Accumulation of environmental chitin in the lungs can lead to pulmonary fibrosis, characterized by inflammatory infiltration and fibrosis in acidic chitinase (Chia)-deficient mice. Transgenic expression of Chia in these mice ameliorated the symptoms, indicating the potential of enzyme supplementation as a promising therapeutic strategy for related lung diseases. This study focuses on utilizing hyperactivated human Chia, which exhibits low activity. We achieved significant activation of human Chia by incorporating nine amino acids derived from the crab-eating monkey (Macaca fascicularis) Chia, known for its robust chitin-degrading activity. The modified human Chia retained high activity across a broad pH spectrum and exhibited enhanced thermal stability. The amino acid substitutions associated with hyperactivation of human Chia activity occurred species specifically in monkey Chia. This discovery highlights the potential of hyperactivated Chia in treating pulmonary diseases resulting from chitin accumulation in human lungs.
- MeSH
- aktivace enzymů účinky léků MeSH
- chitin metabolismus chemie MeSH
- chitinasy * metabolismus genetika chemie MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- Macaca fascicularis MeSH
- myši MeSH
- plíce metabolismus patologie enzymologie MeSH
- stabilita enzymů MeSH
- substituce aminokyselin MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: In a previously published randomised, placebo-controlled trial, 800 mg/day of pharmaceutical-grade chondroitin sulfate (CS) was shown to be superior to placebo in reducing pain and improving function over 6 months in patients with symptomatic knee osteoarthritis (OA). The aim of the current post hoc analyses was to evaluate the cost-effectiveness of CS compared with placebo in a European perspective using individual patient data from this clinical trial. METHODS: Patients with knee OA randomised to CS or placebo were followed up at 1, 3 and 6 months. The algo-functional Lequesne index was used to derive the EuroQol Five-Dimension Five-Level (EQ-5D-5L) score based on a validated formula. The EQ-5D-5L scores at each time point were used to calculate the changes in quality-adjusted life years (QALYs) with the area under the curve method. Costs were assessed using the average price of CS in the countries where the original study took place and where CS is currently marketed. The costs of CS in three countries were then used (i.e. the Czech Republic, Italy and Switzerland). The incremental cost-effectiveness ratio (ICER) threshold for CS to be considered cost-effective was set at 91,870 EUR per QALY (equivalent to the usually recommended threshold of US $100,000). The study used an intention-to-treat population, i.e. patients who received one dose of the study drug, and imputed missing values using the basal observation carried forward method. RESULTS: No significant differences in baseline characteristics were observed between the CS group (N = 199) and the placebo group (N = 205). The mean cost of CS for 6 months of treatment was 194.74 EUR. After 6 months of treatment, CS showed a mean ICER of 33,462 (95% CI 5130-61,794) EUR per QALY gained, indicating cost-effectiveness compared with placebo. The acceptability curve for cost-effectiveness shows that the CS treatment is likely to be cost-effective compared with placebo, with a 93% probability when the ceiling ratio is set at 91,870 EUR per QALY gained. CONCLUSIONS: These results highlight the role of CS as a cost-effective therapeutic option in the management of OA. However, further studies taking into account the use of other healthcare resources are warranted for a more complete understanding.
- MeSH
- analýza nákladové efektivity MeSH
- analýza nákladů a výnosů * MeSH
- artróza kolenních kloubů * farmakoterapie ekonomika MeSH
- chondroitinsulfáty * terapeutické užití ekonomika MeSH
- kvalitativně upravené roky života * MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Geografické názvy
- Česká republika MeSH
- Itálie MeSH
- Švýcarsko MeSH
BACKGROUND: Anticoagulation during extracorporeal membrane oxygenation (ECMO) might still lead to severe bleeding complications. Heparin is the most frequently used anticoagulant, but novel drugs could be promising. Argatroban is a new alternative to heparin. To date, no robust studies have confirmed the clear superiority of argatroban (AG) over heparin, although it has some advantages and may be safer. STUDY DESIGN AND METHODS: An observational study was conducted in all adult veno-venous ECMO patients with COVID-19-associated acute respiratory distress syndrome admitted to the University Hospital Ostrava (n = 63). They were anticoagulated with heparin in the first period and with AG in the second period, targeting the same activated partial thromboplastin time (aPTT; 45-60 s). Bleeding complications requiring transfusion and life-threatening bleeding events were evaluated. The primary objective was to compare heparin and AG in terms of bleeding, transfusion requirements and mortality-related bleeding. RESULTS: The total time on ECMO per patient was 16 days with an in-hospital mortality of 55.6%. The red blood cell consumption in the AG group (median 2.7 transfusions/week) was significantly lower than in the heparin group (median 4.2 transfusions/week, p = 0.011). Life-threatening bleeding complications were higher in the heparin group compared to the AG group (35.7% vs. 10.2%, p = 0.035), and mortality-related bleeding complications were also higher in the heparin group (21.4% vs. 2.0%, p = 0.032). DISCUSSION: Argatroban is an interesting alternative to heparin with less bleeding, less need for red blood cell transfusions and improved safety of ECMO with less mortality-related bleeding.
- MeSH
- antikoagulancia * škodlivé účinky terapeutické užití MeSH
- arginin * analogy a deriváty MeSH
- COVID-19 komplikace MeSH
- dospělí MeSH
- heparin * škodlivé účinky MeSH
- krvácení * chemicky indukované terapie MeSH
- kyseliny pipekolové * terapeutické užití aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- mimotělní membránová oxygenace * MeSH
- mortalita v nemocnicích MeSH
- SARS-CoV-2 MeSH
- senioři MeSH
- sulfonamidy * MeSH
- syndrom dechové tísně terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- srovnávací studie MeSH
BACKGROUND: Unfractionated heparin is used as the most common anticoagulation for venovenous extracorporeal membrane oxygenation (VV ECMO) patients. However, it is accompanied by frequent bleeding and thrombotic complications. The aim of the study was to demonstrate the feasibility of Enoxaparin anticoagulation for VV ECMO patients. METHODS: This study is a retrospective analysis of VV ECMO patients on continuous intravenous Enoxaparin anticoagulation. The primary outcome was the incidence of bleeding, thrombotic, and neurological complications during ECMO support. The secondary outcome was an analysis of secondary and primary hemostasis profiles. RESULTS: Data from 38 patients were analyzed in this study. The incidence of bleeding complications was 5.3%, for thrombotic complications it was 2.6% and for neurological (bleeding/ischemic events) complications it was 10.5%. The targeted anti-Xa activity of 0.4-0.6 IU/mL was achieved and maintained during whole ECMO period in 28 patients (73.8%), not affecting the hemocoagulation profile represented by APTT-r 1.15 ± 0.2, TT 18.67 ± 3.35 s, PT/INR 1.21 ± 0.19, fibrinogen 5.39 ± 1.49 g/L, antithrombin, and platelet count. Primary hemostasis pathology was diagnosed in all patients by PFA 200 tests Col/EPI 279 ± 38 s and Col/ADP 249 ± 66 s. The running time of ECMO was 7.8 ± 3.4 days. CONCLUSIONS: Enoxaparin anticoagulation appears to be feasible for VV ECMO patients without an increase in adverse events. Further larger-sampled and comparative studies are needed in the future to support our findings.
- MeSH
- antikoagulancia aplikace a dávkování terapeutické užití MeSH
- dospělí MeSH
- enoxaparin * aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- inhibitory faktoru Xa aplikace a dávkování terapeutické užití MeSH
- intravenózní podání MeSH
- krvácení * prevence a kontrola etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mimotělní membránová oxygenace * škodlivé účinky metody MeSH
- retrospektivní studie MeSH
- senioři MeSH
- studie proveditelnosti MeSH
- trombóza prevence a kontrola etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: This was a single-center pilot study that sought to describe an innovative use of 4DryField® PH (premix) for preventing the recurrence of intrauterine adhesions (IUAs) after hysteroscopic adhesiolysis in patients with Asherman's syndrome (AS). MATERIAL AND METHODS: Twenty-three patients with AS were enrolled and 20 were randomized (1:1 ratio) to intrauterine application of 4DryField® PH (n = 10) or Hyalobarrier® gel (n = 10) in a single-blind manner. We evaluated IUAs (American Fertility Society [AFS] score) during initial hysteroscopy and second-look hysteroscopy one month later. Patients completed a follow-up symptoms questionnaire three and reproductive outcomes questionnaire six months later. RESULTS: The demographic and clinical characteristics, as well as severity of IUAs, were comparable in both groups. The mean initial AFS score was 9 and 8.5 in the 4DryField® PH and Hyalobarrier® gel groups, respectively (p = .476). There were no between-group differences in AFS progress (5.9 vs. 5.6, p = .675), need for secondary adhesiolysis (7 vs. 7 patients, p = 1), and the follow-up outcomes. CONCLUSION: 4DryField® PH could be a promising antiadhesive agent for preventing the recurrence of IUAs, showing similar effectiveness and safety to Hyalobarrier® gel. Our findings warrant prospective validation in a larger clinical trial. CLINICAL TRIAL REGISTRY NUMBER: ISRCTN15630617.
- MeSH
- adheze tkání prevence a kontrola MeSH
- dospělí MeSH
- gely * MeSH
- gynatrézie prevence a kontrola MeSH
- hysteroskopie * metody MeSH
- jednoduchá slepá metoda MeSH
- kyselina hyaluronová aplikace a dávkování MeSH
- lidé MeSH
- nemoci dělohy prevence a kontrola chirurgie MeSH
- pilotní projekty MeSH
- recidiva MeSH
- sekundární prevence metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
Beta glukany (BG) mají kromě své schopnosti integrovat s imunitním systémem řadu dalších specifických vlastností prospívajících kvalitě pokožky. Potlačují indukci antioxidačních aktivit, redukují rizika environmentálních stresů a tím působí jako přirozený a finančně efektivní přístup k udržení rovnováhy homeostázy pokožky. Rostoucí nabídka preparátů s BG vede k jejich aplikaci jak v kosmetické aplikaci, tak k aplikaci v dermatologii a dalších oborech lékařství. Předkládáme předběžné výsledky úspěšné aplikace krému s BG u seniorů s nálezem plenkové iritační dermatitidy jako proof-of-concept jejich potenciálního využití.
Beta glucans (BG) have not only the ability to cooperate with immune system, but also numerous additional specific properties, which improve quality of the skin. BG suppress induction of antioxidative activities, reduce risk of environmental stress and subsequently act as natural and financially effective method for achieving skin homeostasis. Increasing offer of commercial BG products results in their application in both cosmetics and dermatology and other medical areas. In this study we offer results of our small-scale study using BG-containing cream in senior patients with diaper dermatitis, which might serve as proof-of-concept of BG use.
Breast milk, as the optimal food for infants and young children, contains all the components necessary for proper growth and development. It is a rich source of both essential nutrients and biologically active factors, making breast milk a unique food with scientifically proven health-promoting properties. Among the entire range of biologically active factors, breast milk microorganisms and prebiotic factors, in the form of breast milk oligosaccharides, occupy an important place. The aim of our research was to determine the occurrence of bacteria with probiotic potential, belonging to the Lactobacillaceae family, in the environment of breast milk and breast milk oligosaccharides. The study included 63 human milk samples from breastfeeding women at various stages of lactation. Microorganism identification based on culture tests and MALDI TOF/MS, macronutrient analysis using the MIRIS human milk analyser, as well as analysis of human milk oligosaccharides using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry were performed. The results have shown that breast milk from different breastfeeding women is characterized by great diversity in terms of the presence of Lacto-bacillaceae bacteria in its microbiological composition. These bacteria were present in 22.2 % of the tested breast milk samples. Analysis of the human milk oligosaccharide profile revealed a slightly higher content of prebiotic factors in breast milk samples containing Lactobacillaceae, including 2'-fucosyllactose, oligosaccharide occurring in the highest amount in breast milk.
Už niekoľko desaťročí podiel seniorov v populácii vyspelých krajín rastie, a to aj pre predlžovanie života. To má byť spojené s napĺňaním jedného zo základných princípov geriatrie – s „pridávaním života rokom“, t. j. so zlepšovaním kvality života. Tá je medzi ľuďmi i v odbornej komunite hodnotená rôzne, multidimenzionálne. U nemalej časti starších ľudí pozorujeme stúpajúcu tendenciu akejsi „estetickej komponenty“ vnímania kvality vlastného života – aj seniori stále častejšie dbajú na svoj estetický vzhľad. V tzv. západnom svete je tento trend dokumentovaný dlhšie, v ostatných rokoch ho pozorujeme už aj na Slovensku. Moderná medicína ponúka viacero prístupov, ako naplniť očakávania seniorov, ktorí chcú zlepšiť vlastný pocit zo svojho vzhľadu. Z medicínskeho hľadiska budeme u seniorov aj v tomto prípade preferovať neinvazívne alebo miniinvazívne metódy. Predkladaná práca sa zaoberá možnosťami a obmedzeniami niektorých bežne dostupných minimálne invazívnych „antiageingových“ procedúr u starších ľudí.
For several decades, there has been an increase in the proportion of seniors in developed countries, one of the reasons of which is the prolongation of life expectancy. In accordance with one of the basic principles of geriatrics, it should be one’s aim to „add life to years“, meaning improving the quality of life of the elderly. Quality of life is evaluated differently among people and in the scientific community – it is multi-dimensional. Among a considerable number of elderly people, we observe a rising tendency of an „aesthetic component“ in the perception of the quality of their life – even seniors pay more attention to their aesthetic appearance. In the so-called Western world this trend has been observed for a long time, and in recent years so have we in Slovakia. Modern medicine offers several approaches to meet the expectations of seniors who want to improve perception of their appearance. From a medical point of view, we will prefer noninvasive or mini invasive methods for seniors. The presented work deals with the possibilities and limitations of some commonly available minimally invasive „anti-ageing“ procedures for seniors.
- MeSH
- botulotoxiny typu A farmakologie terapeutické užití MeSH
- dermální výplně MeSH
- estetika * MeSH
- geriatrie * metody MeSH
- kosmetické techniky klasifikace MeSH
- kvalita života MeSH
- kyselina hyaluronová farmakologie terapeutické užití MeSH
- lidé MeSH
- mezoterapie metody MeSH
- miniinvazivní chirurgické výkony metody MeSH
- senioři MeSH
- stárnutí kůže účinky léků MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- přehledy MeSH
V současnosti jsou estetické zákroky pomocí výplňových materiálů (VM) zejména na bázi hyaluronové kyseliny (HA) celosvětově hojně rozšířeny. Tento fenomén však s sebou nese i problémy, jako jsou nekontrolovaná produkce a variabilita kvality výplní, stejně jako neodborné aplikace. Roste proto výskyt nežádoucích reakcí a komplikací, z nichž zejména vaskulární mohou být velmi vážné až fatální. V důsledku rychlé globalizace a rozmachu sociálních médií dochází k posunu vnímání krásy napříč různými generacemi. V tomto kontextu je nezbytné, aby lékař uměl identifikovat motivaci pacienta. Rozlišil mezi tím, co si pacient přeje, a tím, co skutečně potřebuje, a přetvořil často přehnaná očekávání na realistické cíle (1). Komplikace spojené s aplikací dermálních výplní jsou tradičně rozděleny do čtyř základních kategorií: hypersenzitivní reakce, cévní příhody, infekce a opožděné zánětlivé změny. Jiné dělení zohleduje časový průběh komplikací na akutní (vaskulární okluze, zánětlivé reakce, reakce související s injekční aplikací, šíření materiálu) a opožděné (záněty, nodulární léze, dyspigmentace, dislokace výplně). Článek se zabývá pouze nevaskulárními komplikacemi a pro přehlednost je dělí na hypersenzititvní reakce (alergie), infekce, noduly, otoky, změny zabarvení kůže a ostatní. Pro optimální zvládání nežádoucích účinků je zásadní mít k dispozici praktický a přehledný protokol s rozhodovacím algoritmem. Součástí bezpečné praxe by měla být také interdisciplinární spolupráce.
Aesthetic interventions using hyaluronic acid-based filler materials are now widespread worldwide. However, this phenomenon also brings with it problems. Uncontrolled production and variation in the quality of fillers. Application of fillers by non-experts. Increasing incidence of adverse reactions and complications. Vascular complications can be very serious or even fatal. Due to rapid globalization and the rise of social media, there is a shift in the perception of beauty across generations. Therefore, it is essential for the physician to be able to identify the patient's motivation and differentiate between what the patient wants and what he or she actually needs and transform exaggerated expectations into realistic goals (1). Complications associated with the application of dermal fillers are commonly divided into four basic categories: hypersensitivity reactions, vascular events, infections, and delayed inflammatory changes. Another division considers the time course into acute (vascular occlusion, inflammatory reactions, injection-related reactions, spread of material) and delayed (inflammation, nodular lesions, dyspigmentation, dislocation of the filler). The article deals only with non-vascular complications and for clarity divides them into hypersensitivity reactions (allergy), infections, nodules, edema, skin discoloration and others. For optimal management of adverse effects, it is essential to have a practical and clear protocol with a decision-making algorithm. Interdisciplinary collaboration should also be part of safe practice.
BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in critically ill patients, who often have multiple risk factors. Pharmacological thromboprophylaxis is widely applied to lower this risk, but guidelines lack dosing recommendations. OBJECTIVE: This survey aims to assess current thromboprophylaxis preferences and willingness to participate in future randomized clinical trials (RCTs) on this topic. METHOD: We conducted an international online survey between February and May 2023 among intensive care unit (ICU) physicians, including 16 questions about preferences in relation to thromboprophylaxis and preferences on topics for a future RCT. The survey was distributed through the network of the Collaboration for Research in Intensive Care. RESULTS: A total of 715 physicians from 170 ICUs in 23 countries contributed information, with a mean response rate of 36%. In most ICUs, both pharmacological (n = 166, 98%) and mechanical thromboprophylaxis (n = 143, 84%) were applied. A total of 36 pharmacological thromboprophylaxis regimens were reported. Use of low-molecular-weight heparin (LMWH) was most common (n = 149 ICUs, 87%), followed by subcutaneous unfractionated heparin (n = 44 ICUs, 26%). Seventy-five percent of physicians indicated that they used enoxaparin 40 mg (4000 IU), dalteparin 5000 IU, or tinzaparin 4500 IU once daily, whereas 25% reported the use of 16 other LMWH type and dose combinations. Dose adjustment according to weight was common (78 ICUs, 46%). Participants perceived high variation in the application of thromboprophylaxis and were willing to consider an alternative LMWH type (n = 542, 76%) or dose (n = 538, 75%) in the context of an RCT. CONCLUSION: LMWH was the preferred agent for thromboprophylaxis in critically ill patients. There was considerable variation in the application of LMWH for prophylaxis, reflected by the use of different types, doses, and dosing strategies. Most physicians would be willing to participate in an RCT on thromboprophylaxis. EDITORIAL COMMENT: This survey demonstrates current patterns in implementation preferences for critically ill patients. While there is one approach and drug that is commonly preferred, these findings show that there is some variation in practice.
- MeSH
- antikoagulancia * terapeutické užití aplikace a dávkování MeSH
- heparin nízkomolekulární * terapeutické užití aplikace a dávkování MeSH
- internacionalita MeSH
- jednotky intenzivní péče * MeSH
- kritický stav MeSH
- lékaři MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu metody MeSH
- průzkumy a dotazníky MeSH
- žilní tromboembolie * prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
