Cancer is one of the leading causes of global morbidity and mortality and is characterized by its high heterogeneity, genomic instability and adaptive plasticity. Applying Darwin's theory of evolution, the concept of tumor evolution has improved our understanding of the biological behavior of advanced cancer, while technological limitations have long left how to dynamically characterize the evolutionary process unsolved. In recent years, the development of high-throughput sequencing, single-cell and spatial omics, lineage tracing, computational modeling, and noninvasive biopsy technology has helped explain tumor heterogeneity and track the evolutionary trajectory of tumors, which has attracted widespread attention in tumor evolution. Here, we discuss the models and drivers of tumor evolution, focusing on how cancer cells adapt and evolve under multidimensional selective pressure, including the intracellular, extracellular, and exogenous levels. We further summarize key signaling pathways and molecular mechanisms involved in genomic instability, epigenetic regulation, metabolic reprogramming, tumor microenvironment remodeling, immune escape and therapy-induced selection. In addition, emerging therapeutic strategies guided by tumor evolution are also discussed, emphasizing that the identification of key genetic and epigenetic targets, together with dynamic monitoring of clonal changes, is crucial for overcoming treatment resistance and improving patient outcomes. By systematically summarizing the signaling pathways and molecular mechanisms underlying tumor evolution, this review aims to provide new targets and conceptual frameworks for promoting precision treatment strategies in oncology in the future.

In the present case report, the authors describe the deaths of two individuals-an 85-year-old female and her 56-year-old son - both discovered within a shared household, exhibiting advanced postmortem changes. The fatalities occurred in a confined apartment environment. The decedents had been residing under conditions of extreme environmental neglect, characterized by prolonged accumulation of domestic waste and an almost complete absence of interaction with the external community. Postmortem examinations revealed morphological indicators consistent with hypothermia, including pale postmortem lividity, frostbite lesions, and Visnevsky's spots within the gastric mucosa. The terminal causes of death in both cases were determined to be combined cardiovascular and respiratory failure secondary to hypothermia. Relevant comorbidities were identified: in the female, predominantly chronic cardiac and hepatic pathology; in the male, marked malnutrition. In both individuals, ethanol was detected in postmortem blood specimens at concentrations consistent with endogenous production during the late stages of decomposition. In both cases, different degrees of development of hypothermia-related Visnevsky spots were observed, which the authors explain by different reserve capacities of the organism.

The ratio of serum sodium to log(D-dimer) (log-SDR) in different types of chronic heart failure (CHF) is not well established.

A total of 1,221 hospitalized CHF patients from the First Affiliated Hospital of Kunming Medical University between January 2017 and October 2021 were retrospectively analyzed. Patients were categorized into log-SDR-L group (log-SDR < 47.90) and log-SDR-H group (log-SDR ≥ 47.90).Prognostic assessments included Kaplan-Meier survival analysis, Cox survival analyses and time-dependent Receiver operating characteristic (ROC) curves analysis to evaluate predictive performance.

We collected data from 1008 patients with CHF. Kaplan-Meier survival analysis revealed that patients with high log-SDR levels had better overall survival (OS). After multivariate adjustment Cox proportional hazards analysis, the level of log-SDR was still independently related to mortality, regardless of CHF subtype.

log-SDR is an important predictor of all-cause mortality in patients with HF, especially female HFrEF plus HFmrEF(HR:0.927, 95%CI:0.898-0.958, p < 0.001). Lower log-SDR levels are associated with an increased risk of all-cause mortality, irrespective of the HF subtype.

Individuals diagnosed with psychotic disorders have reduced life expectancy, primarily attributed to cardiovascular diseases exacerbated by lifestyle habits and antipsychotic side effects. Poor diet quality, marked by low fruit and vegetable consumption and high discretionary food intake are also at play. Limited information exists on factors influencing healthy dietary habits in this population. This systematic review aims to analyze qualitative and quantitative data, from the past 20 years, on obstacles and facilitators to healthy dietary habits among individuals with psychotic disorders. PsycINFO, PubMed and Google scholar searches with these inclusion criteria were conducted: (a) peer-reviewed articles, (b) participants are adults, (c) at least 30% or more of the sample had a psychotic disorder, and (d) focus on obstacles, facilitators or interventions related to healthy dietary habits. Among 21 identified articles, 14 addressed obstacles 11 discussed facilitators and 12 proposed interventions. This review identified seven key obstacles (cost and accessibility, taste of healthy food, emotional role of food, social environment, cognitive challenges, symptoms, and medication) and four facilitators (social support, health-related motivation, improved self-perception and interventions). Notably, some factors, such as social support and neighborhood environment, emerged as both obstacles and facilitators depending on the context. Access to effective interventions, including educational resources, such as cooking and planning skills, and more research on group therapy and peer-based programs are discussed.

Acute ischemic and hemorrhagic stroke are among the leading causes of mortality and long-term disability worldwide. In addition to the results of randomized clinical trials, registry data reflecting real-world clinical practice play a key role in evaluating the quality of care. The STROKE platform of the Translational Neuroscience National Laboratory provides a comprehensive overview of the patient population treated at a Hungarian comprehensive stroke center. Our objective was to characterize the STROKE platform and summarize the findings of studies based on its data, to synthesize the main clinical and methodological conclusions, and to present its implications for quality improvement in Hungarian stroke care. The platform is based on standardized data collection of patients admitted to the Department of Neurology or Neurosurgery, University of Pécs within 24 hours due to acute ischemic stroke, transient ischemic attack, or hemorrhagic stroke. Demographic, clinical, imaging, laboratory, therapeutic, and 90-day outcome data were recorded. Outcomes were analyzed using multivariable linear and logistic regression models, propensity score matching, and comprehensive machine learning methods. Based on the platform, 77.0% of admitted patients had ischemic stroke, 16.9% transient ischemic attack, and 6.1% hemorrhagic stroke; the mean age was 72.0 ± 12.5 years. Among patients with ischemic stroke, 62.4% received recanalization therapy. The strongest independent predictors of 90-day functional outcome were neurological status at admission, premorbid functional status, extent of early ischemia, and age. The Stroke-SCORE, based on three parameters (age, premorbid status and neurological deficit), demonstrated strong predictive performance for 90-day outcome (area under the curve = 0.86). In patients undergoing reperfusion therapy, door-to-needle time <60 minutes and door-to-groin time <120 minutes were significantly associated with more favorable outcomes. After multivariable adjustment, neither anticoagulant nor antiplatelet therapy proved to be an independent adverse prognostic factor. The STROKE platform confirms that functional outcome is primarily determined by stroke severity, premorbid status, age, extent of ischemia, and timely, well-organized reperfusion care. Real-world data analyzed with advanced statistical methods substantially contribute to clinical decision-making, the reassessment of contraindications, and quality improvement in Hungarian stroke care. Orv Hetil. 2026; 167(29): 1131-1141.

Echocardiography is a foundational imaging modality for assessing cardiac structure and function, with a long history of technological advancement. As artificial intelligence (AI) becomes increasingly embedded across healthcare, its potential to enhance the echocardiography workflow, from image acquisition and analysis to reporting and risk stratification, has expanded rapidly. Research activity in this field has grown substantially, yet clinical adoption remains variable and often limited by practical, technical, and governance challenges. In response, the British Society of Echocardiography has developed this position statement to provide a structured, consensus‑driven evaluation of the opportunities, limitations, and requirements for the safe, equitable, and effective integration of AI into echocardiography services. Although centred on the UK context, the principles outlined may be relevant to other healthcare systems with similar models of echocardiography delivery.

Fluctuations in thyroid function among euthyroid individuals have been linked to cardiovascular disease (CVD). We investigated whether central thyroid hormone sensitivity correlates with CVD risk, CVD-related death, and overall mortality in subjects with normal thyroid function, particularly examining how age modifies these associations.

We analyzed data from 6,374 euthyroid adults enrolled in NHANES 2007-2012. Central thyroid hormone sensitivity was quantified using three indices: the thyroid feedback quantile-based index (TFQI), the thyrotropin-thyroxine resistance index (TT4RI) and the TSH index (TSHI). The Framingham Risk Score (FRS) estimated each participant's 10-year probability of developing CVD. CVD mortality and all-cause mortality were ascertained by linkage to the National Death Index through December 31, 2015. Associations were evaluated using logistic regression (10-year CVD risk) and Cox proportional hazards models (mortality), adjusted for sex and race, with analyses stratified by age (< 40 and ≥ 40 years).

Of the 6,374 participants (mean age 48.24 ± 17.59 years; 52.0% male), 18.5% had a 10-year CVD risk > 10%; during follow-up. In sex- and race-adjusted models, all three indices were positively associated with an elevated 10-year CVD risk (> 10%): TFQI (OR 1.40, 95% CI 1.15-1.71), TSHI (OR 1.27, 95% CI 1.11-1.45), and TT4RI (OR 1.01, 95% CI 1.01-1.02). Each index was also significantly associated with higher CVD mortality and all-cause mortality, with TFQI showing the strongest associations (CVD mortality: HR 3.30, 95% CI 2.24-4.85; all-cause mortality: HR 2.19, 95% CI 1.83-2.62). These associations remained significant in participants aged ≥ 40 years (p < 0.001) but not in those aged < 40 years.

Impaired central thyroid hormone sensitivity shows association with elevated CVD risk, CVD mortality, and all-cause mortality in euthyroid individuals aged 40 years and older.

This study aims to present the clinical and genetic findings of two siblings carrying a homozygous c.470_471del (p.Leu157ArgfsTer4) frameshift mutation in the METTL23 gene, and to compare their phenotypes with previously reported cases.

Two female siblings from a consanguineous family were clinically assessed. Developmental history, dysmorphic features, neurological examination, brain MRI, and EEG findings were systematically reviewed. Genetic analysis was performed using exome sequencing (ES), and the mutation was confirmed by Sanger sequencing.

Both patients exhibited severe intellectual disability, marked delay in speech and self-care, epileptic seizures, and facial dysmorphism (depressed nasal bridge, thin upper lip, high hairline, prognathism, prominent mandibular angle), along with mitral valve prolapse. One patient had nummular eczematous skin lesions. Brain MRI findings were normal. The identified mutation had previously only been reported in compound heterozygous form; this study presents the first known homozygous case.

These cases represent one of the most severe phenotypic presentations of METTL23-related intellectual disability reported to date. The co-occurrence of profound intellectual impairment, epilepsy, systemic involvement (mitral valve prolapse), and dermatologic findings (nummular eczema) suggests that the homozygous form of this frameshift mutation may be associated with a more severe clinical expression. Furthermore, this is the first report of the c.470_471del (p.Leu157ArgfsTer4) variant in a homozygous state, providing novel insights into genotype-phenotype correlations. Our findings significantly broaden the known clinical spectrum of METTL23-associated disorders.

Functional tricuspid regurgitation (FTR) is increasingly prevalent in aging populations with heart failure (HF) and has been associated with adverse outcomes. However, the clinical characteristics and prognosis of patients with isolated severe FTR remain poorly defined. We retrospectively reviewed 108,513 consecutive transthoracic echocardiographic examinations performed between June 2013 and March 2025. Isolated severe FTR was defined as severe FTR without significant left-sided valvular disease and preserved left ventricular ejection fraction (LVEF ≥ 50%). The primary endpoint was all-cause mortality, and the secondary endpoint was cardiovascular death or HF hospitalization. Seventy-four patients met the criteria for isolated severe FTR. Patients were predominantly elderly (mean age: 80.9 ± 5.9 years), 54.0% were New York Heart Association functional class III or IV, 70.2% had HF stage C or D, and chronic kidney disease was present in 86.4% of patients. During a median follow-up of 3.1 years, 13 patients (17%) died, and 31 patients (41%) experienced cardiovascular death or HF hospitalization. Therapeutic intervention for TR was performed in only 14 patients (18.9%). Compared with previously reported cohorts of severe mitral regurgitation, aortic stenosis, and aortic regurgitation, patients with isolated severe FTR were older, more symptomatic, and had worse outcomes despite lower intervention rates. In conclusion, in real-world practice, isolated severe FTR predominantly affects elderly patients with advanced HF and multiple comorbidities and is associated with poor outcomes despite preserved LVEF. Relative to other severe valvular heart diseases, isolated severe FTR appears to represent an underrecognized and undertreated high-risk condition.

The clinical course of acute myocarditis varies widely, making accurate prognostication difficult. Nutritional assessment aids risk stratification in various cardiovascular diseases; however, its role in myocarditis remains unclear. This study examined the association between Geriatric Nutritional Risk Index (GNRI)-defined nutritional risk, and prognosis in acute myocarditis. We analyzed admission data on patients with acute myocarditis hospitalized via emergency medical services from the multicenter Tokyo CCU Network Database between January 2017 and December 2022. Nutritional risk was assessed using the GNRI (≥ 98 normal nutrition; 92 to < 98 low; 82 to < 92 moderate; ≤82 severe). The primary outcome was in-hospital death, and secondary outcomes included hospital length of stay (LOS) and cardiovascular care unit LOS. Multivariable Cox regression assessed the association between GNRI-defined nutritional risk and outcomes, adjusting for patient characteristics. Among 402 patients, the median age was 43 years [27-66], and 24.9% presented with shock. GNRI categories were as follows: normal nutrition 41.5%, low 20.6%, moderate 22.9%, and severe 14.9%. Compared with the normal-nutrition group, the severe-risk group had a higher hazard of in-hospital death (adjusted hazard ratio (aHR) = 12.2; 95% CI 2.64-56; P = 0.0025). Each one-point decrease in GNRI was associated with higher in-hospital mortality after multivariable adjustment (aHR = 1.06; 95% CI 1.03-1.09; P < 0.001). The trend remained similar in models adjusted for inflammation. GNRI-defined nutritional risk was associated with poorer prognosis, and may provide additional prognostic information in patients with acute myocarditis.