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
BACKGROUND: To determine differences in the blood innate gene expression signatures of systemic lupus erythematosus (SLE) patients across various organ manifestations and disease activity, with a focus on lupus nephritis (LN) and central nervous system (CNS) involvement. METHODS: Toll-like receptor family (TLR 1-10) mRNA expression was investigated in peripheral blood mononuclear cells from patients with SLE (n = 74) and healthy controls (n = 34). We compared patients with histologically confirmed active LN or neuropsychiatric systemic lupus erythematosus (NPSLE) with patients without these symptoms. The expression of TLR mRNA was determined by RT‒qPCR using a high-throughput SmartChip Real-Time-qPCR system (WaferGen). Multivariate analysis and nonparametric statistics were used for data analysis to assess the associations between TLRs and disease activity and severity. RESULTS: TLR4 (0.044 vs. 0.081, p = 0.012) was upregulated and TLR10 (0.009 vs. 0.006, p = 0.0007) was downregulated in the whole cohort of SLE patients compared to healthy controls. A comparison of the active LN group with participants without kidney involvement revealed increased expression of TLR2 (0.078 vs. 0.03, p = 0.009), and TLR5 (0.035 vs. 0.017, p = 0.03). Moreover, a significant difference was observed in TLR9 expression between inactive LN and the control group (0.014 vs. 0.009, p = 0.01), together with borderline correlation in TLR2 expression (0.04 vs. 0.03, p = 0.06). Receiver operating characteristic (ROC) curve analysis revealed that TLR1 and TLR2 expression were the best potential diagnostic markers for active LN. The NPSLE group showed upregulation of TLR1 (0.088 vs. 0.048, p = 0.01), TLR4 (0.173 vs. 0.066, p = 0.0003) and TLR6 (0.087 vs. 0.036, 0.007). Our correlation analysis supported the close relationships among the expression of individual TLRs in the whole lupus cohort and its subgroups. CONCLUSION: Our study revealed differences in TLR expression between a lupus cohort and healthy controls. Additionally, our analysis provides insight into specific TLR expression in cases with severe organ manifestations, such as LN and NPSLE. The multiple mutual relationships of TLRs demonstrate the activation of innate immunity in SLE and suggest promising targets for future therapies or diagnostics.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nefritida při lupus erythematodes * genetika krev MeSH
- systémový lupus erythematodes krev genetika MeSH
- toll-like receptory * genetika biosyntéza MeSH
- vaskulitida centrálního nervového systému při lupus erythematodes * krev genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Thyroid eye disease (TED) seriously affects patients' quality of life (QoL), even if the disease is stable and nonactive. Data on clinical factors negatively influencing the QoL of patients with TED and long-term outcomes are limited. This study aims to evaluate the lasting impact of TED on QoL, focusing on the effects of previous TED treatments and identifying factors influencing long-term outcomes. METHODS: A retrospective cohort study included 151 patients treated for active, moderate-to-severe and severe TED, with a mean follow-up of 8 years. RESULTS: Higher clinical activity scores at diagnosis correlated with lower QoL scores. Thyroidectomy before immunosuppressive treatment was associated with lower QoL and an increased likelihood of orbital decompression. Any disease progression necessitating second-line treatments also negatively affected QoL. A decrease in thyrotropin receptor antibodies during active treatment and early treatment initiation positively affected visual functioning. Time-dependent regression analysis demonstrated no significant trend in QoL changes over time. CONCLUSION: Our data reveal that disease severity, the timing of interventions and disease progression contribute to less favorable long-term QoL outcomes, extending years beyond active treatment. Early and accurate diagnosis and appropriate treatment can minimize poor long-term QoL in patients with TED.
- MeSH
- dospělí MeSH
- Gravesova oftalmopatie * psychologie terapie MeSH
- kohortové studie MeSH
- kvalita života * MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- progrese nemoci MeSH
- retrospektivní studie MeSH
- senioři MeSH
- tyreoidektomie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Projekt je zaměřený na využití imunocytometrických/obrazových metod k zpřesnění popisu stavu kloubu u pacientů s gonartrózou (KOA). Tito pacienti jsou dnes léčeni řadou metod s různým stupněm klinické účinnosti. Léčebná metoda je zvolena na základě klinického a rentgenového vyšetření, avšak bez detailnější znalosti konkrétní biologické či biochemické situace postiženého kloubu (týkající se např. zánětlivého/homeostatického stavu, stádia, fáze nemoci). To může vysvětlovat variabilitu v dosažených výsledcích. Navrhujeme proto postižený kloub lépe charakterizovat před léčebnou intervencí (za pomoci průtokové cytometrie, expresních profilů buněk/ synoviální tkáně) a rozlišit specifické subtypy gonartrózy. Syntézou získaných laboratorních a klinických dat vytvoříme podklady pro konkrétní fenotypy KOA a navrhneme elektronický rozhodovací algoritmus, který budeme testovat na skupině léčených pacientů s cílem zefektivnit diagnostický a léčebný proces u KOA.; The project focuses on using immunological/imaging/biochemical methods for better description of the knee joint state in patients with knee osteoarthritis (KOA). These patients are treated with a number of conservative methods of varying degrees of clinical effect. Therapy is chosen on the basis of clinical and x-ray examinations but without detailed knowledge of the particular biological/biochemical state of the affected knee (e.g. in terms of inflammatory/homeostatic status, stage, disease phase). This could explain variability in clinical outcomes. We expect that by synthesizing the obtained laboratory and clinical data, we will distinguish particular KOA phenotypes. Moreover, we will propose an electronic decision support tool that will be tested on a group of treated patients in order to optimise the diagnostic and treatment process of KOA.
BACKGROUND: Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency. METHODS: The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants. RESULTS: Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines. CONCLUSIONS: Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.
- MeSH
- adipokiny * krev MeSH
- adiponektin krev nedostatek MeSH
- biologické markery krev MeSH
- dítě MeSH
- DNA vazebné proteiny krev MeSH
- idiopatické střevní záněty krev komplikace MeSH
- lidé MeSH
- mladiství MeSH
- nedostatek vitaminu D * komplikace krev MeSH
- nukleobindiny krev MeSH
- plazmatické proteiny vázající retinol metabolismus analýza MeSH
- proteiny vázající mastné kyseliny krev MeSH
- proteiny vázající vápník krev MeSH
- resistin krev MeSH
- studie případů a kontrol MeSH
- vitamin D * krev analogy a deriváty MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The burden of chronic and societal diseases is affected by many risk factors that can change over time. The minimalisation of disease-associated risk factors may contribute to long-term health. Therefore, new data-driven health management should be used in clinical decision-making in order to minimise future individual risks of disease and adverse health effects. METHODS: We aimed to develop a health trajectories (HT) management methodology based on electronic health records (EHR) and analysing overlapping groups of patients who share a similar risk of developing a particular disease or experiencing specific adverse health effects. Formal concept analysis (FCA) was applied to identify and visualise overlapping patient groups, as well as for decision-making. To demonstrate its capabilities, the theoretical model presented uses genuine data from a local total knee arthroplasty (TKA) register (a total of 1885 patients) and shows the influence of step by step changes in five lifestyle factors (BMI, smoking, activity, sports and long-distance walking) on the risk of early reoperation after TKA. RESULTS: The theoretical model of HT management demonstrates the potential of using EHR data to make data-driven recommendations to support both patients' and physicians' decision-making. The model example developed from the TKA register acts as a clinical decision-making tool, built to show surgeons and patients the likelihood of early reoperation after TKA and how the likelihood changes when factors are modified. The presented data-driven tool suits an individualised approach to health management because it quantifies the impact of various combinations of factors on the early reoperation rate after TKA and shows alternative combinations of factors that may change the reoperation risk. CONCLUSION: This theoretical model introduces future HT management as an understandable way of conceiving patients' futures with a view to positively (or negatively) changing their behaviour. The model's ability to influence beneficial health care decision-making to improve patient outcomes should be proved using various real-world data from EHR datasets.
- MeSH
- individualizovaná medicína * MeSH
- klinické rozhodování MeSH
- lidé MeSH
- reoperace MeSH
- teoretické modely MeSH
- totální endoprotéza kolene * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: A growing body of evidence highlights the persistent activation of the innate immune system and type I interferon (IFN) signature in the pathogenesis of rheumatoid arthritis (RA) and its association with disease activity. Since the recent study revealed heterogeneity in the IFN signature in RA, we investigated for the first time the heterogeneity in innate signature in RA. METHODS: The innate gene expression signature (10 TLRs, 7 IL1/IL1R family members, and CXCL8/IL8) was assessed in peripheral blood mononuclear cells from RA patients (n=67), both with active (DAS28≥3.2, n=32) and inactive disease (DAS28<3.2, n=35), and in healthy control subjects (n=55). RESULTS: Of the 13 deregulated innate genes (TLR2, TLR3, TLR4, TLR5, TLR8, TLR10, IL1B, IL1RN, IL18, IL18R1, IL1RAP, and SIGIRR/IL1R8) associated with RA, TLR10 and IL1RAP are being reported for the first time. Multivariate analysis based on utilising patient similarity networks revealed the existence of four patient's subsets (clusters) based on different TLR8 and IL1RN expression profiles, two in active and two in inactive RA. Moreover, neural network analysis identified two main gene sets describing active RA within an activity-related innate signature (TLR1, TLR2, TLR3, TLR7, TLR8, CXCL8/IL8, IL1RN, IL18R1). When comparing active and inactive RA, upregulated TLR2, TLR4, TLR6, and TLR8 and downregulated TLR10 (P<0.04) expression was associated with the disease activity. CONCLUSIONS: Our study on the comprehensive innate gene profiling together with multivariate analysis revealed a certain heterogeneity in innate signature within RA patients. Whether the heterogeneity of RA elucidated from diversity in innate signatures may impact the disease course and treatment response deserves future investigations.
- MeSH
- interferon typ I * imunologie MeSH
- leukocyty mononukleární MeSH
- lidé MeSH
- multivariační analýza MeSH
- revmatoidní artritida * genetika imunologie metabolismus MeSH
- toll-like receptory * genetika imunologie metabolismus MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The reliable preoperative identification of patients at a high risk of early reoperations (<2 years after primary surgery) after total knee arthroplasty (TKA) could lead to adjustments of the surgical procedure and counseling, thus lowering the percentage of revision surgeries. METHODS: The unselected cohort consisted of 1885 patients (695 men and 1190 women) who underwent TKA implantation between September 2010 and April 2017 at a single tertiary orthopedic center. Multivariate patient similarity networks were applied to identify patient groups at a high risk of early reoperations based on 25 preoperative parameters. RESULTS: Early reoperations (109 cases, 5.8%) were less frequent in women (4.4%; median time to reoperation, 2.0 months) than in men (8.2%; 7.5 months), reaching the highest incidence in younger men (10.9%; <66 years). Of the tested preoperative parameters, the risk of reoperation in men was more likely associated with smoking or obesity (body mass index [BMI] > 30). In women, low physical activity and high BMI were the most likely risk factors for early reoperations. Other factors did not affect the risk of early reoperations, including the primary diagnosis, comorbidities, and surgeon-implanting TKA. CONCLUSION: This study demonstrates the effect of smoking, physical activity, and BMI on the risk of early reoperation after TKA, with the different contribution in men/women. Identification of patient subgroups with a higher risk of early revision after TKA is needed for clinical implementation of precision medicine in orthopedics.
- MeSH
- cvičení MeSH
- index tělesné hmotnosti MeSH
- kouření škodlivé účinky epidemiologie MeSH
- lidé MeSH
- pohlavní dimorfismus MeSH
- reoperace MeSH
- retrospektivní studie MeSH
- totální endoprotéza kolene * škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: A complex karyotype (CK) is considered a poor prognostic marker in chronic lymphocytic leukemia (CLL). METHODS: The study analyzed 644 untreated CLL patients (pts) using conventional/molecular cytogenetics to reveal the presence of a CK and its composition and to assess its predictive value. The mutational status ofTP53 was detected by next generation sequencing. RESULTS: A CK was detected in 79 pts (12.3%). Patients with a CK showed shorter overall survival (OS) compared to those without a CK (77 months vs. 115 months, p < 0.0001). Chromosomes most frequently included in a CK were 13, 11, 17, 8, 2, and 6. The most common aberrations in a CK were translocations, numerical changes and dicentric chromosomes (with no effect on OS). Patients with aberrations ofTP53 and ATM were shown to have adverse prognosis comparable to patients with a CK without these abnormalities. A stronger impact of a CK on OS of female and older CLL patients was observed. CONCLUSIONS: The determining of the presence of a CK is essential in modern clinical CLL practice. According to recent studies, the presence of a CK affects clinical and treatment decision-making.
- MeSH
- abnormální karyotyp * MeSH
- chromozomální aberace * MeSH
- chronická lymfatická leukemie diagnóza genetika mortalita terapie MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie * MeSH
- hybridizace in situ fluorescenční MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- management nemoci MeSH
- mutace MeSH
- nádorové biomarkery MeSH
- následné studie MeSH
- prognóza MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srovnávací genomová hybridizace 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
- práce podpořená grantem MeSH
