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

BACKGROUND: Diagnosing primary or secondary CNS lymphoma (CNSL) is a clinical challenge due to the limitations of standard biopsy and imaging procedures despite established guidelines. Therefore, accurate biomarkers and analytical methods that are convenient for practical routine use are needed to diagnose and manage these aggressive lymphomas effectively. We evaluated the utility of minimally invasive circulating tumor DNA (ctDNA) detection in a prospective real-world scenario, moving this approach closer to clinical practice. METHODS: A total of 164 plasma, cerebrospinal fluid (CSF), and tumor samples from 56 CNSL patients were collected to analyze tumor DNA by the diagnostic next-generation sequencing (NGS) panel LYNX, enabling simultaneous analysis of gene variants, chromosomal aberrations, and antigen receptor rearrangements in targeted regions. RESULTS: The well-known genetic heterogeneity of CNSL was refined with integrative molecular data, showing the most frequent MYD88, PIM1, and KMT2D mutations and a broad spectrum of chromosomal aberrations, reflecting high genomic complexity. The multi-target approach achieved a substantially higher detection rate of CNS infiltration (90%) than tracking a single variant in gene MYD88 (46%). CSF clearly surpasses plasma if applying a routine (non-ultrasensitive) NGS approach and allows for more reliable evidence of CNS involvement than conventional flow cytometry (91% vs. 21%, p < 0.001). Parallel analysis of tumor DNA in both cell-free and cellular DNA from CSF makes the probability of primary or secondary CNS malignancy detection even higher. CONCLUSIONS: Our prospective, tissue-agnostic approach highlights the feasibility of ctDNA sequencing by a commonplace and affordable method, offering higher sensitivity to detect CNS infiltration with lymphoma than standard cell-analyzing techniques. We accentuate the benefit of a multi-target NGS approach and adequate CSF sampling to obtain satisfactory diagnostic yield. Less invasive liquid biopsy testing by comprehensive NGS complements standard procedures in the diagnostics and management of CNSL patients, especially when encountering limitations.

• Publikační typ
• časopisecké články MeSH

Cell communication systems based on polypeptide ligands use transmembrane receptors to transmit signals across the plasma membrane. In their biogenesis, receptors depend on the endoplasmic reticulum (ER)-Golgi system for folding, maturation, transport and localization to the cell surface. ER stress, caused by protein overproduction and misfolding, is a well-known pathology in neurodegeneration, cancer and numerous other diseases. How ER stress affects cell communication via transmembrane receptors is largely unknown. In disease models of multiple myeloma, chronic lymphocytic leukemia and osteogenesis imperfecta, we show that ER stress leads to loss of the mature transmembrane receptors FGFR3, ROR1, FGFR1, LRP6, FZD5 and PTH1R at the cell surface, resulting in impaired downstream signaling. This is caused by downregulation of receptor production and increased intracellular retention of immature receptor forms. Reduction of ER stress by treatment of cells with the chemical chaperone tauroursodeoxycholic acid or by expression of the chaperone protein BiP resulted in restoration of receptor maturation and signaling. We show a previously unappreciated pathological effect of ER stress; impaired cellular communication due to altered receptor processing. Our findings have implications for disease mechanisms related to ER stress and are particularly important when receptor-based pharmacological approaches are used for treatment.

• MeSH
• chaperon endoplazmatického retikula BiP MeSH
• kyselina taurochenodeoxycholová farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• receptory buněčného povrchu * metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• stres endoplazmatického retikula * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Soccer is a dynamic sport that involves high-intensity running, changes of direction, jumping and contact. Therefore, a proper warm-up duration is of great importance to optimize players'performance and minimize the risk of injury. METHODS: This study examined the responses of amateur young 16 players (age = 17.00 ± 0.81 years; height = 177.38 ± 5.50 cm; weight = 64.50 ± 5.45 kg) 25 min (min), 15 min and 8 min warm-up duration in 4 v 4 small-sided games (SSGs) with mini-goal formats. Participants are assessed using the Participant Classification Framework, they are categorized under Tier 2: Trained/Developmental. The SSG interventions were randomly assigned to three training intervention groups. The features of SSG are determined as size; 25 × 32 m, bout; 4 × 4 min, resting; 4 min. Before the SSG, same protocol was applied at different times in all warm-ups. Warm-up protocols consisted of 13 sections. The intervention time in each section decreased parallel to the total 25 min, 15 min and 8 min warm-up times. The rating of perceived exertion (RPE), heart rate (HR) responses, distance covered and technical activities were consistently recorded during all SSG sessions. A one-way repeated-measures ANOVA was used to assess significant differences in performance among the different warm-up duration. RESULTS: After the interventions, HR, total player load (TPL), successful passes (SP), unsuccessful passes (USP), interceptions and lost ball results demonstrated significant difference between the 25-min, 15-min and 8-min warm-up durations (p < 0.05). Total distance, velocity, RPE and enjoyment results showed no significant difference between the 25-min, 15-min and 8-min warm-up duration (p > 0.05). Results indicate that a 15-min warm-up duration provides an optimal balance between physiological and technical preparation, leading to improved HR responses, SP and interceptions compared to the 25-min and 8-min warm-ups. The 25-min warm-up decreased USP and lost ball occurrences compared to the 15-min and 8-min warm-ups. The 8-min warm-up resulted in a lower TPL, indicating reduced physiological demands. CONCLUSIONS: The 15-min warm-up duration emerged as an optimal protocol, offering a time-efficient approach that enhances both technical performance and physiological readiness while avoiding unnecessary fatigue. This finding provides practical implications for coaches and practitioners in designing warm-up routines that maximize match readiness without overexertion.

• Publikační typ
• časopisecké články 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