PURPOSE: There is lack of evidence regarding the indication for re-transurethral resection of bladder tumor (reTURBT) for Ta high grade (HG) non-muscle invasive bladder cancer (NMIBC). This study aims to evaluate the oncological outcomes of patients with TaHG NMIBC to determine the benefit from performing reTURBT. METHODS: We relied on a multicenter cohort of 317 TaHG NMIBC from 12 centers who underwent TURBT and a subsequent complete Bacillus Calmette-Guérin induction from 2009 to 2021. Kaplan Meier analyses estimated recurrence free survival (RFS) and progression free survival (PFS) according to reTURBT. Sub-analyses evaluated PFS in patients with multiple risk factors indicating necessity for reTURBT according to international guidelines (multifocality, size > 3 cm, recurrent cancer, carcinoma in situ, lymph vascular invasion, histological variant, incomplete and absence of muscle layer at index TURBT). Multivariable cox-regression analysis predicted recurrence and progression. RESULTS: Of the 317 patients, 123 (39%) underwent reTURBT, while 194 (61%) did not. Residual disease was detected in 46% of cases, with a 3.2% upstaging rate. Median follow-up was 30 months. The 3-year RFS was higher in patients who underwent reTURBT (79% vs. 58%, p < 0.001), but no significant difference was observed in PFS. ReTURBT reduced the risk of recurrence [multivariable hazard ratio: 0.45, 95% Confidence interval (CI) 0.29-0.71]. Among patients who did not undergo reTURBT, those with ≥ 2 risk factors had lower 3-year PFS (73% vs. 92%, p < 0.001) than those with 0-1 risk factor, whereas no difference in 3-year PFS was observed in patients who underwent reTURBT regardless of the number of risk factors (85% vs. 87%, p = 0.8). CONCLUSION: ReTURBT demonstrated efficacy in reducing recurrence among patients with TaHG NMIBC, yet its impact on progression remained uncertain. Our study underscores the importance of adhering to current international guidelines, particularly for patients with multiple risk factors indicating necessity for reTURBT.
- MeSH
- cystektomie * metody MeSH
- invazivní růst nádoru * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru epidemiologie MeSH
- nádory močového měchýře * chirurgie patologie MeSH
- reoperace MeSH
- retrospektivní studie MeSH
- senioři MeSH
- stupeň nádoru MeSH
- transuretrální resekce močového měchýře MeSH
- uretra MeSH
- výsledek terapie MeSH
- Check Tag
- 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 aims to review the existing knowledge on the cost-effectiveness and item costs related to the diagnosis and treatment of gastroesophageal reflux disease (GERD) patients at different stages. METHODS: The study adhered to the PRISMA guidelines. The systematic search involved several steps: finding and identifying relevant articles, filtering them according to the set criteria, and examining the final number of selected articles to obtain the primary information. The number of articles published between 2013 and September 2024 in the Web of Science and PubMed databases was considered. The CHEERS checklist was used for the risk of bias assessment. Ultimately, 36 studies were included. RESULTS: Regarding the cost-effectiveness of GERD treatment, Proton pump inhibitors (PPIs) appeared to be the dominant solution for non-refractory patients. However, this might change with the adoption of the novel drug vonoprazan, which is more effective and cheaper. With advancements in emerging technologies, new diagnostic and screening approaches such as Endosheath, Cytosponge, and combined multichannel intraluminal impedance and pH monitoring catheters should be considered, with potential implications for optimal GERD management strategies. DISCUSSION: The new diagnostic methods are reliable, safe, and more comfortable than standard procedures. PPIs are commonly used as the first line of treatment for GERD. Surgery, such as magnetic sphincter augmentation or laparoscopic fundoplication, is only recommended for patients with treatment-resistant GERD or severe symptoms. OTHER: Advances in emerging technologies for diagnostics and screening may lead to a shift in the entire GERD treatment model, offering less invasive options and potentially improving patients' quality of life.
- MeSH
- analýza nákladů a výnosů * MeSH
- gastroezofageální reflux * diagnóza terapie ekonomika farmakoterapie MeSH
- inhibitory protonové pumpy * terapeutické užití ekonomika MeSH
- lidé MeSH
- osobní újma zaviněná nemocí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Age-related brain changes affect sleep and are reflected in properties of sleep slow-waves, however, the precise mechanisms behind these changes are still not completely understood. Here, we adapt a previously established whole-brain model relating structural connectivity changes to resting state dynamics, and extend it to a slow-wave sleep brain state. In particular, starting from a representative connectome at the beginning of the aging trajectory, we have gradually reduced the inter-hemispheric connections, and simulated sleep-like slow-wave activity. We show that the main empirically observed trends, namely a decrease in duration and increase in variability of the slow waves are captured by the model. Furthermore, comparing the simulated EEG activity to the source signals, we suggest that the empirically observed decrease in amplitude of the slow waves is caused by the decrease in synchrony between brain regions.
- MeSH
- dospělí MeSH
- elektroencefalografie * MeSH
- konektom * MeSH
- lidé středního věku MeSH
- lidé MeSH
- modely neurologické * MeSH
- mozek * fyziologie MeSH
- počítačová simulace MeSH
- senioři MeSH
- spánek pomalých vln * fyziologie MeSH
- stárnutí * fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Functional and molecular alterations in the cerebellum are among the most widely recognised associates of autism spectrum disorders (ASD). As a critical computational hub of the brain, the cerebellum controls and coordinates a range of motor, affective and cognitive processes. Despite well-described circuits and integrative mechanisms, specific changes that underlie cerebellar impairments in ASD remain elusive. Studies in experimental animals have been critical in uncovering molecular pathology and neuro-behavioural correlates, providing a model for investigating complex disease conditions. Herein, we review commonalities and differences of the most extensively characterised genetic lines of ASD with reference to the cerebellum. We revisit structural, functional, and molecular alterations which may contribute to neurobehavioral phenotypes. The cross-model analysis of this study provides an integrated outlook on the role of cerebellar alterations in pathobiology of ASD that may benefit future translational research and development of therapies.
BACKGROUND: The clinical impact of a chronic total occlusion (CTO) in patients with 3-vessel coronary artery disease undergoing fractional flow reserve-guided percutaneous coronary intervention (PCI) with current-generation drug-eluting stents or coronary artery bypass grafting (CABG) is unclear. METHODS: The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) compared fractional flow reserve-guided PCI with CABG in patients with 3-vessel coronary artery disease. The primary end point was major adverse cardiac and cerebrovascular events, a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. In this substudy, the 3-year outcomes were analyzed in patients with or without a CTO. RESULTS: Of the patients randomized to PCI or CABG in the FAME 3 trial, 305 (21%) had a CTO. In the PCI arm, revascularization of the CTO was attempted in 61% with a procedural success rate of 88%. The incidence of major adverse cardiac and cerebrovascular events at 3 years was not significantly different between those with or without a CTO in both the PCI (15.2% versus 20.1%; adjusted hazard ratio, 0.62 [95% CI, 0.38-1.03]; P=0.07) and the CABG (13.0% versus 12.9%; adjusted hazard ratio, 0.96 [95% CI, 0.55-1.66]; P=0.88) arms. In those without a CTO, PCI was associated with a significantly higher risk of major adverse cardiac and cerebrovascular events compared with CABG (adjusted hazard ratio, 1.61 [95% CI, 1.20-2.17]; P<0.01) but not in those with a CTO (adjusted hazard ratio, 1.21 [95% CI, 0.64-2.28]; P=0.56; Pinteraction=0.31). CONCLUSIONS: The presence of a CTO did not significantly impact the treatment effect of PCI versus CABG at 3 years in patients with 3-vessel coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02100722.
- MeSH
- časové faktory MeSH
- chronická nemoc MeSH
- frakční průtoková rezerva myokardu * MeSH
- koronární angiografie * MeSH
- koronární angioplastika * škodlivé účinky mortalita MeSH
- koronární bypass * škodlivé účinky mortalita MeSH
- koronární okluze * diagnostické zobrazování mortalita terapie patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci koronárních tepen terapie mortalita diagnostické zobrazování patofyziologie MeSH
- prediktivní hodnota testů MeSH
- rizikové faktory MeSH
- senioři MeSH
- stenty uvolňující léky * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
CONTEXT: Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies. OBJECTIVE: To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients. EVIDENCE ACQUISITION: We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators. EVIDENCE SYNTHESIS: We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively. CONCLUSIONS: MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain. PATIENT SUMMARY: Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.
- MeSH
- antagonisté androgenů škodlivé účinky MeSH
- doba přežití bez progrese choroby MeSH
- hormony MeSH
- lidé MeSH
- nádory prostaty * farmakoterapie MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
- MeSH
- elektrická stimulace MeSH
- fekální inkontinence * terapie MeSH
- inkontinence moči * terapie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
