BACKGROUND: Atherosclerotic cardiovascular diseases (ACVDs), a condition characterised by lipid accumulation in arterial walls, which is often exacerbated by chronic inflammation disorders, is the major cause of mortality and morbidity worldwide. Colchicine, with its first medicinal use in ancient Egypt, is an inexpensive drug with anti-inflammatory properties. However, its role in primary prevention of ACVDs in the general population remains unknown. OBJECTIVES: To assess the clinical benefits and harms of colchicine as primary prevention of cardiovascular outcomes in the general population. SEARCH METHODS: We searched the Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, Web of Science, and LILACS. We searched ClinicalTrials.gov and WHO ICTRP for ongoing and unpublished studies. We also scanned the reference lists of relevant included studies, reviews, meta-analyses, and health technology reports to identify additional studies. There were no limitations on language, date of publication, or study setting. The search results were updated on 31 May 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs) in any setting, recruiting adults without pre-existing cardiovascular disease. We included trials that compared colchicine versus placebo, non-steroidal anti-inflammatory drugs, corticosteroids, immunomodulating drugs, or usual care. Our primary outcomes were all-cause mortality, non-fatal myocardial infarction, stroke, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors independently selected studies, extracted data, and performed risk of bias and GRADE assessments. MAIN RESULTS: We identified 15 RCTs (1721 participants randomised; 1412 participants analysed) with follow-up periods ranging from 4 to 728 weeks. The intervention was oral colchicine compared with placebo, immunomodulating drugs, or usual care or no treatment. Due to biases and imprecision, the evidence was very uncertain for all outcomes. All trials but one had a high risk of bias. Five out of seven meta-analyses included fewer than six trials (71.4%). The objectives of the review were to assess cardiovascular outcomes in the general population, but many of the included trials focused on liver disease. Colchicine compared to placebo Colchicine may reduce all-cause mortality compared to placebo in primary prevention, but the evidence is very uncertain (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.51 to 0.91; 6 studies, 463 participants; very low-certainty evidence; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 6 to 67). Colchicine may result in little to no difference in non-fatal myocardial infarction, but the evidence is very uncertain (RR 0.87, 95% CI 0.41 to 1.82; 1 study, 100 participants; very low-certainty evidence). Colchicine may not reduce the incidence of stroke, but the evidence is very uncertain (RR 2.43, 95% CI 0.67 to 8.86; 1 study, 100 participants; very low-certainty evidence). Regarding adverse events, colchicine may increase the incidence of diarrhoea (RR 3.99, 95% CI 1.44 to 11.06; 8 studies, 605 participants; very low-certainty evidence; number needed to treat for an additional harmful outcome (NNTH) 10, 95% CI 6 to 17), and may have little to no effect on neurological outcomes such as seizure or mental confusion (RR 0.72, 95% CI 0.31 to 1.66; 2 studies, 155 participants; very low-certainty evidence), but the evidence is very uncertain. The effect of colchicine on cardiovascular mortality is also very uncertain (RR 1.27, 95% CI 0.03 to 62.43; 2 studies, 160 participants; very low-certainty evidence). Colchicine may not reduce post-cardiac procedure atrial fibrillation, but the evidence is very uncertain (RR 0.74, 95% CI 0.25 to 2.19; 1 study, 100 participants). We found no trials reporting on pericardial effusion, peripheral artery disease, heart failure, or unstable angina. Colchicine compared to methotrexate (immunomodulating drug) Colchicine may result in little to no difference in all-cause mortality compared to methotrexate, but the evidence is very uncertain (RR 0.42, 95% CI 0.12 to 1.51; 1 study, 85 participants; very low-certainty evidence). We found no trials reporting other cardiovascular outcomes or adverse events for this comparison. Colchicine compared to usual care or no treatment The evidence is very uncertain about the effect of colchicine compared with usual care on all-cause mortality in primary prevention (RR 1.07, 95% CI 0.90 to 1.27; 2 studies, 729 participants; very low-certainty evidence). Regarding adverse events, colchicine may increase the incidence of diarrhoea compared to usual care, but the evidence is very uncertain (RR 3.32, 95% CI 1.56 to 7.03; 2 studies, 729 participants; very low-certainty evidence; NNTH 18, 95% CI 12 to 42). No trials reported other cardiovascular outcomes for this comparison. AUTHORS' CONCLUSIONS: This Cochrane review evaluated the clinical benefits and harms of using colchicine for the primary prevention of cardiovascular events in the general population. Comparisons were made against placebo, immunomodulating medications, or usual care or no treatment. However, the certainty of the evidence for the predefined outcomes was very low, highlighting the pressing need for high-quality, rigorous studies to ascertain colchicine's clinical impact definitively. We identified numerous biases and inaccuracies in the included studies, limiting their generalisability and precluding a conclusive determination of colchicine's efficacy in preventing cardiovascular events. The existing evidence regarding colchicine's potential cardiovascular benefits or harms for primary prevention is inconclusive owing to the limitations inherent in the current studies. More robust clinical trials are needed to bridge this evidence gap effectively.
- MeSH
- antiflogistika nesteroidní terapeutické užití škodlivé účinky MeSH
- antiflogistika terapeutické užití škodlivé účinky MeSH
- cévní mozková příhoda prevence a kontrola mortalita MeSH
- infarkt myokardu * prevence a kontrola mortalita epidemiologie MeSH
- kardiovaskulární nemoci * prevence a kontrola mortalita MeSH
- kolchicin * terapeutické užití škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- příčina smrti MeSH
- primární prevence * metody MeSH
- randomizované kontrolované studie jako téma * MeSH
- zkreslení výsledků (epidemiologie) MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
The opportunistic pathogen Candida parapsilosis is a major causative agent of candidiasis leading to death in immunocompromised individuals. Azoles are the first line of defense in their treatment. The purpose of this study was to characterize eight fluconazole-resistant and sensitive C. parapsilosis hospital isolates through a battery of phenotypic tests that target pathogenicity attributes such as virulence, biofilm formation, stress resistance, and ergosterol content. Whole genome sequencing was carried out to identify mutations in key pathogenicity and resistance genes. Phylogenetic comparison was performed to determine strain relatedness and clonality. Genomic data and phylogenetic analysis revealed that two isolates were C. orthopsilosis and C. metapsilosis misidentified as C. parapsilosis. Whole genome sequencing analysis revealed known and novel mutations in key drug resistance and pathogenicity genes such as ALS6, ALS7, SAPP3, SAP7, SAP9, CDR1, ERG6, ERG11 and UPC2. Phylogenetic analysis revealed a high degree of relatedness and clonality within our C. parapsilosis isolates. Our results showed that resistant isolates exhibited an increase in biofilm content compared to the sensitive isolates. In conclusion, our study is the first of its kind in Lebanon to describe phenotypic and genotypic characteristics of nosocomial C. parapsilosis complex isolates having a remarkable ability to form biofilms.
- MeSH
- antifungální látky * farmakologie MeSH
- biofilmy * růst a vývoj MeSH
- Candida parapsilosis * genetika izolace a purifikace klasifikace MeSH
- fenotyp * MeSH
- flukonazol farmakologie MeSH
- fungální léková rezistence * genetika MeSH
- fylogeneze * MeSH
- genotyp * MeSH
- infekce spojené se zdravotní péčí mikrobiologie MeSH
- kandidóza * mikrobiologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- nemocnice MeSH
- sekvenování celého genomu * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Libanon MeSH
Background/Objectives: To evaluate the effectiveness of curative (chemo)radiotherapy in patients with hypopharyngeal carcinoma and to identify prognostic factors influencing treatment outcomes. Methods: We conducted a retrospective study of 173 consecutive patients, treated with definitive or postoperative (chemo)radiotherapy from 2002 to 2020 [median age 60 years; current/former smokers 95%; UICC stage III/IV 96%]. Radiation therapy was preceded by a radical resection of a primary tumor in 32% of patients. One hundred patients received chemotherapy. Results: The median total dose of radiotherapy achieved was 70 Gy. The five- and ten-year locoregional controls were 63%, and the five- and ten-year distant controls were 77% and 76%, respectively. The five- and ten-year overall survival rates were 24% and 9%, respectively. Conclusions: The results demonstrate the limited effectiveness of curative (chemo)radiotherapy in patients with hypopharyngeal carcinoma with long-term locoregional and distant control of half of the treated patients. The multivariate analysis indicated that initial surgery, chemotherapy, comorbidity score (as assessed by ACE-27), pretreatment tracheostomy, hemoglobin level and initial response to treatment were the strongest prognostic factors in predicting survival. Using these factors, corresponding predictive models were constructed.
- Publikační typ
- časopisecké články MeSH
Investigating prenatal hypoxia is difficult in mammals, as there are confounding factors stemming from maternal adaptations and compensatory mechanisms. We have thus established an avian model of hypoxic incubation (starting after 2 days of normoxia, 15% O2, normobaric, until the time of sampling at embryonic day 8) to study embryonic reactions to low oxygen concentration. Our previous studies have shown increased vascularization, oedema, and ventricular wall thinning preceding the lethality at mid-gestation. Analysis of the cardiac proteome after 6 days of hypoxic incubation showed strong upregulation of enzymes involved in anaerobic glycolysis as well as an increase in apoptosis-related proteins, cell adhesion proteins, and secretory activity.
- MeSH
- apoptóza MeSH
- glykolýza MeSH
- hypoxie * metabolismus MeSH
- kuřecí embryo MeSH
- myokard metabolismus MeSH
- proteom metabolismus MeSH
- proteomika * metody MeSH
- srdce * embryologie MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Over the recent years, our understanding of the cell death machinery of mature erythrocytes has been greatly expanded. It resulted in the discovery of several regulated cell death (RCD) pathways in red blood cells. Apoptosis (eryptosis) and necroptosis of erythrocytes share certain features with their counterparts in nucleated cells, but they are also critically different in particular details. In this review article, we summarize the cell death subroutines in the erythroid precursors (apoptosis, necroptosis, and ferroptosis) in comparison to mature erythrocytes (eryptosis and erythronecroptosis) to highlight the consequences of organelle clearance and associated loss of multiple components of the cell death machinery upon erythrocyte maturation. Recent advances in understanding the role of erythrocyte RCDs in health and disease have expanded potential clinical applications of these lethal subroutines, emphasizing their contribution to the development of anemia, microthrombosis, and endothelial dysfunction, as well as their role as diagnostic biomarkers and markers of erythrocyte storage-induced lesions. Fas signaling and the functional caspase-8/caspase-3 system are not indispensable for eryptosis, but might be retained in mature erythrocytes to mediate the crosstalk between both erythrocyte-associated RCDs. The ability of erythrocytes to switch between eryptosis and necroptosis suggests that their cell death is not a simple unregulated mechanical disintegration, but a tightly controlled process. This allows investigation of eventual pharmacological interventions aimed at individual cell death subroutines of erythrocytes.
- MeSH
- apoptóza MeSH
- buněčná smrt MeSH
- eryptóza * MeSH
- erytrocyty * metabolismus cytologie MeSH
- ferroptóza MeSH
- lidé MeSH
- nekroptóza MeSH
- regulovaná buněčná smrt MeSH
- signální transdukce * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Spray drying and hot-melt extrusion are among the most prevalent preparation techniques used in the pharmaceutical industry to produce amorphous solid dispersions (ASDs). This study advances previous research by integrating sample production, comprehensive analytical characterization, intrinsic dissolution rate measurements, and assessments of the behavior of ASDs under elevated temperature and humidity conditions. The study focuses on indomethacin, a widely used model for poorly soluble drugs, processed with PVP K30 or HPMC E5, both commonly used polymers. The findings demonstrate that hot-melt extruded samples exhibit superior stability against recrystallization, whereas spray dried samples achieve higher intrinsic dissolution rates. Furthermore, PVP K30 significantly outperforms HPMC E5 in the co-processing of indomethacin, enhancing both the intrinsic dissolution rate and the stability.
- MeSH
- deriváty hypromelózy chemie MeSH
- farmaceutická chemie metody MeSH
- indomethacin * chemie MeSH
- krystalizace * MeSH
- povidon chemie MeSH
- příprava léků metody MeSH
- rozpustnost * MeSH
- sprejové sušení * MeSH
- stabilita léku * MeSH
- technologie extruze tavenin * metody MeSH
- uvolňování léčiv MeSH
- vlhkost MeSH
- vysoká teplota MeSH
- vysoušení metody MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: This study aimed to compare the image quality of the Siemens Biograph mCT40 (photomultiplier-based system - PMT) and the Siemens Vision600 (silicon photomultiplier-based system - SiPM) using a modified NEMA IEC Body phantom (Data Spectrum). METHODS: SiPM-based Vision600 has a smaller crystal size (3.2 × 3.2 mm vs. 4.0 × 4.0 mm in the PMT-based mCT40), resulting in better spatial resolution. Enhanced time-of-flight (TOF) timing and higher sensitivity leads to nearly four times higher effective sensitivity. The standard NEMA IEC Body phantom was modified with a 3D-printed holder to accommodate also Hollow and Micro Hollow Spheres of 15.4 mm, 12.4 mm, 7.9 mm, 6.2 mm, 5.0 mm, and 4.0 mm. Each of the three acquisition sessions per scanner included 18 time points and spanned 5.6 half-lives to assess system performance at varying activity concentrations in the field of view. RESULTS: Recovery curves for both systems were similar when identical post-reconstruction filters were applied. The SiPM-based Vision600 system detected smaller sources at significantly lower activity concentrations, and the variations in standardized uptake value (SUVmax, SUVA50) measurements were generally smaller compared to those of the PMT-based system. The two smallest sources became undetectable below 63 MBq and 16 MBq on the PMT system, versus 20 MBq and 6.5 MBq on the SiPM system. CONCLUSIONS: SiPM technology demonstrated superior performance compared to PMT in detecting small sources in low-activity scenarios and provided more robust quantification results. It is recommended to use averaged SUV metrics, such as SUVA50 or SUVpeak.
BACKGROUND: PICC is routinely inserted with assistance of ultrasonography and/or ECG navigation (RI- routine insertion). Only in a minority of patients the insertion of a PICC is difficult and fluoroscopic visualization with introduction of special guidewire is necessary for the success of the procedure (DI-difficult insertion). The aim of the study was to evaluate whether DI can be predicted and associated with a risk of complications during follow-up. METHODS: The study included patients who had a PICC insertion in 2022. The number of patients with RI and DI was recorded and the significance of selected parameters during insertion and the frequency of complications during 1 month follow-up was compared. RESULTS: About 1404 patients had successful PICC insertion in 2022, RI in 1360 (96.8%) and DI in 44 patients (3.2%). There was no significant effect of age, gender, selected vein, its size, insertion site, and tunneling on the course of PICC insertion. However the number of punctures for needle insertion was higher in DI. The complication rate during 1 month follow-up in DI was 9 (20.4%) versus 101 patients (7.4%) in RI (p = 0.002). CONCLUSION: PICC insertion was successful in both RI and DI patients. Of the analyzed parameters, the number of needle punctures was associated with DI, and complications during the 1-month follow-up were more frequently noted in the DI group.
- MeSH
- časové faktory MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- intervenční radiografie škodlivé účinky MeSH
- intervenční ultrasonografie * MeSH
- katetrizace centrálních vén škodlivé účinky přístrojové vybavení MeSH
- lidé středního věku MeSH
- lidé MeSH
- periferní katetrizace * škodlivé účinky MeSH
- punkce * MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Initially, molecular hydrogen was considered a physiologically inert and non-functional gas. However, experimental and clinical studies have shown that molecular hydrogen has anti-inflammatory, anti-apoptotic, and strong selective antioxidant effects. This study aimed to evaluate the effects of 60 minutes of molecular hydrogen inhalation on respiratory gas analysis parameters using a randomized, double-blind, placebo-controlled, crossover design. The study was conducted at Faculty of Physical Culture, Palacký University Olomouc from September 2022 to March 2023. Twenty, physically active female participants aged 22.1 ± 1.6 years who inhaled either molecular hydrogen or ambient air through a nasal cannula (300 mL/min) for 60 minutes while resting were included in this study. Metabolic response was measured using indirect calorimetry. Breath-by-breath data were averaged over four 15-minute intervals. Compared with placebo (ambient air), molecular hydrogen inhalation significantly decreased respiratory exchange ratio and ventilation across all intervals. Furthermore, the change in respiratory exchange ratio was negatively correlated with body fat percentage from 30 minutes onwards. In conclusion, 60 minutes of resting molecular hydrogen inhalation significantly increased resting fat oxidation, as evidenced by decreased respiratory exchange ratio, particularly in individuals with higher body fat percentages.
- MeSH
- aplikace inhalační MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- klinické křížové studie MeSH
- lidé MeSH
- mladý dospělý MeSH
- odpočinek * MeSH
- placebo MeSH
- vodík * aplikace a dávkování farmakologie MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
