Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones.

• MeSH
• autologní transplantace MeSH
• dospělí MeSH
• lenalidomid aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * diagnóza   mortalita   terapie   patologie   MeSH
• prognóza MeSH
• průtoková cytometrie * metody   MeSH
• retrospektivní studie MeSH
• reziduální nádor * diagnóza   MeSH
• senioři MeSH
• staging nádorů MeSH
• transplantace hematopoetických kmenových buněk metody   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
• multicentrická studie MeSH

BACKGROUND: This study examines the perspectives of individuals with coronary heart disease (CHD) on a nurse-led eHealth cardiac rehabilitation (NeCR) program, which included a website, tele-monitoring device, and social media chatroom. METHODS: Using a descriptive qualitative approach, semi-structured interviews were conducted with 18 participants to capture their feedback and experiences with the NeCR program. RESULTS: Participants found the NeCR program valuable in addressing gaps in cardiac rehabilitation services in China, empowering them to make behavioral changes and enhancing their social motivation. However, they also highlighted the need for a more user-friendly website, better symptom management during exercise, and stronger privacy protections in the peer networking chatroom. The study concludes that the NeCR program is feasible in providing accessible rehabilitative services at home post-discharge. Recommendations include improving the self-monitoring platform for ease of use, incorporating immediate symptom management guidance during exercise, and ensuring a secure environment for online peer support. CONCLUSIONS: These findings offer crucial insights for developing patient-centered eHealth cardiac rehabilitation services, emphasizing the importance of user-friendly design, effective symptom management features, and privacy protection in promoting participant engagement with e-platforms. TRIAL REGISTRATION: ChiCTR1800020411 (http://www.chictr.org.cn/showprojen.aspx?proj=33906).

• MeSH
• dospělí MeSH
• kardiovaskulární rehabilitace * metody   MeSH
• koronární nemoc rehabilitace   ošetřování   MeSH
• kvalitativní výzkum * MeSH
• lidé středního věku MeSH
• lidé MeSH
• rozhovory jako téma MeSH
• senioři MeSH
• telemedicína * MeSH
• zpětná vazba MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Čína MeSH

High-grade B-cell lymphomas (HGBCLs) are aggressive blood cancers with a severe disease course, especially when the central nervous system (CNS) is involved. Standard histological examination depends on tissue availability and is currently supplemented with molecular tests, as the status of MYC, BCL2, or BCL6 gene rearrangements is required for proper lymphoma classification. This case report demonstrates the relevance of cerebrospinal fluid (CSF) cell-free DNA testing by integrative next-generation sequencing (NGS) panel. The benefit of this approach resided in tumor genotyping alongside the proof of CNS progression despite MRI negativity, revealing a clonal relationship with the primary tumor lesion. In addition, our strategy allowed us to classify the tumor as DLBCL/HGBL-MYC/BCL2 entity. In clinical practice, such a minimally invasive approach provides a more sensitive tool than standard imaging and cell analyzing techniques, enabling more accurate disease monitoring and relapse prediction in particular cases.

• MeSH
• B-buněčný lymfom genetika   patologie   diagnóza   diagnostické zobrazování   MeSH
• cirkulující nádorová DNA genetika   MeSH
• difúzní velkobuněčný B-lymfom genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   genetika   MeSH
• magnetická rezonanční tomografie * MeSH
• nádorové biomarkery genetika   MeSH
• nádory centrálního nervového systému genetika   patologie   diagnostické zobrazování   MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: Multiple myeloma (MM) represents the second most common hematological malignancy characterized by the infiltration of the bone marrow by plasma cells that produce monoclonal immunoglobulin. While the quality and length of life of MM patients have significantly increased, MM remains a hard-to-treat disease; almost all patients relapse. As MM is highly heterogenous, patients relapse at different times. It is currently not possible to predict when relapse will occur; numerous studies investigating the dysregulation of non-coding RNA molecules in cancer suggest that microRNAs could be good markers of relapse. RESULTS: Using small RNA sequencing, we profiled microRNA expression in peripheral blood in three groups of MM patients who relapsed at different intervals. In total, 24 microRNAs were significantly dysregulated among analyzed subgroups. Independent validation by RT-qPCR confirmed changed levels of miR-598-3p in MM patients with different times to relapse. At the same time, differences in the mass spectra between groups were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry. All results were analyzed by machine learning. CONCLUSION: Mass spectrometry coupled with machine learning shows potential as a reliable, rapid, and cost-effective preliminary screening technique to supplement current diagnostics.

• Publikační typ
• časopisecké články MeSH

Nutritional support is associated with improved clinical outcomes in critically ill patients; however, loss of muscle mass during critical illness leads to weakness, delayed return to work, and increased healthcare consumption. Animal data have suggested that intermittent feeding decreases protein catabolism. This study was aimed at determining whether the mode of enteral nutrition administration might lead to differences in meeting nutritional goals, tolerance, and complications. A prospective, randomized, single-center clinical trial was conducted in four intensive care units in the Czech Republic. Critically ill adult patients with high nutritional risk were randomized to continuous or intermittent enteral nutrition administration through a tolerance-driven protocol. The primary outcome was the time to reach the energetic target. Secondary outcomes included assessment of tolerance (high gastric residual volume, vomitus, and diarrhea), complications (aspiration or ventilator-associated pneumonia), and 28-day mortality. A total of 300 patients were randomized, and 294 were analyzed: 148 in the continuous arm and 146 in the intermittent arm. Regarding the primary outcome, log-rank test indicated that the intermittent group, compared with continuous group, had a statistically significantly shorter time (p = 0.009) and greater diarrhea occurrence (7 (4.7%) vs. 16 (11%), p = 0.049). No statistically significant differences in ventilator-associated pneumonia incidence (18 (12.2%) vs. 18 (12.3%), p = 0.965), 28-day mortality (46 (31.1%) vs. 40 (27.4%), p = 0.488), and other secondary outcomes were observed between groups. Thus, intermittent enteral nutrition was superior to continuous enteral nutrition in terms of time to reach the energetic target with the tolerance-driven administration protocol but was associated with higher diarrhea incidence. No statistically significant differences in the other secondary outcomes were observed.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• enterální výživa * metody   MeSH
• jednotky intenzivní péče * MeSH
• kritický stav * terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nutriční stav MeSH
• prospektivní studie 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
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH

Large-scale next-generation sequencing (NGS) studies revealed extensive genetic heterogeneity, driving a highly variable clinical course of chronic lymphocytic leukaemia (CLL). The evolution of subclonal populations contributes to diverse therapy responses and disease refractoriness. Besides, the dynamics and impact of subpopulations before therapy initiation are not well understood. We examined changes in genomic defects in serial samples of 100 untreated CLL patients, spanning from indolent to aggressive disease. A comprehensive NGS panel LYNX, which provides targeted mutational analysis and genome-wide chromosomal defect assessment, was employed. We observed dynamic changes in the composition and/or proportion of genomic aberrations in most patients (62%). Clonal evolution of gene variants prevailed over the chromosomal alterations. Unsupervised clustering based on aberration dynamics revealed four groups of patients with different clinical behaviour. An adverse cluster was associated with fast progression and early therapy need, characterized by the expansion of TP53 defects, ATM mutations, and 18p- alongside dynamic SF3B1 mutations. Our results show that clonal evolution is active even without therapy pressure and that repeated genetic testing can be clinically relevant during long-term patient monitoring. Moreover, integrative NGS testing contributes to the consolidated evaluation of results and accurate assessment of individual patient prognosis.

• MeSH
• chronická lymfatická leukemie * genetika   farmakoterapie   MeSH
• genomika MeSH
• lidé MeSH
• mutace MeSH
• prognóza MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: Pediatric sarcomas are bone and soft tissue tumors that often exhibit high metastatic potential and refractory stem-like phenotypes, resulting in poor outcomes. Aggressive sarcomas frequently harbor a disrupted p53 pathway. However, whether pediatric sarcoma stemness is associated with abrogated p53 function and might be attenuated via p53 reactivation remains unclear. METHODS: We utilized a unique panel of pediatric sarcoma models and tumor tissue cohorts to investigate the correlation between the expression of stemness-related transcription factors, p53 pathway dysregulations, tumorigenicity in vivo, and clinicopathological features. TP53 mutation status was assessed by next-generation sequencing. Major findings were validated via shRNA-mediated silencing and functional assays. The p53 pathway-targeting drugs were used to explore the effects and selectivity of p53 reactivation against sarcoma cells with stem-like traits. RESULTS: We found that highly tumorigenic stem-like sarcoma cells exhibit dysregulated p53, making them vulnerable to drugs that restore wild-type p53 activity. Immunohistochemistry of mouse xenografts and human tumor tissues revealed that p53 dysregulations, together with enhanced expression of the stemness-related transcription factors SOX2 or KLF4, are crucial features in pediatric osteosarcoma, rhabdomyosarcoma, and Ewing's sarcoma development. p53 dysregulation appears to be an important step for sarcoma cells to acquire a fully stem-like phenotype, and p53-positive pediatric sarcomas exhibit a high frequency of early metastasis. Importantly, reactivating p53 signaling via MDM2/MDMX inhibition selectively induces apoptosis in aggressive, stem-like Ewing's sarcoma cells while sparing healthy fibroblasts. CONCLUSIONS: Our results indicate that restoring canonical p53 activity provides a promising strategy for developing improved therapies for pediatric sarcomas with unfavorable stem-like traits.

• MeSH
• dítě MeSH
• Krüppel-like faktor 4 * MeSH
• lidé MeSH
• mladiství MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky * metabolismus   patologie   MeSH
• nádorový supresorový protein p53 * metabolismus   genetika   MeSH
• předškolní dítě MeSH
• regulace genové exprese u nádorů MeSH
• sarkom * genetika   patologie   metabolismus   MeSH
• signální transdukce MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

MRI is becoming increasingly available and more common. However, it is a long examination, within a limited space, and making strong demands on the patient for proper co-operation. Using survey data collected by prospective questionnaire, this work examines the influence of patient preparation and type of MRI device on patients' subjective perception of the examination. The work analysed 800 patient questionnaires from 7 radiology centres, 12 MRI machines from 3 manufacturers. It was shown that 20% of patients were not informed at all or only insufficiently about the MRI examination by the referring physician, and this had a statistically significant effect on subjective perception as to the length of the examination. In claustrophobic patients, there was no significant difference in the perception of MRI examination between machine types (open vs. closed) or between bore size. This work demonstrated the influence of technical parameters of MRI devices on some other evaluated aspects in terms of patients' perception of MRI examinations (such as noise perception or peripheral nerves irritation) and that the preparation prior to the examination itself plays also an important role. Sufficient explanation from the referring physician, good workplace time management, and sufficient communication with the patient influence the subjective perception of the examination and thus indirectly its diagnostic benefit.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• percepce MeSH
• prospektivní studie MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The CYCS gene is highly evolutionarily conserved, with only a few pathogenic variants that cause thrombocytopenia-4 (THC4). Here, we report a novel CYCS variant NM_018947.6: c.59C>T [NP_061820.1:p.(Thr20Ile)] segregating with thrombocytopenia in three generations of a Czech family. The phenotype of the patients corresponds to THC4 with platelets of normal size and morphology and dominant inheritance. Intriguingly, a gradual decline in platelet counts was observed across generations. CRISPR/Cas9-mediated gene editing was used to introduce the new CYCS gene variant into a megakaryoblast cell line (MEG-01). Subsequently, the adhesion, shape, size, ploidy, viability, mitochondrial respiration, cytochrome c protein (CYCS) expression, cell surface antigen expression and caspase activity were analysed in cells carrying the studied variant. Interestingly, the variant decreases the expression of CYCS while increasing mitochondrial respiration and the expression of CD9 cell surface antigen. Surprisingly, the variant abates caspase activation, contrasting with previously known effects of other CYCS variants. Some reports indicate that caspases may be involved in thrombopoiesis; thus, the observed dysregulation of caspase activity might contribute to thrombocytopenia. The findings significantly enhance our understanding of the molecular mechanisms underlying inherited thrombocytopenia and may have implications for diagnosis, prognosis and future targeted therapies.

• MeSH
• kaspasy * metabolismus   genetika   MeSH
• lidé MeSH
• rodokmen MeSH
• trombocytopenie * genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: To evaluate and compare the diagnostic power of [18F]FLT-PET with ceMRI in patients with brain tumours or other focal lesions. METHODS: 121 patients with suspected brain tumour or those after brain tumour surgery were enroled in this retrospective study (61 females, 60 males, mean age 37.3 years, range 1-80 years). All patients underwent [18F]FLT-PET/MRI with gadolinium contrast agent application. In 118 of these patients, a final diagnosis was made, verified by histopathology or by follow-up. Agreement between ceMRI and [18F]FLT-PET of the whole study group was established. Further, sensitivity and specificity of ceMRI and [18F]FLT-PET were calculated for differentiation of high-grade vs. low-grade tumours, high-grade vs. low-grade tumours together with non-tumour lesions and for differentiation of high-grade tumours from all other verified lesions. RESULTS: [18F]FLT-PET and ceMRI findings were concordant in 119 cases (98%). On closer analysis of a subset of 64 patients with verified gliomas, the sensitivity and specificity of both PET and ceMRI were identical (90% and 84%, respectively) for differentiating low-grade from high-grade tumours, if the contrast enhancement and [18F]FLT uptake were considered as hallmarks of high-grade tumour. For differentiation of high-grade tumours from low-grade tumours and lesions of nontumorous aetiology (e.g., inflammatory lesions or post-therapeutic changes) in a subgroup of 93 patients by visual evaluation, the sensitivity of both PET and ceMRI was 90%, whereas the specificity of PET was slightly higher (61%) compared to ceMRI (57%). By receiver operating characteristic analysis, the sensitivity and specificity were 82% and 74%, respectively, when the threshold of SUVmax in the tumour was set to 0.9 g/ml. CONCLUSION: We demonstrated a generally very high correlation of [18F]FLT accumulation with contrast enhancement visible on ceMRI and a comparable diagnostic yield in both modalities for differentiating high-grade tumours from low-grade tumours and lesions of other aetiology.

• MeSH
• dideoxynukleosidy MeSH
• dítě MeSH
• dospělí MeSH
• gadolinium * farmakokinetika   MeSH
• kojenec MeSH
• kontrastní látky MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• multimodální zobrazování metody   MeSH
• nádory mozku * diagnostické zobrazování   patologie   metabolismus   MeSH
• pozitronová emisní tomografie * metody   MeSH
• předškolní dítě MeSH
• radiofarmaka MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH