation of 5-carboxymethylaminomethyl(-2-thio)uridine into RNA sequences by phosphoramidite chemistry.

5-Carboxymethylaminomethyluridine (cmnm(5)U) and 5-carboxymethylaminomethyl-2-thiouridine (cmnm(5)s(2)U) are located at the wobble position in several cytosolic and mitochondrial tRNA sequences. In this paper, we report the first site-selected incorporation of cmnm(5)U and cmnm(5)s(2)U into RNA sequences by phosphoramidite chemistry on a CPG solid support. Trifluoroacetyl and 2-(trimethylsilyl)ethyl were selected for the protection of the amine and carboxyl functions, respectively.

Platelet Reactivity and Intramyocardial Hemorrhage in Patients With ST-Segment Elevation Myocardial Infarction.

The aim of the study was to analyze the relation between platelet reactivity and intramyocardial hemorrhage (IMH) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Platelet reactivity was measured in 49 patients with means of impedance aggregometry (Multiplate) before reperfusion and repeated in the subacute phase of STEMI. Cardiovascular magnetic resonance was used to detect IMH, which was found in 16 (33%) patients. There were no differences in platelet reactivity between patients with and without IMH before reperfusion. Reassessment in the subacute phase of STEMI demonstrated that patients with IMH had lower thrombin receptor activating peptide (TRAP)-induced platelet aggregation (P = .004) and trends toward lower values of ristocetin and collagen-induced platelet aggregation (P = .09 and P = .07). The TRAP-induced platelet aggregation and initial perfusion grade were the factors independently associated with IMH. Intramyocardial hemorrhage is related to more potent inhibition of platelet aggregation in the subacute phase of STEMI.