"CZ.02.1.01/0.0/0.0/16_019/0000787"
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OBJECTIVES: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. DESIGN: Prospective randomized large-animal peritoneal septic shock experiment. SETTING: Laboratory investigation. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 μg/kg/min (LATE, n = 8). INTERVENTIONS: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. CONCLUSIONS: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Kidney transplant recipients are at risk for a severe course of COVID-19 with a high mortality rate. A considerable number of patients remains without a satisfactory serological response after the baseline and adjuvant SARS-CoV-2 vaccination schedule. METHODS: In this prospective, randomized study, we evaluated the efficacy and safety of one and two booster doses of mRNA vaccines (either mRNA-1273 or BNT162b2) in 125 COVID-19 naive, adult kidney transplant recipients who showed an insufficient humoral response (SARS-CoV-2 IgG <10 AU/ml) to the previous 2-dose vaccination schedule. The primary outcome was the difference in the rate of a positive antibody response (SARS-CoV-2 IgG ≥10 AU/ml) between one and two booster doses at 1 month after the final booster dose. RESULTS: A positive humoral response was observed in 36 (62%) patients receiving two booster doses and in 28 (44%) patients receiving one booster dose (odds ratio [OR], 2.10, 95% confidence interval [CI], 1.02-4.34, p = .043). Moreover, median SARS-CoV-2 IgG levels were higher with two booster doses (p = .009). The number of patients with positive virus neutralizing antibody (VNA) levels was numerically higher with two booster doses compared to one booster dose, but without statistical significance (66% vs. 50%, p = .084). There was no significant difference in positive seroconversions rate and antibody levels between mRNA-1273 and BNT162b2. CONCLUSION: A higher number of kidney transplant recipients achieved a positive antibody response after two booster doses compared to one booster dose.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- dospělí MeSH
- imunoglobulin G MeSH
- lidé MeSH
- mRNA vakcíny MeSH
- příjemce transplantátu MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- transplantace ledvin * škodlivé účinky MeSH
- vakcína BNT162 MeSH
- vakcína firmy Moderna proti COVID-19 MeSH
- vakcíny proti COVID-19 škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
For liver fibrosis assessment, the liver biopsy is usually stained with Masson's trichrome (MT) or picrosirius red (PSR) to quantify liver connective tissue (LCT) for fibrosis scoring. However, several concerns of such semiquantitative assessments have been raised, and when searching for data on the amount of LCT in healthy rats, the results vastly differ. Regarding the ongoing reproducibility crisis in science, it is necessary to inspect the results and methods, and to design an unbiased and reproducible method of LCT assessment. We searched the Medline database using search terms related to liver fibrosis, LCT and collagen, rat strains, and staining methods. Our search identified 74 eligible rat groups in 57 studies. We found up to 170-fold differences in the amount of LCT among healthy Wistar and Sprague-Dawley rats, with significant differences even within individual studies. Biased sampling and quantification probably caused the observed differences. In addition, we also found incorrect handling of liver fibrosis scoring. Assessment of LCT using stereological sampling methods (such as systematic uniform sampling) would provide us with unbiased data. Such data could eventually be used not only for the objective assessment of liver fibrosis but also for validation of noninvasive methods of the assessment of early stages of liver fibrosis.
- Publikační typ
- časopisecké články MeSH
The coronavirus disease (COVID-19) pandemic caused unprecedented research activity all around the world but publications from Central-Eastern European countries remain scarce. Therefore, our aim was to characterise the features of the pandemic in the intensive care units (ICUs) among members of the SepsEast (Central-Eastern European Sepsis Forum) initiative. We conducted a retrospective, international, multicentre study between March 2020 and February 2021. All adult patients admitted to the ICU with pneumonia caused by COVID-19 were enrolled. Data on baseline and treatment characteristics, organ support and mortality were collected. Eleven centres from six countries provided data from 2139 patients. Patient characteristics were: median 68, [IQR 60-75] years of age; males: 67%; body mass index: 30.1 [27.0-34.7]; and 88% comorbidities. Overall mortality was 55%, which increased from 2020 to 2021 (p = 0.004). The major causes of death were respiratory (37%), cardiovascular (26%) and sepsis with multiorgan failure (21%). 1061 patients received invasive mechanical ventilation (mortality: 66%) without extracorporeal membrane oxygenation (n = 54). The rest of the patients received non-invasive ventilation (n = 129), high flow nasal oxygen (n = 317), conventional oxygen therapy (n = 122), as the highest level of ventilatory support, with mortality of 50%, 39% and 22%, respectively. This is the largest COVID-19 dataset from Central-Eastern European ICUs to date. The high mortality observed especially in those receiving invasive mechanical ventilation renders the need of establishing national-international ICU registries and audits in the region that could provide high quality, transparent data, not only during the pandemic, but also on a regular basis.
- MeSH
- COVID-19 * epidemiologie terapie MeSH
- dospělí MeSH
- jednotky intenzivní péče MeSH
- kyslík MeSH
- lidé MeSH
- registrace MeSH
- respirační insuficience * epidemiologie terapie MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- sepse * epidemiologie MeSH
- syndrom dechové tísně * MeSH
- umělé dýchání MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Spinocerebellar ataxias (SCAs) represent a large group of hereditary degenerative diseases of the nervous system, in particular the cerebellum, and other systems that manifest with a variety of progressive motor, cognitive, and behavioral deficits with the leading symptom of cerebellar ataxia. SCAs often lead to severe impairments of the patient's functioning, quality of life, and life expectancy. For SCAs, there are no proven effective pharmacotherapies that improve the symptoms or substantially delay disease progress, i.e., disease-modifying therapies. To study SCA pathogenesis and potential therapies, animal models have been widely used and are an essential part of pre-clinical research. They mainly include mice, but also other vertebrates and invertebrates. Each animal model has its strengths and weaknesses arising from model animal species, type of genetic manipulation, and similarity to human diseases. The types of murine and non-murine models of SCAs, their contribution to the investigation of SCA pathogenesis, pathological phenotype, and therapeutic approaches including their advantages and disadvantages are reviewed in this paper. There is a consensus among the panel of experts that (1) animal models represent valuable tools to improve our understanding of SCAs and discover and assess novel therapies for this group of neurological disorders characterized by diverse mechanisms and differential degenerative progressions, (2) thorough phenotypic assessment of individual animal models is required for studies addressing therapeutic approaches, (3) comparative studies are needed to bring pre-clinical research closer to clinical trials, and (4) mouse models complement cellular and invertebrate models which remain limited in terms of clinical translation for complex neurological disorders such as SCAs.
BACKGROUND: There is variation in the reported incidence rates of levator avulsion (LA) and paucity of research into its risk factors. OBJECTIVE: To explore the incidence rate of LA by mode of birth, imaging modality, timing of diagnosis and laterality of avulsion. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL, AMED and MIDIRS with no language restriction from inception to April 2019. STUDY ELIGIBILITY CRITERIA: A study was included if LA was assessed by an imaging modality after the first vaginal birth or caesarean section. Case series and reports were not included. DATA COLLECTION AND ANALYSIS: RevMan v5.3 was used for the meta-analyses and SW SAS and STATISTICA packages were used for type and timing of imaging analyses. RESULTS: We included 37 primary non-randomised studies from 17 countries and involving 5594 women. Incidence rates of LA were 1, 15, 21, 38.5 and 52% following caesarean, spontaneous, vacuum, spatula and forceps births, respectively, with no differences by imaging modality. Odds ratio of LA following spontaneous birth versus caesarean section was 10.69. The odds ratios for LA following vacuum and forceps compared with spontaneous birth were 1.66 and 6.32, respectively. LA was more likely to occur unilaterally than bilaterally following spontaneous (P < 0.0001) and vacuum-assisted (P = 0.0103) births but not forceps. Incidence was higher if assessment was performed in the first 4 weeks postpartum. CONCLUSIONS: LA incidence rates following caesarean, spontaneous, vacuum and forceps deliveries were 1, 15, 21 and 52%, respectively. Ultrasound and magnetic resonance imaging were comparable tools for LA diagnosis. TWEETABLE ABSTRACT: Levator avulsion incidence rates after caesarean, spontaneous, vacuum and forceps deliveries were 1, 15, 21 and 52%, respectively.
- MeSH
- císařský řez škodlivé účinky statistika a číselné údaje MeSH
- incidence MeSH
- lidé MeSH
- onemocnění dna pánevního epidemiologie etiologie MeSH
- těhotenství MeSH
- vakuová extrakce porodnická škodlivé účinky statistika a číselné údaje MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
BACKGROUND: The range of the ornate dog tick Dermacentor reticulatus is rapidly expanding in Europe. This tick species is the vector of canine babesiosis, caused by Babesia canis, and also plays a role in the transmission of Theileria equi and Babesia caballi in equids. METHODS: The geographic range of D. reticulatus in the Czech Republic was re-assessed, and an up-to-date distribution map is presented based on material and data obtained during a nationwide citizen science campaign. Received and flagged individuals of D. reticulatus were also analysed for the presence of B. canis DNA. RESULTS: In striking contrast to historical records, D. reticulatus was found in all regions of the Czech Republic, with most reports coming from the southeast and northwest of the country. Between February 2018 and June 2021, the project team received 558 photo reports of ticks and 250 packages containing ticks. Of the former, 71.1% were identified as Dermacentor sp. with the remainder identified as Ixodes sp., Haemaphysalis sp., Argas sp. or Hyalomma sp. The majority of specimens in the subset of ticks that were received (N = 610) were D. reticulatus (N = 568, 93.7%), followed by Ixodes ricinus and Hyalomma spp. A total of 783 adult D. reticulatus, either received (568) or collected by flagging (215), were tested for the presence of B. canis DNA using species-specific nested PCR targeting part of the 18S rRNA gene; B. canis DNA was demonstrated in 22 samples (2.81%). CONCLUSIONS: The continuous spread of D. reticulatus in the Czech Republic was documented in this study. In addition, DNA of B. canis was also detected in a number of ticks, suggesting the establishment of B. canis in the Czech Republic. These results suggest that veterinarians need to consider the possibility of canine babesiosis even in dogs without a history of travel.
- MeSH
- Babesia * genetika MeSH
- babezióza * epidemiologie MeSH
- Dermacentor * MeSH
- infestace klíšťaty * epidemiologie veterinární MeSH
- Ixodidae * MeSH
- klíště * MeSH
- nemoci psů * epidemiologie MeSH
- občanská věda * MeSH
- psi MeSH
- Rhipicephalus sanguineus * MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Bimatoprost is a synthetic prostaglandin structural analogue used among other indications to increase eyelash growth. The aim of this prospective, open-label study was to evaluate the safety and efficacy of topical bimatoprost in the treatment of eyelash loss in alopecia areata totalis (AT) and universalis (AU). Study subjects applied ophthalmic bimatoprost (0.3 mg/ml) solution to the eyelid margins once nightly for at least 12 weeks (mean treatment period was 30.6 weeks). A total of 16 out of 17 subjects completed the study. Only the subjects with eyelashes present at baseline experienced an increase in eyelash length and thickness. No new eyelash regrowth was induced. In patients with AT and AU topical bimatoprost affected existing eyelashes, but failed to induce regrowth of new eyelashes.
- MeSH
- alopecia areata * MeSH
- alopecie diagnóza farmakoterapie MeSH
- bimatoprost škodlivé účinky MeSH
- lidé MeSH
- oční řasy * MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Bone tissue engineering tries to simulate natural behavior of hard tissues. This study aimed to produce scaffolds based on polyvinyl alcohol (PVA) and hyaluronic acid (HA) with hydroxyapatite (HAp) incorporated in two different ways, by in situ synthesis and physical mixing of pre-prepared HAp. In situ synthesis resulted in calcium deficient form of HAp with lower crystallinity. The proliferation of human osteoblast-like cells MG-63 proved to be better in the scaffolds with in situ synthesized HAp compared to those with physically mixed pre-prepared HAp. For scaffolds with PVA/HA/HAp ratio 3:1:2, there was significantly higher initial adhesion (p = 0.0440), as well as the proliferation in the following days (p < 0.001). It seemed to be advantageous improve the properties of the scaffold by in situ synthesizing of HAp directly in the organic matrix.
- MeSH
- biokompatibilní materiály chemie MeSH
- buněčná adheze MeSH
- hemolýza MeSH
- hydrogely chemie MeSH
- hydroxyapatit chemie MeSH
- kyselina hyaluronová chemie MeSH
- lidé MeSH
- osteoblasty cytologie MeSH
- polyvinylalkohol chemie MeSH
- proliferace buněk MeSH
- testování materiálů MeSH
- tkáňové inženýrství MeSH
- tkáňové podpůrné struktury chemie MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The aim of this study was to explore the risk of levator ani muscle (LAM) avulsion and enlargement of the levator hiatus following vaginal birth after Cesarean section (VBAC) in comparison with vaginal delivery in primiparous women. METHODS: In this two-center observational case-control study, we identified all women who had a term VBAC for their second delivery at the Departments of Obstetrics and Gynecology at the Faculty of Medicine in Pilsen and the 1st Faculty of Medicine in Prague, Charles University, Czech Republic, between 2012 and 2016. Women with a repeat VBAC, preterm birth or stillbirth were excluded from the study. As a control group, we enrolled a cohort of primiparous women who delivered vaginally during the study period. To increase our control sample, we also invited all primiparous women who delivered vaginally in both participating units between May and June 2019 to participate. All participants were invited for a four-dimensional pelvic floor ultrasound scan to assess LAM trauma. LAM avulsion and the area of the levator hiatus were assessed offline from the stored pelvic floor volumes obtained at rest, during maximum contraction and during Valsalva maneuver. The laterality of the avulsion was also noted. The cohorts were then compared using the χ2 test and Wilcoxon's two-sample test according to the normality of the distribution. P < 0.05 was considered statistically significant. Multivariate regression analysis, controlling for age and body mass index (BMI), was also performed. RESULTS: A total of 356 women had a VBAC for their second delivery during the study period. Of these, 152 (42.7%) attended the ultrasound examination and full data were available for statistical analysis for 141 women. The control group comprised 113 primiparous women. A significant difference was observed between the VBAC group and the control group in age (32.7 vs 30.1 years; P < 0.05), BMI (28.4 vs 27.4 kg/m2 ; P < 0.05) and duration of the first and second stages of labor (293.1 vs 345.9 min; P < 0.05 and 27.6 vs 35.3 min; P < 0.05, respectively) at the time of the index birth. The LAM avulsion rate was significantly higher in the VBAC compared with the control group (32.6% vs 18.6%; P = 0.01). The difference between the groups was observed predominantly in the rate of unilateral avulsion and remained significant after controlling for age and BMI (adjusted odds ratio 2.061 (95% CI, 1.103-3.852)). There was no statistically significant difference in the area of the levator hiatus at rest (12.0 vs 12.6 cm2 ; P = 0.28) or on maximum Valsalva maneuver (18.6 vs 18.7 cm2 ; P = 0.55) between the VBAC and control groups. The incidence of levator hiatal ballooning was comparable between the groups (17.7% and 18.6%; P = 0.86). CONCLUSIONS: VBAC is associated with a significantly higher rate of LAM avulsion than is vaginal birth in nulliparous women. The difference was significant even after controlling for age and BMI. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
- MeSH
- anální kanál diagnostické zobrazování zranění MeSH
- dospělí MeSH
- komplikace porodu diagnostické zobrazování etiologie MeSH
- lidé MeSH
- poranění měkkých tkání diagnostické zobrazování etiologie MeSH
- studie případů a kontrol MeSH
- těhotenství MeSH
- ultrasonografie prenatální * MeSH
- vaginální porod po císařském řezu škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH