PURPOSE: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. METHODS: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. RESULTS: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. CONCLUSION: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance.

• MeSH
• dospělí MeSH
• glukokortikoidy terapeutické užití   MeSH
• Gravesova oftalmopatie * farmakoterapie   krev   MeSH
• imunoglobuliny stimulující tyreoideu krev   MeSH
• imunologické faktory terapeutické užití   MeSH
• léková rezistence * MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rituximab * terapeutické užití   MeSH
• senioři MeSH
• výsledek 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

In the study, we employ an affordable, tissue-saving, and precise simultaneous multiplex immunofluorescence method with heat-induced antibody stripping to identify and structurally analyse nigral Lewy bodies in dopaminergic neurones. Analysis of different alpha-synuclein epitopes and proteoforms reveals an almost uniform, onion-like morphology of the Lewy bodies. The N-terminal and C-terminal domains are predominantly accessible to antibody binding in the peripheral shell of the bodies.

• MeSH
• alfa-synuklein * metabolismus   analýza   MeSH
• demence s Lewyho tělísky patologie   MeSH
• dopaminergní neurony metabolismus   patologie   MeSH
• fluorescenční protilátková technika metody   MeSH
• Lewyho tělíska * metabolismus   patologie   MeSH
• lidé MeSH
• substantia nigra * metabolismus   patologie   MeSH
• vysoká teplota MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Acute mesenteric ischaemia (AMI) is a sudden onset of impaired bowel perfusion. Has a high mortality rate and is difficult to diagnose. Therapy involves endovascular, surgical, or a combination of both. Because of baseline differences, the comparison between endovascular and open surgical treatment is subject to selection bias. The aim of this study was to evaluate the results of treatment of AMI by open or endovascular approach in combination with laparotomy, and evaluation of treatment strategy in similar situations. Clinical data from 21 patients treated for AMI between 2018 and 2022 were retrospectively reviewed and compared. The primary endpoint of the study was in-hospital mortality. The secondary endpoint was the statistical evaluation of risk factors for mortality. All patients underwent acute endovascular revascularisation. Aspiration thromboembolectomy was performed in nine patients, stenting in seven, PTA in one and surgery in three. Endovascular therapy was unsuccessful for technical reasons in 3 patients. None of the monitored parameters reached statistical significance. The best results were achieved in the early diagnosis group. The overall mortality of acute mesenteric ischaemia in our cohort was 34.8%. Acute mesenteric ischaemia is a serious condition affecting mainly elderly patients with a high mortality rate, but the diagnosis of mesenteric ischaemia is not an automatic death sentence. To achieve the best therapeutic outcome, mesenteric ischaemia needs to be diagnosed and treated at an early stage. The best therapeutic outcomes are achieved in centres with 24-hour access to endovascular revascularisation and surgical therapy.

• MeSH
• akutní nemoc MeSH
• endovaskulární výkony * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezenteriální ischemie * chirurgie   mortalita   MeSH
• mortalita v nemocnicích MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stenty MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Antiphospholipid syndrome (APS) is associated with recurrent pregnancy morbidity, yet the underlying mechanisms remain elusive. We performed multifaceted characterization of the biological and transcriptomic signatures of mouse placenta and uterine natural killer (uNK) cells in APS. Histological analysis of APS placentas unveiled placental abnormalities, including disturbed angiogenesis, occasional necrotic areas, fibrin deposition, and nucleated red blood cell enrichment. Analyses of APS placentas showed a reduced cell proliferation, lower protein content and thinning of endothelial cells. Disturbances in APS trophoblast cells were linked to a cell cycle shift in cytotrophoblast cells, and a reduced number of spiral artery-associated trophoblast giant cells (SpA-TGC). Transcriptomic profiling of placental tissue highlighted disruptions in cell cycle regulation with notable downregulation of genes involved in developmental or signaling processes. Cellular senescence, metabolic and p53-related pathways were also enriched, suggesting potential mechanisms underlying placental dysfunction in APS. Thrombotic events, though occasionally detected, appeared to have no significant impact on the overall pathological changes. The increased number of dysfunctional uNK cells was not associated with enhanced cytotoxic capabilities. Transcriptomic data corroborated these findings, showing prominent suppression of NK cell secretory capacity and cytokine signaling pathways. Our study highlights the multifactorial nature of APS-associated placental pathologies, which involve disrupted angiogenesis, cell cycle regulation, and NK cell functionality.

• MeSH
• antifosfolipidový syndrom * imunologie   patologie   MeSH
• buňky NK * imunologie   metabolismus   MeSH
• modely nemocí na zvířatech * MeSH
• myši MeSH
• placenta * metabolismus   patologie   MeSH
• proliferace buněk MeSH
• stanovení celkové genové exprese MeSH
• těhotenství MeSH
• transkriptom MeSH
• trofoblasty metabolismus   patologie   imunologie   MeSH
• uterus * patologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Vaccination is an important tool in the fight against the COVID-19 pandemic in patients with haematologic malignancies. The paper provides an analysis of the course of breakthrough SARS-CoV-2 infection in a group of vaccinated patients with haematological malignancy and a comparison with a historical cohort of 96 non-vaccinated patients with haematologic malignancies and bone marrow failure syndromes (two patients) in the treatment of COVID-19. A severe or critical course of COVID-19 was significantly less frequent in the group of vaccinated patients (10.2% vs. 31.4%, p = 0.003). The need for hospitalisation due to COVID-19 was significantly lower in vaccinated patients (27.1% vs. 72.6%, p < 0.0001) and the duration of hospitalisation was significantly shorter (10 vs. 14 days, p = 0.045). Vaccinated patients were insignificantly less likely to require oxygen therapy during infection. COVID-19 mortality was significantly higher in non-vaccinated patients (15.6% vs. 5.1%, p = 0.047). The paper demonstrated a significant positive effect of vaccination against COVID-19 on a less severe clinical course of infection, lower need for hospitalisation and mortality. However, the results need to be evaluated even in the context of new antivirals and monoclonal antibodies against SARS-CoV-2 or virus mutations with different biological behaviour.

• Publikační typ
• časopisecké články MeSH

We designed a concept of 3D-printed attachment with porous glass filter disks-SLIDE (Sweat sampLIng DevicE) for easy sampling of apocrine sweat. By applying advanced mass spectrometry coupled with the liquid chromatography technique, the complex lipid profiles were measured to evaluate the reproducibility and robustness of this novel approach. Moreover, our in-depth statistical evaluation of the data provided an insight into the potential use of apocrine sweat as a novel and diagnostically relevant biofluid for clinical analyses. Data transformation using probabilistic quotient normalization (PQN) significantly improved the analytical characteristics and overcame the 'sample dilution issue' of the sampling. The lipidomic content of apocrine sweat from healthy subjects was described in terms of identification and quantitation. A total of 240 lipids across 15 classes were identified. The lipid concentrations varied from 10-10 to 10-4 mol/L. The most numerous class of lipids were ceramides (n = 61), while the free fatty acids were the most abundant ones (average concentrations of 10-5 mol/L). The main advantages of apocrine sweat microsampling include: (a) the non-invasiveness of the procedure and (b) the unique feature of apocrine sweat, reflecting metabolome and lipidome of the intracellular space and plasmatic membranes. The SLIDE application as a sampling technique of apocrine sweat brings a promising alternative, including various possibilities in modern clinical practice.

• MeSH
• lidé MeSH
• lipidomika metody   MeSH
• lipidy analýza   MeSH
• metabolomika metody   MeSH
• odběr biologického vzorku * MeSH
• pot chemie   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Direct oral anticoagulants are an alternative to anticoagulants based on vitamin K antagonists. Monitoring of direct oral anticoagulant concentration levels is necessary in specific cases (e.g. in emergency conditions, for determination of the cause of bleeding, adverse effects, risk of drug-direct oral anticoagulants interaction); therefore, a sensitive and specific method is needed. A methanol protein precipitation method followed by liquid chromatography with high-resolution mass spectrometry was developed for simultaneous separation and determination of apixaban, betrixaban, edoxaban, dabigatran, rivaroxaban and ximelagatran. The proposed method was fully validated in terms of linearity, the limits of detection and quantification, intra- and inter-day trueness and precision, recovery, matrix effect, process efficiency and stability. The method shows a strong correlation (Pearson's correlation coefficients > 0.92) with coagulation assays of apixaban, dabigatran and rivaroxaban (dilute thrombin time for gatrans and anti Xa factor (anti-Xa) activity for xabans). In addition, the developed method was applied for the identification and determination of apixaban and dabigatran in post-mortem serum samples. The developed method is a good alternative to coagulation tests which may show various interferences.

• MeSH
• antikoagulancia * aplikace a dávkování   krev   izolace a purifikace   toxicita   MeSH
• aplikace orální MeSH
• chromatografie kapalinová metody   MeSH
• hmotnostní spektrometrie metody   MeSH
• lidé MeSH
• lineární modely MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• vyšetření krevní srážlivosti metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Ventilator-associated pneumonia (VAP) is one of the most severe complications affecting mechanically ventilated patients. The condition is caused by microaspiration of potentially pathogenic bacteria from the upper respiratory tract into the lower respiratory tract or by bacterial pathogens from exogenous sources such as healthcare personnel, devices, aids, fluids and air. The aim of our prospective, observational study was to confirm the hypothesis that in the etiology of VAP, an important role is played by etiological agents from the upper airway bacterial microflora. At the same time, we studied the hypothesis that the vertical spread of bacterial pathogens is more frequent than their horizontal spread among patients. A total of 697 patients required mechanical ventilation for more than 48 h. The criteria for VAP were met by 47 patients. Clonality of bacterial isolates from 20 patients was determined by comparing their macrorestriction profiles obtained by pulsed-field gel electrophoresis (PFGE). Among these 20 patients, a total of 29 PFGE pulsotypes of Klebsiella spp. and Escherichia spp. strains were observed. The high variability of clones proves that there was no circulation of bacterial pathogens among hospitalized patients. Our finding confirms the development of VAP as a result of bacterial microaspiration and therefore the endogenous origin of VAP.

• Publikační typ
• časopisecké články MeSH

The early identification of asymptomatic yet infectious cases is vital to curb the 2019 coronavirus (COVID-19) pandemic and to control the disease in the post-pandemic era. In this paper, we propose a fast, inexpensive and high-throughput approach using painless nasal-swab self-collection followed by direct RT-qPCR for the sensitive PCR detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This approach was validated in a large prospective cohort study of 1038 subjects, analysed simultaneously using (1) nasopharyngeal swabs obtained with the assistance of healthcare personnel and analysed by classic two-step RT-qPCR on RNA isolates and (2) nasal swabs obtained by self-collection and analysed with direct RT-qPCR. Of these subjects, 28.6% tested positive for SARS-CoV-2 using nasopharyngeal swab sampling. Our direct RT-qPCR approach for self-collected nasal swabs performed well with results similar to those of the two-step RT-qPCR on RNA isolates, achieving 0.99 positive and 0.98 negative predictive values (cycle threshold [Ct] < 37). Our research also reports on grey-zone viraemia, including samples with near-cut-off Ct values (Ct ≥ 37). In all investigated subjects (n = 20) with grey-zone viraemia, the ultra-small viral load disappeared within hours or days with no symptoms. Overall, this study underscores the importance of painless nasal-swab self-collection and direct RT-qPCR for mass testing during the SARS-CoV-2 pandemic and in the post-pandemic era.

• MeSH
• COVID-19 diagnóza   prevence a kontrola   MeSH
• diagnostické testy rutinní metody   MeSH
• klinické laboratorní techniky metody   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• odběr biologického vzorku metody   MeSH
• plošný screening metody   MeSH
• průzkumy a dotazníky MeSH
• samovyšetření metody   MeSH
• SARS-CoV-2 genetika   MeSH
• senzitivita a specificita MeSH
• testování na COVID-19 metody   MeSH
• virová nálož metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH

Inflammatory bowel diseases (IBDs), chronic inflammatory disorders affecting the gastrointestinal tract, include Crohn's disease and ulcerative colitis. There are increasing clinical and experimental data showing that obesity, especially visceral adiposity, plays a substantial role in the pathogenesis of IBD. Obesity seems to be an important risk factor also for IBD disease severity and clinical outcomes. Visceral adipose tissue is an active multifunctional metabolic organ involved in lipid storage and immunological and endocrine activity. Bowel inflammation penetrates the surrounding adipose tissue along the mesentery. Mesenteric fat serves as a barrier to inflammation and controls immune responses to the translocation of gut bacteria. At the same time, mesenteric adipose tissue may be the principal source of cytokines and adipokines responsible for inflammatory processes associated with IBD. This review is particularly focusing on the potential role of adipokines in IBD pathogenesis and their possible use as promising therapeutic targets.

• MeSH
• abdominální obezita imunologie   metabolismus   MeSH
• adipokiny metabolismus   MeSH
• idiopatické střevní záněty imunologie   metabolismus   MeSH
• lidé MeSH
• nitrobřišní tuk imunologie   metabolismus   MeSH
• tuková tkáň imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH