Diseases (Basel, Switzerland)最新文献

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Precision medicine, which relies on genomic, multi-omic, phenotypic, and environmental data, has the potential to transform healthcare from population-focused heuristics to individualized prevention, diagnosis, and treatment. Moreover, recent advances in sequencing, molecular profiles, wearable sensors, and machine learning have created opportunities for rapid translational innovation: rapid genomic diagnosis in neonatal and paediatric rare diseases, targeted oncology, pharmacogenomic-based prescribing strategies, and individual sport performance. Nevertheless, the vast majority of innovations remain in centers of specialism or pilot programs, rather than routinely or equitably integrated into clinical or athletic practice. This narrative review synthesizes translational evidence across the life course-in pregnancy, paediatrics, adult medicine, geriatrics, and sportomics-to find reproducible clinical and performance examples which enable precision-based alternative approaches to management, outcome, or preparation; and to reshape those examples into pragmatic, scalable priorities which minimize inequity, and maximize benefit. We undertook a structured narrative synthesis of peer-reviewed literature, trials, clinician translation programs, implementation studies, and sportomics reports, prioritizing examples that demonstrate utility, reproducibility, and impact. Important findings suggest that multi-omics and rapid sequencing improve diagnostic yield and time to diagnosis. Molecular profiling and circulating tumor DNA help realize adaptive treatment selection. Integrated genomics, metabolomics, wearable physiology, and AI analytics facilitate individualized training, injury-risk stratification, and recovery optimization. But systematic value is limited by insufficient representative validation, dataset bias, poor interoperability, regulatory uncertainty, workforce preparedness, and inequities of access. Converting a promise into population- and performance-level value requires coordinated action across four fronts: representative validation; interoperable, privacy-preserving infrastructures; clinician- and coach-centered implementation; and templates for scalable, cost-sensitive deployment.

Background: Accurate prediction of survival in septic patients remains a major challenge in intensive care medicine. Established severity scores such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) are widely used to estimate prognosis, while biochemical markers such as serum lactate may provide complementary information. However, the prognostic interplay between these scores, lactate dynamics, vasopressor requirement, and infection focus has not been fully elucidated in septic populations.

Methods: We conducted a retrospective observational study of 146 adult patients with sepsis admitted to the intensive care unit (ICU) of the Hospital Clínico Universitario de Valladolid (HCUV), Spain, between 2022 and 2024. Demographic data, APACHE II and SOFA scores at admission, lactate levels at admission and 24 h, albumin, and procalcitonin were recorded. Vasopressor use (categorized by intensity) and infection focus (urinary vs. non-urinary) were documented. The primary outcome was ICU mortality. Correlation analyses (Pearson or Spearman as appropriate) were performed separately for urinary and non-urinary subgroups. Multivariable logistic regression models were constructed using APACHE II, SOFA, log-transformed lactate at 24 h, vasopressor use, and urinary focus as predictors. Model performance was assessed using Nagelkerke R², area under the ROC curve (AUC), and classification accuracy.

Results: ICU mortality was 23.3%. APACHE II (OR 1.092; p = 0.004) and SOFA (OR 1.185; p = 0.023) were independent predictors of ICU mortality, while log-transformed lactate at 24 h showed a positive trend (OR 1.920; p = 0.066). The addition of urinary focus (protective effect, OR 0.19; p = 0.035) and vasopressor requirement (OR 2.20; p = 0.04) modestly improved model discrimination (Nagelkerke R² = 0.395). ROC analyses showed AUCs of 0.800 for APACHE + SOFA + log-lactate, 0.824 for the vasopressor model, and 0.833 for the urinary focus model. The best-performing models achieved >85% overall accuracy, with specificity consistently above 95%.

Conclusions: In septic ICU patients, APACHE II and SOFA scores remain independent predictors of ICU mortality, and lactate at 24 h adds prognostic value-particularly in non-urinary infections. Vasopressor requirement and infection focus modestly improved model discrimination, underscoring their clinical relevance. These findings suggest that integrating severity scores with selected metabolic and clinical variables may modestly refine survival prediction in septic patients.

Background/objectives: Published prevalences of depression are mainly based on measurements of depressive symptoms, whereas data on clinical depressions are lacking. Our aim was to map the prevalence of ICD-10 diagnoses of depression made by physicians in routine healthcare, during the last year of life in non-cancer conditions and to study associations with clinical variables.

Methods: A registry study on all persons in ordinary accommodation, dying in 2015-2023 in non-cancer conditions.

Results: Of 62,228 persons dying from non-cancer conditions, 4391 (7.1%) were formally diagnosed with depression during the last year in life. Depression was significantly more common in women than in men, 8.0% vs. 6.3% (p < 0.001); adjusted odds ratio (aOR) 1.46 (95%CI 1.37-1.55). Prevalence of depression was highest in persons 18-44 years (18.3%) and lowest in persons >85 years old (5.7%) (p < 0.001); aOR 4.12 (95%CI 3.66-4.63). It was also more common in persons living in more affluent areas, aOR 1.19 (95%CI 1.10-1.29). The condition was most frequent in persons with Parkinson's disease (9.4%) and COPD (8.2%). Depression was associated with more emergency room visits, 89.5% vs. 81.3% (p < 0.001), and visits in psychiatric services in the last year in life, 41.4% vs. 8.8% (p < 0.001). Depression was less prevalent in persons admitted to palliative care (p = 0.007).

Conclusions: The highest frequencies were found in women, younger persons, and those living in affluent areas, but also in certain diagnoses such as Parkinson's disease and COPD. Clinical depression in the last year of life is associated with more emergency room visits and utilization of psychiatric services.

Cancer is one of the biggest health burdens for women in the Middle East and North Africa (MENA), with the incidence of breast, cervical and colorectal cancer on the rise. Although preventive measures such as the HPV vaccination and population-based screening are available, access to them remains very unequal. Women in rural, low-income and refugee communities face additional barriers, cultural stigmatisation, low health literacy, gender norms and fragile health systems, leading to delayed diagnoses and poorer outcomes. This review summarises the results of 724 peer-reviewed publications to assess the current situation of cancer screening in MENA and Mediterranean countries. The studies were classified into four dimensions: cancer type (breast, cervical, colorectal), behavioural constructs (awareness, uptake, education), vulnerability factors (e.g., migrants, refugees, low-literacy groups), and geography (indigenous MENA populations versus diaspora and Mediterranean immigrant communities). The results show large inequalities in access and participation due to fragmented policies, socio-cultural resistance and infrastructure gaps. Nevertheless, promising approaches are emerging: community-led outreach, mobile screening programmes, AI-assisted triage and culturally appropriate digital health interventions. Comparisons between the local and diaspora populations make it clear that systemic and cultural barriers persist even in well-equipped facilities. Closing the screening gap requires a culturally sensitive, digitally enabled and policy aligned approach. Key priorities include engaging religious and community leaders, promoting men's engagement in women's health and securing sustainable funding. With coordinated action across all sectors, MENA countries can build inclusive screening programmes that reach vulnerable women and reduce preventable cancer mortality.

Introduction: Cardiomyopathies (DCM, HCM, and ACM) and primary arrhythmogenic disorders (BrS, LQTS, and CPVT) represent the most common causes of sudden cardiac death (SCD) in young individuals. Systematic genome-wide single-nucleotide polymorphism (SNP) analyses and genome-wide association studies (GWASs) have enabled the identification of numerous genetic variants associated with cardiovascular diseases. Body: Genetic testing for cardiomyopathies and inherited channelopathies primarily involves panel testing of genes with definitive and strong evidence of disease association; genes supported by moderate evidence may also be considered. Cardiomyocytes express a variety of proteins implicated in the pathogenesis of genetic cardiomyopathies, including sarcomeric, cytoskeletal, desmosomal, and nuclear envelope proteins. Inherited cardiac channelopathies result from mutations in genes encoding cellular components that influence calcium ion availability or affect membrane ion channels, including sodium, potassium, and calcium channels. Common variants associated with SCD are found in genes encoding cardiac ion channels (e.g., SCN5A, KCNQ1, and KCNH2), calmodulin (CALM2), sarcomeric proteins (MYH7, MYBPC3, TTN, and TNNI3), and desmosomal proteins (RyR2 and DES).

Conclusions: This review demonstrates that specific genetic variants are significantly associated with an increased risk of SCD. The evidence underscores the importance of genetic screening and early intervention in individuals with a family history of SCD or other risk factors for inherited cardiac disorders predisposing to SCD. Future research should focus on gene-specific management strategies for familial cardiomyopathies and inherited channelopathies, with the goal of improving targeted genetic therapies and reducing the burden of sudden cardiac death.

Background/Objectives: Cardiovascular diseases are the leading cause of death worldwide. The preventive efforts to reduce the burden are crucial. Primary causes of cardiovascular diseases include lipid disorders. The variety of available medications influences cardiovascular risk and allows for improvement. However, discontinuation or infrequent initiation of lipid-lowering therapies remains a problem. This study aimed to investigate predictors of lipid-lowering therapy escalation. Methods: 431 patients with known concentrations of Lipoprotein (a) (Lp (a)) acquired as part of routine cardiovascular risk assessment from the HELPE-R registry, hospitalised in the University Clinical Hospital in Białystok were included in this study. Escalation of treatment was defined as the initiation of any form of lowering therapy or an increase in the potency or dose of statins. The analysis of the influence of various factors on the decision about escalation was performed. Results: The median age was 69.00 years. The escalation of therapy occurred in 48.49% of patients. Not reaching the LDL-C goal was the strongest predictor of escalation (OR: 9.177). The other factors increasing the probability of escalation included acute coronary syndrome (OR: 3.913), prediabetes (OR: 2.372), chronic coronary syndrome (OR: 2.217), dyslipidemia (OR: 2.354), hypertension (OR: 1.734), carotid artery stenosis (OR: 1.625), and obesity (OR: 1.543). There was no effect of past MI and stroke on the escalation of lipid profile. Lp (a) did not affect the escalation. Conclusions: The decision about escalation of lipid-lowering therapy is mainly influenced by classical risk factors and established atherosclerotic disease. Lp (a) did not affect the escalation, despite growing interest among medical practitioners.

Background/Objectives: Many heart failure (HF) patients exhibit a suboptimal response to cardiac resynchronization therapy (CRT). This study investigated whether sacubitril/valsartan, a drug known to beneficially impact cardiac remodeling, could improve outcomes for patients undergoing CRT implantation. Methods: In this single-center, observational study, 90 HF patients (left ventricular ejection fraction [LVEF] ≤ 35%) receiving a CRT-defibrillator were stratified into a sacubitril/valsartan group (n = 39) and a control group (n = 51). The primary endpoint was a CRT response at 12 months, defined as improvement in New York Heart Association (NYHA) class, left ventricular reverse remodeling (≥15% reduction in left ventricular end-systolic volume [LVESV] or ≥5% improvement in LVEF), and freedom from HF hospitalization. Results: The sacubitril/valsartan group had a significantly higher CRT response rate (87.2% vs. 64.7%, p = 0.016). They also showed greater improvement in the 6 min walk test (p = 0.013), NYHA class (p = 0.017), reduction in LVESV (p = 0.025), and QRS duration (p = 0.005). Multivariable analysis confirmed sacubitril/valsartan as an independent predictor of CRT response (OR = 4.43; 95% CI: 1.33-14.71; p = 0.015). Conclusions: In this study of HF patients receiving CRT, sacubitril/valsartan was independently associated with superior reverse remodeling, enhanced electrical resynchronization, and a higher rate of CRT response. These findings suggest a potential synergistic role for sacubitril/valsartan in optimizing post-CRT outcomes; however, as this was an observational study, they should be considered hypothesis-generating and require validation in larger, randomized controlled trials.

Background: Mucopolysaccharidosis type IIIC (MPS IIIC) is a rare lysosomal storage disorder caused by pathogenic variants in the HGSNAT gene. Data from large patient cohorts remain scarce, particularly in Latin America.

Methods: We retrospectively analyzed clinical, biochemical, and genetic data from patients diagnosed with MPS IIIC through the MPS Brazil Network. Diagnosis was based on reduced activity of acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), elevated urinary glycosaminoglycans (uGAGs), and/or molecular genetics tests.

Results: A total of 101 patients were confirmed with MPS IIIC, representing one of the largest cohorts worldwide. Females accounted for 60% of cases. The mean age at symptom onset was 5.4 ± 3.9 years, while the mean age at diagnosis was 11.7 ± 6.9 years, reflecting a 6-year diagnostic delay. Most patients initially presented with developmental delay (82%) and facial dysmorphism (80%), whereas behavioral manifestations were less frequently identified (25%), suggesting a milder phenotype than previously reported. Genetic information was available for 28% of patients, showing recurrent alleles (c.372-2A>G, c.252dupT) and several novel mutations, which expand the mutational spectrum of the disease. Genotype-phenotype similarities with Portuguese, Italian, and Chinese cases suggest shared ancestry contributions. Regional differences included earlier diagnoses in the North of Brazil and high consanguinity rates in the Northeast region.

Conclusions: This study describes the largest Brazilian cohort of MPS IIIC, documenting novel variants and regional heterogeneity. Findings highlight diagnostic delays, ancestry influences, and the urgent need for disease-modifying therapies.

Purpose: Previous data showed an increased risk of developing urinary incontinence in breast cancer patients. However, there is a lack of studies including both pre and postmenopausal women. The aim of this study was to analyze the incidence of subsequent urinary incontinence in breast cancer patients and variables associated with an increased urinary incontinence.

Methods: This study utilized IQVIA Disease Analyzer database to examine the five-year cumulative incidence of urinary incontinence among 68,066 women diagnosed with breast cancer in gynecological practices in Germany between January 2005 and December 2021 by using Kaplan-Meier curves, stratified by age group. Multivariable Cox regression models were conducted to assess the association between age, co-diagnoses, and endocrine therapy (tamoxifen, aromatase inhibitors) and incident urinary incontinence.

Results: Within five years of the start of follow-up, 5.8% of women were diagnosed with urinary incontinence. Age (HR = 1.36; 95% CI = 1.21-1.54 for age 51-60; HR = 2.06; 95% CI = 1.84-2.31 for age group 61-70 and HR = 2.71; 95% CI = 2.42-3.04 for age group >70 as compared to age group ≤50), depression (HR = 1.41; 95% CI: 1.25-1.59) and menopausal and other perimenopausal disorders (HR = 1.21; 95% CI: 1.10-1.27) were associated with an increased urinary incontinence risk. The association was negative and statistically significant for aromatase inhibitor therapy (HR = 0.71; 95% CI: 0.66-0.78) as compared to women without endocrine therapy, whereas tamoxifen therapy was not associated with decreased or increased urinary incontinence risk.

Conclusions: In conclusion, this study reports an 5.8% incidence of urinary incontinence within five years after breast cancer diagnosis. Age-related differences and co-diagnoses should be taken into account.