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

PURPOSE: To compare the ability of Prostate Health Index (PHI) to diagnose csPCa, with that of total PSA, PSA density (PSAD) and the multiparametric magnetic resonance (mpMRI) of the prostate. METHODS: We analysed a group of 395 men planned for a prostate biopsy who underwent a mpMRI of the prostate evaluated using the PIRADS v1 criteria. All patients had their PHI measured before prostate biopsy. In patients with an mpMRI suspicious lesions, an mpMRI/ultrasound software fusion-guided biopsy was performed first, with 12 core systematic biopsy performed in all patients. A ROC analysis was performed for PCa detection for total PSA, PSAD, PIRADS score and PHI; with an AUC curve calculated for all criteria and a combination of PIRADS score and PHI. Subsequent sub-analyses included patients undergoing first and repeat biopsy. RESULTS: The AUC for predicting the presence of csPCa in all patients was 59.5 for total PSA, 69.7 for PHI, 64.9 for PSAD and 62.5 for PIRADS. In biopsy naive patients it was 61.6 for total PSA, 68.9 for PHI, 64.6 for PSAD and 63.1 for PIRADS. In patients with previous negative biopsy the AUC for total PSA, PHI, PSAD and PIRADS was 55.4, 71.2, 64.4 and 69.3, respectively. Adding of PHI to PIRADS increased significantly (p = 0.007) the accuracy for prediction of csPCa. CONCLUSION: Prostate Health Index could serve as a tool in predicting csPCa. When compared to the mpMRI, it shows comparable results. The PHI cannot, however, help us guide prostate biopsies in any way, and its main use may, therefore, be in pre-MRI or pre-biopsy triage.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• multiparametrická magnetická rezonance * MeSH
• nádory prostaty diagnostické zobrazování   patologie   MeSH
• prediktivní hodnota testů MeSH
• retrospektivní studie MeSH
• senioři MeSH
• ultrazvukem navigovaná biopsie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH

Gap junctional intercellular communication (GJIC) is a vital cellular process required for maintenance of tissue homeostasis. In vitro assessment of GJIC represents valuable phenotypic endpoint that could be effectively utilized as an integral component in modern toxicity testing, drug screening or biomedical in vitro research. However, currently available methods for quantifying GJIC with higher-throughputs typically require specialized equipment, proprietary software and/or genetically engineered cell models. To overcome these limitations, we present here an innovative adaptation of traditional, fluorescence microscopy-based scrape loading-dye transfer (SL-DT) assay, which has been optimized to simultaneously evaluate GJIC, cell density and viability. This multiparametric method was demonstrated to be suitable for various multiwell microplate formats, which facilitates an automatized image acquisition. The assay workflow is further assisted by an open source-based software tools for batch image processing, analysis and evaluation of GJIC, cell density and viability. Our results suggest that this approach provides a simple, fast, versatile and cost effective way for in vitro high-throughput assessment of GJIC and other related phenotypic cellular events, which could be included into in vitro screening and assessment of pharmacologically and toxicologically relevant compounds.

• MeSH
• fluorescenční mikroskopie metody   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• mezerový spoj * MeSH
• mezibuněčná komunikace * MeSH
• molekulární zobrazování metody   MeSH
• počet buněk * MeSH
• počítačové zpracování obrazu metody   MeSH
• viabilita buněk * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cíl: Zjištění možností multiparametrického MR zobrazení při hodnocení efektu a predikci odpovědi na neoadjuvantní chemoradioterapii (CRT) u lokálně pokročilého karcinomu rekta (KR). Metodika: Provedli jsme retrospektivní analýzu multiparametrických MR vyšetření a histologických nálezů u 22 nemocných před zahájením a po skončení neoadjuvantní CRT. Kromě standardních nativních a post-kontrastních MR obrazů zahrnoval vyšetřovací protokol i dynamické postkontrastní vyšetření a difuzně vážené obrazy (DWI). Provedli jsme statistickou analýzu našich výsledků. Pro hodnocení predikce léčebné odpovědi byl použit Mannův-Whitneyův U-test pro nezávislé vzorky. Pro srovnání respondérů a non-respodérů před a po CRT Wilcoxonův párový test. Výsledky: Z hodnocení stagingu nádoru pouze nativním MR vyšetřením a nedynamickým postkontrastním vyšetřením je patrná tendence k nadhodnocování rozsahu nádorových hmot po léčbě ve skupině s dobrou odpovědí. Srovnáváme-li vzájemně hodnoty farmakokinetických parametrů (FKP) a apparentního difuzního koeficientu (ADC) u vstupního vyšetření v rámci skupiny respondérů a non-respondérů, nalézáme statisticky významně nižší hodnotu u parametru V u skupiny respondérů (p = 0, 013). Při srovnání výsledků vstupního vyšetření s vyšetřením po léčbě odděleně v rámci skupiny respondérů a non-respondérů je ve skupině respondérů patrná statisticky významná odchylka hodnot u parametrů ADC (p < 0,001), Kttims (p < 0,001), Kp (p = 0,002) a iAUC (p = 0,048). U skupiny non-respondérů je statisticky významná odchylka pouze u parametru V (p = 0,027). Závěr: Z našeho výzkumu je zřejmé, že ač je MR nejsenzitivnější metodou k hodnocení pokročilejších stadií karcinomu rekta, není v současnosti z jejích výsledků možné vstupně jednoznačně odlišit pacienty, kteří budou dobře reagovat na neoadjuvantní léčbu. Zdá se, že na základě porovnání výsledků FKA a hodnot ADC vstupního vyšetření a vyšetření po léčbě lze rozhodnout, že se jedná o pacienta, který dobře zareagoval na léčbu, a je tedy vhodným kandidátem na méně radikální operační výkon či na sledování v protokolu Watch and wait.

Aim: Evaluation of capability of multiparametric MR imaging (MRI) in the prediction and evaluation of response to neoadjuvant chemoradiotherapy in locally advanced rectal carcinoma. Metod: We performed a retrospective analysis of multiparametric MRI examinations on 3T scanner and histological findings in 22 patients before and after neoadjuvant chemoradiotherapy. In addition to the standard noncontrast and postcontrast MRI, the examinations included dynamic contrast-enhanced scans and diffusion-weighted images. Results: The assessment of tumor staging using only noncontrast MRI and nondynamic postcontrast scans has a tendency to overestimate the extent of tumors in the group of neoadjuvant treatment responders. If we compared pharmakokinetic parameters and apparent diffusion coefficient (ADC) values from the baseline MRI within the group of responders and nonresponders, we find significantly lower value for the parameter V in the group of responders (p = 0,013), differencies in all other parameters were nonsignificant. Comparison of the results of the baseline examination with examination after treatment separately in the group of responders and nonresponders, we found statistically significant changes in values ADC (p < 0,001), Kttims (p < 0,001), Kp (p = 0,002) and iAUC (p = 0,048) in the group of responders. In the group of non-responders is a statistically significant difference only in the parameter V (p = 0,027). Conclusion: From our research it is noticeable that although MRI is the most sensitive method for evaluation of the advanced stages of rectal cancer, is impossible to use it for prediction of the therapeutic effect in patients before neoadjuvant chemoradio-therapy It seems, that based of the comparison of results of pharmakokinetic analysis and ADC values from baseline and post-treatment MRI, it is possible to select patients with good response to the treatment, that can be candidates for less radical surgery or application of Watch and Wait protocol.

• Klíčová slova
• difúzně vážené obrazy, farmakokinetická analýza,
• MeSH
• kolorektální chirurgie MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• nádory rekta * diagnóza   chirurgie   terapie   MeSH
• neoadjuvantní terapie * MeSH
• staging nádorů MeSH
• statistika jako téma MeSH
• výzkum MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Background: The annually recorded incidence of primary hepatic carcinomas has significantly increased over the past two decades accounting for over 800 thousand of annual deaths caused by hepatocellular carcinoma (HCC) alone globally. Further, secondary liver malignancies are much more widespread compared to primary hepatic carcinomas: almost all solid malignancies are able to metastasise into the liver. The primary tumours most frequently metastasising to the liver are breast followed by colorectal carcinomas. Given the increased incidence of both primary and metastatic liver cancers, a new, revised approach is needed to advance medical care based on predictive diagnostics, innovative screening programmes, targeted preventive measures, and patient stratification for treatment algorithms tailored to individualised patient profile. Advantages of the approach taken: The current pilot study took advantage of systemic alterations characteristic for liver malignancies, utilising liquid biopsy (blood samples) and specific biomarker patterns detected. Key molecular pathways relevant for pathomechanisms of liver cancers have been considered opening a perspective for both-individualised diagnostics and targeted treatment. Systemic alterations have been analysed prior to the therapy application avoiding molecular biological effects potentially diminishing predictive power of the biomarker-panel proposed. Multi-omics at DNA and protein (both expression and activity) levels has been applied. An established biomarker panel is considered as a powerful tool for individualised patient profiling and improved multi-level diagnostics-both predictive and prognostic ones. Results and conclusions: Biomarker panels have been created for the patient stratification, prediction of a more optimal therapy and prognosis of survival based on the individualised patient profiling. Although there are some limitations of the pilot study performed, the results are encouraging, as it may be possible, through further research along these lines, to find a clinically and cost-effective means of stratifying liver cancer patients for personalised care and therapy. The benefits to the patient and society of accurate treatment stratification cannot be overemphasised.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: To predict worsening heart failure hospitalizations (WHFHs), the HeartInsight multiparametric algorithm calculates a heart failure (HF) Score based on temporal trends of physiologic parameters obtained through automatic daily remote monitoring of implantable cardioverter-defibrillators (ICDs). OBJECTIVE: We studied the association of the baseline HF Score, determined at algorithm activation, with long-term patient outcomes. METHODS: Data from 9 clinical trials were pooled, including 1841 ICD patients with a preimplantation ejection fraction ≤35%, New York Heart Association class II/III, and no long-standing atrial fibrillation. The primary end point was a composite of death or WHFH. RESULTS: After a median follow-up of 631 days (interquartile range, 385-865 days), there were 243 WHFHs in 173 patients (9.4%) and 122 deaths (6.6%), 52 of which (42.6%) were cardiovascular. The primary end point occurred in 265 patients (14.4%). A multivariable time-to-first-event analysis showed that a high baseline HF Score (>23, as determined by a time-dependent receiver operating characteristics curve analysis) was significantly associated with the occurrence of the primary end point (adjusted hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.54-2.71; P < .0001), all-cause death (HR, 2.37; CI, 1.56-3.58; P < .0001), cardiovascular death (HR, 2.19; CI, 1.14-4.22; P = .019), and WHFH (HR, 1.91; CI, 1.35-2.71; P = .0003). In a hierarchical event analysis of all-cause death as the outcome with highest priority and WHFHs as repeated event outcomes, the win ratio was 2.47 (CI, 1.89-3.24; P < .0001). CONCLUSION: Based on a retrospective analysis of clinical trial data with adjudicated events, baseline HF Score derived from device-monitored variables was able to stratify patients at higher long-term risk of death or WHFH.

• MeSH
• algoritmy MeSH
• časové faktory MeSH
• defibrilátory implantabilní * MeSH
• klinické zkoušky jako téma MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• senioři MeSH
• srdeční selhání * terapie   patofyziologie   mortalita   MeSH
• technologie dálkového snímání metody   MeSH
• tepový objem fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Carotid body tumours (CBT), also called carotid body paraganglioma, are highly vascular and histologically portray paraganglion cells. They are typically found at the carotid bifurcation and result in the splaying of the internal and external carotid arteries (ICA and ECA). Recent literature supports the role of chronic hypoxia in the etiology of CBT. This pictorial essay discusses how CBT is an uncommon etiology for common clinical problems such as transient ischemic attacks. It also discusses imaging techniques to precisely map out the tumour for surgical resection using advanced imaging modalities and techniques.

• MeSH
• arteria carotis externa MeSH
• arteria carotis interna MeSH
• arteriae carotides MeSH
• krk MeSH
• lidé MeSH
• tumor karotického glomu * diagnostické zobrazování   chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide. Detecting different biomarkers together on single cells by novel method mass cytometry could contribute to more precise screening. Liquid-based cytology (LBC) cervical samples were collected (N = 53) from women categorized as normal and precancerous lesions. Human papillomavirus was genotyped by polymerase chain reaction, while simultaneous examination of the expression of 29 proteins was done by mass cytometry (CyTOF). Differences in cluster abundances were assessed with Spearman's rank correlation as well as high dimensional data analysis (t-SNE, FlowSOM). Cytokeratin (ITGA6, Ck5, Ck10/13, Ck14, Ck7) expression patterns allowed determining the presence of different cells in the cervical epithelium. FlowSOM analysis enabled to phenotype cervical cells in five different metaclusters and find new markers that could be important in CC screening. The markers Ck18, Ck18, and CD63 (Metacluster 3) showed significantly increasing associated with severity of the precancerous lesions (Spearman rank correlation rho 0.304, p = 0.0271), while CD71, KLF4, LRIG1, E-cadherin, Nanog and p53 (Metacluster 1) decreased with severity of the precancerous lesions (Spearman rank correlation rho -0.401, p = 0.0029). Other metaclusters did not show significant correlation, but metacluster 2 (Ck17, MCM, MMP7, CD29, E-cadherin, Nanog, p53) showed higher abundance in low- and high-grade intraepithelial lesion cases. CyTOF appears feasible and should be considered when examining novel biomarkers on cervical LBC samples. This study enabled us to characterize different cells in the cervical epithelium and find markers and populations that could distinguish precancerous lesions.

• MeSH
• cervix uteri patologie   metabolismus   MeSH
• dospělí MeSH
• dysplazie děložního hrdla diagnóza   patologie   MeSH
• infekce papilomavirem patologie   diagnóza   virologie   MeSH
• Krüppel-like faktor 4 * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery * genetika   metabolismus   MeSH
• nádory děložního čípku * diagnóza   patologie   genetika   MeSH
• prekancerózy * patologie   diagnóza   MeSH
• průtoková cytometrie * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVE: Biparametric magnetic resonance imaging (bpMRI), excluding dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), is a potential replacement for multiparametric MRI (mpMRI) in diagnosing clinically significant prostate cancer (csPCa). An extensive international multireader multicase observer study was conducted to assess the noninferiority of bpMRI to mpMRI in csPCa diagnosis. METHODS: An observer study was conducted with 400 mpMRI examinations from four European centers, excluding examinations with prior prostate treatment or csPCa (Gleason grade [GG] ≥2) findings. Readers assessed bpMRI and mpMRI sequentially, assigning lesion-specific Prostate Imaging Reporting and Data System (PI-RADS) scores (3-5) and a patient-level suspicion score (0-100). The noninferiority of patient-level bpMRI versus mpMRI csPCa diagnosis was evaluated using the area under the receiver operating curve (AUROC) alongside the sensitivity and specificity at PI-RADS ≥3 with a 5% margin. The secondary outcomes included insignificant prostate cancer (GG1) diagnosis, diagnostic evaluations at alternative risk thresholds, decision curve analyses (DCAs), and subgroup analyses considering reader expertise. Histopathology and ≥3 yr of follow-up were used for the reference standard. KEY FINDINGS AND LIMITATIONS: Sixty-two readers (45 centers and 20 countries) participated. The prevalence of csPCa was 33% (133/400); bpMRI and mpMRI showed similar AUROC values of 0.853 (95% confidence interval [CI], 0.819-0.887) and 0.859 (95% CI, 0.826-0.893), respectively, with a noninferior difference of -0.6% (95% CI, -1.2% to 0.1%, p < 0.001). At PI-RADS ≥3, bpMRI and mpMRI had sensitivities of 88.6% (95% CI, 84.8-92.3%) and 89.4% (95% CI, 85.8-93.1%), respectively, with a noninferior difference of -0.9% (95% CI, -1.7% to 0.0%, p < 0.001), and specificities of 58.6% (95% CI, 52.3-63.1%) and 57.7% (95% CI, 52.3-63.1%), respectively, with a noninferior difference of 0.9% (95% CI, 0.0-1.8%, p < 0.001). At alternative risk thresholds, mpMRI increased sensitivity at the expense of reduced specificity. DCA demonstrated the highest net benefit for an mpMRI pathway in cancer-averse scenarios, whereas a bpMRI pathway showed greater benefit for biopsy-averse scenarios. A subgroup analysis indicated limited additional benefit of DCE MRI for nonexperts. Limitations included that biopsies were conducted based on mpMRI imaging, and reading was performed in a sequential order. CONCLUSIONS AND CLINICAL IMPLICATIONS: It has been found that bpMRI is noninferior to mpMRI in csPCa diagnosis at AUROC, along with the sensitivity and specificity at PI-RADS ≥3, showing its value in individuals without prior csPCa findings and prostate treatment. Additional randomized prospective studies are required to investigate the generalizability of outcomes.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• multiparametrická magnetická rezonance * MeSH
• nádory prostaty * diagnostické zobrazování   patologie   MeSH
• odchylka pozorovatele MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: SARS-CoV-2, which causes COVID-19, has killed more than 7 million people worldwide. Understanding the development of postinfectious and postvaccination immune responses is necessary for effective treatment and the introduction of appropriate antipandemic measures. OBJECTIVES: We analysed humoral and cell-mediated anti-SARS-CoV-2 immune responses to spike (S), nucleocapsid (N), membrane (M), and open reading frame (O) proteins in individuals collected up to 1.5 years after COVID-19 onset and evaluated immune memory. METHODS: Peripheral blood mononuclear cells and serum were collected from patients after COVID-19. Sampling was performed in two rounds: 3-6 months after infection and after another year. Most of the patients were vaccinated between samplings. SARS-CoV-2-seronegative donors served as controls. ELISpot assays were used to detect SARS-CoV-2-specific T and B cells using peptide pools (S, NMO) or recombinant proteins (rS, rN), respectively. A CEF peptide pool consisting of selected viral epitopes was applied to assess the antiviral T-cell response. SARS-CoV-2-specific antibodies were detected via ELISA and a surrogate virus neutralisation assay. RESULTS: We confirmed that SARS-CoV-2 infection induces the establishment of long-term memory IgG+ B cells and memory T cells. We also found that vaccination enhanced the levels of anti-S memory B and T cells. Multivariate comparison also revealed the benefit of repeated vaccination. Interestingly, the T-cell response to CEF was lower in patients than in controls. CONCLUSION: This study supports the importance of repeated vaccination for enhancing immunity and suggests a possible long-term perturbation of the overall antiviral immune response caused by SARS-CoV-2 infection.

• MeSH
• B-lymfocyty imunologie   MeSH
• buněčná imunita imunologie   MeSH
• COVID-19 * imunologie   MeSH
• dospělí MeSH
• ELISPOT MeSH
• glykoprotein S, koronavirus imunologie   MeSH
• humorální imunita MeSH
• imunologická paměť MeSH
• leukocyty mononukleární imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protilátky virové * krev   imunologie   MeSH
• SARS-CoV-2 * imunologie   MeSH
• senioři MeSH
• T-lymfocyty imunologie   MeSH
• vakcíny proti COVID-19 imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH