Paroxysmální noční hemoglobinurie (PNH) je lionální onemocnění kmenové krvetvorné buňky charakterizované deficitem inhibitorů komplementu na povrchu buněk. Nekontrolovaná aktivace komplementu vede k intravaskulární hemoiýze erytrocytů s vysokým rizikem trombotických komplikací a k selhání kostní dřeně. Anemie a cytopenie v dalších krevních řadách patří společně s hemoglobinurií a vysokou incidencí trombotických komplikací k hlavním příznakům onemocnění. Onemocnění vede k postižení orgánů, zejména k renální insuficienci a plicní hypertenzi. V diagnostice hraje zásadní roii detekce deficitu inhibitorů pomocí průtokové cytometrie. Na PNH je třeba myslet u stavů s negativním Coombsovým testem na hemolytickou anemii, zejména se současnou cytopenií v dalších řadách, u aplastické anemie či při suspekci na myeiodysplastický syndrom a rovněž u nemocných s trombózou, zejména v atypických lokalizacích u mladších nemocných. V léčbě se používají u stavů s opakovanou těžkou hemolýzou inhibitory složky C5 a C3 komplementu. Nemocní s hypoplastickou formou PNH a selháním kostní dřeně jsou indikováni k transliantaci krvetvorných buněk, alternativou u těchto nemocných je podání kombinované imunosuprese.

Paroxysmal nocturnal hemoglobinuria (PNH) represents a clonal disorder of pluripotent hematopoietic stem cell. The disease is characterized by deficiency of complement inhibitors on the cell surface. Uncontrolled activation of complement leads to intravascular hemolysis of red blood cells with high risk of thrombotic complications. The disease is usually connected with chronic kidney disease and pulmonary hypertension. Detection of a lack of inhibitory molecules on cell surface by flow cytometry plays a crucial role in the diagnosis of the disease. PNH should be considered in all patients with Coombs negative hemolytic anemia, especially in those with combination of cytopenia in other cell lines as well as in patients with aplastic anemia or suspected myelodysplastic syndrome. PNH must be also excluded in patients with thrombotic complications, mainly in those with thrombosis occurring in atypical localizations and at a younger age. PNH patients with recurrent episodes of severe intravascular hemolysis are indicated for treatment with inhibitors of C3 or C5 part of complement. Patients with hypoplastic PNH are candidates for hematopoietic stem cell transplantation, an alternative treatment approach to these patients may be combination immune suppression.

Myelodysplastic syndromes (MDS) are myeloid malignancies with heterogeneous genotypes and phenotypes, characterized by ineffective haematopoiesis and a high risk of progression towards acute myeloid leukaemia (AML). Prognosis for patients treated with hypomethylating agents (HMAs), as is azacytidine, the main drug used as frontline therapy for MDS is mostly based on cytogenetics and next generation sequencing (NGS) of the initial myeloid clone. Although the critical influence of the epigenetic landscape upon cancer cells survival and development as well on tumour environment establishment is currently recognized and approached within current clinical practice in MDS, the heterogenous response of the patients to epigenetic therapy is suggesting a more complex mechanism of action, as is the case of RNA methylation. In this sense, the newly emerging field of epitranscriptomics could provide a more comprehensive perspective upon the modulation of gene expression in malignancies, as is the proof-of-concept of MDS. We initially did RNA methylation sequencing on MDS patients (n = 6) treated with azacytidine and compared responders with non-responders. Afterwards, the genes identified were assessed in vitro and afterwards validated on a larger cohort of MDS patients treated with azacytidine (n = 58). Our data show that a more accurate prognosis could be based on analysing the methylome and thus we used methylation sequencing to differentially split high-grade MDS patients with identical demographical and cytogenetic features, between azacytidine responders and non-responders.

• MeSH
• antimetabolity antitumorózní terapeutické užití   farmakologie   MeSH
• azacytidin * farmakologie   terapeutické užití   MeSH
• epigeneze genetická účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methylace RNA MeSH
• metylace DNA * účinky léků   MeSH
• myelodysplastické syndromy * genetika   farmakoterapie   patologie   MeSH
• prognóza MeSH
• sekvenční analýza RNA MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• transkriptom genetika   účinky léků   MeSH
• vysoce účinné nukleotidové sekvenování 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

INTRODUCTION: Inherited bone marrow failure (IBMF) syndromes are caused by mutations forming pathologic germline variants resulting in the production of defective hematopoietic stem cells (HSC) and in congenital failure in the production of one or more blood lineages. An acquisition of subsequent somatic mutations is determining further course of the disease. Nevertheless, a certain number of patients with IBMF may escape correct diagnosis in childhood, especially those with mild cytopenia and minimal clinical features without non-hematologic symptoms. These patients usually present in the third decade of life with unexplained cytopenia or myelodysplastic syndrome (MDS). METHODS AND RESULTS: We report 2 patients with IBMF who were correctly diagnosed between 20 and 40 years of age when they were referred with progressive MDS with adverse prognostic factors that affected their outcome. DISCUSSION: IBMF syndromes should be excluded in all patients below 40 years of age with unexplained cytopenia. Early hematopoietic stem cell transplantation (HSCT) is the treatment of choice in these patients.

• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The precise link between inflammation and pathogenesis of myelodysplastic syndrome (MDS) is yet to be fully established. We developed a novel method to measure ASC/NLRP3 protein specks which are specific for the NLRP3 inflammasome only. We combined this with cytokine profiling to characterise various inflammatory markers in a large cohort of patients with lower risk MDS in comparison to healthy controls and patients with defined autoinflammatory disorders (AIDs). The ASC/NLRP3 specks were significantly elevated in MDS patients compared to healthy controls (p < 0.001) and these levels were comparable to those found in patients with AIDs. The distribution of protein specks positive only for ASC was different to ASC/NLRP3 ones suggesting that other ASC-containing inflammasome complexes might be important in the pathogenesis of MDS. Patients with MDS-SLD had the lowest levels of interleukin (IL)-1β, tumour necrosis factor (TNF), IL-23, IL-33, interferon (IFN) γ and IFN-α2, compared to other diagnostic categories. We also found that inflammatory cytokine TNF was positively associated with MDS progression to a more aggressive form of disease and IL-6 and IL-1β with time to first red blood cell transfusion. Our study shows that there is value in analysing inflammatory biomarkers in MDS, but their diagnostic and prognostic utility is yet to be fully validated.

• MeSH
• biologické markery krev   MeSH
• cytokiny * krev   MeSH
• dospělí MeSH
• inflamasomy MeSH
• lidé středního věku MeSH
• lidé MeSH
• myelodysplastické syndromy * krev   MeSH
• protein NLRP3 krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• zánět krev   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

Úvod: Ve své klasické podobě je onemocnění covid-19 respirační chorobou, která však může mít značně heterogenní průběh. Hrudní komplikace vznikají u malého procenta nemocných. Naším cílem je vyhodnotit dosavadní zkušenosti s touto chorobou a jejími hrudními projevy a stanovení reálného stavu péče o tyto nemocné. Metody: Tato práce je retrospektivní, single-insitution analýzou souboru pacientů hospitalizovaných s akutní a postakutní covid-19 pneumonií v pražské Thomayerově nemocnici v období 12/2020 až 03/2022, u kterých byl indikován hrudně-chirurgický zákrok. Výsledky: V době vrcholící pandemie nemoci covid-19 jsme provedli hrudně chirurgický zákrok u 46 pacientů. Nejčastější torakochirurgickou intervencí byla hrudní drenáž (18× pro pneumotorax, 3× pro fluidotorax, 2× CT navigovaná drenáž plicního abscesu a 2× CT navigovaná drenáž pneumatokély). V 10 případech byla provedena pleurektomie s dekortikací. Dále bylo provedeno 12 plicní parenchym šetřících resekcí, přičemž ve dvou případech si stav vyžádal resekci celého laloku. U 2 pacientů byla indikována resekce postintubační stenózy trachey po těžkém průběhu pneumonie covid-19. Závěr: Onemocnění covid-19 může i po lehkém průběhu výrazně morfologicky a funkčně alterovat dýchací ústrojí. Nejčastějšími komplikacemi pneumonie covid-19 vyžadující torakochirurgickou intervenci jsou patologie spojené se vznikem airleaku s kumulací vzduchu (pneumotorax, pneumomediastinum a podkožní emfyzém). Rozvoj plicních nekróz, symptomatických bronchiektázií, pneumatokél, bulózně-fibrotických formací mohou v ojedinělých případech vyústit v pneumotorax, hemotorax nebo hrudní empyém. Včasná torakochirurgická intervence hrudních komplikací pneumonie covid-19 může vést ke zlepšení přežívání covid nemocných.

Introduction: COVID-19 is considered a respiratory virosis in its classic form, although it may present with heterogeneous symptoms. Thoracic complications occur in a small percentage of patients. Our objective was to evaluate existing experience with this disease and its thoracic manifestations and to determine the real-world status of care of these patients. Methods: This study is a retrospective, single-institution analysis of a group of patients hospitalized with acute and post-acute COVID-19 pneumonia at Thomayer Hospital in Prague in the period from December 2020 to March 2022 and indicated for a thoracic surgical procedure. Results: During the peak of COVID-19 pandemic, a thoracic intervention was performed in 46 admitted patients. Thoracic drainage (due to pneumothorax in 18 cases, fluidothorax in 3 cases, CT-guided lung abscess drainage in 2 cases, and CT-guided pneumatocele drainage in 2 cases) were the most common thoracic surgical procedures. Pleurectomy/decortication surgery was done in 10 cases. Additionally, 12 lung parenchyma-sparing resections were performed, while lobectomy was required in 2 cases. Resection of postintubation tracheal stenosis due to a severe course of COVID-19 pneumonia was indicated in 2 patients. Conclusion: Even mild COVID-19 may cause a considerable morphological a functional alteration of the respiratory system. The most common complications of COVID-19 pneumonia that require a thoracic surgical intervention include pathologies associated with an air leak and accumulation of air (pneumothorax, pneumomediastinum and subcutaneous emphysema). The development of pulmonary necrosis, symptomatic bronchiectasis, pneumatocele, and bullous-fibrotic formations may result in pneumothorax, hemothorax or thoracic empyema in sporadic cases. An early thoracic surgical intervention to treat thoracic complications of COVID-19 pneumonia can improve the survival of COVID-19 patients.

• MeSH
• chirurgie plic metody   statistika a číselné údaje   MeSH
• hrudní chirurgické výkony * metody   statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pneumonie chirurgie   etiologie   komplikace   patologie   MeSH
• počítačová rentgenová tomografie MeSH
• postakutní syndrom COVID-19 * chirurgie   diagnostické zobrazování   mortalita   patologie   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

Patients with myelodysplastic neoplasms (MDS) are classified according to the risk of acute myeloid leukemia transformation. Some lower-risk MDS patients (LR-MDS) progress rapidly despite expected good prognosis. Using diagnostic samples, we aimed to uncover the mechanisms of this accelerated progression at the transcriptome level. RNAseq was performed on CD34+ ribodepleted RNA samples from 53 LR-MDS patients without accelerated progression (stMDS) and 8 who progressed within 20 months (prMDS); 845 genes were differentially expressed (ІlogFCІ > 1, FDR < 0.01) between these groups. stMDS CD34+ cells exhibited transcriptional signatures of actively cycling, megakaryocyte/erythrocyte lineage-primed progenitors, with upregulation of cell cycle checkpoints and stress pathways, which presumably form a tumor-suppressing barrier. Conversely, cell cycle, DNA damage response (DDR) and energy metabolism-related pathways were downregulated in prMDS samples, whereas cell adhesion processes were upregulated. Also, prMDS samples showed high levels of aberrant splicing and global lncRNA expression that may contribute to the attenuation of DDR pathways. We observed overexpression of multiple oncogenes and diminished differentiation in prMDS; the expression of ZEB1 and NEK3, genes not previously associated with MDS prognosis, might serve as potential biomarkers for LR-MDS progression. Our 19-gene DDR signature showed a significant predictive power for LR-MDS progression. In validation samples (stMDS = 3, prMDS = 4), the key markers and signatures retained their significance. Collectively, accelerated progression of LR-MDS appears to be associated with transcriptome patterns of a quiescent-like cell state, reduced lineage differentiation and suppressed DDR, inherent to CD34+ cells. The attenuation of DDR-related gene-expression signature may refine risk assessment in LR-MDS patients.

• MeSH
• buněčná adheze MeSH
• buněčný cyklus MeSH
• kinasy NEK genetika   metabolismus   MeSH
• lidé MeSH
• myelodysplastické syndromy * genetika   MeSH
• nádory * MeSH
• oprava DNA MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Publikace se zaměřuje na různé aspekty krevních nemocí. Určeno odborné veřejnosti.

• MeSH
• krevní nemoci MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• hematologie a transfuzní lékařství
• NLK Publikační typ
• kolektivní monografie

Information on causes of death (CoDs) and the impact of myelodysplastic syndromes (MDS) on survival in patients with lower-risk MDS (LR-MDS) is limited. A better understanding of the relationship between disease characteristics, clinical interventions and CoDs may improve outcomes of patients with LR-MDS. We prospectively collected data on patients with LR-MDS in the European MDS registry from 2008 to 2019. Clinical, laboratory and CoDs data were obtained. To examine MDS-specific survival, relative survival (RS) was estimated using national life tables. Of 2396 evaluated subjects, 900 died (median overall survival [OS]: 4.7 years; median follow-up: 3.5 years). The most common CoDs were acute myeloid leukaemia/MDS (20.1%), infection (17.8%) and cardiovascular disease (CVD; 9.8%). Patients with isolated del(5q) and with red cell transfusion needed during the disease course, had a higher risk of fatal CVD. The 5-year OS was 47.3% and the 5-year RS was 59.6%, indicating that most patients died due to their underlying MDS. Older patients (aged >80 years) and the lowest-risk patients were more likely to die from competing causes. This study shows that MDS and its related complications play crucial role in the outcome of patients with LR-MDS.

• MeSH
• akutní myeloidní leukemie * MeSH
• kardiovaskulární nemoci * MeSH
• lidé MeSH
• myelodysplastické syndromy * MeSH
• příčina smrti MeSH
• progrese nemoci MeSH
• registrace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH