In the rapidly evolving field of primary immunodeficiencies (PID), the EuroFlow consortium decided to develop a PID orientation and screening tube that facilitates fast, standardized, and validated immunophenotypic diagnosis of lymphoid PID, and allows full exchange of data between centers. Our aim was to develop a tool that would be universal for all lymphoid PIDs and offer high sensitivity to identify a lymphoid PID (without a need for specificity to diagnose particular PID) and to guide and prioritize further diagnostic modalities and clinical management. The tube composition has been defined in a stepwise manner through several cycles of design-testing-evaluation-redesign in a multicenter setting. Equally important appeared to be the standardized pre-analytical procedures (sample preparation and instrument setup), analytical procedures (immunostaining and data acquisition), the software analysis (a multidimensional view based on a reference database in Infinicyt software), and data interpretation. This standardized EuroFlow concept has been tested on 250 healthy controls and 99 PID patients with defined genetic defects. In addition, an application of new EuroFlow software tools with multidimensional pattern recognition was designed with inclusion of maturation pathways in multidimensional patterns (APS plots). The major advantage of the EuroFlow approach is that data can be fully exchanged between different laboratories in any country of the world, which is especially of interest for the PID field, with generally low numbers of cases per center.

• MeSH
• dítě MeSH
• dospělí MeSH
• imunitní systém patologie   MeSH
• imunofenotypizace metody   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• primární imunodeficience diagnóza   MeSH
• průtoková cytometrie metody   MeSH
• referenční standardy MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

• MeSH
• diferenciální diagnóza MeSH
• gynekologická onemocnění mikrobiologie   parazitologie   virologie   MeSH
• infekce diagnóza   farmakoterapie   MeSH
• kontrola infekce MeSH
• pánev MeSH
• zánět diagnóza   farmakoterapie   prevence a kontrola   MeSH

The EuroFlow PID consortium developed a set of flow cytometry tests for evaluation of patients with suspicion of primary immunodeficiency (PID). In this technical report we evaluate the performance of the SCID-RTE tube that explores the presence of recent thymic emigrants (RTE) together with T-cell activation status and maturation stages and discuss its applicability in the context of the broader EuroFlow PID flow cytometry testing algorithm for diagnostic orientation of PID of the lymphoid system. We have analyzed peripheral blood cells of 26 patients diagnosed between birth and 2 years of age with a genetically defined primary immunodeficiency disorder: 15 severe combined immunodeficiency (SCID) patients had disease-causing mutations in RAG1 or RAG2 (n = 4, two of them presented with Omenn syndrome), IL2RG (n = 4, one of them with confirmed maternal engraftment), NHEJ1 (n = 1), CD3E (n = 1), ADA (n = 1), JAK3 (n = 3, two of them with maternal engraftment) and DCLRE1C (n = 1) and 11 other PID patients had diverse molecular defects [ZAP70 (n = 1), WAS (n = 2), PNP (n = 1), FOXP3 (n = 1), del22q11.2 (DiGeorge n = 4), CDC42 (n = 1) and FAS (n = 1)]. In addition, 44 healthy controls in the same age group were analyzed using the SCID-RTE tube in four EuroFlow laboratories using a standardized 8-color approach. RTE were defined as CD62L+CD45RO-HLA-DR-CD31+ and the activation status was assessed by the expression of HLA-DR+. Naïve CD8+ T-lymphocytes and naïve CD4+ T-lymphocytes were defined as CD62L+CD45RO-HLA-DR-. With the SCID-RTE tube, we identified patients with PID by low levels or absence of RTE in comparison to controls as well as low levels of naïve CD4+ and naïve CD8+ lymphocytes. These parameters yielded 100% sensitivity for SCID. All SCID patients had absence of RTE, including the patients with confirmed maternal engraftment or oligoclonally expanded T-cells characteristic for Omenn syndrome. Another dominant finding was the increased numbers of activated CD4+HLA-DR+ and CD8+HLA-DR+ lymphocytes. Therefore, the EuroFlow SCID-RTE tube together with the previously published PIDOT tube form a sensitive and complete cytometric diagnostic test suitable for patients suspected of severe PID (SCID or CID) as well as for children identified via newborn screening programs for SCID with low or absent T-cell receptor excision circles (TRECs).

• MeSH
• HLA-DR antigeny analýza   MeSH
• imunofenotypizace metody   MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• primární imunodeficience diagnóza   imunologie   MeSH
• průtoková cytometrie metody   MeSH
• T-lymfocyty imunologie   MeSH
• těžká kombinovaná imunodeficience imunologie   MeSH
• thymus imunologie   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies, but their B-cell defects and underlying genetic alterations remain largely unknown. OBJECTIVE: We investigated patients with PADs for the distribution of 41 blood B-cell and plasma cell (PC) subsets, including subsets defined by expression of distinct immunoglobulin heavy chain subclasses. METHODS: Blood samples from 139 patients with PADs, 61 patients with common variable immunodeficiency (CVID), 68 patients with selective IgA deficiency (IgAdef), 10 patients with IgG subclass deficiency with IgA deficiency, and 223 age-matched control subjects were studied by using flow cytometry with EuroFlow immunoglobulin isotype staining. Patients were classified according to their B-cell and PC immune profile, and the obtained patient clusters were correlated with clinical manifestations of PADs. RESULTS: Decreased counts of blood PCs, memory B cells (MBCs), or both expressing distinct IgA and IgG subclasses were identified in all patients with PADs. In patients with IgAdef, B-cell defects were mainly restricted to surface membrane (sm)IgA+ PCs and MBCs, with 2 clear subgroups showing strongly decreased numbers of smIgA+ PCs with mild versus severe smIgA+ MBC defects and higher frequencies of nonrespiratory tract infections, autoimmunity, and affected family members. Patients with IgG subclass deficiency with IgA deficiency and those with CVID showed defects in both smIgA+ and smIgG+ MBCs and PCs. Reduced numbers of switched PCs were systematically found in patients with CVID (absent in 98%), with 6 different defective MBC (and clinical) profiles: (1) profound decrease in MBC numbers; (2) defective CD27+ MBCs with almost normal IgG3+ MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG2+ MBCs; and (6) with IgA1+ MBCs. CONCLUSION: Distinct PAD defective B-cell patterns were identified that are associated with unique clinical profiles.

• MeSH
• dítě MeSH
• dospělí MeSH
• imunoglobuliny nedostatek   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• plazmatické buňky imunologie   MeSH
• počet buněk MeSH
• podskupiny B-lymfocytů imunologie   MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• syndromy imunologické nedostatečnosti imunologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

B-cell precursors (BCP) arise from hematopoietic stem cells in bone marrow (BM). Identification and characterization of the different BCP subsets has contributed to the understanding of normal B-cell development. BCP first rearrange their immunoglobulin (Ig) heavy chain (IGH) genes to form the pre-B-cell receptor (pre-BCR) complex together with surrogate light chains. Appropriate signaling via this pre-BCR complex is followed by rearrangement of the Ig light chain genes, resulting in the formation, and selection of functional BCR molecules. Consecutive production, expression, and functional selection of the pre-BCR and BCR complexes guide the BCP differentiation process that coincides with corresponding immunophenotypic changes. We studied BCP differentiation in human BM samples from healthy controls and patients with a known genetic defect in V(D)J recombination or pre-BCR signaling to unravel normal immunophenotypic changes and to determine the effect of differentiation blocks caused by the specific genetic defects. Accordingly, we designed a 10-color antibody panel to study human BCP development in BM by flow cytometry, which allows identification of classical preB-I, preB-II, and mature B-cells as defined via BCR-related markers with further characterization by additional markers. We observed heterogeneous phenotypes associated with more than one B-cell maturation pathway, particularly for the preB-I and preB-II stages in which V(D)J recombination takes place, with asynchronous marker expression patterns. Next Generation Sequencing of complete IGH gene rearrangements in sorted BCP subsets unraveled their rearrangement status, indicating that BCP differentiation does not follow a single linear pathway. In conclusion, B-cell development in human BM is not a linear process, but a rather complex network of parallel pathways dictated by V(D)J-recombination-driven checkpoints and pre-BCR/BCR mediated-signaling occurring during B-cell production and selection. It can also be described as asynchronous, because precursor B-cells do not differentiate as full population between the different stages, but rather transit as a continuum, which seems influenced (in part) by V-D-J recombination-driven checkpoints.

• MeSH
• buněčná diferenciace genetika   imunologie   MeSH
• dítě MeSH
• lidé MeSH
• prekurzorové B-lymfoidní buňky imunologie   MeSH
• průtoková cytometrie metody   MeSH
• receptory antigenů B-buněk genetika   imunologie   MeSH
• syndromy imunologické nedostatečnosti genetika   imunologie   MeSH
• těžké řetězce imunoglobulinů genetika   MeSH
• V(D)J rekombinace genetika   imunologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Acute respiratory distress syndrome (ARDS) is a disease that has a high reported mortality rate. The treatment for ARDS typically involves mechanical ventilation that is tailored to each patient's needs. A crucial aspect of this treatment is maintaining adequate oxygen saturation of haemoglobin by setting the fraction of inspired oxygen. This paper proposes a design method of robust proportional-integral-derivative (PID) controllers using a gas exchange model during ARDS. Several PID controllers were synthesized for different sub-operational ranges defined by measurable quantities of the mechanical ventilator and the patient using a mixed sensitivity H∞ approach. In simulations, the controller demonstrated high robustness to external changes and changes in the patient's condition, with saturation always above 88%. Although further validation of the controller is required, the results indicate that the presented robust control method has the potential to be clinically relevant.

• MeSH
• algoritmy MeSH
• kyslík krev   MeSH
• lidé MeSH
• oxygenoterapie metody   MeSH
• počítačová simulace MeSH
• syndrom dechové tísně patofyziologie   terapie   MeSH
• umělé dýchání * metody   MeSH
• výměna plynů v plicích MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVES: The article aims at introducing the concept of “policies by people with intellectual disabilities”. THEORETICAL BASE: The idea that action plans pursued by people with intellectual disabilities (PID) can be seen as “policies” is derived from Street-level Bureaucracy (Lipsky, 1980), interpreted as suggesting the notion of bottom-level policies. METHOD: Action plans to promote PID opportunities were identified by analysing interviews devoted to the question of “what should be done for PID”, conducted in 2019/2020 in a selected local community. Two of the action plans, namely those formulated by PID, are examined in the article. An analogy between the features of street-level policies by Lipsky and the action plans by PID was identified. Hence, the PID action plans are interpreted as “policies by PID”. OUTCOMES: Two types of such policies by PID were identified, namely “personal supporting network” and “participation in public affairs”. SOCIAL WORK IMPLICATIONS: The PID narrations of PID concerning their social workers convey the message that social workers are expected to listen to the policies by PID and to contribute to their autonomous implementation by supporting PID in dealing with practical matters and in promoting their self-esteem.

• MeSH
• formální sociální kontrola MeSH
• lidé MeSH
• postižení * MeSH
• sociální pracovníci MeSH
• veřejná politika MeSH
• zranitelné populace MeSH
• Check Tag
• lidé MeSH

Do studie bylo zařazeno celkem 144 pacientů. Na začátku studie nebyly mezi skupinami žádné rozdíly, co se týče demografických ukazatelů a závažnosti onemocnění. Průměrné trvání nemoci bylo 8 let, průměrná bolest kolem 60 mm na VAS a Lequesnův index 12. V hodnotě základní ukazatel (pain invisity diference – PID) došlo na konci k signifikantně vyššímu poklesu u Geladrinku Forte oproti placebu (29 ± 3,0 mm vs. 19,0 ± 3,0 mm, p = 0,0427). Rozdíl nebyl signifikantní u kolagenního hydrolyzátu oproti placebu (25 ± 3,6 vs. 19,0 ± 3,0, p = 0,12) v populaci ITT. Při hodnocení pacientů, kteří dokončili studii, byl rozdíl oproti placebu významný jak u Geladrinku Forte (p = 0,016), tak u kolagenního hydrolyzátu (p = 0,04). Rozdíly u algofunkčního indexu nebyly významné. Pacienti u Geladrinku Forte užívali o 40 % méně záchranné medikace. V toleranci léčených skupin nebyly žádné rozdíly. Složený přípravek Geladrink Forte je účinný v léčbě bolestivé gonartrózy.

A total of 144 patients were included in the study. In the beginning there were no differences between the groups concerning demographic parameters or the severity of the disease. The average duration of the disease was 8 years; the average pain was around 60 mm on VAS and Lequesne index 12. There was a significantly greater decline in the value of the basic parameters (pain intensity difference – PID) at the end in Geladrink Forte compared to the placebo (29 ± 3.0 mm compared to 19.0 ± 3.0 mm, p = 0.0427). The difference was not significant in collagenous hydrolysate compared to the placebo (25 ± 3.6 against 19.0 ± 3.0, p = 0.12) in population ITT. The difference during the evaluation of the patients who completed the study compared to the placebo was significant in Geladrink Forte (p = 0.016) as well as in collagenous hydrolysate (p= 0.04). Differences in the algo-functional index were not significant. Patients on Geladrink Forte used 40% less emergency medication. There was no difference in the tolerance of the treatment groups. The Geladrink Forte composite preparation is efficient in the treatment of painful knee osteoarthritis.

• Klíčová slova
• Geladrink forte,
• MeSH
• aminokyseliny účinky léků   MeSH
• artróza kolenních kloubů farmakoterapie   MeSH
• bolest farmakoterapie   MeSH
• chůze MeSH
• dvojitá slepá metoda MeSH
• hodnocení léčiv MeSH
• kloubní chrupavka účinky léků   MeSH
• kolagen terapeutické užití   MeSH
• léky bez předpisu MeSH
• lidé MeSH
• multicentrické studie jako téma statistika a číselné údaje   MeSH
• potravní doplňky MeSH
• randomizované kontrolované studie jako téma statistika a číselné údaje   MeSH
• statistika jako téma MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVES: The development of External Quality Assessment Schemes (EQAS) for clinical flow cytometry (FCM) is challenging in the context of rare (immunological) diseases. Here, we introduce a novel EQAS monitoring the primary immunodeficiency Orientation Tube (PIDOT), developed by EuroFlow, in both a 'wet' and 'dry' format. This EQAS provides feedback on the quality of individual laboratories (i.e., accuracy, reproducibility and result interpretation), while eliminating the need for sample distribution. METHODS: In the wet format, marker staining intensities (MedFIs) within landmark cell populations in PIDOT analysis performed on locally collected healthy control (HC) samples, were compared to EQAS targets. In the dry format, participants analyzed centrally distributed PIDOT flow cytometry data (n=10). RESULTS: We report the results of six EQAS rounds across 20 laboratories in 11 countries. The wet format (212 HC samples) demonstrated consistent technical performance among laboratories (median %rCV on MedFIs=34.5 %; average failure rate 17.3 %) and showed improvement upon repeated participation. The dry format demonstrated effective proficiency of participants in cell count enumeration (range %rCVs 3.1-7.1 % for the major lymphoid subsets), and in identifying lymphoid abnormalities (79.3 % alignment with reference). CONCLUSIONS: The PIDOT-EQAS allows laboratories, adhering to the standardized EuroFlow approach, to monitor interlaboratory variations without the need for sample distribution, and provides them educational support to recognize rare clinically relevant immunophenotypic patterns of primary immunodeficiencies (PID). This EQAS contributes to quality improvement of PID diagnostics and can serve as an example for future flow cytometry EQAS in the context of rare diseases.

• MeSH
• imunofenotypizace * normy   metody   MeSH
• lidé MeSH
• průtoková cytometrie * normy   metody   MeSH
• řízení kvality MeSH
• syndromy imunologické nedostatečnosti diagnóza   imunologie   MeSH
• zajištění kvality zdravotní péče MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Introduction : Le diabète sucré (DS) était la septième cause de décès en 2006. Le nombre de patients devrait doubler d'ici à 2050. Le simple non-respect du suivi des directrices par les médecins est une cause importante de morbidité et de mortalité. Notre objectif était d'étudier l'impact d'un modèle électronique sur le respect des direc- tives de l'ADA pour le traitement du diabète par interniste général. Méthodes : Nous avons conçu un modèle électronique basées sur les 8 points directives de l'ADA pour la gestion du diabète de type 2, y compris : l'hémoglobine glycosy- lée (HgbA1c) l'évaluation, de la pression artérielle (PA), le contrôle des lipides, le counselling anti tabagique, les exa- mens du pied chez le diabétique, la vaccination anti pneu- mococcique (PCV ), l'évaluation rénale et l'examen annuel de la rétine. Le modèle a été utilisé par les médecins pen- dant 6 mois et un groupe témoin de pré-intervention a été choisi au hasard indépendamment de l'âge et du sexe de la base de données de patients existants. Ces mêmes patients n'ont pas été suivis dans le groupe témoin et le groupe expérimental. Résultats : Notre groupe expérimental se composait de 212 sujets, ils ont été comparés à un groupe témoin de 154. Des améliorations significatives ont été détectées dans les tests HbA1c (57,5% contre 94,1%, p <0,001), PA(pression artérielle) Témoin/ Expérimental effectué (53,3% contre 89,1%, p <0,001), lipoprotéines de basse densité (LDL) Témoin/ Expérimental effectué (65,6% contre 90,0%, p <0,001), le respect des examens du pied chez le diabétique (88,3% contre 99,1%, p 0,001), le respect des examens annuels des yeux (38,3% contre 94,8%, p <0,001). Des améliorations non significatives ont été détectées dans le counselling anti tabagique (97,3% contre 100%, p 0,578), la micro albuminurie (92,8% à 92,9%, p 0,72). Les don- nées sur lhématocrite nétaient pas disponibles, donc au- cune comparaison na été faite. Conclusion : L'utilisation d'un modèle dans le dossier mé- dical électronique a montré une amélioration significative dans le traitement du diabète notamment dans l'évaluation HbA1c, la PA, le contrôle de LDL, l'examen des pieds, et l'examen annuels des yeux. Lutilisation de modèles dans les systèmes de dossiers médicaux électroniques a montré un respect accru des lignes directrices par les médecins, cela pourrait sextrapoler à d'autres maladies chroniques.

Introduction: Diabetes mellitus (DM) was the seventh leading cause of death in 2006. The number of patients is expected to double by 2050. Simple non-adherence to fol- low guidelines by physicians is a significant source of mor- bidity and mortality. Our goal was to study the impact of an electronic template on adherence to follow ADA guide- lines for diabetes care by general internist. Methods: We designed an electronic template based on the 8 point ADA guidelines for management of dia- betes type 2 including: glycosylated hemoglobin (HgbA1c) assessment, blood pressure (BP), lipid control, smoking cessation counseling, diabetic foot exams, pneumococcal vaccination (PCV), renal assessment and annual retina exam.A randomly selected pre-intervention control group was compared after 6 months of template use to a ran- domly selected post-intervention group independent of age and sex variables. Same patients were not followed in the control and intervention group. Results: Our intervention group consisted of 212 subjects, they were compared with a control group of 154. Significant improvements were detected in HbA1c testing (57.5% vs. 94.1%; p<0.001), BP control/intervention done (53.3% vs. 89.1%; p<0.001), low-density lipopro- tein (LDL) control/intervention done (65.6% vs. 90.0%; p<0.001), compliance with diabetic foot exams (88.3% vs. 99.1%; p 0.001), compliance with annual eye exams (38.3% vs. 94.8%; p<0.001). Non-significant improve- ments were detected in smoking cessation counseling (97.3% vs 100%; p 0.578), renal assessment (92.8% to 92.9%; p 0.72). No pre intervention data on PCV was available, so no comparisons were done. Conclusion: Utilization of a template in the EMR showed a significant improvement in diabetes care including HbA1c assessment, BP control, LDL control, foot examination, and annual eye examination. Use of templates in the EMR system showed increased adherence to guidelines by physi- cians, this might extrapolate to other chronic diseases.

• MeSH
• diabetes mellitus 2. typu * diagnóza   prevence a kontrola   MeSH
• dodržování směrnic * MeSH
• elektronické zdravotní záznamy využití   MeSH
• hodnocení výsledků zdravotní péče statistika a číselné údaje   MeSH
• lidé MeSH
• primární zdravotní péče MeSH
• připomínače a organizéry * využití   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH