Blood malignancies remain a therapeutic challenge despite the development of numerous treatment strategies. The phosphatidylinositol-3 kinase (PI3K)/protein kinase B/mammalian target of rapamycin ...(PI3K/Akt/mTOR) signaling pathway plays a central role in regulating many cellular functions, including cell cycle, proliferation, quiescence, and longevity. Therefore, dysregulation of this pathway is a characteristic feature of carcinogenesis. Increased activation of PI3K/Akt/mTOR signaling enhances proliferation, growth, and resistance to chemo- and immunotherapy in cancer cells. Overactivation of the pathway has been found in various types of cancer, including acute and chronic leukemia. Inhibitors of the PI3K/Akt/mTOR pathway have been used in leukemia treatment since 2014, and some of them have improved treatment outcomes in clinical trials. Recently, new inhibitors of PI3K/Akt/mTOR signaling have been developed and tested both in preclinical and clinical models. In this review, we outline the role of the PI3K/Akt/mTOR signaling pathway in blood malignancies’ cells and gather information on the inhibitors of this pathway that might provide a novel therapeutic opportunity against leukemia.
Inhibitors of 3-hydroxy-3methylgultaryl-coenzyme A reductase (statins) are one of the main groups of drugs used in preventing and treating cardiovascular diseases worldwide. They are widely ...available, cheap, and well-tolerated. Based on statins’ pleiotropic properties, including improvement of endothelial dysfunction, antioxidant properties, atherosclerotic plaque stabilization, and inhibition of inflammatory responses, it can be hypothesized that the use of statins, at least as an adjuvant in antiviral therapy, may be justified. All these effects might be especially beneficial in patients with COVID-19, suffering from endothelial dysfunction, microvascular and macrovascular thrombosis, and cytokine storm. Here, we review the recent data regarding the pathophysiology of SARS-CoV-2 activity in host cells, proposed COVID-19 therapy, the pleiotropic activity of statins, and statins in clinical trials in respiratory infections. According to the guidelines of the European and American Cardiac Societies, in patients with cardiovascular disease or high cardiovascular risk with concomitant COVID-19 it is recommended to continue statin treatment. However, the initiation of statin therapy de novo in COVID-19 treatment should only be done as part of a clinical trial.
Aims
Endothelin‐1 (ET‐1) is a potent vasoconstrictor, which regulates renal and vascular function. We aimed to relate plasma levels of ET‐1 with the clinical picture and outcomes in acute heart ...failure (AHF).
Methods and results
We studied 113 patients with AHF mean age 65 ± 13 (years), median (upper and lower quartiles) N‐terminal pro‐B‐type natriuretic peptide, 5422 (2689; 8582) (pg/mL), in whom plasma levels of ET‐1 were serially measured at admission (10.8 ± 5.2), Day 1 (9.5 ± 3.4), and Day 2 (8.9 ± 3.8) (pg/mL). The population was divided into tertiles across baseline ET‐1 levels. Patients in the highest ET‐1 tertile had predominant clinical signs of peripheral congestion; however, no difference was observed in pulmonary congestion and severity of dyspnoea. They also presented lower spot urine sodium at admission (75 ± 35 vs. 99 ± 43 vs. 108 ± 30), 6 h (84 ± 34 vs. 106 ± 43 vs. 106 ± 35), and Day 1 (75 ± 38 vs. 96 ± 36 vs. 100 ± 35) (mmol/L), when compared with the second and first tertile, respectively (all P < 0.05); furthermore, they received higher doses of intravenous furosemide from Day 2 and had longer intravenous diuretics, as median switch to oral furosemide was 4 (3; 4) vs. 3 (2; 4) vs. 2 (2; 3) (days), respectively, P < 0.05. There was no difference in serum creatinine, urea, and renal injury biomarkers (kidney injury molecule‐1, serum cystatin C, and urine neutrophil gelatinase‐associated lipocalin) between the ET‐1 tertiles. Higher values of ET‐1 measured at each time point were related with a higher risk of 1 year mortality.
Conclusions
Elevation of ET‐1 is related to clinical signs of peripheral congestion, low urine sodium excretion, and poor outcome in AHF.
Myocardial infarction (MI) remains a major burden for healthcare systems. Therefore, we intended to analyze the determinants of cost management of patients hospitalized for MI in Poland.
Data on ...patients hospitalized and discharged with the diagnosis of acute MI were derived from the public payer claims database. Adult patients, reported between October 1, 2017 and December 31, 2019, were included. Costs of hospitalization for acute MI and cumulative one-year follow-up were analyzed.
The median (IQR) of the total direct cost was €3804.7 (2674.1-5712.7) per patient and 29% (€1113.6 380.5-2490.4) of these were costs related to the use of post-hospitalization healthcare resources. The median cost of cardiovascular disease management was €3624.7 (2582.1-5258.5), and 26% of this sum were follow-up costs. The analysis of the total cost for individual years showed a slight increase in median costs in subsequent years: €3450.7 (2407.8-5205.2) in 2017, €3753.8 (2642.6-5681.9) in 2018, and €3944.9 (2794.8-5844.4) in 2019. Male sex, heart failure, atrial fibrillation, diabetes, kidney disease, chronic obstructive pulmonary disease, and history of stroke in addition to hospitalization in a department other than cardiology or internal disease were independently related to the cost of MI patient management.
The high cost of management of MI patients was independently related to sex, heart failure, atrial fibrillation, diabetes, kidney disease, chronic obstructive pulmonary disease, and history of stroke as well as hospitalization in other than cardiology or internal disease department.
In this study,we used publicly available data from the Centrum e-Zdrowia (CeZ) Polish Databank proposing a possible correlation between influenza vaccination and mortality due to COVID-19. We limited ...our search to the patients with positive COVID‑19 laboratory tests from 1 January 2020 to 31 March 2021 and who filled a prescription for any influenza vaccine during the 2019-2020 influenza season. In total, we included 116,277 patients and used a generalized linear model to analyze the data.We found out that patients aged 60+ who received an influenza vaccination have a lower probability of death caused by COVID-19 in comparison to unvaccinated, and the magnitude of this difference grows with age. For people below 60 years old, we did not observe an influence of the vaccination. Our results suggest a potential protective effect of the influenza vaccine on COVID-19 mortality of the elderly. Administration of the influenza vaccine before the influenza season would reduce the burden of increased influenza incidence, the risk of influenza and COVID‑19 coinfection and render the essential medical resources accessible to cope with another wave of COVID-19. To our knowledge, this is the first study showing a correlation between influenza vaccination and the COVID-19 mortality rate in Poland.
Aims
Iron deficiency (ID) is frequent in heart failure (HF), linked with exercise intolerance and poor prognosis. Intravenous iron repletion improves clinical status in HF patients with left ...ventricular ejection fraction (LVEF) ≤45%. However, uncertainty exists about the accuracy of serum biomarkers in diagnosing ID. The aims of this study were (i) to identify the iron biomarker with the greatest accuracy for the diagnosis of ID in bone marrow in patients with ischaemic HF, and (ii) to establish the prevalence of ID using this biomarker and its prognostic value in HF patients.
Methods and results
Bone marrow was stained for iron in 30 patients with ischaemic HF with LVEF ≤45% and 10 healthy controls, and ID was diagnosed for 0–1 grades (Gale scale). A total of 791 patients with HF with LVEF ≤45% were prospectively followed up for 3 years. Serum ferritin, transferrin saturation, soluble transferrin receptor (sTfR) were assessed as iron biomarkers. Most patients with HF (n = 25, 83%) had ID in bone marrow, but none of the controls (P < 0.001). Serum sTfR had the best accuracy in predicting ID in bone marrow (area under the curve 0.920, 95% confidence interval 0.761–0.987, for cut‐off 1.25 mg/L sensitivity 84%, specificity 100%). Serum sTfR was ≥1.25 mg/L in 47% of HF patients, in 56% and 46% of anaemics and non‐anaemics, respectively (P < 0.05). The reclassification methods revealed that serum sTfR significantly added the prognostic value to the baseline prognostic model, and to the greater extent than plasma N‐terminal pro B‐type natriuretic peptide. Based on internal derivation and validation procedures, serum sTfR ≥1.41 mg/L was the optimal threshold for predicting 3‐year mortality, independent of other established variables.
Conclusions
High serum sTfR accurately reflects depleted iron stores in bone marrow in patients with HF, and identifies those with a high 3‐year mortality.
Atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) is generally associated with deterioration of the clinical status, functional capacity, and quality of life. It is also an ...independent risk factor for stroke and death. Studies evaluating the effectiveness of AF ablation in this cohort are relatively scant, have included relatively few patients, and their results are somewhat conflicting. Thus, the aim of this study was to assess the safety and efficacy of catheter ablation of AF in patients with HCM.
Thirty patients (10 females; mean age 48.7 ± 11 years) with drug-refractory paroxysmal (n = 14), persistent (n = 7), or long-persistent (> 1 year; n = 9) AF were prospectively recruited into the study. Eleven patients were in New York Heart Association (NYHA) class I, 13 patients were in NYHA class II, and 6 patients were in NYHA class III. Mean atrial volume was 180 ± 47 mL, interventricular septum thickness was 20.5 ± 6.3 mm, and left atrial area was 29.8 ± 6.2 cm2. Ablation protocol was adjusted to the clinical and electrophysiological status of the patients. Pulmonary vein isolation and bidirectional cavo-tricuspid isthmus block were performed in all patients. In addition, left atrial linear lesions were created and complex fragmented atrial potentials were ablated in patients with persistent and long-persistent AF, as well as during repeated procedures.
At 12 months, stable sinus rhythm (SR) was present in 16 (53%) patients, significantly more frequently in patients with paroxysmal AF (71% in SR) compared to those with persistent (57.1% in SR) or long-persistent (22% in SR) AF. A significant reduction of AF burden was observed in 85.7% of patients with paroxysmal AF, 71.4% of patients with persistent AF, and 55.5% of patients with long-persistent AF. Single procedure success rate was 33% (10 patients), and repeat ablation procedures were performed in 13 patients. No periprocedural complications occurred. Thromboembolic events were noted in 2 patients with arrhythmia recurrence during the follow-up, including stroke in 1 patient and peripheral embolism in the other patient. In both these patients, heart failure worsening was observed during these events, and anticoagulation was inadequate in one of them. Five of 16 patients in whom stable SR was observed during the follow-up were off antiarrhythmic drug therapy at final evaluation. In the other 6 patients, antiarrhythmic drug therapy was continued due to ventricular arrhythmias. Successfully treated patients more often had paroxysmal AF (successful ablation: paroxysmal AF in 10 of 16 patients; unsuccessful ablation: paroxysmal AF in 4 of 14 patients; p = 0.009) and were younger (45 ± 11.5 years vs. 52.6 ± 9.2 years; p = 0.046). In addition, a trend toward a reduced need for cardioversion at the end of the procedure was also observed in these patients (3 patients in the successful ablation group vs. 8 patients in the unsuccessful ablation group; p = 0.056). In multivariate regression analysis, paroxysmal AF was the only independent predictor of a successful outcome.
Catheter ablation of AF in patients with HCM is an effective and safe therapeutic option, particularly in patients with paroxysmal AF. Effectiveness of ablation is significantly smaller in patients with persistent AF and even more so in those with long-persistent AF. Repeated procedures were often necessary. Continued antiarrhythmic drug therapy is often required due to a significant degree of atrial remodelling.
Monitoring tobacco use on a regular schedule is a basic tool of tobacco control policy. This study aimed (1) to assess the current prevalence and patterns of tobacco and e-cigarette use, as well as ...(2) to identify socioeconomic factors associated with smoking behavior among adults in Poland. This cross-sectional study was carried out in March 2022 on a nationwide, representative sample of 1090 adults in Poland. The computer-assisted web interview (CAWI) technique was used. Daily tobacco smoking was declared by 28.8% of respondents (27.1% of females and 30.8% of males;
= 0.2) and 4.2% were occasional smokers (4.2% of females and 4.3% of males;
= 0.8). Most of the current smokers (62.1%) smoked regular cigarettes and 25.2% smoked hand-rolled cigarettes. The prevalence of daily e-cigarette use was 4.8% (4.0% among females and 5.6% among males;
= 0.2). Daily heated tobacco use was declared by 4.0% of respondents (5.1% of females and 2.9% of males;
= 0.07). Age, having children, and educational level were significantly associated with current daily tobacco smoking. This study revealed a high prevalence of tobacco and e-cigarette use among adults in Poland. The presented data underscore the importance of further improvements in adopting a comprehensive tobacco control strategy in Poland.
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