Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), "lower is better for longer", and recent data have strongly emphasised the need for also "the earlier the better". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of "extremely high-risk" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries.
- MeSH
- akutní koronární syndrom * krev farmakoterapie etiologie MeSH
- anticholesteremika terapeutické užití MeSH
- ateroskleróza * krev komplikace farmakoterapie MeSH
- hypolipidemika * terapeutické užití MeSH
- LDL-cholesterol krev MeSH
- lidé MeSH
- přehledová literatura jako téma MeSH
- statiny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
Protection against water- and air-borne bacteria as well as their detection at very low levels is a big challenge for the health care profession. The study’s main goal was to prepare bacterial filters with a tunable trapping effectivity. We revealed that the trapping efficiency of Escherichia coli estimated from the optical density of bacteria passed through the filter was exponentially dependent on the surface density of the polyacrylonitrile nanofibre membranes. This log/linear regression profile was proven for bacterial trapping efficiency higher than 99.9% which opens a door for easy and tunable constructions of ultrasensitive filters and/or nanosensors as well as for the standardization and quality control of nanofibre membranes.
Western-type diet with high salt and sugar, sedentary behavior, obesity, tobacco and alcoholism are important risk factors for hypertension. This review aims to highlight the role of western diet-induced oxidative stress and inflammation in the pathogenesis of hypertension and the role of various types of diets in its prevention with reference to dietary approaches to stop hypertension (DASH) diet. It seems that it is crucial to alter the western type of diet because such diets can also predispose all CVDs. Western diet-induced oxidative stress is characterized by excessive production of reactive oxygen species (ROS) with an altered oxidation-reduction (redox) state, leading to a marked increase in inflammation and vascular dysfunction. Apart from genetic and environmental factors, one important cause for differences in the prevalence of hypertension in various countries may be diet quality, deficiency in functional foods, and salt consumption. The role of the DASH diet has been established. However, there are gaps in knowledge about the role of some Indo-Mediterranean foods and Japanese foods, which have been found to decrease blood pressure (BP) by improving vascular function. The notable Indo-Mediterranean foods are pulses, porridge, spices, and millets; fruits such as guava and blackberry and vegetables, which may also decrease BPs. The Japanese diet consists of soya tofu, whole rice, in particular medical rice, vegetables and plenty of fish rich in fish oil, fish peptides and taurine that are known to decrease BPs. Epidemiological studies and randomized, controlled trials have demonstrated the role of these diets in the prevention of hypertension and metabolic diseases. Such evidence is still meager from Japan, although the prevalence of hypertension is lower (15-21%) compared to other developed countries, which may be due to the high quality of the Japanese diet. Interestingly, some foods, such as berries, guava, pumpkin seeds, carrots, soya beans, and spices, have been found to cause a decrease in BPs. Omega-3 fatty acids, fish peptide, taurine, dietary vitamin D, vitamin C, potassium, magnesium, flavonoids, nitrate and l-arginine are potential nutrients that can also decrease BPs. Larger cohort studies and controlled trials are necessary to confirm our views.
The exact pathophysiology of heart failure (HF) is not yet known. Western diet, characterized by highly sweetened foods, as well as being rich in fat, fried foods, red meat and processed meat, eggs, and sweet beverages, may cause inflammation, leading to oxidative dysfunction in the cardiac ultra-structure. Oxidative function of the myocardium and how oxidative dysfunction causes physio-pathological remodeling, leading to HF, is not well known. Antioxidants, such as polyphenolics and flavonoids, omega-3 fatty acids, and other micronutrients that are rich in Indo-Mediterranean-type diets, could be protective in sustaining the oxidative functions of the heart. The cardiomyocytes use glucose and fatty acids for the physiological functions depending upon the metabolic requirements of the heart. Apart from toxicity due to glucose, lipotoxicity also adversely affects the cardiomyocytes, which worsen in the presence of deficiency of endogenous antioxidants and deficiency of exogenous antioxidant nutrients in the diet. The high-sugar-and-high-fat-induced production of ceramide, advanced glycation end products (AGE) and triamino-methyl-N-oxide (TMAO) can predispose individuals to oxidative dysfunction and Ca-overloading. The alteration in the biology may start with normal cardiac cell remodeling to biological remodeling due to inflammation. An increase in the fat content of a diet in combination with inducible nitric oxide synthase (NOSi) via N-arginine methyl ester has been found to preserve the ejection fraction in HF. It is proposed that a greater intake of high exogenous antioxidant restorative treatment (HEART) diet, polyphenolics and flavonoids, as well as cessation of red meat intake and egg, can cause improvement in the oxidative function of the heart, by inhibiting oxidative damage to lipids, proteins and DNA in the cell, resulting in beneficial effects in the early stage of the Six Stages of HF. There is an unmet need to conduct cohort studies and randomized, controlled studies to demonstrate the role of the HEART diet in the treatment of HF.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Manažment dyslipidémií ostáva výzvou napriek objemu kvalitných dát a dostupnosti liečebných modalít. Epidémia aterosklerotického kardiovaskulárneho ochorenia je dominantnou príčinou chorobnosti a úmrtnosti vo vyspelom svete. Prienik Odporúčaní pre manažment dyslipidémií do ostatných dokumentov dokazuje význam tejto problematiky. Nové poznatky vedú k sprísneniu cieľových hodnôt pre LDL-cholesterol podľa stupňa kardiovaskulárneho rizika. Ročná mortalita po akútnom koronárnom syndróme v porovnaní s vyspelejšími krajinami neúmerne rastie. Analýza príčin poukazuje na zlý manažment rizikových faktorov po prepustení z hospitalizácie. Možnosti zlepšenia okrem iného smerujú k zmene indikačných obmedzení pre PCSK9-inhibítory.
The management of dyslipidemia remains a challenge despite the volume of EBM data and the availability of treatment modalities. The ASCVD epidemic is the dominant cause of morbidity and mortality in the developed world. The integration of the Guidelines for the Management of Dyslipidemias into other documents demonstrates the importance of this issue. New findings lead to the tightening of LDL-C target values according to CV risk levels. Annual mortality after ACS in Slovakia is rising disproportionately compared to more developed countries. The root cause analysis points to poor management of risk factors after hospital discharge. Opportunities for improvement include, inter alia, the changing of the indication restrictions for PCSK9 inhibitors.
- MeSH
- akutní koronární syndrom * patologie MeSH
- dyslipidemie * farmakoterapie MeSH
- LDL-cholesterol krev škodlivé účinky MeSH
- lidé MeSH
- management nemoci MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Slovenská republika MeSH
Dead space after rectal resection in colorectal surgery is an area with a high risk of complications. In this study, our goal was to develop a novel 3D implant based on composite hydrogels enriched with fractionalized nanofibers. We employed, as a novel approach in abdominal surgery, the application of agarose gels functionalized with fractionalized nanofibers on pieces dozens of microns large with a well-preserved nano-substructure. This retained excellent cell accommodation and proliferation, while nanofiber structures in separated islets allowed cells a free migration throughout the gel. We found these low-concentrated fractionalized nanofibers to be a good tool for structural and biomechanical optimization of the 3D hydrogel implants. In addition, this nano-structuralized system can serve as a convenient drug delivery system for a controlled release of encapsulated bioactive substances from the nanofiber core. Thus, we present novel 3D nanofiber-based gels for controlled release, with a possibility to modify both their biomechanical properties and drug release intended for 3D lesions healing after a rectal extirpation, hysterectomy, or pelvic exenteration.
- Publikační typ
- časopisecké články MeSH
Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), "lower is better for longer", and the recent data have strongly emphasized the need of also "the earlier the better". In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual's calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an 'Extremely High Risk' group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients.
- MeSH
- akutní koronární syndrom krev farmakoterapie MeSH
- anticholesteremika škodlivé účinky terapeutické užití MeSH
- ateroskleróza krev farmakoterapie MeSH
- ezetimib škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- lipidy krev MeSH
- management nemoci MeSH
- PCSK9 inhibitory škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Somatostatin analogs mantain their major role in the treatment of patients with advanced neuroendocrine tumors (NETs) and have multiple modulatory effects on the immune system. Here, we evaluated the effects of lanreotide treatment on expression of Th1, Th2 cytokine patterns in serum of patients with NETs and in bronchial and pancreatic NET cell lines. Our results showed that lanreotide treatment promoted a Th1 cytotoxic immune-phenotype in patients with NETs originated by intestinal sites. Similar results were obtained also in vitro where lanreotide induced expression of Th1 cytokines only in pancreatic and not in bronchial-derived NET cell lines. It seems, therefore, that cytokinomics can represent a useful tool for the identification of tumor biomarkers for the early diagnosis and evaluation of the response to therapy in NET patients. To avoid the drug-resistance induced by everolimus (mTOR inhibitor), we made the pancreatic NET cell line resistant to this drug. After treatment with lanreotide we found that the drug reduced its viability compared to that of sensitive cells. These data may have direct implications in design of future translation combination trial on NET patients.
- Publikační typ
- časopisecké články MeSH
Stem cells are undifferentiated elements capable to acquire a specific cellular phenotype under the influence of specific stimuli, thus being involved in tissue integrity and maintenance. In the skin tissue self-renewal and wound healing after injury is a complex process, especially in adulthood, due to the aging process and the continuous exposure to damaging agents. The importance of stem cells in regenerative medicine is well known and defining or improving their isolation methods is therefore a primary and crucial step. In the present paper we present a novel method to isolate stem cells from human skin, including the involvement of a novel medium for the maintenance and expansion of in vitro cultures. The biopsies were mechanically digested and put in culture. The migrating cells were positive selected with magnetic cell sorting, characterized by flow-cytometry analysis, and viability detected by MTT assay. Cells exhibited a mesenchymal phenotype, as demonstrated by the positive acquirement of an osteogenic or adipogenic phenotype when cultured in specific conditioned media. Taken together our results disclose a novel method for culturing and expanding stem cells from skin and pave the way for future clinical applications in tissue regeneration.
- MeSH
- kmenové buňky * MeSH
- kůže cytologie MeSH
- lidé MeSH
- separace buněk metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
The aim of the study was to evaluate the safety and efficacy of a new therapeutic approach to skin defects resulting from split thickness grafting. Within the study, nanofiber-based dressings fabricated using polyvinyl alcohol (PVA) and poly-ε-caprolactone (PCL) were used, with different mass density. The study was performed in 1 female minipig. Nine defects (approx. 4x4 cm) were made in the superficial skin layer. The tested materials were applied to the squared skin defect and covered by a Jelonet paraffin gauze, sutured in the corners of the defects. The animal was monitored daily during the healing process (21 days). On day 5, 12, and 27, the healing of the wound was evaluated, and a biopsy was performed for further histologic testing. At the end of the study (on day 27 after the procedure), the animal was euthanized, and a standard pathologic evaluation was performed. We can conclude that the nanofiber scaffold which was well tolerated, could be used as a smart skin cover which could be functionalized with another bioactive substances directly on the surgeon table, among potential bioactive substances belong platelet derivatives, antibiotics, etc.
- MeSH
- hojení ran * MeSH
- miniaturní prasata MeSH
- nanovlákna terapeutické užití MeSH
- obvazy * MeSH
- polyestery MeSH
- polyvinylalkohol MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
