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
• algoritmy MeSH
• B-lymfocyty * patologie   MeSH
• imunofenotypizace * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfoproliferativní nemoci * diagnóza   klasifikace   MeSH
• průtoková cytometrie * metody   MeSH
• senioři MeSH
• support vector machine MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in critically ill patients, who often have multiple risk factors. Pharmacological thromboprophylaxis is widely applied to lower this risk, but guidelines lack dosing recommendations. OBJECTIVE: This survey aims to assess current thromboprophylaxis preferences and willingness to participate in future randomized clinical trials (RCTs) on this topic. METHOD: We conducted an international online survey between February and May 2023 among intensive care unit (ICU) physicians, including 16 questions about preferences in relation to thromboprophylaxis and preferences on topics for a future RCT. The survey was distributed through the network of the Collaboration for Research in Intensive Care. RESULTS: A total of 715 physicians from 170 ICUs in 23 countries contributed information, with a mean response rate of 36%. In most ICUs, both pharmacological (n = 166, 98%) and mechanical thromboprophylaxis (n = 143, 84%) were applied. A total of 36 pharmacological thromboprophylaxis regimens were reported. Use of low-molecular-weight heparin (LMWH) was most common (n = 149 ICUs, 87%), followed by subcutaneous unfractionated heparin (n = 44 ICUs, 26%). Seventy-five percent of physicians indicated that they used enoxaparin 40 mg (4000 IU), dalteparin 5000 IU, or tinzaparin 4500 IU once daily, whereas 25% reported the use of 16 other LMWH type and dose combinations. Dose adjustment according to weight was common (78 ICUs, 46%). Participants perceived high variation in the application of thromboprophylaxis and were willing to consider an alternative LMWH type (n = 542, 76%) or dose (n = 538, 75%) in the context of an RCT. CONCLUSION: LMWH was the preferred agent for thromboprophylaxis in critically ill patients. There was considerable variation in the application of LMWH for prophylaxis, reflected by the use of different types, doses, and dosing strategies. Most physicians would be willing to participate in an RCT on thromboprophylaxis. EDITORIAL COMMENT: This survey demonstrates current patterns in implementation preferences for critically ill patients. While there is one approach and drug that is commonly preferred, these findings show that there is some variation in practice.

• MeSH
• antikoagulancia * terapeutické užití   aplikace a dávkování   MeSH
• heparin nízkomolekulární * terapeutické užití   aplikace a dávkování   MeSH
• internacionalita MeSH
• jednotky intenzivní péče * MeSH
• kritický stav MeSH
• lékaři MeSH
• lidé MeSH
• péče o pacienty v kritickém stavu metody   MeSH
• průzkumy a dotazníky MeSH
• žilní tromboembolie * prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.86) for 8151 variants. Our information-dense mapping provides a generalizable approach to advance multiple dimensions of rare genetic disorders.

• MeSH
• deep learning * MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp * MeSH
• genetická variace MeSH
• genetické asociační studie MeSH
• genomika metody   MeSH
• hormony štítné žlázy metabolismus   genetika   MeSH
• lidé MeSH
• mentální retardace vázaná na chromozom X genetika   metabolismus   MeSH
• mladiství MeSH
• mutace ztráty funkce MeSH
• předškolní dítě MeSH
• přenašeče monokarboxylových kyselin * genetika   metabolismus   MeSH
• stupeň závažnosti nemoci MeSH
• svalová atrofie genetika   metabolismus   patologie   MeSH
• svalová hypotonie genetika   metabolismus   MeSH
• symportéry * genetika   metabolismus   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disorder. Several new treatment concepts have emerged in recent years, but access to these treatments varies due to differing national reimbursement regulations, leading to disparities across Europe. This highlights the need for high-quality data collection by stakeholders to establish MG registries. A European MG registry could help bridge the treatment access gap across different countries, offering critical data to support regulatory decisions, foster international collaborations, and enhance clinical and epidemiological research. Several national MG registries already exist or are in development. To avoid duplication and ensure harmonization in data collection, a modified Delphi procedure was implemented to identify essential data elements for inclusion in national registries. RESULTS: Following a literature review, consultations with patient associations and pharmaceutical companies, and input from multiple European MG experts, 100 data elements were identified. Of these, 62 reached consensus for inclusion and classification, while only 1 item was agreed for exclusion. 30 items failed to reach the ≥ 80% agreement threshold and were excluded. Among the 62 accepted items, 21 were classified as mandatory data elements, 32 optional, and 9 items pertained to the informed consent form. CONCLUSIONS: Through a modified Delphi procedure, consensus was successfully achieved. This consensus-based approach represents a crucial step toward harmonizing MG registries across Europe. The resulting dataset will facilitate the sharing of knowledge and enhance European collaborations. Furthermore, the harmonized data may assist in regulatory or reimbursement decisions regarding novel therapies, as well as address treatment access disparities between European countries.

• MeSH
• delfská metoda * MeSH
• konsensus MeSH
• lidé MeSH
• myasthenia gravis * terapie   diagnóza   MeSH
• registrace * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Observational data on composite scores often comes with missing component information. When a complete-case (CC) analysis of composite scores is unbiased, preferable approaches of dealing with missing component information should also be unbiased and provide a more precise estimate. We assessed the performance of several methods compared to CC analysis in estimating the means of common composite scores used in axial spondyloarthritis research. METHODS: Individual mean imputation (IMI), the modified formula method (MF), overall mean imputation (OMI), and multiple imputation of missing component values (MI) were assessed either analytically or by means of simulations from available data collected across Europe. Their performance in estimating the means of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) in cases where component information was set missing completely at random was compared to the CC approach based on bias, variance, and coverage. RESULTS: Like the MF method, IMI uses a modified formula for observations with missing components resulting in modified composite scores. In the case of an unbiased CC approach, these two methods yielded representative samples of the distribution arising from a mixture of the original and modified composite scores, which, however, could not be considered the same as the distribution of the original score. The IMI and MF method are, thus, intrinsically biased. OMI provided an unbiased mean but displayed a complex dependence structure among observations that, if not accounted for, resulted in severe coverage issues. MI improved precision compared to CC and gave unbiased means and proper coverage as long as the extent of missingness was not too large. CONCLUSIONS: MI of missing component values was the only method found successful in retaining CC's unbiasedness and in providing increased precision for estimating the means of BASDAI, BASFI, and ASDAS-CRP. However, since MI is susceptible to incorrect implementation and its performance may become questionable with increasing missingness, we consider the implementation of an error-free CC approach a valid and valuable option. TRIAL REGISTRATION: Not applicable as study uses data from patient registries.

• MeSH
• ankylózující spondylitida MeSH
• axiální spondyloartritida * MeSH
• C-reaktivní protein analýza   MeSH
• interpretace statistických dat MeSH
• lidé MeSH
• stupeň závažnosti nemoci MeSH
• výzkumný projekt MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

OBJECTIVES: We aimed to compare various methods for imputing disease activity in longitudinally collected observational data of patients with axial spondyloarthritis (axSpA). METHODS: We conducted a simulation study on data from 8583 axSpA patients from ten European registries. Disease activity was assessed by the Axial Spondyloarthritis Disease Activity Score (ASDAS) and the corresponding low disease activity (LDA; ASDAS<2.1) state at baseline, 6 and 12 months. We focused on cross-sectional methods which impute missing values of an individual at a particular time point based on the available information from other individuals at that time point. We applied nine single and five multiple imputation methods, covering mean, regression and hot deck methods. The performance of each imputation method was evaluated via relative bias and coverage of 95% confidence intervals for the mean ASDAS and the derived proportion of patients in LDA. RESULTS: Hot deck imputation methods outperformed mean and regression methods, particularly when assessing LDA. Multiple imputation procedures provided better coverage than the corresponding single imputation ones. However, none of the evaluated methods produced unbiased estimates with adequate coverage across all time points, with performance for missing baseline data being worse than for missing follow-up data. Predictive mean and weighted predictive mean hot deck imputation procedures consistently provided results with low bias. CONCLUSIONS: This study contributes to the available methods for imputing disease activity in observational research. Hot deck imputation using predictive mean matching exhibited the highest robustness and is thus our suggested approach.

• MeSH
• axiální spondyloartritida * diagnóza   epidemiologie   MeSH
• dospělí MeSH
• interpretace statistických dat MeSH
• lidé MeSH
• longitudinální studie MeSH
• pozorovací studie jako téma * MeSH
• průřezové studie MeSH
• registrace MeSH
• spondylartritida diagnóza   MeSH
• stupeň závažnosti nemoci * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

The Arteriovenous Access Stage (AVAS) classification simplifies information about suitability of vessels for vascular access (VA). It's been previously validated in a clinical study. Here, AVAS performance was tested against multiple ultrasound mapping measurements using machine learning. A prospective multicentre international study (NCT04796558) with patient recruitment from March 2021-July 2024. Demographics, risk factors, vessels parameters, types of predicted and created VA (pVA, cVA) were collected. We modelled pVA and cVA using the Random Forest algorithm. Model performance was estimated and compared using Bayesian generalized linear models. ROC AUC with 95% credible intervals was the performance metric. 1151 patients were included. ROC AUC for pVA prediction by AVAS was 0.79 (0.77;0.82) and by mapping was 0.85 (0.83;0.88). ROC AUC for cVA prediction by AVAS was 0.71 (0.69;0.74) and by mapping was 0.8 (0.78;0.83). Using AVAS with other parameters increased the ROC AUC to 0.87 for pVA (0.84;0.89) and 0.82 (0.79;0.84) for cVA. Using mapping with other parameters increased the ROC AUC to 0.88 for pVA (0.86;0.91) and 0.85 (0.83;0.88) for cVA. Multiple mapping measurements showed higher performance at VA prediction than AVAS. However, AVAS is simpler and quicker, so may be preferable for routine clinical practice.

• MeSH
• arteriovenózní zkrat MeSH
• Bayesova věta MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• ROC křivka MeSH
• senioři MeSH
• strojové učení * MeSH
• ultrasonografie * metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

• MeSH
• buněčné jádro patologie   MeSH
• folikulární adenokarcinom * patologie   epidemiologie   diagnóza   MeSH
• lékařská praxe - způsoby provádění statistika a číselné údaje   MeSH
• lidé MeSH
• nádory štítné žlázy * epidemiologie   patologie   diagnóza   MeSH
• papilární karcinom štítné žlázy epidemiologie   patologie   diagnóza   MeSH
• papilární karcinom patologie   epidemiologie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH
• Oceánie MeSH
• Severní Amerika MeSH

Many biological agents are epidemic or pandemic in nature (Ebola 2013, Spanish influenza 1918, Russian influenza 1989, SARS-CoV-2 2019). Recognising the onset of the spread of epidemics and pandemics remains a major challenge even in the 21st century despite the technologies and scientific knowledge at our disposal, as is the successful management of such situations. The reason concerns the existence of biological diversity and the laws that govern it, which are very difficult to predict and which are virtually uncontrollable. It is gradually becoming apparent that the current spread of SARS-CoV-2 that causes COVID-19 (9 million deaths since the beginning of the pandemic according to WHO) is characterised by very different characteristics (e.g. the exposure, transmission and spread of the viral infectious agent) in different populations and risk groups.Social services workers in the Czech Republic have been on the frontline for the duration of the pandemic and have been required to work in a high-risk infectious environment. This has led to the need for changes in their established working practices and approaches. Considerable creativity had to be employed particularly in the first year of the pandemic due to the scarcity of information on the new viral agent, the availability of which increased only slowly as the scientific community studied and analysed the various factors involved. Globally, the scientific community released its experimental data as soon as it became available; however, unfortunately, due to the nature of biomedical research, the release of the outputs failed to match the time requirements for their necessity in practice.Based on qualitative and quantitative research, the following text provides an analysis of the specific measures and the related difficulties, and the struggle to find solutions, that providers of selected types of social services faced during the spread of the COVID-19 pandemic.The survey results revealed that the issues in question had a common thread across the various types of social services, as well as a number of common features and challenges. The analysis of the results showed a noticeable shift between the initial period, which was characterised by the rapid onset of the spread of the pandemic, and the situation after 18 months of life under pandemic conditions, which was characterised by the lower incidence of problems and difficulties. One of the major outcomes of the study concerns the identification of the need for social service providers to be provided with a unified, clear and centrally managed process that is able to provide individualised methodological support. The results are based on a study conducted as part of "The Changes in Selected Social Services for People with Disabilities during the State of Emergency Instigated by a Viral Disease" project.

• MeSH
• COVID-19 * prevence a kontrola   MeSH
• lidé MeSH
• přístup k informacím MeSH
• průzkumy a dotazníky MeSH
• sociální práce organizace a řízení   MeSH
• sociální pracovníci * statistika a číselné údaje   MeSH
• statistika jako téma MeSH
• zjišťování skupinových postojů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), slowly expanding lesions were shown to be associated with worse disability and prognosis. Their timely detection from cross-sectional data at early disease stages could be clinically relevant to inform treatment planning. Here, we propose to use multiparametric, quantitative MRI to allow a better cross-sectional characterization of lesions with different longitudinal phenotypes. METHODS: We analysed T1 and T2 relaxometry maps from a longitudinal cohort of MS patients. Lesions were classified as enlarging, shrinking, new or stable based on their longitudinal volumetric change using a newly developed automated technique. Voxelwise deviations were computed as z-scores by comparing individual patient data to T1, T2 and T2/T1 normative values from healthy subjects. We studied the distribution of microstructural properties inside lesions and within perilesional tissue. RESULTS AND CONCLUSIONS: Stable lesions exhibited the highest T1 and T2 z-scores in lesion tissue, while the lowest values were observed for new lesions. Shrinking lesions presented the highest T1 z-scores in the first perilesional ring while enlarging lesions showed the highest T2 z-scores in the same region. Finally, a classification model was trained to predict the longitudinal lesion type based on microstructural metrics and feature importance was assessed. Z-scores estimated in lesion and perilesional tissue from T1, T2 and T2/T1 quantitative maps carry discriminative and complementary information to classify longitudinal lesion phenotypes, hence suggesting that multiparametric MRI approaches are essential for a better understanding of the pathophysiological mechanisms underlying disease activity in MS lesions.

• MeSH
• dospělí MeSH
• fenotyp * MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• multiparametrická magnetická rezonance MeSH
• progrese nemoci MeSH
• průřezové studie MeSH
• roztroušená skleróza * diagnostické zobrazování   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH