Immunophenotyping by flow cytometry (FCM) is a worldwide mainstay in leukemia diagnostics. For concordant multicentric application, however, a gap exists between available classification systems, technologic standardization, and clinical needs. The AIEOP-BFM consortium induced an extensive standardization and validation effort between its nine national reference laboratories collaborating in immunophenotyping of pediatric acute lymphoblastic leukemia (ALL). We elaborated common guidelines which take advantage of the possibilities of multi-color FCM: marker panel requirements, immunological blast gating, in-sample controls, tri-partite antigen expression rating (negative vs. weak or strong positive) with capturing of blast cell heterogeneities and subclone formation, refined ALL subclassification, and a dominant lineage assignment algorithm able to distinguish "simple" from bilineal/"complex" mixed phenotype acute leukemia (MPAL) cases, which is essential for choice of treatment. These guidelines are a first step toward necessary inter-laboratory standardization of pediatric leukemia immunophenotyping for a concordant multicentric application. © 2017 International Clinical Cytometry Society.
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis MeSH
- Acute Disease MeSH
- Child MeSH
- Phenotype MeSH
- Immunophenotyping standards MeSH
- Consensus MeSH
- Humans MeSH
- Flow Cytometry standards MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
Schizophrenia is a psychiatric disorder with heterogeneous clinical manifestations and complex aetiology. Notably, the triple-network model proposes an interesting framework for investigating abnormal neurocircuit activity at rest in schizophrenia. The present study on 30 chronic schizophrenia individuals and 30 controls aimed to explore the differences in EEG resting state effective connectivity within a triple-network model using source-localization-based Directed Transfer Function. Our findings revealed multiband effective connectivity disturbances within default mode (DMN), central executive (CEN), and salience (SN) networks in schizophrenia. The most significant difference was manifested in a global DMN hyperconnectivity, accompanied by low-band hyperconnectivity and high-band hypoconnectivity in CEN, along with the aberrant information flows in SN. In conclusion, our study presents novel insights into schizophrenia neuropathology, with a particular emphasis on the reversed directionality in information flows between hubs of SN, DMN, and CEN. This may be suggested as a promising biomarker of schizophrenia.
- MeSH
- Default Mode Network * physiopathology MeSH
- Adult MeSH
- Electroencephalography MeSH
- Connectome * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Nerve Net * physiopathology diagnostic imaging MeSH
- Schizophrenia * physiopathology diagnostic imaging MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Humans MeSH
- Multiple Myeloma * diagnosis therapy MeSH
- Flow Cytometry MeSH
- Reference Standards MeSH
- Neoplasm, Residual MeSH
- Feasibility Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Letter MeSH
- Research Support, Non-U.S. Gov't MeSH
Východiska: Akupunktura je jednou z nejstarších léčebných metod. Tradiční pohled na akupunkturu ji vnímá jako ovlivnění energetických drah prostřednictvím stimulace specifických bodů. Původní meridiánová teorie, která pracuje s předpokladem normalizace proudící energie Qi v organizmu, je se vzrůstající evidencí doplňována informacemi o biologickém dopadu užití akupunktury z pohledu západní medicíny. Specifická stimulace konkrétních bodů na těle vede k aktivaci hypotalamu a hypofýzy, což má za následek široké spektrum systémových účinků. Stimulací nervů ve svalu, které pak přenášejí signál do míchy, středního mozku a hypotalamo-hypofyzárního systému, dochází k uvolňování celé řady neurotransmiterů, endogenních opioidních peptidů či hormonů. Stimulací akupunkturních bodů se mění i hladiny prozánětlivých cytokinů vč. IL-1-beta, IL-6, IL-17 a TNF-alfa. V současnosti jsou dle doporučení National Comprehensive Cancer Network (NCCN) k léčbě akupunkturou indikovány tyto symptomy: bolest vč. bolesti neuropatické, artralgie a myalgie (zvláště při léčbě inhibitory aromatázy), nevolnost a zvracení, únava, vazomotorické symptomy u žen a vazomotorické symptomy u mužů v souvislosti s androgen deprivační terapií. Akupunktura se zdá být efektivní a bezpečnou metodou terapie řady symptomů nádorových onemocnění, případně nežádoucích účinků onkologické léčby; stejně jako jakákoliv jiná léčebná metoda má však své indikace a kontraindikace. Cíl: Cílem této práce je podat ucelený přehled o využití akupunktury v definovaných indikacích, dle aktuálních mezinárodních doporučení. Lze tak rozšířit terapeutické možnosti symptomatické léčby nádorových onemocnění a léčby nežádoucích účinků onkologické terapie.
Background: Acupuncture is one of the oldest therapeutic methods. The traditional view of acupuncture is represented by influencing energy pathways through stimulation of specific points. The original meridian theory, which works with the assumption of normalization of the flowing energy Qi in the organism is, with increasing evidence, supplemented with information about the biological impact of the use of acupuncture from the perspective of Western medicine. Specific stimulation of particular points on the body leads to the activation of hypothalamus and pituitary gland through neurotransmitters, resulting in a wide range of systemic effects. Stimulation of nerves in the muscle, which then transmits a signal to the spinal cord, midbrain, and hypothalamic-pituitary system, releases neurotransmitters, endogenous opioid peptides, or hormones. Stimulation of acupuncture points changes the levels of proinflammatory cytokines, including IL-1-beta, IL-6, IL-17, and TNF-alpha. Currently, according to the National Comprehensive Cancer Network (NCCN) guidelines, the following symptoms are indicated for acupuncture treatment: pain including neuropathic pain, arthralgia, and myalgia, especially in the aromatase inhibitors therapy, nausea, and vomiting, fatigue, vasomotor symptoms in women and vasomotor symptoms in men caused by androgen deprivation therapy. Acupuncture seems to be an effective and safe treatment method for many of the cancer symptoms or the side effects of cancer treatment, but, like any other treatment method, it has its indications and contraindications. Purpose: This work aims to provide a comprehensive overview of the use of acupuncture in defined indications, according to current international guidelines. Thus, the therapeutic possibilities of symptomatic treatment of cancer and therapy of adverse events of oncological treatment can be extended.
- MeSH
- Acupuncture * MeSH
- Acupuncture Therapy methods MeSH
- Arthralgia therapy MeSH
- Humans MeSH
- Evidence-Based Medicine MeSH
- Myalgia therapy MeSH
- Cancer Pain therapy MeSH
- Neoplasms * complications MeSH
- Practice Guidelines as Topic MeSH
- Fatigue therapy MeSH
- Vomiting therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Technologický rozvoj průtokové cytometrie (flow cytometry, FC) spolu s nejnovějšími poznatky z oblasti imunofenotypizace monoklonálních gamapatií (MG) odhalil nezbytnost tohoto vyšetření zejména pro jeho diagnostický, prognostický a prediktivní význam. Cílem Evropské myelomové sítě (European Myeloma Network, EMN) je standardizovat tuto analytickou metodu a zařadit ji mezi rutinní klinická vyšetření. Jelikož celkový význam a možné aplikace FC jsou stále analyzovány, je zřejmé, že standardizace může napomoci zisku relevantních klinických výstupů z oblasti patofyziologie MG.
The technological development of flow cytometry (FC) together with new findings reveal the need for immunophenotyping in research of monoclonal gammopathy (MG) because of its diagnostic, prognostic and predictive significance. The aim of the European Myeloma Network (EMN) is to standardize this analytical method and implement it into routine clinical examination. Since the overall significance and application of FC are still analysed, standardisation could help obtain more clinical relevant information in terms of MG pathophysiology.
- Keywords
- plazmatická buňka,
- MeSH
- Antigens, CD analysis MeSH
- Financing, Organized MeSH
- Immunophenotyping MeSH
- Humans MeSH
- Multiple Myeloma MeSH
- Paraproteinemias immunology pathology MeSH
- Plasma Cells immunology classification MeSH
- Flow Cytometry methods standards MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Angina pectoris bez obstrukce koronárních tepen je častý nález u pacientů s bolestmi na hrudi, v jehož patofyziologii se uplatňují zejména dva mechanismy – strukturální nebo funkční poškození mikrocirkulace či funkční poškození epikardiálních tepen, případně jejich kombinace. Souhrnný článek se zabývá dia- gnostikou koronární mikrovaskulární dysfunkce se zaměřením na kontinuální termodiluci jako bezpečnou, jednoduchou, rychlou a na operatérovi nezávislou metodu. Popisuje teoretický základ i praktické aspekty s grafickými ukázkami měření.
Angina with non-obstructive coronary artery disease is a frequent finding in patients with chest pain. Its pathophysiology involves two main mechanisms: structural and functional dysfunction of microcircula- tion, functional dysfunction of epicardial arteries, and their combination. The review article focuses on the diagnostics of microvascular dysfunction, particularly continuous thermodilution, as a safe, easy, fast, and operator-independent method. It describes both theoretical background and practical aspects with graphical examples of measurements.
- Keywords
- koronární průtok,
- MeSH
- Angina Pectoris * diagnosis classification physiopathology MeSH
- Hemodynamic Monitoring methods MeSH
- Coronary Vessels pathology MeSH
- Humans MeSH
- Microvessels pathology MeSH
- Microcirculation MeSH
- Pericardium physiology MeSH
- Thermodilution * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Flow cytometry immunophenotyping is critical for the diagnostic classification of mature/peripheral B-cell neoplasms/B-cell chronic lymphoproliferative disorders (B-CLPD). Quantitative driven classification approaches applied to multiparameter flow cytometry immunophenotypic data can be used to extract maximum information from a multidimensional space created by individual parameters (e.g., immunophenotypic markers), for highly accurate and automated classification of individual patient (sample) data. Here, we developed and compared five diagnostic classification algorithms, based on a large set of EuroFlow multicentric flow cytometry data files from a cohort 659 B-CLPD patients. These included automatic population separators based on Principal Component Analysis (PCA), Canonical Variate Analysis (CVA), Neighbourhood Component Analysis (NCA), Support Vector Machine algorithms (SVM) and a variant of the CA(Canonical Analysis) algorithm, in which the number of SDs (Standard Deviations) varied for each of the comparisons of different pairs of diseases (CA-vSD). All five classification approaches are based on direct prospective interrogation of individual B-CLPD patients against the EuroFlow flow cytometry B-CLPD database composed of tumor B-cells of 659 individual patients stained in an identical way and classified a priori by the World Health Organization (WHO) criteria into nine diagnostic categories. Each classification approach was evaluated in parallel in terms of accuracy (% properly classified cases), precision (multiple or single diagnosis/case) and coverage (% cases with a proposed diagnosis). Overall, average rates of correct diagnosis (for the nine B-CLPD diagnostic entities) of between 58.9 % and 90.6 % were obtained with the five algorithms, with variable percentages of cases being either misclassified (4.1 %-14.0 %) or unclassifiable (0.3 %-37.0 %). Automatic population separators based on CA, SVM and PCA showed a high average level of correctness (90.6 %, 86.8 %, and 86.0 %, respectively). Nevertheless, this was at the expense of proposing a considerable number of multiple diagnoses for a significant proportion of the test cases (54.5 %, 53.5 %, and 49.6 %, respectively). The CA-vSD algorithm generated the smaller average misclassification rate (4.1 %), but with 37.0 % of cases for which no diagnosis was proposed. In contrast, the NCA algorithm left only 2.7 % of cases without an associated diagnosis but misclassified 14.0 %. Among correctly classified cases (83.3 % of total), 91.2 % had a single proposed diagnosis, 8.6 % had two possible diagnoses, and 0.2 % had three. We demonstrate that the proposed AI algorithms provide an acceptable level of accuracy for the diagnostic classification of B-CLPD patients and, in general, surpass other algorithms reported in the literature.
- MeSH
- Algorithms MeSH
- B-Lymphocytes * pathology MeSH
- Immunophenotyping * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphoproliferative Disorders * diagnosis classification MeSH
- Flow Cytometry * methods MeSH
- Aged MeSH
- Support Vector Machine MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Imunofenotypizace myelomových buněk přináší dostatek informací k charakterizaci a odlišení těchto heterogenních neoplastických plazmocytů od jejich normálních protějšků a své uplatnění tedy nalézá v diferenciální diagnostice. Stanovení antigenního profilu PC může též napomoci identifikaci prognostických markerů, které by vedly jednak k jednoznačnému stanovení diagnózy a určení pravděpodobnosti progrese u asymptomatických monoklonálních gamapatií, ale také k případnému hodnocení minimální reziduální choroby či účinnosti léčby u mnohočetného myelomu. Je snahou Evropské myelomové sítě (European Myeloma Network), EMN, sjednotit a standardizovat fl owcytometrické vyšetření plazmocytů v rámci monoklonálních gamapatií.
Immunophenotyping of myeloma cells is used to characterize the malignant plasma cells and to distinguish them from their normal counterparts. Flow cytometry is mostly used for the diagnosis of plasma cell proliferations but a detailed analysis of plasma cell immunophenotype can identify disease markers that are associated with the progression of monoclonal gammopathy of unknown signifi cance to multiple myeloma (MM), the prognosis of MM, the response to treatment, and the presence of minimal residual disease. The aim of the European Myeloma Network (EMN) is to unify and standardize immunophenotyping methods for the analysis of plasma cells in monoclonal gammopathies.
- MeSH
- Immunophenotyping MeSH
- Bone Marrow MeSH
- Humans MeSH
- Multiple Myeloma * genetics physiopathology MeSH
- Plasma Cells * cytology MeSH
- Flow Cytometry * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Gene flow between species may last a long time in plants. Reticulation inevitably causes difficulties in phylogenetic reconstruction. In this study, we looked into the genetic divergence and phylogeny of 20 Lilium species based on multilocus analyses of 8 genes of chloroplast DNA (cpDNA), the internally transcribed nuclear ribosomal DNA (nrITS) spacer and 20 loci extracted from the expressed sequence tag (EST) libraries of L. longiflorum Thunb. and L. formosanum Wallace. The phylogeny based on the combined data of the maternally inherited cpDNA and nrITS was largely consistent with the taxonomy of Lilium sections. This phylogeny was deemed the hypothetical species tree and uncovered three groups, i.e., Cluster A consisting of 4 taxa from the sections Pseudolirium and Liriotypus, Cluster B consisting of the 4 taxa from the sections Leucolirion, Archelirion and Daurolirion, and Cluster C comprising 10 taxa mostly from the sections Martagon and Sinomartagon. In contrast, systematic inconsistency occurred across the EST loci, with up to 19 genes (95%) displaying tree topologies deviating from the hypothetical species tree. The phylogenetic incongruence was likely attributable to the frequent genetic exchanges between species/sections, as indicated by the high levels of genetic recombination and the IMa analyses with the EST loci. Nevertheless, multilocus analysis could provide complementary information among the loci on the species split and the extent of gene flow between the species. In conclusion, this study not only detected frequent gene flow among Lilium sections that resulted in phylogenetic incongruence but also reconstructed a hypothetical species tree that gave insights into the nature of the complex relationships among Lilium species.
- MeSH
- DNA, Chloroplast genetics MeSH
- Phylogeny MeSH
- Lilium classification genetics MeSH
- Genes, Plant * MeSH
- Gene Flow * MeSH
- Publication type
- Journal Article MeSH
Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.
- Publication type
- Journal Article MeSH