AIMS: Cardiac resynchronization therapy (CRT) is guideline recommended for the treatment of symptomatic heart failure (HF) with reduced left ventricular ejection fraction and prolonged QRS. However, patients with common comorbidities, such as persistent/permanent atrial fibrillation (AF), are often under-represented in clinical trials. METHODS: The Strategic Management to Optimize Response to Cardiac Resynchronization Therapy (SMART) registry (NCT03075215) was a global, multicentre, registry that enrolled de novo CRT implants, or upgrade from pacemaker or implantable cardioverter defibrillator to CRT-defibrillator (CRT-D), using a quadripolar left ventricular lead in real-world clinical practice. The primary endpoint was CRT response between baseline and 12 month follow-up defined as a clinical composite score (CCS) consisting of all-cause mortality, HF-associated hospitalization, New York Heart Association (NYHA) class and quality of life global assessment. RESULTS: The registry enrolled 2035 patients, of which 1558 had completed CCS outcomes at 12 months. The patient cohort was 33.0% female, mean age at enrolment was 67.5 ± 10.4 years and the mean left ventricular ejection fraction was 29.6 ± 7.9%. Notably, there was a high prevalence of mildly symptomatic patients (NYHA class I/II 51.3%), non-left bundle branch block (LBBB) morphology (38.0%), AF (37.2%) and diabetes mellitus (34.7%) at baseline. CCS at 12 months improved in 58.9% (n = 917) of patients; 20.1% (n = 313) of patients stabilized and 21.0% (n = 328) worsened. Several patient characteristics were associated with a lower likelihood of response to CRT including older age, ischaemic aetiology, renal dysfunction, AF, non-LBBB morphology and diabetes. Higher HF hospitalization (P < 0.001) and all-cause mortality (P < 0.001) were observed in patients with AF. These patients also had lower percentages of ventricular pacing than patients in sinus rhythm at baseline and follow-up (P < 0.001, both). A further association between AF and non-LBBB was observed with 81.4% of AF non-LBBB patients experiencing an HF hospitalization compared with 92.5% of non-AF LBBB patients (P < 0.001). Mortality between subgroups was also statistically significant (P = 0.019). CONCLUSIONS: This large, global registry enrolled a CRT-D population with higher incidence of comorbidities that have been historically underrepresented in clinical trials and provides new insight into factors influencing response to CRT. As defined by CCS, 58.9% of patients improved and 20.1% stabilized. Patients with AF had particularly worse clinical outcomes, higher HF hospitalization and mortality rates and lower percentages of ventricular pacing. High incidence of HF hospitalization in patients with AF and non-LBBB in this real-world cohort suggests that ablation may play an important role in increasing future CRT response rates.

• MeSH
• celosvětové zdraví MeSH
• funkce levé komory srdeční * fyziologie   MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• registrace * MeSH
• senioři MeSH
• srdeční resynchronizační terapie * metody   MeSH
• srdeční selhání * terapie   patofyziologie   mortalita   MeSH
• tepový objem * fyziologie   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 AND OBJECTIVE: Bladder cancer (BCa) imposes a substantial economic burden on health care systems and patients. Understanding these financial implications is crucial for effective resource allocation and optimization of treatment cost effectiveness. Here, we aim to systematically review and analyze the financial burden of BCa from the health care and patient perspectives. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant systematic review was conducted, searching PubMed/Medline, Embase, and public sources for studies evaluating the financial impact of BCa, encompassing costs, cost effectiveness, and financial toxicity (FT). KEY FINDINGS AND LIMITATIONS: Non-muscle-invasive BCa (NMIBC) incurs significant costs for surveillance and treatment, with costs exceeding $200 000 after 5 yr for high-risk NMIBC patients progressing after bacillus Calmette-Guerin (BCG) treatment (including inpatient, outpatient, and physician service expenses). Muscle-invasive BCa generates substantial costs from radical cystectomy (RC) and neoadjuvant chemotherapy, averaging $30 000-40 000 from surgical costs of RC, with additional expenses in case of complications. Trimodal therapy has higher costs (1-yr management cost >$200 000) than RC because of higher outpatient, radiology, and medication costs. Metastatic BCa incurs the highest financial burden, with systemic therapy costs ranging from $40 000 to over $100 000 per five-cycle course, increasing further with combination therapies (ie, enfortumab vedotin and pembrolizumab), treatment-related toxicity, and supportive care. FT is particularly prevalent among younger, less educated, and minority populations. CONCLUSIONS AND CLINICAL IMPLICATIONS: BCa treatment, particularly in advanced stages, imposes a substantial economic burden. Innovations in care, while improving oncologic outcomes, necessitate detailed cost-effectiveness assessments. Addressing these economic challenges is essential for optimizing BCa management, targeting patients at a higher risk of FT, and improving patient quality of life.

• MeSH
• analýza nákladů a výnosů MeSH
• cystektomie ekonomika   škodlivé účinky   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory močového měchýře * ekonomika   terapie   patologie   MeSH
• náklady na zdravotní péči * MeSH
• osobní újma zaviněná nemocí * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

PURPOSE OF REVIEW: Men face distinctive health-related challenges as a result of biological, behavioral, and sociocultural factors. In addition, the modern healthcare system does not offer men equal opportunities and options to ensure sex-specific access and delivery to health services. Men's health concerns are, indeed, often not addressed or even forgotten. In this review, we wanted to assess the impact of biology and sociocultural effects on sex-specific life-expectancy. RECENT FINDINGS: Globally, men have a shorter life expectancy than women. With a 5.8 years gender gap in the USA and 5.4 in the EU-27 (both in 2022). Cardiovascular disease, cancer, and accidents continue to represent the primary causes of mortality for both genders with all having disproportional preponderance in men. In recent years, there has been a notable decline in age-adjusted mortality rates related to cancer, while there has been an increase in deaths from accidental and intentional self-harm. Moreover, in the United States, men are more likely than women to develop and die from nonsex-specific cancers. As a result, men's poor health affects productivity, absenteeism, and employment. SUMMARY: The status of men in healthcare is complex. It is rooted in history, culture, and institutions. To address disparities, we need a comprehensive approach that includes policy reforms, sociocultural changes, and a fair and equitable public discourse. Grassroots and top-down strategies are needed to ensure a value-based societal healthcare system acknowledging the unique health needs of men.

• MeSH
• disparity zdravotní péče statistika a číselné údaje   MeSH
• disparity zdravotního stavu MeSH
• dostupnost zdravotnických služeb statistika a číselné údaje   MeSH
• lidé MeSH
• naděje dožití * MeSH
• poskytování zdravotní péče statistika a číselné údaje   MeSH
• rovnost ve zdraví MeSH
• sexuální faktory MeSH
• zdraví mužů * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Spojené státy americké MeSH

OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.

• MeSH
• dítě MeSH
• elektroencefalografie * metody   MeSH
• epilepsie MeSH
• fokální kortikální dysplazie MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• malformace mozkové kůry, skupina I * chirurgie   komplikace   diagnostické zobrazování   MeSH
• malformace mozkové kůry chirurgie   komplikace   diagnostické zobrazování   MeSH
• mladiství MeSH
• pozitronová emisní tomografie MeSH
• předškolní dítě MeSH
• refrakterní epilepsie * chirurgie   diagnostické zobrazování   patofyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The tumor microenvironment (TME) is a complex, highly structured, and dynamic ecosystem that plays a pivotal role in the progression of both primary and metastatic tumors. Precise assessment of the dynamic spatiotemporal features of the TME is crucial for understanding cancer evolution and designing effective therapeutic strategies. Cancer is increasingly recognized as a systemic disease, influenced not only by the TME, but also by a multitude of systemic factors, including whole-body metabolism, gut microbiome, endocrine signaling, and circadian rhythm. In this review, we summarize the intrinsic, extrinsic, and systemic factors contributing to the formation of 'cold' tumors within the framework of the cancer-immunity cycle. Correspondingly, we discuss potential strategies for converting 'cold' tumors into 'hot' ones to enhance therapeutic efficacy.

• MeSH
• cirkadiánní rytmus MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   MeSH
• nádory * patologie   terapie   MeSH
• střevní mikroflóra MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Crude oil contamination has been shown to impair reproduction in aquatic animals through carcinogenic and genotoxic properties. Here, we assessed the endocrine-disrupting function of crude oil on male reproductive system based on testicular histology, sex steroid hormones, and fertility endpoints in adult male goldfish (Carassius auratus), which were exposed to 0.02- to 2-mg/L crude oil for 21 days (Experiment #1) or to 5- to 250-mg/L crude oil for 9 days (Experiment #2). The crude oil contained 0.22-mg/L nickel (Ni), 1.10-mg/L vanadium (V), and 12.87-mg/L polycyclic aromatic hydrocarbons (PAHs). Twenty-four hours after adding crude oil, the sum of PAHs ranged from 0.30 to 2.28 μg/L in the aquaria containing 0.02- and 250-mg/L crude oil, respectively. Water analyses for heavy metals in Experiment #2 showed high concentrations (mg/L) of Ni (0.07-0-09) and V (0.10-0.21). For both experiments, exposure to crude oil did not impact gonadosomatic index; however, testes showed histopathological defects including hyperplasia or hypertrophy of Sertoli cells, depletion of the Leydig cells, necrosis of germ cells, and fibrosis of lobular wall. In Experiment #1, sperm production and motility, testosterone (T), and 17β-estradiol (E2) were not significantly different among treatments. In Experiment #2, the number of spermiating males decreased by ~50% following exposure to 250-mg/L crude oil. Sperm production, motility kinematics, T, and the T/E2 ratio significantly decreased in males exposed to ≥ 50-mg/L crude oil; however, E2 remained unchanged. Results show crude oil-induced imbalance of sex steroid hormones disrupts spermatogenesis resulting in diminished sperm production and motility.

• MeSH
• chemické látky znečišťující vodu * toxicita   MeSH
• endokrinní disruptory * toxicita   MeSH
• karas zlatý * fyziologie   MeSH
• motilita spermií * účinky léků   MeSH
• pohlavní steroidní hormony * metabolismus   krev   MeSH
• ropa * toxicita   MeSH
• rozmnožování účinky léků   MeSH
• spermie * účinky léků   patologie   MeSH
• testis * účinky léků   patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Introduction. Vagal nerve stimulation (VNS) is a therapeutical option for the treatment of drug-resistant epileptic patients. The response to VNS varies from patient to patient and is difficult to predict. The proposed study is based on our previous work, identifying relative mean power in pre-implantation EEG as a reliable marker for VNS efficacy prediction in adult patients. Our study has two main tasks. Firstly, to confirm the utility of relative mean power as a feature correlating with VNS efficacy in children. The second is to validate the applicability of our prediction classifier, Pre-X-Stim, in the pediatric population. Material and Methods. We identified a group of children with drug-resistant epilepsy. We included only children in whom EEG contained photic stimulation (Task 1) or was recorded based on the defined acquisition protocol used for development Pre-X-Stim (Task 2). Relative mean powers were calculated. VNS responders and non-responders were compared based on relative mean powers' values. In the next step, we evaluate the utility of our classifier, Pre-X-Stim, in the children population. Results: We identified 57 children treated with VNS - 17 patients were recruited for the Task 1 and 7 patients for the Task 2. When focusing on relative mean powers in EEG spectra, we observed statistically significant differences in theta range. The Pre-X-Stim algorithm was able to predict VNS efficacy correctly in 6 out of 7 patients (the accuracy 83.3%, the sensitivity 75%, the specificity 100%). Conclusions. Based on our results, it seems that children and adults share a similar pattern of EEG relative mean power changes. These changes can be used for pre-implantation prediction of VNS efficacy.

• MeSH
• dítě MeSH
• elektroencefalografie * metody   MeSH
• epilepsie * terapie   patofyziologie   MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• refrakterní epilepsie * terapie   patofyziologie   MeSH
• skalp MeSH
• vagová stimulace * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Zosuquidar (LY335979) is a widely used experimental P-glycoprotein (P-gp) inhibitor, which is commended as very potent but also as very specific for P-gp. In this in vitro and in silico study, we demonstrated for the first time that zosuquidar also inhibits organic cation transporters (OCT) 1-3, albeit less potently than P-gp. This still has to be kept in mind when zosuquidar is used to inhibit cellular efflux of P-gp substrates that are concurrently transported into the cells by OCTs. To avoid interference in these assays, zosuquidar concentrations should be kept below 1 μM.

• MeSH
• chinoliny * farmakologie   MeSH
• dibenzocyklohepteny MeSH
• HEK293 buňky MeSH
• lidé MeSH
• P-glykoprotein * antagonisté a inhibitory   MeSH
• proteiny přenášející organické kationty * antagonisté a inhibitory   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• tisková chyba MeSH

PURPOSE: To evaluate treatment outcomes and toxicity in patients with stage T1-3N0M0 oral cancer treated with surgery followed by high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Retrospective study of 50 patients with stage T1-T3N0 tongue and floor-of-mouth cancer who underwent tumour excision (+ elective neck dissection) followed by postoperative HDR-BT due to the presence of negative prognostic factors (close or positive resection margins, lymphovascular and/or perineural invasion, deep invasion). The plastic tube technique (dose: 18 x 3 Gy b.i.d.) was used. Survival outcomes, toxicity, and prognostic factors were evaluated. RESULTS: At a median follow-up of 81 months (range, 4-121), actuarial 5-year local control (LC), nodal control (NC) and progression-free survival (PFS) rates were 79%, 69%, and 64%. After salvage treatment (surgery + external beam radiotherapy), LC, NC, and PFS increased to 87%, 77%, and 72.3%, respectively. Five-year overall survival and cancer-specific survival (CSS) rates were 73% and 77%. Treatmentrelated toxicity included two cases of mandibular osteoradionecrosis and five cases of small soft tissue necrosis. T stage was significantly correlated with nodal control (p=0.02) and CSS (p=0.04). Tumour grade correlated with DFS (p=0.01). CONCLUSION: Postoperative HDR-BT 18 x 3 Gy b.i.d. seems to be an effective method in patients with T1-3N0M0 oral cancer with negative prognostic factors after tumour resection.

• MeSH
• brachyterapie * metody   MeSH
• celková dávka radioterapie * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory úst * radioterapie   patologie   chirurgie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH