Search Results (3,492)

Diagnostic failure in invasive fungal infections (IFIs) remains a relevant and underrecognized cause of mortality, morbidity, delayed therapy, unnecessary antifungal exposure, and pharmacological selective pressure. Although major advances have been achieved in biomarkers, rapid diagnostic tests, molecular methods, imaging studies, and microbiological identification, timely diagnosis continues to be influenced by the interaction among host factors, pathogen-related factors, diagnostic tools, and healthcare system–related factors. This narrative review analyzes diagnostic failure in IFIs as a dynamic process that includes delayed, incorrect, and incomplete diagnosis. It examines its determinants and consequences in high-risk populations—critically ill patients, patients with hematologic diseases or hematopoietic stem cell transplant recipients, and neonates—as well as in invasive candidiasis, aspergillosis, mucormycosis, cryptococcosis, endemic mycoses, and infections caused by rare or emerging fungi. It also reviews how delayed sampling, decontextualized interpretation of biomarkers, incomplete microbiological identification, absence of antifungal susceptibility testing when clinically relevant, and fragmentation between clinical and laboratory teams contribute to adverse outcomes. Finally, it proposes a diagnostic-centered antifungal stewardship framework (AFSP-Dx) based on syndromic bundles, population-specific diagnostic algorithms, 48–72 h reassessment, and auditable indicators intended to support earlier recognition, more precise therapeutic decisions, and rational antifungal use. Full article

Background/Objectives: Ovarian cancer (OC) is a leading cause of cancer-related mortality in women, largely driven by late-stage diagnosis. Five-year survival is just 30% for advanced-stage (III-IV) disease but exceeds 90% for early-stage disease, underscoring the critical need for effective early detection tools. Current standard-of-care biomarkers show limited sensitivity for early-stage OC and lack specificity in symptomatic populations. Most biomarker studies in OC serum evaluate single molecular classes or compare OC to healthy controls, limiting understanding of coordinated biological alterations in circulating proteins, lipids, and metabolites in clinically relevant populations. Methods: We performed integrated multi-omics profiling of serum from a retrospective, case–control cohort of women presenting with vague abdominal symptoms (VAS), including early- and late-stage OC, borderline tumors, benign gynecologic conditions including adnexal masses, GI disorders, and healthy controls. Protein biomarkers were quantified by ELISA, lipidomic profiling was performed by untargeted LC-MS, and ganglioside and metabolomic profiling were performed by semi-targeted LC-MS with metabolite annotation performed against a curated reference library. Results: Consistent with known limitations for early-stage OC detection, CA125 and HE4 levels overlapped substantially with benign gynecologic conditions. Additional proteins also showed limited separation in their expression between early-stage OC and symptomatic controls. In contrast, OC showed unique lipid and metabolite profiles: phospholipids and glycerolipids were decreased, and sphingolipid composition was altered. Borderline and benign conditions exhibited lipid profiles that fall between healthy and OC groups, suggesting a continuum of metabolic changes rather than distinct states between OC and non-OC controls. Sphingolipid alterations included changes in ceramides and sphingomyelins, along with broader dysregulation of ganglioside profiles, including an elevated GD2;O2-to-GD1;O2 ratio. Metabolic profiling showed decreased amino acids and enriched cysteine metabolism in OC, consistent with altered redox balance, along with changes in fatty acids and acyl-carnitines, suggesting altered lipid metabolism and inflammatory mechanisms. Lower levels of glycolytic and TCA cycle intermediates in OC suggested altered mitochondrial metabolism and energetic reprogramming. Pairwise comparisons revealed a gradient of significance between groups, with differences between OC and healthy controls across lipid classes (LPC, PC, PE, TG, SM), gangliosides (GD1, GD2, GD2/GD1 ratio), and metabolites (amino acids, Cys/CySS, TCA cycle); borderlines occupied an intermediate space. Integration of these datasets revealed coordinated cross-omics relationships, identifying links between metabolite, lipid, and protein features. Together, these connections highlight structured, system-level alterations related to lipid remodeling, redox balance, immune signaling, and energy metabolism that no single modality would have revealed in isolation. Conclusions: This study presents an integrated analysis of the lipidome, gangliosome, metabolome, and protein biomarkers within a single clinically relevant symptomatic cohort enriched with multiple stages and subtypes of OC. This multi-omics framework demonstrates that molecular alterations in OC are biologically interconnected across molecular classes. While these findings are discovery-based and require independent validation prior to clinical application, they support the development of clinically deployable multi-omics biomarker strategies for early detection and potential pathways for therapeutic intervention. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, largely due to late-stage diagnosis and the limited sensitivity of current screening approaches for early lesions. In recent years, the gut microbiota has emerged as a key factor in colorectal carcinogenesis, offering promising opportunities for the development of novel, non-invasive diagnostic and therapeutic strategies. Specific bacterial species and microbial metabolites have been implicated in colorectal carcinogenesis and are under investigation as potential biomarkers for CRC detection. However, despite growing evidence of association, most remain investigational and require further clinical validation before routine implementation. Among the proposed bacterial biomarkers, Fusobacterium nucleatum is one of the most promising candidates for clinical implementation, with encouraging evidence supporting its use in non-invasive stool-based CRC detection. Streptococcus gallolyticus subsp. gallolyticus and Clostridium septicum currently serve primarily as clinical warning markers due to their well-established association with occult colorectal malignancy rather than as screening biomarkers. In contrast, pks⁺Escherichia coli, enterotoxigenic Bacteroides fragilis, Enterococcus faecalis, and Peptostreptococcus anaerobius remain investigational. Helicobacter pylori has limited value for CRC detection because of its inconsistent association and low specificity. Overall, this review summarizes the most extensively studied bacterial species and microbial metabolites involved in colorectal cancer development, with particular emphasis on their underlying pathogenic mechanisms and highlighting their potential value as diagnostic biomarkers and therapeutic targets. It also highlights emerging bacterial taxa and microbial signatures that have been associated with early tumorigenesis in recent studies. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide in both males and females. Despite recent advances in precision-targeted therapeutics, mortality rates remain high, largely due to delayed diagnoses when curative interventions are no longer feasible. Recent studies from our group demonstrated that the LINE-1 mRNA and associated miRNA cargo of plasma exosomes can be used as sensitive and specific diagnostic and prognostic biomarkers of non-small-cell lung cancer (NSCLC). Because exosomes from various cancer types can be detected in urine, we extended our investigation to examine these analytes in urine exosomes from NSCLC patients. LINE-1 ORF1 and ORF2 mRNA levels, along with miR-21-5p, miR-126-3p, miR-210-3p, miR-221-3p, Let-7b-5p, miR-146a-5p, miR-222-3p, miR-9-5p, and miR-1277-5p, were higher in urine exosomes from NSCLC patients compared to healthy controls. The cargo of urine-derived exosomes often mirrored that of plasma exosomes and correlated with several clinicopathologic characteristics. The strong predictive performance of urine exosomal RNAs distinguishing NSCLC patients from controls suggests these measurements may serve as a complementary and readily accessible source for noninvasive assessment of patients with NSCLC. Full article

Cardiovascular disease remains the leading cause of mortality among women worldwide, yet coronary syndromes in women continue to be under-recognized and insufficiently represented in clinical research. This review summarizes sex-specific pathophysiological mechanisms, risk factors, clinical presentation, and management considerations in women with coronary syndromes. Women are more likely than men to present with non-obstructive and non-atherosclerotic ischemic phenotypes, including ischemia or angina with non-obstructive coronary arteries, coronary microvascular dysfunction, myocardial infarction with non-obstructive coronary arteries, spontaneous coronary artery dissection, vasospastic angina, and Takotsubo syndrome. These entities often require diagnostic strategies beyond the detection of flow-limiting epicardial stenosis, including cardiac magnetic resonance imaging, intracoronary imaging, and coronary function testing. Traditional cardiovascular risk factors remain important, but several female-specific risk enhancers, including premature menopause, adverse pregnancy outcomes, polycystic ovary syndrome, autoimmune disease, and psychosocial stressors, further modify risk and remain incompletely integrated into routine clinical assessment. Women may also experience diagnostic delays due to symptom misclassification, lower baseline troponin concentrations, and clinical algorithms historically derived from male-predominant populations. Management should follow guideline-directed therapy when appropriate, while recognizing sex-related differences in pharmacology, bleeding risk, revascularization outcomes, and the need for phenotype-specific treatment in INOCA, MINOCA, SCAD, and Takotsubo syndrome. Finally, transgender and gender-diverse individuals remain largely absent from cardiovascular trials, highlighting the need for inclusive research frameworks that distinguish sex, gender identity, and hormone exposure. Improved recognition of sex- and gender-related differences is essential to advance equitable cardiovascular care. Full article

Clostridioides difficile infection (CDI) is a leading healthcare-associated infection worldwide, causing significant morbidity, mortality, healthcare burden, and costs. Clinical manifestations range from mild, self-limiting diarrhea to severe, life-threatening complications such as toxic megacolon and septic shock. Early identification of patients at high risk of severe disease is essential to guide clinical decision-making and optimize therapy. This narrative review summarizes recent epidemiological data, current trends, and known risk factors as clinical context for severity prediction and then examines the utility and limitations of biomarkers that may predict CDI severity, including inflammatory, hematological, fecal, renal, and immune-response biomarkers. While some markers are already used in guideline-based assessment or routine clinical practice (e.g., C-reactive protein, white blood cell count, serum creatinine), they have limited specificity. Other markers emerging from CDI research, including procalcitonin, interleukins, and presepsin, may provide complementary prognostic information. The key challenge is not simply to identify additional biomarkers but to determine which biomarkers are clinically useful, at which stage of CDI progression, and in which patients they add value beyond conventional severity criteria. Validated predictive models integrating combinations of these biomarkers with clinical and microbiological data are needed to support early risk stratification and therapeutic decision-making at the time of diagnosis. Full article

5q spinal muscular atrophy (5q-SMA) is a leading genetic cause of infant mortality. Presymptomatic intervention with disease-modifying therapies significantly improves motor outcomes, but effectiveness depends on early detection through newborn screening (NBS). Despite global 5q-SMA NBS expansion and recent Brazilian federal legislation, regional disparities and a lack of systematic monitoring hinder access to timely diagnosis and care. This study addresses these gaps by evaluating a statewide pilot program in São Paulo. We used multiplex real-time PCR to detect SMN1 exon 7 deletions in dried blood spots, confirming SMN1/2 copy numbers via MLPA in positive cases. Under real-world conditions, timeliness key performance indicators were evaluated to assess operational efficiency. 194,714 newborns were screened with 14 positive cases, yielding a prevalence of 1:13,908. First-tier results and treatment initiation occurred at a median of 10.8 and 28 days of life, respectively. Notably, 78.6% of patients had two SMN2 copies, of which approximately half were symptomatic by the first evaluation, highlighting the critical need for rapid screening to prevent irreversible motor decline. Screening achieved 100% specificity. This pilot demonstrates the feasibility of 5q-SMA NBS within the Brazilian public health system, providing essential evidence to overcome logistical and socioeconomic barriers and support nationwide expansion. Full article

Post-dissection thoracoabdominal aortic aneurysm (PD-TAAA) is a late sequela of chronic aortic dissection. Complex endovascular aneurysm repair (EVAR), including fenestrated and branched techniques (F/B-EVAR), enables aneurysm exclusion while preserving visceral perfusion; however, bridging stents are not specifically designed for PD-TAAA and are frequently used off-label. Evidence on bridging stent performance is largely derived from degenerative aneurysm cohorts, and PD-TAAA-specific data remain limited. This study evaluated outcomes of the VBX Stent Graft when used as a bridging stent during F/B-EVAR for PD-TAAA. This retrospective analysis included patients with PD-TAAA from the EMBRACE registry (ClinicalTrials.gov: NCT05143138), a multicenter, single-arm registry with retrospective and prospective components, with all outcomes core-laboratory-adjudicated. Procedural, early (thirty-day), and midterm outcomes at one and three years were assessed. The primary endpoints were all-cause mortality and freedom from target vessel instability, defined as loss of durable target vessel reconstruction. Twenty-one patients (mean age 61.5 years; range, 28–77 years) underwent F/B-EVAR with at least one VBX Stent Graft. In total, 82 visceral arteries were treated, of which 51 were bridged with a VBX Stent Graft. Technical success was 100%. Two serious adverse events occurred perioperatively, one requiring reintervention, with no thirty-day mortality or major adverse events. Freedom from all-cause mortality was 95.2% at one year and 90.5% at three years, with two deaths during follow-up. Freedom from target vessel instability at the patient level was 85.7% at both one and three years (95% CI, 62.0–95.2%). VBX Stent Grafts used as bridging stents during F/B-EVAR for PD-TAAA demonstrated high technical success, low early morbidity and mortality, and acceptable mid-term survival and target vessel stability, supporting their use in this challenging anatomical setting within the limitations of a small PD-TAAA cohort. Full article

Background: Traditional cardiovascular risk models often overlook “residual risk” driven by psychopathological factors. This study investigates the exploratory prognostic baseline associations of Type D personality (TDP) and specific symptomatic dimensions with long-term all-cause mortality in patients with coronary artery disease (CAD). Methods: We conducted a retrospective case study based on hospital records evaluating 221 patients with confirmed CAD. Anatomical complexity was quantified via the SYNTAX Score (SS). Psychological profiling utilized the DS14 scale for TDP and the SCL-90 for granular symptoms (depression, anxiety, and hostility). Mortality was analyzed over a mean follow-up of 1026 days using multivariate Cox proportional hazards models. Results: Over a mean follow-up of 1026 days, the overall all-cause mortality rate was 33.0% ($n=73$). TDP prevalence was 19.0% ($n=42$) and significantly correlated with higher anatomical complexity (SS: 26.21 vs. 15.49; $p<0.001$). In the adjusted psychological model, baseline anxiety symptom severity presented an exploratory, borderline relationship with survival (HR = 0.941; $p=0.049$), with the 95% confidence interval upper bound reaching the null threshold (1.000), suggesting a potential, hypothesis-generating “Anxiety Paradox”. The psychological model demonstrated variations in descriptive validation indices (C-index = 0.624) compared to a baseline model integrating trait metrics and anatomical severity (C-index = 0.527). Significant correlations were confirmed between SS and psychological distress ($r=0.493$). Conclusions: TDP components and granular psychological tracks show significant baseline associations with coronary anatomical distributions, while anxiety dimensions present an exploratory relationship with long-term survival. Given the lack of adjustment for major clinical determinants of mortality (such as age, comorbidities, or ventricular function), these findings must be interpreted strictly as hypothesis-generating and exploratory. Full article

Background and Objectives: Rheumatic diseases confer excess cardiovascular risk, yet prognosis after acute coronary syndrome (ACS) in contemporary angiography-treated care remains incompletely characterized, particularly when psychiatric multimorbidity is considered. We evaluated whether documented rheumatic disease was associated with psychiatric comorbidity and post-discharge mortality after ACS. Materials and Methods: We retrospectively analyzed a predefined two-center registry extract of 2950 consecutive patients who underwent coronary angiography for ACS. Documented rheumatic disease was identified from diagnoses recorded in admission history, prior medical records, or discharge documentation and was not re-adjudicated. The primary outcome was post-discharge all-cause mortality. Results: Documented rheumatic disease was present in 106 patients (3.6%). Compared with patients without documented rheumatic disease, exposed patients were older, more often women, more often hypertensive, and more likely to have a documented psychiatric disorder (25.5% vs. 14.1%). Short-term mortality was similar, whereas crude overall long-term mortality was higher (27.4% vs. 19.3%). Among hospital survivors with usable follow-up, post-discharge survival was worse (log-rank p = 0.013). Documented rheumatic disease was associated with higher post-discharge mortality in unadjusted analysis (hazard ratio 1.66, 95% confidence interval 1.11–2.48) and in a prespecified parsimonious model (adjusted hazard ratio 1.56, 95% confidence interval 1.04–2.34); the association attenuated and was no longer statistically significant in a broader exploratory model (adjusted hazard ratio 1.35, 95% confidence interval 0.87–2.07). Documented psychiatric disorder independently predicted mortality. Conclusions: In angiography-treated ACS, documented rheumatic disease was associated with greater psychiatric comorbidity and worse post-discharge survival in a small, documentation-defined, heterogeneous subgroup. Because the signal attenuated in broader exploratory adjustment and exposure ascertainment was documentation-based, the findings should be regarded as hypothesis-generating rather than disease-specific or causal. Full article

Introduction: Prostate cancer (PC) is a highly prevalent malignant tumour associated with significant morbidity and mortality. While physical activity has been linked to a lower risk of PC and exercise has been shown to reduce mortality, the evidence for the association between physical activity and mortality is limited. Objective: This study aimed to assess the association between physical activity and mortality risk in men with or at risk of PC. Methods: A systematic search was conducted in Medline, Scopus and Web of Science from inception until April 2026. Observational studies analysing physical activity and all-cause and PC-specific mortality were included. The data were synthesised and interpreted using a synthesis without meta-analysis (SWiM) approach. The quality of the studies was assessed using the NHLBI tool. The certainty of the evidence was assessed using the GRADE framework. Results: Fifteen observational studies were included. The hazard ratio (HR) was the predominant effect measure. Physical activity was associated with a reduction in all-cause mortality (HRs: 0.40–0.88; highest versus lowest categories), and a dose–response gradient was observed within two cohorts. Associations with PC-specific mortality were less consistent, with significant inverse findings concentrated in post-diagnosis assessments. The quality of the studies was generally poor, and the certainty of the evidence was very low for both outcomes. Conclusions: Physical activity was associated with lower all-cause mortality risk in men with or at risk of PC, and the most consistent inverse estimates were observed in post-diagnostic assessments. These findings are observational and should not be interpreted as a clinical recommendation. A dose–response pattern was noted within individual studies, although the certainty of evidence was very low for this outcome. Additionally, evidence for PC-specific mortality was inconsistent and of very low certainty. Prospective studies with standardised, objective measures of physical activity are required. Full article

Background/Objectives: Chronic heart failure (CHF) is a leading cause of global morbidity and mortality, particularly among older adults, significantly impacting their quality of life and imposing a substantial economic burden. While pharmacological and surgical treatments remain essential, non-pharmacological interventions led by nurses are gaining prominence due to their comprehensive approach and biopsychosocial impact. The objective of this study was to synthesise and integrate such interventions for community-dwelling older adults with CHF. Methods: An integrative review was conducted in accordance with the Joanna Briggs Institute protocols and the PRISMA statement, utilising a systematic search across databases including PubMed and Cochrane. Qualitative, quantitative, and mixed-methods studies evaluating non-pharmacological interventions in the home setting were included, whilst those targeting non-specific populations were excluded. Following a rigorous screening process, 12 studies were selected, and their methodological quality was appraised based on study design. Results: The 12 included studies involved a total of 2466 participants and addressed interventions across the domains of education, physical activity, telehealth, and nutrition, with programme durations ranging from 4 weeks to 16 months. Notable improvements were observed in physical capacity, cognitive function, quality of life, and self-care capabilities, alongside potential reductions in hospitalisations reported in some studies. However, considerable methodological variability was identified across the literature. Conclusions: This review synthesises non-pharmacological nursing interventions for older adults with CHF, demonstrating varied benefits across multiple biopsychosocial domains. The findings emphasise the critical need for further research to evaluate the economic viability of these programmes and to adapt interventions to enhance the delivery of community-based care. Full article

Extreme temperatures are an emerging public health concern due to their significant impact on humans, yet the evidence remains limited in tropical countries. This study examined the non-linear relationship between ambient temperature and non-accidental and cause-specific mortality in two northern parts of Peninsular Malaysia, from 2011 to 2019. Daily mortality and meteorological data were analyzed using a quasi-Poisson Generalized Linear Model with a Distributed Lag-Non-Linear model to estimate the relationship between temperature and mortality. A U-shaped and J-shaped relationship was observed for the cumulative effects of 21-day lag periods for Kedah and Penang, respectively. The minimum mortality temperature (MMT) at 27.4 °C in Kedah and 28.2 °C in Penang was observed. Extremely high temperatures were associated with an increased non-accidental mortality, with a 16% increase at cumulative lag days 0–3 in Kedah and a 21% increase at cumulative lag days 0–7 in Penang. Vulnerable groups included individuals with respiratory diseases, the elderly, both genders and those residing in both urban and rural areas. These findings highlight the acute impact of heat on mortality in Malaysia and underscore the need for targeted public health interventions. Strengthening heat-health warning systems, improving healthcare preparedness, and prioritizing vulnerable populations are essential to mitigate the health impacts of rising temperatures in tropical regions. Full article

The increasing spread of invasive alien species (IAS) represents one of the major causes of biodiversity loss, making containment practices necessary. In this regard, the circular economy framework proposes to reuse the biomass from IAS in growing sectors such as aquaculture, in which more sustainable practices are required. This study evaluated the possibility of using biomass derived from two widespread freshwater IAS, Procambarus clarkii and Silurus glanis, as dietary ingredients for Oncorhynchus mykiss. Experimental diets were formulated by incorporating 20% of IAS-derived muscle powder into a commercial feed, and their effects were assessed through a 35-day feeding trial. Chemical analyses confirmed the nutritional suitability of the formulated diets and the absence of antibiotic residues. No mortality or significant differences in growth performance were observed among treatments. Blood biochemical parameters showed limited variations, remaining within physiological ranges, while oxidative stress biomarkers indicated only minor, diet-specific responses without evidence of oxidative damage. An increase in Hsp70 expression suggested adaptive physiological responses rather than pathological stress. Histological analyses of liver and gut tissues revealed no structural alterations across experimental groups. Overall, the results demonstrate that the inclusion of IAS-derived biomass at 20% is well tolerated by O. mykiss and does not impair fish health. These findings support the potential of invasive species valorization as a sustainable strategy for aquaculture feed production, contributing to both resource efficiency and ecosystem management. Full article

Background: Inherited arrhythmic syndromes (IAS) are an important but under-recognized cause of sudden cardiac death (SCD), particularly in younger individuals. Understanding long-term mortality trends is essential to evaluate their public health impact. Objective: To assess temporal trends and demographic disparities of IAS-related sudden cardiac death among individuals aged 5–44 years in the United States using CDC WONDER data. Methods: This retrospective observational study utilized the CDC WONDER Multiple Cause-of-Death database from 1999 to 2024. Deaths were identified using ICD-10 codes for non-ischemic arrhythmogenic conditions (I42, I44, I45, I47, I49) in combination with sudden cardiac arrest or unexplained death (I46, R96). Ischemic heart disease (I20–I25) was excluded to enhance specificity for inherited causes. Crude and age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated and stratified by age, sex, race/ethnicity, region, urbanization, and place of death. Joinpoint software helped us calculate the average annual percentage change (AAPC)/annual percent change (APC) in AAMRs and the 95% CIs for these changes. Results: A total of 8879 deaths were identified over the study period. The AAMR increased from 1.46 (95% CI: 1.27–1.64) in 1999 to 3.15 (95% CI: 2.89–3.42) in 2024, peaking at 4.54 in 2021, with an overall AAPC of 3.71% (p < 0.000001). Mortality was higher in males; however, females demonstrated a greater relative increase over time. Non-Hispanic Black individuals exhibited the highest mortality rates and fastest rise. The 25–44-year age group accounted for most deaths and showed the steepest increase. Regional and urban–rural disparities were observed, with higher mortality rates in the South and rural areas. Conclusions: It is concluded that mortality related to inherited arrhythmic syndromes and sudden cardiac death is rising among young individuals in the United States. The findings highlight a growing burden of potentially inherited arrhythmogenic conditions and underscore the need for early detection strategies, including genetic screening and targeted public health interventions, to reduce premature cardiovascular mortality. Full article