Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.
- MeSH
- ankylózující spondylitida krev diagnóza imunologie MeSH
- axiální spondyloartritida krev diagnóza MeSH
- biologické markery * krev MeSH
- C-reaktivní protein analýza metabolismus MeSH
- HLA-B27 antigen genetika imunologie MeSH
- idiopatické střevní záněty * krev imunologie diagnóza komplikace MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: The spread of tau pathology closely correlates with the disease course and cognitive decline in Alzheimer's disease (AD). Tau-targeting immunotherapies are being developed to stop the spread of tau pathology and thus halt disease progression. In this post hoc analysis of the ADAMANT clinical trial, we examined the performance of AADvac1, an active immunotherapy targeting the microtubule-binding region (MTBR) of tau, in a subgroup of participants with elevated plasma p-tau217, indicating AD-related neuropathological changes. METHODS: ADAMANT was a 24-month, randomized, placebo-controlled, parallel-group, double-blinded, multicenter, phase 2 clinical trial in subjects with mild AD. The trial participants were randomized 3:2 to receive six doses of AADvac1 or placebo at 4-week intervals, followed by five booster doses at 14-week intervals. The primary outcome was safety. The secondary outcomes were the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer's Disease Cooperative Study - Activities of Daily Living score for Mild Cognitive Impairment 18-item version (ADCS-ADL-MCI-18), and immunogenicity. Volumetric MRI, plasma neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were exploratory outcomes. The inclusion criterion for this post-hoc analysis was a baseline plasma p-tau217 level above the cutoff for AD. RESULTS: Among 196 ADAMANT participants, 137 were positive for plasma p-tau217 (mean age 71.4 years, 59% women). AADvac1 was safe and well tolerated in this subgroup. AADvac1 reduced the rate of accumulation of log-plasma NfL by 56% and that of GFAP by 73%. The treatment differences in the CDR-SB and ADCS-ADL-MCI-18 scores favored AADvac1 but were not statistically significant. AADvac1 had no effect on whole-brain volume but nonsignificantly reduced the loss of brain cortical tissue in several regions. Importantly, the impact on the study outcomes was more pronounced in participants with higher anti-tau antibody levels. CONCLUSIONS: These results suggest that AADvac1 tau immunotherapy can reduce plasma biomarkers of neurodegeneration and neuroinflammation. These findings and possible observations on brain atrophy and cognition are hypothesis-generating and warrant further evaluation in a larger clinical trial. TRIAL REGISTRATION: EudraCT 2015-000630-30 (primary) and NCT02579252.
- MeSH
- aktivní imunoterapie metody MeSH
- Alzheimerova nemoc * krev terapie imunologie MeSH
- biologické markery krev MeSH
- dvojitá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- proteiny tau * krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- testy pro posouzení mentálních funkcí a demence MeSH
- výsledek terapie 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
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Acute cellular rejection (ACR) frequently occurs following lung transplantation (LuTx) and represents a risk factor for the development of chronic lung allograft dysfunction (CLAD) as well as long-term survival. The histopathological diagnosis of ACR carries a burden of interobserver variability. The widespread utilization and cost-effectiveness of immunohistochemistry (IHC) was proven beneficial in diagnosing rejection in human kidney transplantations and LuTx rat models. However, its potential for ACR detection in patients remains unexplored. We analyzed surface markers (CD3, CD4, CD8, CD20, CD68, CD47, PD-1, PD-L1, and CD31/PECAM-1) on lung tissue cryobiopsy samples collected within 6 months post-LuTx from 60 LuTx recipients, 48 of whom were diagnosed with ACR. Additionally, serum samples from 51 patients were analyzed using a multiplex bead-based Luminex assay. The cytokines and markers included PD-L1, IL2, TNFα, IFNγ, and Granzyme B. We observed a significant increase in PD-L1 tissue expression within the rejection group, suggesting a concerted effort to suppress immune responses, especially those mediated by T-cells. Furthermore, we noted significant differences in PECAM-1 levels between ACR/non-ACR. Additionally, peripheral blood C-reactive-protein levels tended to be higher in the ACR group, while Luminex serum analyses did not reveal any significant differences between groups. In conclusion, our findings suggest the potential value of PECAM-1 and PD-L1 markers in diagnosing ACR.
- MeSH
- akutní nemoc MeSH
- antigeny CD274 * metabolismus krev MeSH
- antigeny CD31 * metabolismus MeSH
- biologické markery * krev metabolismus MeSH
- dospělí MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- plíce patologie MeSH
- rejekce štěpu * diagnóza krev MeSH
- senioři MeSH
- transplantace plic * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Age-related macular degeneration (AMD) is a progressive chronic disease causing visual impairment or central vision loss in the elderly. We hypothesized that successful rheopheresis would be associated with positive changes in soluble endoglin (sENG), PSCK9, alpha-2-macroglobulin (A2M), and hs-CRP levels. 31 elderly patients with the dry form of AMD, treated with rheopheresis with a follow-up period of at least 5 years and an average age of 68 ± 4 years, were evaluated. Each treated patient received a series of 8 procedures in 10 weeks and, after the 2-year period, another 2 procedures within 1 week. Then, the patients were followed up every 6 months and divided into the successfully treated and therapeutic failure group according to best-corrected visual acuity (BCVA), size of the drusen area, and the drusenoid pigment epithelium detachment (DPED). Based on the ophthalmological assessment, rheopheresis treatment was successful in 73% of AMD patients. The therapy was associated with a significant decrease in total cholesterol, LDL-C, HDL-C, apoprotein B, lipoprotein (a) levels, and rheologically important parameters, irrespective of the therapy's success or failure. The success of rheopheresis therapy was exclusively related to a significant decrease in sENG and A2M levels. Over the long term, rheopheresis prevented the decline of BCVA, reduced the DPED and area of macular drusen, and improved the preservation of an intact photoreceptor ellipsoid zone in most patients. Moreover, we showed for the first time that sENG and A2M could be potentially sensitive biomarkers of successful rheopheresis procedure, irrespective of lipid parameters changes.
- MeSH
- biologické markery * krev MeSH
- endoglin * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- makulární degenerace * terapie krev MeSH
- senioři MeSH
- výsledek terapie MeSH
- zraková ostrost MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Hypoalbuminemia, a biomarker of malnutrition, has been associated with adverse surgical outcomes;, however, its impact on breast reduction surgery is not yet well-documented. METHODS: We queried the American college of surgeons national surgical quality improvement program database to identify patients who underwent breast reduction surgery between 2008 and 2022. Patients were grouped by preoperative normal albumin levels (≥3.5 g/dL) and hypoalbuminemia (<3.5 g/dL). Preoperative, intraoperative, and 30-day postoperative outcomes, including complications and readmissions, were compared using the univariate tests and multivariable logistic regression. RESULTS: We included a total of 7277 cases, among whom 96% (n = 6964) had normal albumin values and 4% (n = 298) had hypoalbuminemia (n = 298). Patients with hypoalbuminemia showed a significantly higher body mass index (37.1 ± 8.1 vs. 33.3 ± 6.3 kg/m2, p < 0.001) and were more likely to be Black or African American (49.0 vs. 27.8%, p < 0.001). Comorbidities such as diabetes (14.7 vs. 7.4%, p < 0.001), chronic obstructive pulmonary disease (4.0 vs. 1.0%, p < 0.001), and hypertension (35.2 vs. 26.3%, p = 0.002) were significantly more prevalent in the hypoalbuminemia group. Hypoalbuminemia was associated with a significantly increased risk of complications (13.8 vs. 6.1%, p < 0.001), with higher rates of superficial incisional infections (7.0 vs. 2.6%, p = 0.001) and unplanned readmissions (3.4 vs. 1.4%, p = 0.05). Multivariable analysis confirmed hypoalbuminemia as an independent predictor of postoperative complications (OR 1.96, p = 0.001), medical complications (OR 2.62, p = 0.02), and surgical complications (OR 1.91, p = 0.02). CONCLUSION: Hypoalbuminemia significantly raises the risk of 30-day postoperative complications in breast reduction surgery. Preoperative nutritional assessment and optimization are crucial in improving surgical outcomes, particularly in patients with high body mass index and comorbidities.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- hypoalbuminemie * komplikace krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mamoplastika * škodlivé účinky metody MeSH
- pooperační komplikace * epidemiologie etiologie krev MeSH
- předoperační období MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- znovupřijetí pacienta statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. METHODS: Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. α-Smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. RESULTS: By week 14, cGMP increased by 94 (78)% with riociguat and 10 (39)% with placebo (P < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (P = 0.004 and P = 0.008, respectively). There were no differences in skin collagen markers between the two groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies was associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). CONCLUSION: Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02283762.
- MeSH
- biologické markery * krev MeSH
- biopsie MeSH
- difuzní sklerodermie * farmakoterapie patologie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- fibróza farmakoterapie MeSH
- guanosinmonofosfát cyklický krev metabolismus MeSH
- kůže * patologie účinky léků metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- pyrazoly * terapeutické užití MeSH
- pyrimidiny * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- randomizované kontrolované studie MeSH
This study aimed to evaluate the ability of selected microRNAs as biomarkers of atrial fibrillation (AF) in ischemic stroke patients in comparison with other established biochemical biomarkers. A prospective case-control study of consecutive ischemic stroke patients with AF admitted to a comprehensive stroke center was conducted. The control group consisted of patients with ischemic stroke with no AF detected on prolonged (at least 3 weeks) Holter ECG monitoring. As potential biomarkers of AF, we analyzed the plasma levels of microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) and 13 biochemical biomarkers at admission. The predictive accuracy of biomarkers was assessed by calculating the area under the receiver operating characteristic curve. The data of 117 patients were analyzed (61 with AF, 56 with no AF, 46% men, median age 73 years, median National Institutes of Health Stroke Scale 6). Biochemical biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and total triglycerides) were significantly associated with AF. NT-proBNP had the best diagnostic performance for AF with area under the receiver operating characteristic curve 0.92 (95%, CI 0.86-0.98); a cutoff value of >528 ng/L had a sensitivity of 79% and a specificity of 97%. None of the other biomarkers, including microRNAs, was associated with AF. Conventional biochemical biomarkers (NT-proBNP, high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and triglycerides), but not microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) were significantly associated with AF in our ischemic stroke cohort.
- MeSH
- biologické markery * krev MeSH
- C-reaktivní protein analýza MeSH
- fibrilace síní * krev diagnóza genetika MeSH
- ischemická cévní mozková příhoda * krev diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- natriuretický peptid typu B krev MeSH
- peptidové fragmenty krev MeSH
- prospektivní studie MeSH
- ROC křivka MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol 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
- pozorovací studie MeSH
Kontext: Poškození myokardu po nekardiálním chirurgickém výkonu (myocardial injury after non-cardiac surgery, MINS) představuje závažný problém přímo související s mortalitou do 30 dnů po výkonu. V diagnostice poškození myokardu se přednostně používají hodnoty vysoce senzitivního srdečního troponinu (high-sensitivity cardiac troponin, hs troponin), protože se v současnosti jedná o nejcitlivější a nejspecifičtější srdeční biomarker vhodný pro zjišťování MINS. Cílem této studie je analyzovat vztah mezi změnami v hodnotách hs troponinu a riziky spojenými s chirurgickým výkonem u pacientů podstupujících nekardiální chirurgické výkony, které by ukazovaly na poškození myokardu. Metoda: Naše studie je analytickou observační průřezovou studií, do níž byli zařazováni všichni pacienti pod-tupující nekardiální chirurgický výkon ve fakultní nemocnici Airlangga University Hospital. Krevní vzorky byly odebírány metodou náhodného vzorku (consecutive sampling) a hodnoty hs troponinu se stanovovaly před operací a 24 hodin po ní. Míra operačního rizika se hodnotila pomocí kritérií doporučených postupů ESAIC-ESC 2022. Statistická analýza se prováděla s použitím Spearmanova korelačního koeficientu. Výsledky: Do studie bylo zařazeno 75 pacientů, 39 mužů a 36 žen, ve věku s mediánem 54 let. Výsledky prokázaly statisticky významnou korelaci mezi hodnotami hs troponinu a mírou operačního rizika, a to jak předoperačními hodnotami, tak i pooperačními a jejich změnami. Medián hodnoty (mezikvartilové rozpětí) hs troponinu při nízkém operačním riziku před operací vs. po operaci činil 1,2 ng/l (0,0), resp. 1,2 ng/l (0,0), s mediánem rozdílu 0,0 ng/l (0,0); p < 0,001. Medián hodnoty hs troponinu při středně vysokém operačním riziku před operací vs. po operaci byl 1,2 ng/l (0,0) vs. 1,2 ng/l (0,0), s mediánem rozdílu 0,0 ng/l (1,6); p < 0,001. Medián hodnoty hs troponinu při vysokém operačním riziku před operací vs. po operaci byl 1,7 ng/l (18,8) vs. 11,9 ng/l (27,6); medián rozdílu činil 5,3 ng/l (11,4); p < 0,001. Závěr: Byla nalezena statisticky významná korelace mezi změnami hodnot hs troponinu a mírou operačního rizika a přítomností komplikací.
Background: Myocardial injury after non-cardiac surgery (MINS) is an important issue, directly related to the mortality rate within 30 days after surgery. High sensitivity cardiac troponin (HS troponin) is the preferred biomarker for diagnosing myocardial damage because it is the most sensitive and specific heart biomarker currently available, making it suitable for detecting MINS. The aim of this study is to analyse the relationship between changes in HS troponin levels and surgery-related risks in non-cardiac surgery patients as a marker of myocardial injury. Method: This study is an analytical observational cross sectional study that included all patients who underwent non-cardiac surgery in the Airlangga University Hospital. Samples were taken using the consecutive sampling method. HS troponin values were measured before surgery and 24 hours after surgery. The level of surgical risk was assessed based on the criteria from ESAIC-ESC 2022. Statistical analysis used Spear- man's correlation.
- MeSH
- anestezie škodlivé účinky MeSH
- biologické markery krev MeSH
- chirurgie operační * škodlivé účinky MeSH
- dospělí MeSH
- kardiomyopatie diagnóza etiologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- průřezové studie MeSH
- riziko MeSH
- senioři MeSH
- statistika jako téma MeSH
- troponin * krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- pozorovací studie MeSH
Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.
- MeSH
- biologické markery krev MeSH
- chronická bolest krev diagnóza etiologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neuralgie * krev diagnóza etiologie MeSH
- neuronové sítě (počítačové) * MeSH
- poranění míchy * komplikace krev MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice * metody MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Environmental noise exposure is associated with adiposity. However, less is known about the individual vulnerability to environmental noise in abnormal adiposity development, particularly in relation to mental health. This study investigated the association between environmental noise exposure and four adiposity biomarkers and tested the moderation effect of depressive symptoms. METHODS: A cross-sectional population-based sample of 2031 participants aged 25-64 years (54.70% women) was drawn from the Kardiovize study in 2013. Global combined (road, railway, and airport) Lden (day-evening-night) noise exposures were obtained from the geographical prediction modelling for the 2nd report of Strategic noise mapping in the Czech Republic (2012). Four adiposity biomarkers (BMI, body fat percentage, waist circumference, and visceral fat area) were assessed. Depressive symptoms were measured by PHQ-9. Linear regression was used to estimate the separate effects of quartiles of noise exposure and depressive symptoms on adiposity biomarkers and to examine the interaction between noise exposure and depressive symptoms. RESULTS: The average noise exposure was 53.79 dB, ranging from 42.50 dB to 66.97 dB. All biomarkers were significantly elevated in the highest noise exposure quartile (>56 dB), compared to the lowest quartile (<51 dB) (p < 0.05). The association between noise and adiposity biomarkers was modified by presence of depressive symptoms; the increase in all adiposity biomarkers in the highest quartile of noise was significantly larger among subjects with moderate to severe depressive symptoms (p < 0.005). CONCLUSION: The study confirmed the association between environmental noise exposure and several adiposity measures. The association was stronger in the presence of depressive symptoms.
- MeSH
- adipozita * MeSH
- biologické markery * krev MeSH
- deprese * epidemiologie MeSH
- dospělí MeSH
- hluk škodlivé účinky MeSH
- index tělesné hmotnosti MeSH
- lidé středního věku MeSH
- lidé MeSH
- obvod pasu MeSH
- průřezové studie MeSH
- vystavení vlivu životního prostředí MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH