Díky novým technologiím a vyššímu důrazu kladenému na bezpečnostní profil léčiv dochází k postupnému zlepšování lékových forem, což je také případ inhalačního kortikosteroidu beklometason dipropionátu, kdy jeho extra-fine formulace vede vklinické praxi ke snížení jeho nominální dávky až 2,5krát. Článek podrobněji popisuje dopady této transformace vefixních kombinovaných přípravcích, tj. depozici extra-fine částic vcentrální i periferní části plic, nižší systémovou expozici a v neposlední řadě taky pozitivní vliv u skupiny pacientů s astmatem, CHOPN a snížení rizika výskytu pneumonie.
Thanks to advancements and increased emphasis on the safety profile of medications, there is a gradual improvement in the development of pharmaceutical forms. One such change has been implemented in the inhaled corticosteroid beclomethasone dipropionate, resulting in a 2.5× reduction in its nominal clinical dose. The article provides a detailed description of the effects of this transformation in fixed combination preparations, i.e., the deposition of extra-fine particles in both the central and peripheral parts of the lungs, lower systemic exposure, and, last but not least, the positive impact on patients with asthma, COPD, and a reduced risk of pneumonia.
- MeSH
- aplikace inhalační MeSH
- beklomethason * aplikace a dávkování farmakologie terapeutické užití MeSH
- bronchiální astma * farmakoterapie MeSH
- chronická obstrukční plicní nemoc * farmakoterapie MeSH
- fixní kombinace léků MeSH
- formoterol fumarát aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- pneumonie prevence a kontrola MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
Poznatky, získané hlavne v posledných dvoch desaťročiach, umožnili lepšie porozumieť mechanizmom a dráham, prostredníctvom ktorých nervový systém, a tým aj stres, ovplyvňuje procesy súvisiace so vznikom a progresiou nádorových chorôb. Neurobiologický výskum nádorových chorôb pritom nie len rozšíril poznanie etiopatogenézy nádorového procesu, ale vytvoril podklady aj pre zavedenie nových terapeutických metód v onkológii, založených na modulácii prenosu signálov medzi nervovým systémom a nádorovým tkanivom. Bolo tiež zistené, že monitorovanie aktivity zložiek autonómneho nervového systému je možné využiť nie len na určenie miery stresu u daného pacienta, ale aj na posúdenie prognózy jeho onkologickej choroby. Jednu z efektívnych metód, umožňujúcich sledovanie flexibility a rovnováhy pôsobenia zložiek autonómneho nervového systému a nepriamo aj miery stresu u onkologických pacientov, predstavuje určovanie variability srdcovej frekvencie (HRV). Na opodstatnenosť využitia tejto metódy v onkológii poukazujú aj zistenia, že pacienti s vyššími hodnotami HRV vykazujú dlhšie prežívanie v porovnaní s pacientmi, u ktorých sú hodnoty HRV nižšie. Zámerom tohto textu je priblížiť súčasné poznatky týkajúce sa vplyvu stresu na nádory hlavy a krku a načrtnúť možnosti využitia stanovenia HRV ako prognostického markera u týchto pacientov. Diskutované sú aj možnosti využitia metód, ktoré sú zamerané na zvýšenie HRV a ich prípadné využitie v liečbe pacientov s nádormi hlavy a krku.
Knowledge, mainly gained in the last two decades, has provided a better understanding of the mechanisms and pathways through which the nervous system, and thus stress, influences processes related to cancer initiation and progression. Neurobiological research on cancer has not only increased the knowledge of the aetiopathogenesis of the tumour process, but also has laid the foundation for the introduction of new therapeutic methods in oncology based on the modulation of the transmission of signals between the nervous system andtumour tissue. It also has been found that monitoring the activity of components of the autonomic nervous system can be used not only to determine the degree of stress in a given patient, but also to assess the prognosis of his or her oncological disease. One of the effective methods to monitor the flexibility and balance of the autonomic nervous system components and indirectly the level of stress in cancer patients is the determination of heart rate variability (HRV). The validity of the use of this method in oncology is indicated by the findings that patients with higher HRV values show longer survival compared to patients with lower HRV values. The aim of this text is to review the current knowledge regarding the impact of stress on head and neck cancer and to outline the possibilities of using HRV determination as a prognostic marker in these patients. The potential use of methods aimed at increasing HRV and their potential use in the management of patients with head and neck tumours are also discussed.
Tato kazuistika popisuje případ totální atrioventrikulární blokády (TAVB) s pozitivními anti-Ro/SSA protilátkami u transgender muže, který byl sledován ve 31. týdnu a 3. dni gestace. Navzdory mnoha neshodám ohledně tohoto pacienta byly doporučeny kortikosteroidy. Komorová frekvence plodu při druhé týdenní návštěvě byla 50 tepů/min a ke zvýšení srdeční frekvence bylo zahájeno podávání terbulinu. Pro lepší kontrolu mateřských symptomů a sledování vitálních funkcí plodu bylo přikročeno k hospitalizaci a nitrožilnímu podání terbutalinu po dobu 3 dnů a rovněž ke každodennímu monitorování komorové frekvence. Došlo ke zvýšení výchozí komorové frekvence přibližně o 15 %. Po propuštění z nemocnice byla navíc k indexům navrženým Huhtou pro echokardiografické hodnocení srdeční funkce plodu prováděna týdenní kontrolní echokardiografie plodu. Fetální komorová frekvence u ambulantních kontrol neklesla na < 55 tepů/min. Císařský řez byl indikován ve 35. týdnu a 4. dni gestace z důvodu předčasné ruptury ovulárních membrán. Byl porozen novorozenec mužského pohlaví o hmotnosti 2 250 g s Apgar skóre 8 v 1. minutě a 9 v 5. minutě. Po 88 dnech života kojenec vážil 4 580 g a bez komplikací mu byl implantován trvalý dvoukomorový epikardiální kardiostimulátor. Kardiostimulátor je indikován i v případě, že při použití terbutalinu dojde k přechodnému zvýšení komorové frekvence plodu. Porod by měl proběhnout v termínu, aby plod mohl dosáhnout adekvátní hmotnosti a plicní zralosti pro implantaci trvalého kardiostimulátoru.
This case report describes a case of total atrioventricular block (TAVB) with positive anti-Ro/SSA antibodies in a transgender man who began follow-up at 31 weeks and 3 days of gestation. Despite many disagreements regarding treatment, corticosteroids were recommended for this patient. The fetal ventricular rate at the second weekly visit was 50 bpm and terbulin was started to increase heart rate. Hospitalization and intravenous terbutaline for 3 days was chosen to better control maternal symptoms and monitor fetal vital signs, as well as daily monitoring of the ventricular rate. There was an increase in baseline ventricular rate of approximately 15%. After discharge from the hospital, weekly control fetal echocardiography was performed in addition to the indices proposed by Huhta for echocardiographic assessment of fetal cardiac function. Fetal ventricular rate in ambulatory controls did not fall below 55 bpm. Cesarean section was indicated at 35 weeks and 4 days of gestation due to premature rupture of ovular membranes. A male newborn was delivered weighing 2,250 grams with Apgar scores of 8 and 9 at the 1st and 5th minute, respectively. After 88 days of life, the infant was weighing 4,580 grams and a definitive bicameral epicardial pacemaker was implanted without complications. Even if there is a transient increase in fetal ventricular rate with the use of terbutaline, a pacemaker is indicated. Delivery should be at term to allow the fetus to achieve adequate weight and pulmonary maturity for definitive pacemaker implantation.
- MeSH
- atrioventrikulární blokáda * diagnóza MeSH
- císařský řez MeSH
- lidé MeSH
- prenatální diagnóza MeSH
- systémový lupus erythematodes diagnóza MeSH
- těhotenství MeSH
- terbutalin terapeutické užití MeSH
- transgender osoby MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Hyperkalaemia is a life-threatening electrolyte disturbance and also a potential cause of cardiac arrest. The objective was to assess the effects of acute pharmacological interventions for the treatment of hyperkalaemia in patients with and without cardiac arrest. METHODS: The review was reported according to PRISMA guidelines and registered on PROSPERO (CRD42023440553). We searched OVID Medline, EMBASE, and CENTRAL on September 9, 2024 for randomized trials, non-randomized trials, observational studies, and experimental animal studies. Two investigators performed abstract screening, full-text review, data extraction, and bias assessment. Outcomes included potassium levels, ECG findings, and clinical outcomes. Certainty of evidence was evaluated using GRADE. RESULTS: A total of 101 studies were included, with two studies including patients with cardiac arrest. In meta-analyses including adult patients without cardiac arrest, treated with insulin in combination with glucose, inhaled salbutamol, intravenous salbutamol dissolved in glucose, or a combination, the average reduction in potassium was between 0.7 and 1.2 mmol/l (very low to low certainty of evidence). The use of bicarbonate had no effect on potassium levels (very low certainty of evidence). In neonatal and paediatric populations, inhaled salbutamol and intravenous salbutamol reduced the average potassium between 0.9 and 1.0 mmol/l (very low to low certainty of evidence). There was no evidence to support a clinical beneficial effect of calcium for treatment of hyperkalemia. CONCLUSIONS: Evidence supports treatment with insulin in combination with glucose, inhaled or intravenous sal-butamol, or the combination. No evidence supporting a clinical effect of calcium or bicarbonate for hyperkalaemia was identified.
- MeSH
- albuterol * aplikace a dávkování terapeutické užití MeSH
- aplikace inhalační MeSH
- draslík krev MeSH
- glukosa aplikace a dávkování MeSH
- hydrogenuhličitany aplikace a dávkování MeSH
- hyperkalemie * farmakoterapie MeSH
- inzulin * aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- srdeční zástava farmakoterapie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
BACKGROUND/OBJECTIVES: Crohn's disease is known for being associated with an abnormal composition of the bacterial flora, dysbiosis and intestinal function disorders. Metabolites produced by gut microbiota play a pivotal role in the pathogenesis of CD, and the presence of unspecific extraintestinal manifestations. METHODS: The aim of this study was a determination of the level of bacterial metabolites in blood plasma in patients with Crohn's disease. CD patients (29) and healthy individuals (30) were recruited for this study. Bacterial metabolites (SCFAs and TMAO panel) were measured by a liquid chromatography-mass spectrometry system. RESULTS: A significant correlation (p-value < 0.05) between CD and bacterial metabolites was obtained for three of eight tested SCFAs; acetic acid (reduced in CD; FC 1.7; AUC = 0.714), butyric acid (increased; FC 0.68; AUC = 0.717), 2MeBA (FC 1.168; AUC = 0.702), and indoxyl (FC 0.624). The concentration of CA (FC 0.82) and choline (FC 0.78) in plasma was significantly disturbed according to the biological treatment. Choline level (FC 1.28) was also significantly disturbed in the patients treated with glucocorticoids. In total, 68.97% of Crohn's patients presented extraintestinal manifestations (EIMs) of Crohn's disease, mainly osteoarticular complications. The level of BA was statistically significantly elevated in patients with extraintestinal (FC 0.602) manifestations, while in the group of patients with osteoarticular complications, a significant difference in the level of betaine (FC 1.647) was observed. CONCLUSIONS: The analyzed bacterial metabolites of plasma may significantly help in the diagnostic process, and in the monitoring of the disease course and treatment, in a lowly invasive way, as biomarkers after additional research on a larger group of patients.
- MeSH
- Bacteria MeSH
- biologické markery krev MeSH
- cholin krev MeSH
- Crohnova nemoc * krev mikrobiologie MeSH
- dospělí MeSH
- dysbióza krev mikrobiologie MeSH
- kyseliny mastné těkavé krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- methylaminy krev MeSH
- mladý dospělý MeSH
- střevní mikroflóra * MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- beta blokátory aplikace a dávkování klasifikace terapeutické užití MeSH
- erektilní dysfunkce farmakoterapie MeSH
- fixní kombinace léků MeSH
- hydrochlorthiazid aplikace a dávkování farmakologie terapeutické užití MeSH
- hypertenze * MeSH
- lidé MeSH
- nebivolol * aplikace a dávkování farmakologie škodlivé účinky terapeutické užití MeSH
- srdeční selhání * farmakoterapie MeSH
- výběr pacientů MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Albumin administration is suggested in patients with sepsis and septic shock who have received large volumes of crystalloids. Given lack of firm evidence, clinical practice variation may exist. To address this, we investigated if patient characteristics or trial site were associated with albumin use in septic shock. METHODS: We conducted a post-hoc study of the CLASSIC international, randomised clinical trial of fluid volumes in septic shock. Associations between selected baseline variables and trial site with albumin use during ICU stay were assessed in Cox models considering death, ICU discharge, and loss-to-follow-up as competing events. Baseline variables were first assessed individually, adjusted for treatment allocation (restrictive vs. standard IV fluid), and then adjusted for allocation and the other baseline variables. Site was assessed in a model adjusted for allocation and baseline variables. RESULTS: We analysed 1541 of 1554 patients randomised in CLASSIC (99.2%). During ICU stay, 36.3% of patients in the restrictive-fluid group and 52.6% in the standard-fluid group received albumin. Gastrointestinal focus of infection and higher doses of norepinephrine were most strongly associated with albumin use (subgroup with highest quartile of norepinephrine doses, hazard ratio (HR) 2.58, 95% CI 1.89 to 3.53). HRs for associations between site and albumin use ranged from 0.11 (95% CI 0.05 to 0.26) to 1.70 (95% CI 1.06 to 2.74); test for overall effect of site: p < .001. CONCLUSIONS: In adults with septic shock, gastrointestinal focus of infection and higher doses of norepinephrine at baseline were associated with albumin use, which also varied substantially between sites.
- MeSH
- albuminy terapeutické užití MeSH
- dospělí MeSH
- lidé MeSH
- noradrenalin terapeutické užití MeSH
- sepse * farmakoterapie etiologie MeSH
- septický šok * farmakoterapie komplikace MeSH
- tekutinová terapie škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
G protein-coupled estrogen receptor 1 (GPER-1) has gained recognition for its role in conferring cardioprotection. However, the extent to which GPER-1 exerts equally important effects in both sexes remains unclear. The study found similar expressions of GPER-1 in rat heart apex in both sexes. In male rats, administering epinephrine (Epi) at a dose of 31.36 microg/100 g resulted in a rapid decline in cardiac function, accompanied by a sharp increase in bax/bcl-2 levels. In contrast, female rats did not display significant changes in cardiac function under the same conditions. Additionally, compared to the injection of Epi alone (at a dose of 15.68 microg/100 g), the administration of G15 (GPER-1 antagonist) further decreased cardiac function in both male and female rats. However, it only increased mortality and lung coefficient in male rats. Conversely, G1 (GPER-1 agonist) administration improved cardiac function in both sexes. Notably, the apex of the male heart exhibited lower levels of inhibitory G protein (Galphai). Furthermore, female and male rats treated with Epi displayed elevated phosphorylated protein kinase B (p-Akt). Compared to their respective Epi groups, the administration of G15 increased p-Akt levels in female rat hearts but decreased them in male rat hearts. Conversely, the administration of G1 decreased p-Akt levels in females but rapidly increased them in male rats. Our study uncovers the vital role of GPER-1 in protecting against stress-induced heart injuries in a sex-specific manner. These findings hold immense potential for advancing targeted cardiac therapies and enhancing outcomes for both females and males.
- MeSH
- adrenalin MeSH
- fyziologický stres fyziologie MeSH
- krysa rodu rattus MeSH
- pohlavní dimorfismus MeSH
- potkani Sprague-Dawley * MeSH
- protoonkogenní proteiny c-akt * metabolismus MeSH
- receptory pro estrogeny metabolismus MeSH
- receptory spřažené s G-proteiny * metabolismus MeSH
- sexuální faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The combination of aminophylline and salbutamol is frequently used in clinical practice in the treatment of obstructive lung diseases. While the side effects (including arrhythmias) of the individual bronchodilator drugs were well described previously, the side effects of combined treatment are almost unknown. We aimed to study the arrhythmogenic potential of combined aminophylline and salbutamol treatment in vitro. For this purpose, we used the established atomic force microscopy (AFM) model coupled with cardiac organoids derived from human pluripotent stem cells (hPSC-CMs). We focused on the chronotropic, inotropic, and arrhythmogenic effects of salbutamol alone and aminophylline and salbutamol combined treatment. We used a method based on heart rate/beat rate variability (HRV/BRV) analysis to detect arrhythmic events in the hPSC-CM based AFM recordings. Salbutamol and aminophylline had a synergistic chronotropic and inotropic effect compared to the effects of monotherapy. Our main finding was that salbutamol reduced the arrhythmogenic effect of aminophylline, most likely mediated by endothelial nitric oxide synthase activated by beta-2 adrenergic receptors. These findings were replicated and confirmed using hPSC-CM derived from two cell lines (CCTL4 and CCTL12). Data suggest that salbutamol as an add-on therapy may not only deliver a bronchodilator effect but also increase the cardiovascular safety of aminophylline, as salbutamol reduces its arrhythmogenic potential.
- MeSH
- albuterol * farmakologie MeSH
- aminofylin * farmakologie MeSH
- bronchodilatancia farmakologie MeSH
- buněčné linie MeSH
- kardiomyocyty účinky léků metabolismus MeSH
- lidé MeSH
- mikroskopie atomárních sil MeSH
- pluripotentní kmenové buňky účinky léků cytologie MeSH
- srdeční arytmie * farmakoterapie MeSH
- srdeční frekvence účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Monitoring nociception during general anaesthesia remains a substantial challenge. The Conox monitor uses two EEG indices, the qCon and the qNox. The qNox refers to the probability that a nociceptive stimulation triggers a movement of the patient and the response probability of reaction to nociceptive stimulation. We decided to test the feasibility of monitoring the qNOX index during adult cardiac surgery and to investigate whether this index correlates with hemodynamic and hormonal signs of nociceptive stimulation. METHOD: We enrolled 19 patients undergoing elective cardiac surgery. These were randomised to 2 groups receiving different doses of sufentanil via target controlled infusion: group A (n=9) 0.25 ng/mL and group B (n=10) 0.75 ng/mL. All patients were maintained at the same depth of anaesthesia. We recorded the Conox monitor indices (qNOX, qCON, electromyographic), hemodynamic variables and plasmatic levels of cortisol and noradrenaline. RESULTS: There was significantly higher blood pressure (P=0.013) and plasmatic cortisol (P=0.003) in group A and a significant increase in plasmatic noradrenaline with increasing intensity of surgical stimulation in both groups: A (P=0.001), B (P=0.008). We found no significant corresponding changes in the qNOX index. There was a positive correlation between qNOX and hemodynamic signs of stimulation (P=0.012) and between the qNOX and EMG indices (P=0.013) after endotracheal intubation, but not later after EMG index dropped. CONCLUSION: Our results do not support the assumption that signs of nociceptive stimulation during adult cardiac surgery will be reflected by the qNOX index. This may be related to compounding of qNOX processing and use of muscle relaxants. Further investigation on this field is needed.
- MeSH
- celková anestezie MeSH
- dospělí MeSH
- elektroencefalografie MeSH
- hydrokortison * MeSH
- kardiochirurgické výkony * MeSH
- lidé MeSH
- nocicepce MeSH
- noradrenalin MeSH
- studie proveditelnosti MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
