168 research outputs found
ISAR-REACT 5 — czy to badanie powinno zmienić praktykę kliniczną?
Prasugrel and ticagrelor are oral P2Y12 receptor inhibitors indicated by the European Society of Cardiology as the preferred antiplatelet therapy in patients with acute coronary syndrome (ACS). Despite the long-term and widespread presence of these agents in clinical practice, to date they have never been directly compared in a large, randomised clinical trial. ISAR-REACT 5 was the first such study, and it reported the superiority of prasugrel over ticagrelor. However, due to the arguable methodology of both the planning and the execution of this study, its results should be interpreted with caution, and they should not be considered sufficient to justify any changes to the current treatment strategies for patients with ACS.Prasugrel i tikagrelor są doustnymi inhibitorami receptora P2Y12 wskazywanymi w wytycznych Europejskiego Towarzystwa Kardiologicznego jako preferowane leczenie przeciwpłytkowe u pacjentów z ostrymi zespołami wieńcowymi (ACS). Mimo wieloletniej i coraz powszechniejszej obecności w praktyce klinicznej obu tych leków, dotychczas nigdy nie porównywano ich bezpośrednio w dużym, randomizowanym badaniu klinicznym. Pierwszym takim badaniem była próba kliniczna ISAR-REACT 5, w której wykazano wyższość prasugrelu nad tikagrelorem. Tym niemniej, ze względu na wątpliwości odnośnie do metodologii planowania i przeprowadzenia tej próby klinicznej, jej wyniki należy interpretować z ostrożnością i nie powinno się ich uznawać za wystarczające do wprowadzenia zmian w dotychczasowej strategii leczenia pacjentów z ACS
Creative scientific dispute — different points of view on the protocol and execution of the ISAR-REACT 5 trial
Discordant interpretations of the results of clinical trials often drive scientific disputes. Our position concerning the protocol and performance of the ISAR-REACT 5 trial have been termed as false and groundless in the recently published article. We deeply disagree with this judgement and still maintain all our opinions expressed in the previous publications, without any exceptions. As demonstrated in multiple studies, prasugrel has excellent effectiveness and predictability. In our previous publications, it was not the drug itself that we put under criticism, but rather the quality of the trial assessing the drug. As a consequence of this critical approach, we stated that taking into account the serious limitations of the ISAR-REACT 5 trial, its results should be taken with cautiousness. To summarize, we remain open to further creative scientific dispute enriching both readers and authors
The dual role of Escherichia coli in the course of ulcerative colitis
BACKGROUND: This study examines the dual role of Escherichia coli in the course of ulcerative colitis (UC). The intestinal microbiota is considered to play an important role in UC pathogenesis, but how E. coli contributes to inflammation in UC is still unknown. On the one hand, we demonstrated that there was a significant increase in the number of E. coli at the sites of inflammation in patients with UC, which can lead to immune system activation, whilst, on the other hand, E. coli may contribute to the resolution of inflammatory reactions since E. coli can inhibit hydroxyl radical formation by eliminating substrates of the Fenton reaction, by assimilating ferrous iron (Fe(2+)) and inducing the decomposition of hydrogen peroxide (H(2)O(2)). On this way, E. coli may affect the initiation and/or prolongation of remission stages of UC. METHODS: Ten E. coli strains were isolated from the colonic mucosa of patients in the acute phase of UC. Using PCR, we examined the presence of genes encoding catalases (katG and katE) and proteins participating in iron acquisition (feoB, fepA, fhuA, fecA, iroN, fyuA, and iutA) in these E. coli strains. To determine if iron ions influence the growth rate of E. coli and its ability to decompose H(2)O(2), we grew E. coli in defined culture media without iron (M9(-)) or with ferrous ions (M9(Fe(2+))). Expression levels of genes encoding catalases were examined by real-time PCR. RESULTS: All investigated E. coli strains had catalase genes (katG, katE), genes coding for receptors for Fe(2+) (feoB) and at least one of the genes responsible for iron acquisition related to siderophores (fepA, fhuA, fecA, iroN, fyuA, iutA). E. coli cultured in M9(Fe(2+)) grew faster than E. coli in M9(-). The presence of Fe(2+) in the media contributed to the increased rate of H(2)O(2) decomposition by E. coli and induced katG gene expression. CONCLUSIONS: E. coli eliminates substrates of the Fenton reaction by assimilating Fe(2+) and biosynthesizing enzymes that catalyze H(2)O(2) decomposition. Thus, E. coli can inhibit hydroxyl radical formation, and affects the initiation and/or prolongation of remission stages of UC
A case of a patient treated with percutaneous edge-to-edge mitral valve repair, percutaneous left atrial appendage occlusion and implantable cardioverter-defibrillator
The article presents the case of a 55-year-old woman who suffered from anterior myocardial infarction andchronic complications of the underlying disease, heart failure with reduced left ventricular ejection fraction,severe secondary mitral regurgitation, and paroxysmal atrial fibrillation. Due to the severity of symptoms,which persisted despite the optimal pharmacotherapy, after exclusion of reversible causes, the patient wasqualified for different advanced percutaneous treatment methods. Within two years from the onset of thedisease, three percutaneous procedures were performed: mitral valve correction with the MitraClip system,left atrial appendage occlusion using the Watchman system, and implantation of cardioverter-defibrillator
Introgression of LTP2 gene through marker assisted backcross in barley (Hordeum vulgare L.)
AbstractBackgroundMarker-assisted introgression currently represents the most widely spread application of DNA markers as an aid to selection in plant breeding. New barley germplasm should be supplemented by genes that facilitate growth and development under stressful conditions. The homology search against known genes is a fundamental approach to identify genes among the generated sequences. This procedure can be utilized for SNP search in genes of predicted function of interest and associated gene ontology (GO).ResultsBackcross breeding enhanced by marker selection may become a powerful method to transfer one or a few genes controlling a specific trait. In the study, the integrated approach of combining phenotypic selection with marker assisted backcross breeding for introgression of LTP2 gene, in the background of semi-dwarf spring barley cultivar, was employed. This study discusses the efficiency of molecular marker application in backcrossing targeted on the selected gene.ConclusionsBC6 lines developed in this study can serve as a unique and adequate plant material to dissect the role of LTP2 gene. Due to its role in lipid transfer, the LTP2 may be crucial in lipidome modification in response to abiotic stress
Prevalence of electrocardiographic left ventricular hypertrophy among patients with coronary artery disease and diabetes mellitus
Introduction. Electrocardiography (ECG) is a widely used non-invasive diagnostic method for assessment of patients with cardiovascular diseases. Numerous different electrocardiographic criteria exist for detection of left ventricular hypertrophy (LVH). LVH is an important risk factor in patients with coronary artery disease (CAD) or diabetes mellitus and its presence is associated with increased cardiovascular morbidity and mortality. The aim of this study was to evaluate the prevalence of the most frequently used electrocardiographic left ventricular hypertrophy (ECG-LVH) criteria among patients with CAD and diabetes.
Methods. A cross-sectional, multicenter study was conducted in outpatient clinics across Poland. Family physicians performed physical examinations and collected relevant information about: onset of CAD and diabetes, presence and onset of hypertension, dyslipidemia, heart failure, diabetic complications, history of acute coronary syndrome and pharmacotherapy. In order to detect LVH, we used seven ECG criteria: 1) the Sokolow-Lyon voltage, 2) the Gubner voltage, 3) the criterion of the R wave amplitude on the leads V5–V6 and 4) aVL, 5) the gender specific Cornell voltage and 6) product, and 7) the Romhilt-Estes point score. Centralized manual assessment of the obtained ECG tracings were performed.
Results. We enrolled 1001 patients (48.5% women, 51.5% men, mean age 65 ± 11 years) into the study. At least one ECG-LVH criterion was met in 20.0% (n = 200) of the study participants. The ECG-LVH diagnosis was the most common when using the Romhilt-Estes point score (n = 138; 13.8%). The corresponding prevalence rates for the Cornell voltage, the Cornell product, the R wave amplitude on the lead aVL, the Sokolow-Lyon voltage, the Gubner voltage and the R wave amplitude on the leads V5-V6 criteria were 5.5% (n = 55), 5.2% (n = 52), 3.2% (n = 32), 2.2% (n = 22), 1.9% (n = 19) and 1.3% (n = 13) respectively. Subsequently, the prevalence of the three most frequently used in clinical practice electrocardiographic criteria for LVH (the Sokolow-Lyon voltage, the Cornell voltage and the Romhilt-Estes point score) was analyzed. At least one of them was fulfilled in 185 ECGs. All three criteria at the same time were met only in 5 ECGs (2.7% of 185). Two and only one out of three criteria were fulfilled in 20 (10.8%) and 160 (86.5%) ECGs respectively.
Conclusions. The co-occurrence of all assessed ECG-LVH criteria, including the three most frequently applied in clinical practice, is very low in diabetic CAD patients. The Romhilt-Estes point score identifies the highest number of ECG-LVH cases in this setting. However, it seems reasonable to use routinely several ECG criteria for detection of LVH. Further studies are needed to compare diagnostic values of ECG-LVH criteria with imaging methods and to assess prognostic values of various ECG-LVH criteria
Impact of ticagrelor administration strategy on its pharmacokinetics and pharmacodynamics in patients with unstable angina pectoris: a protocol of a randomized study
Introduction. Dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor constitutes an essential part of the management of patients with acute coronary syndromes (ACS). Based on the favorable results of the PLATO trial, ticagrelor is currently recommended as the first line P2Y12 receptor inhibitor in a broad spectrum of ACS patients. According to the recently published data, several conditions, including concurrent analgesia with morphine and clinical presentation as an ACS, may alter ticagrelor absorption and its antiplatelet effect. Therefore, the goal of the present study was to investigate pharmacokinetics and pharmacodynamics of new ticagrelor administration strategies aimed to overcome limitations of the standard ticagrelor loading regimen.
Methods/design. The study is designed as a phase IV, single center, randomized, investigator-initiated, parallel-group, open-label, interventional study comparing the influence of various ticagrelor administration strategies on its pharmacokinetics and pharmacodynamics. Patients with unstable angina pectoris will be randomized in a 1:1:1 ratio into one of three arms, each receiving a 180 mg ticagrelor loading dose (LD). Ticagrelor administration strategies comprise: 1) pulverized ticagrelor administered sublingually, 2) pulverized ticagrelor in 10 mL suspension in tap water administered orally and 3) integral ticagrelor tablets administered orally. An internal pilot study including 30 (10 in each of the arms) is planned in order to determine the final sample size. The primary endpoint of the trial is time (tmax) required for ticagrelor and its active metabolite AR-C124900XX to reach maximum plasma concentration within time frame of six hours after administration of ticagrelor LD. The secondary endpoints include ticagrelor and AR-C124900XX maximum plasma concentration, area under the plasma concentration-time curve for ticagrelor and AR-C124900XX (AUC 0–6h) and platelet reactivity assessed with Multiple Electrode Aggregometry using the Multiplate™ Analyzer prior to and within time frame of six hours following ticagrelor LD.
Discussion. This study is expected to provide essential evidence-based data on the impact of ticagrelor administration strategy on its pharmacokinetics and pharmacodynamics in patients with unstable angina pectoris. Hopefully, based on its results, further clinical outcome-powered trials on new ticagrelor administration strategies will be designed and conducted.
Diabetogenic effect of statins: a comprehensive review on the clinical relevance, underlying pathomechanisms and rationale for tailored statin therapy
Statins are potent hypolipidemic drugs effectively reducing low-density lipoprotein (LDL) cholesterol serum concentration, but also exerting a wide range of pleiotropic effects. In numerous clinical trials statins were proven to substantially decrease cardiovascular morbidity and mortality both in primary and secondary prevention. However, a growing body of evidence suggests that statins, although safe and generally well-tolerated, are associated with an increased occurrence of new-onset diabetes mellitus (DM). The aim of this review is to explore the relationship between statin therapy and new-onset DM, including its clinical relevance and underlying pathomechanisms, and to discuss the concept of tailored statin therapy. According to our recently published comprehensive network meta-analysis including 113,394 patients, the high-dose statin regimens were connected with an elevated risk of new-onset DM as compared with moderate-dose statin regimens and a gradient for the risk of new-onset DM across different types and doses of statins was demonstrated. There are multiple possible mechanisms explaining the diabetogenic effect of statins (e.g., decreased insulin secretion, induction of b-cell apoptosis, increased insulin resistance or compromised glucose transport into the cells). Statins are among the most widely used drugs worldwide and physicians should be aware of the fact that there is a risk of new-onset DM across different types and doses of statins. Selection of adequate statin that suits patient’s needs remains the challenge of hypolipidemic therapy. The identification of individuals who would benefit more from smaller doses and/or use of less diabetogenic compounds could help to optimize the treatment and reduce the number of patients developing DM. The non-pharmacological approach such as adequate physical activity, weight reduction and low fat diet should not be neglected either. These actions create a chance to decrease baseline LDL-cholesterol concentration and reduce the number of both cardiovascular and DM risk factors. All in all, statins with their exceptional cardiovascular benefits will undoubtedly defend their position of a cornerstone of cardiovascular prevention because profits derived from statin therapy far exceed the potential harms connected with statin-induced impairments of glucose metabolism
ISAR-REACT 5 — czy to badanie powinno zmienić praktykę kliniczną?
Prasugrel and ticagrelor are oral P2Y12 receptor inhibitors indicated by the European Society of Cardiology as the preferred antiplatelet therapy in patients with acute coronary syndromes (ACS). Despite the long-term and widespread presence of these agents in clinical practice, until now they have never been directly compared in a large, randomised clinical trial. ISAR-REACT 5 was the first such study, and it has reported the superiority of prasugrel over ticagrelor. However, due to the questionable methodology of both the planning and the execution of this study, its results should be interpreted with caution, and they should not be considered sufficient to justify any changes to the current treatment strategies for patients with ACS.Prasugrel i tikagrelor są doustnymi inhibitorami receptora P2Y12 wskazywanymi w wytycznych Europejskiego Towarzystwa Kardiologicznego jako preferowane leczenie przeciwpłytkowe u pacjentów z ostrymi zespołami wieńcowymi (ACS). Mimo wieloletniej i coraz powszechniejszej obecności w praktyce klinicznej obu tych leków, dotychczas nigdy nie porównywano ich bezpośrednio w dużym, randomizowanym badaniu klinicznym. Pierwszym takim badaniem była próba kliniczna ISAR-REACT 5, w której wykazano wyższość prasugrelu nad tikagrelorem. Tym niemniej, ze względu na wątpliwości odnośnie do metodologii planowania i przeprowadzenia tej próby klinicznej, jej wyniki należy interpretować z ostrożnością i nie powinno się ich uznawać za wystarczające do wprowadzenia zmian w dotychczasowej strategii leczenia pacjentów z ACS
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