Search Results (85)

Excess post-exercise oxygen consumption (EPOC) reflects cardiorespiratory fitness, energy metabolism and the residual physiological effects of preceding exercise. We aimed to compare EPOC profiles of master swimmers across different age groups and performance levels. Fourteen male master swimmers performed a 200 m all-out front crawl and breath-by-breath gas exchange and their heart rates were recorded during exercise and for 5 min post-exercise. A single exponential regression model was fitted to the post-exercise oxygen uptake kinetics to determine the EPOC amplitude, time constant and time delay. The EPOC magnitude was calculated as the area under the oxygen uptake–time curve. Swimmers were grouped into younger vs. older and faster vs. slower clusters using the 50th percentile, and the associations between age, performance and physiological variables were examined. Older swimmers were slower and showed a lower peak oxygen uptake than their younger counterparts (213.9 ± 27.9 vs. 165.7 ± 24.9 s and 39.1 ± 4.8 vs. 50.2 ± 8.1 mL∙kg⁻¹∙min⁻¹; p < 0.05). Slower swimmers were older and displayed a lower EPOC amplitude than faster performers (69.8 ± 7.3 vs. 45.7 ± 1.7 years and 23.2 ± 4.0 vs. 36.8 ± 10.2 mL∙kg⁻¹∙min⁻¹; p < 0.05). Although many of the variables did not differ between groups, effect sizes were moderate to very large (except for time constant and time delay). The swimmers’ age related directly to their performance and inversely to their peak oxygen uptake, peak heart rate and EPOC amplitude, while performance presented inverse associations with peak oxygen uptake, peak heart rate, EPOC amplitude and EPOC magnitude (p < 0.05). Master swimmers of different ages and performance levels exhibited distinct EPOC characteristics, which may provide relevant information regarding the individualisation of training and recovery strategies in this population. Full article

Background: Staphylococcus aureus bacteremia (SAB) is a common and life-threatening bloodstream infection often caused by methicillin-resistant SA (MRSA) isolates. Up to 35% of SAB patients fail to clear infection with gold-standard anti-MRSA antibiotics, even if the isolate meets susceptibility breakpoints in conventional assays in vitro. Such outcomes are termed persistent and may involve small colony variant (SCV) adaptation of SA in vivo. Methods: In this study, we assessed virulence phenotypes and mechanisms in persistent (PB) vs. resolving (RB) MRSA isolates from SAB. Results: Overall, PB isolates caused less hemolysis or biofilm formation than RB isolates, but proteolysis was equivalent. Attenuation of these virulence phenotypes increased longitudinally during the course of SAB. Although PB vs. RB isolates had similar human endothelial cell invasion rates, PB isolates more frequently formed SCVs intracellularly and inversely correlated with pH. Study PB and RB isolates exhibited distinct susceptibilities to prototypic human host defense peptides (HDPs), which were influenced by antibiotics and pH. Furthermore, mechanistic signatures of HDPs differed between PB and RB isolates. Conclusions: Together, these results reveal that MRSA isolates from PB vs. RB outcomes of SAB have differential virulence profiles that suggest coordinated immune subversion in PB. Understanding MRSA adaptations that promote persistence in SAB may enable innovative agents and strategies to address these challenging infections. Full article

Objectives: Head and neck tumors have been associated with varying risks for venous thromboembolism (VTE). Through a cross-tumor comparison, we assessed site-specific coagulation-related gene expression changes in head and neck squamous cell carcinoma (HNSCC) compared to squamous cell tumors in the esophagus (ESCCa) and lung (LUSC). Further, we assessed the relationship between clinicopathologic features of HNSCC and coagulome gene expression. Methods: RNA-sequencing data from primary tumor tissues of HNSCCa, ESCCa, and LUSC were obtained from The Cancer Genome Atlas (TCGA). Three previously identified pro-thrombotic genes (F3, SERPINE1, and SERPINB2) were analyzed and, for pan-cancer comparisons, gene expression was Z-standardized and summarized as a composite coagulome score. For HNSCCa-specific analyses, gene expression was compared using log2 RSEM counts, contrasting between HPV status, primary tumor site, tumor stage, grade, and demographic characteristics. Results: HNSCCa demonstrated the highest composite coagulome activation (mean Z-score = 0.29, 95% CI: 0.23–0.35) compared with LUSC and ESCCa (mean Z-scores = −0.27 and −0.16, respectively; p < 0.001). Among 487 HNSCCa tumors, HPV-negative tumors exhibited significantly higher composite coagulome expression than HPV-positive tumors (mean ± SD, 11.25 ± 1.39 vs. 10.14 ± 1.30; p < 0.001). Oral cavity tumors demonstrated the highest coagulome expression, while oropharyngeal tumors were most suppressed. Higher histologic grade was inversely associated with coagulome expression (p < 0.001). Patient age, sex, and race were not significantly associated with coagulome expression. Conclusions: HNSCCa exhibits a tumor-specific pro-thrombotic expression profile with substantial heterogeneity driven by HPV status and primary tumor site. Despite elevated tumor-specific pro-coagulant signaling, these findings reflect tumor-specific pro-thrombotic potential rather than clinical VTE risk in HNSCCa, which likely remains context-dependent and may require additional inflammatory or treatment-related triggers to clinically manifest. Full article

Background: The relationship between testosterone and coronary artery disease (CAD) remains a subject of debate. Most studies suggest an inverse association—lower testosterone, higher risk. However, data from Central European populations undergoing coronary angiography are limited. Objectives: To investigate the association between serum testosterone levels and angiographically confirmed coronary artery stenosis in a Slovak population. Methods: This cross-sectional study included 129 consecutive stable patients (84 men, 45 women; mean age 64.3 ± 9.7 years) undergoing elective coronary angiography for suspected stable coronary artery disease. Significant coronary stenosis was defined as ≥50% luminal narrowing in any major epicardial vessel. Serum testosterone, lipid profile, and traditional risk factors were assessed. Univariate and multivariate logistic regression models were constructed to evaluate independent associations of coronary stenosis. Results: Coronary stenosis ≥ 50% was present in 74 patients (57.4%). Notably, patients with stenosis had significantly higher testosterone levels (6.62 ± 2.79 vs. 4.85 ± 3.50 ng/mL, p = 0.002). In univariate analysis, testosterone showed a significant association (OR 1.197 per ng/mL, OR 1.784 per SD, p = 0.003). In multivariate analysis adjusted for age, sex, diabetes mellitus, and LDL (low-density lipoprotein) cholesterol, testosterone remained independently associated (adjusted OR 2.043 per SD, 95% CI 1.221–3.420, p = 0.007), as did diabetes mellitus (OR 2.60, p = 0.032). Conclusions: Elevated serum testosterone is paradoxically associated with increased prevalence of coronary stenosis in our cohort. These findings from stable, chronic CAD patients may work fundamentally differently from what is observed in acute coronary syndromes, where stress-induced testosterone suppression may confound observed associations. Full article

Background: Early diagnosis of familial hypercholesterolemia (FH) is crucial to improve long-term outcomes. FH diagnosis relies on elevated low-density lipoprotein cholesterol (LDL-C) levels, familial clinical characteristics, and identification of pathogenic variants in FH-related genes. Secondary factors, such as overweight and obesity, are known to influence lipid profiles in the general population. More recently, polygenic risk scores based on single-nucleotide polymorphisms (SNPs) have been proposed as additional determinants of LDL-C levels. Methods: We enrolled 214 pediatric subjects with LDL-C levels ≥95th percentile (after 6 months of dietary intervention) and with at least one parent with LDL-C levels ≥ 95th percentile. All participants underwent biochemical and auxological assessment and genetic testing for FH. In a subgroup of 60 subjects, LDL-C polygenic scores based on 6- and 12-SNPs were calculated. Results: Pathogenic variants confirming heterozygous FH were identified in 190 subjects (variant-positive, V+); 17 were variant-negative (V−), yielding a mutation detection rate of 91.8%. An additional seven patients carrying variants of uncertain significance were excluded from the primary analysis. LDL-C was modestly higher in V+ than V− subjects using both Friedewald (212 vs. 188 mg/dL; p = 0.035) and Martin–Hopkins formulas (208 vs. 187 mg/dL; p = 0.041), while the other main clinical and laboratory parameters were similar. In V+, LDL-C was higher in subjects with null variants, compared to those with defective variants. Body mass index (BMI SDS) was inversely correlated with HDL-C (p < 0.001), and obesity (BMI z-score > 2 SDS) was associated with lower HDL-C and higher LDL-C, non-HDL-C, and ApoB. With regard to the polygenic scores, 12- and 6-SNP scores showed overlap between V+ and V−, and published cut-offs did not discriminate lipid severity in our population; however, in V+ subjects, the 12-SNP score acted as a phenotype modifier, being independently associated with higher LDL-C and non-HDL-C levels after adjustment for age, sex, and BMI SDS. Conclusions: In children selected by LDL-C ≥ 95th percentile, together with autosomal dominant familial hypercholesterolemia, genetic confirmation of FH is achieved in the vast majority of cases. Variant type (null vs. defective), BMI, and polygenic background contribute to phenotypic heterogeneity, supporting the need to address other factors alongside genetic diagnosis. Further validation is needed before polygenic scores can be implemented in routine clinical practice. Full article

Background: Persistent inflammation and endothelial dysfunction have been proposed as key mechanisms of post-COVID cardiovascular sequelae and may contribute to atrial fibrillation (AF). We examined whether inflammatory/prothrombotic biomarkers and endothelial function differ between post-COVID patients and controls, and whether baseline inflammation/endothelial dysfunction relates to AF burden at 12 months. Methods: In this single-center, retrospective observational study, 198 outpatients were enrolled: 99 post-COVID patients evaluated 3–6 months after documented SARS-CoV-2 infection (Group 1) and 99 age- and sex-matched controls without prior COVID-19 (Group 2). At baseline (t0), clinical characteristics, inflammatory/prothrombotic biomarkers, brachial artery flow-mediated dilation (FMD), and 24 h Holter ECG were assessed in both groups. Univariable linear regression tested associations between baseline variables and FMD in Group 1. At 12 months (t1), 24 h Holter ECG was repeated in both groups. Quartile analyses were performed according to baseline neutrophil-to-lymphocyte ratio (NLR) to explore AF distribution across inflammatory strata. Results: At baseline, post-COVID patients had higher inflammatory and prothrombotic markers than controls (ESR, CRP, fibrinogen, and D-dimer; all p < 0.0001) and markedly lower FMD (7.72 vs. 13.72; p < 0.0001). In Group 1, FMD was inversely associated with multiple inflammatory/prothrombotic markers (all p < 0.0001), with the strongest association for ESR (R² = 0.6297). Holter-detected AF prevalence at baseline did not differ significantly between groups (25/99 [25.3%] vs. 18/99 [18.2%]). At 12 months, AF prevalence was numerically higher in the post-COVID group (32/99 [32.3%] vs. 21/99 [21.2%]); on two-sided testing, this difference was borderline (p = 0.047) and should be interpreted cautiously. Across increasing baseline NLR quartiles, AF prevalence increased stepwise in both groups (post-COVID: 2/25, 5/25, 10/24, 15/25; controls: 1/25, 3/25, 7/24, 10/25), consistent with the enrichment of AF in higher-inflammatory strata. Conclusions: Post-COVID patients exhibited a persistent inflammatory–prothrombotic profile and pronounced endothelial dysfunction at baseline. At 12 months, AF burden was numerically higher post-COVID, and AF clustered in strata characterized by higher baseline NLR and lower FMD, consistent with an inflammation–endothelial dysfunction axis associated with subsequent AF burden. Prospective studies with standardized rhythm monitoring and comprehensive multivariable adjustment are warranted. Full article

Background: Menopause is accompanied by hormonal alterations that are closely linked to changes in body composition, insulin sensitivity, and cardiovascular risk in women. Gremlin-1 has recently been identified as an adipokine involved in metabolic and reproductive aging; however, its associations with endocrine and lipid biomarkers across the menopausal transition remain incompletely defined. Objectives: To evaluate the relationships between plasma Gremlin-1 and IGF-1, HDL cholesterol, estradiol, and age in reproductive-aged and postmenopausal women. Methods: This cross-sectional study included 88 women aged 18–65 years, stratified by menopausal status (reproductive-aged vs. postmenopausal). Plasma concentrations of Gremlin-1, growth hormone, IGF-1, insulin, estradiol (E2), glucose, HbA1c, and a standard lipid profile were measured. Results: Plasma Gremlin-1 concentrations were significantly higher in postmenopausal women compared with reproductive-aged women (p < 0.001). Age (p = 0.013), but not menopause status (p = 0.874), was associated with Gremlin-1 levels. Gremlin-1 showed a strong inverse association with IGF-1 (p = 0.003) and a negative correlation with HDL cholesterol (p = 0.03) in non-obese women; however this association disappeared after adjustment for age. Conclusion: Circulating Gremlin-1 primarily reflects chronological aging and associated endocrine–metabolic changes rather than menopausal status or adiposity per se. While unadjusted associations with metabolic biomarkers are detectable, these relationships are largely attributable to aging. Gremlin-1 may therefore serve as a marker of systemic aging-related endocrine–metabolic remodeling rather than a specific indicator of ovarian aging or adipose tissue dysfunction. Full article

Background/Objectives: Sex-based differences in clinical profiles and outcomes following percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) remain poorly understood. We sought to examine the association between sex and long-term clinical outcomes following CTO-PCI in a contemporary real-world cohort. Methods: We conducted a retrospective study of 928 consecutive patients (788 men, 140 women) undergoing CTO-PCI at a high-volume centre between 2011 and 2024. The primary endpoint was a composite of major adverse cardiac events (MACE: all-cause death, myocardial infarction [MI], or stroke) at a 6-year follow-up. To account for baseline differences, an Inverse Probability of Treatment Weighting (IPTW)-adjusted Cox regression analysis was performed. Results: Women were significantly older (69.7 ± 10 vs. 64.1 ± 10 years; p < 0.001) and had a higher prevalence of diabetes and hypertension. However, women exhibited lower angiographic complexity, with lower J-CTO scores (2 [1–2] vs. 2 [1–3]; p < 0.001) and less frequent severe calcification or tortuosity. Technical and procedural success rates were comparable between sexes (85.4% vs. 86.7%; p = 0.695). Unadjusted MACE rates were higher in women (29.3% vs. 22.1%; hazard ratio (HR) 1.51, 95% CI: 1.08–2.13; p = 0.017). After adjustment, the female sex was no longer associated with the primary endpoint (aHR 1.15, 95% CI: 0.76–1.74; p = 0.517), but the risk of MI remained significantly higher in this group (aHR 2.85, 95% CI: 1.23–6.63; p = 0.015). Conclusions: CTO-PCI appeared to be equally safe and effective in women and men. Over long-term follow-up, although the overall adjusted MACE risk was similar between sexes, the female sex was associated with a higher risk for MI. Full article

Background: The coronary slow flow phenomenon (CSFP) is an angiographic entity increasingly recognized in patients with angina and/or ischemia but non-obstructive coronary arteries (ANOCA/INOCA), associated with systemic inflammation, endothelial dysfunction, and microvascular abnormalities. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a novel immunonutritional index that may reflect this multifactorial risk profile. Methods: This retrospective single-center case–control study included 122 patients with CSFP and 126 age- and sex-matched controls with normal coronary flow, all presenting with symptoms of chronic coronary syndrome. CSFP was diagnosed via corrected TIMI frame count. HALP and other inflammatory indices (NLR, PLR, SII, SIRI) were calculated from baseline laboratory values. Associations were evaluated using multivariable logistic regression, ROC analysis, and restricted cubic spline (RCS) modeling. Results: The HALP score was significantly lower in CSFP patients (mean 56.2 vs. 65.9, p < 0.001). In multivariable analysis, HALP was independently associated with CSFP (adjusted OR: 0.951; 95% CI: 0.930–0.972; p < 0.001), whereas NLR lost significance. PLR, SII, and SIRI remained independently associated. HALP showed the highest diagnostic performance (AUC: 0.698), significantly outperforming all other indices (DeLong p < 0.001). A HALP cutoff ≤ 56.4 provided 58.2% sensitivity and 77.0% specificity. RCS analysis demonstrated a significant non-linear inverse relationship (p for non-linearity = 0.034). Subgroup analyses confirmed consistent associations across age, sex, hypertension, and diabetes strata. Conclusions: The HALP score is independently associated with CSFP and outperforms traditional inflammatory indices. Its low cost and accessibility make it a promising tool for clinical risk stratification in ANOCA/INOCA patients, pending validation in multicenter prospective studies. Full article

Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region. Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8–9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1–14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 10⁶ IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance. Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways. Full article

Glioblastoma (GBM) shows extensive epigenetic heterogeneity. In IDH-wildtype (IDH-WT) GBM, promoter DNA methylation may regulate lineage programs influencing tumor evolution and prognosis; here, we systematically profiled promoter-level methylation dynamics across longitudinal tumors. Genome-wide DNA methylation data were obtained from the publicly available Gene Expression Omnibus (GEO; GSE279073) dataset, comprising a longitudinal cohort of 226 IDH-wildtype glioblastomas profiled on the Illumina Infinium EPIC 850K array across primary and recurrent stages at the University of California, San Francisco. From 333 Gene Ontology gliogenesis-annotated genes (GO:0042063), a 48-gene promoter panel was derived, with ≥2 probes per gene. Promoter methylation was summarized as the median β-value and tested using one-sample Wilcoxon with FDR correction. Functional enrichment, longitudinal variation, and patient-level methylation burden were assessed. Validation analyses were performed using independent IDH-wildtype GBM datasets from The Cancer Genome Atlas (RNA-seq and 450K methylation; n = 347). Promoter hypomethylation predominated across all stages, with 25 genes consistently hypomethylated and 7 hypermethylated. Functional enrichment highlighted gliogenesis, glial cell differentiation, neurogenesis, and Notch-related signaling. In TCGA, promoter methylation inversely correlated with expression for 11 of 33 genes (FDR < 0.05). An Expression Score contrasting hypomethylated and hypermethylated genes was positively associated with improved overall survival, where higher scores predicted better outcome (HR = 0.87, p = 0.016; Q4 vs. Q1 HR = 0.68, p = 0.025), and a complementary Methylation Score showed that higher promoter hypermethylation predicted poorer outcome (HR = 1.73, p < 0.001). CNTN2 and TSPAN2 were adverse prognostic genes (FDR < 0.05). The Expression Score was highest in Proneural tumors and lowest in Mesenchymal tumors (p < 0.001), reflecting a proneural-like state associated with better prognosis. Promoter methylation within gliogenesis genes defines a stable yet prognostically informative epigenetic signature in IDH-WT GBM. Hypomethylation promotes transcriptional activation and a favorable outcome, whereas hypermethylation represses lineage programs and predicts poorer survival. Full article

Background: In malignant pleural mesothelioma, epithelioid histology is traditionally considered a favorable prognostic marker. However, it remains clinically undetermined whether the intensity of an oncogenic insult can disrupt this link. Radiation-induced cases serve as an unconfounded biological model to dissect such trajectories masked by asbestos confounding. Methods: We performed an Individual Patient Data (IPD) synthesis of 20 strictly asbestos-unexposed human cases, applying clinically established dose stratification (intermediate: 20–45 Gy vs. high: >45 Gy). To confirm the observed pattern, we examined data from 829 dogs in the Colorado State University (CSU) Beagle Study. Results: In the intermediate-dose group (n = 13), a significant positive correlation persisted between age at radiotherapy and the latent period (ρ = 0.567, p = 0.043). Conversely, high-dose exposure (>45 Gy) showed a disruption of this age-dependent pattern, with a trend toward inverse correlation (ρ = −0.754, p = 0.084). Interaction analysis confirmed a statistically significant divergence between these dose-dependent trends (p = 0.005). The CSU Beagle Study (n = 829) demonstrated the physical basis of this phenomenon: in the canine model, high-dose exposure (≥0.74 Gy) triggered a “Step-Jump” in cumulative incidence (30.4% at 0.5 years), indicating instantaneous carcinogenic onset distinct from cumulative biological aging. Conclusions: This kinetic divergence points to a “Diagnostic Trap.” We propose a ‘Single- to Double-Brake’ framework where intermediate doses preserve age-dependent progression, whereas high doses likely trigger catastrophic genomic failure (chromothripsis) that bypasses the time required for morphological dedifferentiation. Consequently, morphologically indolent epithelioid tumors in high-dose survivors may harbor aggressive molecular profiles not predicted by histology alone, necessitating risk-stratified precision surveillance. Full article

Background/Objectives: Platelet-rich plasma (PRP) is increasingly used in musculoskeletal medicine. Variability in PRP composition, driven by preparation- and donor-related factors, is considered a major contributor to inconsistent clinical outcomes. This study investigated whether habitual dietary patterns are associated with the cellular and molecular composition of leukocyte-poor PRP (LP-PRP). Methods: In this cross-sectional study, 75 healthy adults (25 vegans, 25 vegetarians, and 25 omnivores) who adhered to their dietary patterns for ≥6 months were enrolled. LP-PRP was prepared by a standardized protocol. Cell profiles were quantified in whole blood and LP-PRP; LP-PRP proteins (IL-6, IGF-1, HGF, and PDGF-BB) were measured by ELISA. Group differences, correlations, and multivariable regressions were performed. Results: Whole blood differed by diet with respect to total leukocytes, lymphocytes, and basophils, while platelet and erythrocyte counts did not. In LP-PRP, platelet enrichment ratios and leukocyte counts were comparable across diets. IL-6 in LP-PRP was lower in vegans vs. omnivores (p = 0.017); the Animal-Based Diet Score correlated positively with LP-PRP IL-6 and remained independently associated in regression (β = 0.35, p = 0.004). While IGF-1, HGF, and PDGF-BB did not differ between dietary groups, intake-based analyses revealed associations between specific dietary components and LP-PRP proteins; notably, the fruit and vegetable intake correlated inversely with PDGF-BB, and platelet–growth factor coupling was most pronounced among omnivores. Conclusions: Dietary patterns were associated with selected molecular components of LP-PRP—most consistently IL-6—while cell counts remain largely unchanged. However, interventional studies are needed to establish causality and determine whether dietary modification can influence clinical outcomes. Full article

Background/Objectives: Colorectal cancer (CRC) is one of the most common malignancies worldwide, with systemic inflammation increasingly recognised as a determinant of disease progression. This study aimed to establish a taxonomy-based classification of patients with newly diagnosed primary CRC using systemic inflammatory, haematological, and anthropometric markers, and to evaluate its association with tumour stage. Methods: A total of 229 patients (111 women, 118 men) undergoing surgery for primary CRC were included. Blood samples were analysed for haemoglobin, leukocytes, neutrophils, lymphocytes, platelets, C-reactive protein (CRP), and carcinoembryonic antigen (CEA). Anthropometric data were collected. Taxonomic clustering and ordinal logistic regression were used to explore associations with TNM and Astler–Coller classifications. Results: Men had higher neutrophil and leukocyte counts, elevated CEA concentrations (132.8 vs. 81.3 ng/mL), and higher NLR values (4.74 vs. 4.23) compared with women. Logistic regression confirmed that platelet count (OR 1.003; p = 0.004), PLR (OR 1.003; p = 0.003), and CEA (OR 1.03; p < 0.001) were positively associated with advanced TNM stage, while haemoglobin was inversely correlated (OR 0.88; p = 0.045). Among 84 clustering models, two taxonomies were the most clinically informative: Taxonomy I (BMI, neutrophils, platelets) and Taxonomy II (age, lymphocytes, platelets), both significantly associated with T, N, M, overall TNM stage, and Astler–Coller grade. Taxonomy I identified three patient groups. Type 3 represented the poorest phenotype, characterised by low BMI and haemoglobin, high platelets, elevated CEA and PLR, and predominance of TNM IIIC tumours, consistent with a cachectic–inflammatory profile. Type 1 displayed higher BMI, lower inflammation, and earlier-stage disease. Type 2 was characterized by elevated neutrophils and leukocytes. Taxonomy II distinguished four groups, with Type 2 demonstrating the most favourable profile (high haemoglobin and lymphocytes, low NLR and PLR, early TNM stage). Conclusions: Systemic inflammatory markers, haemoglobin, platelets, and CEA strongly predict CRC advancement. The proposed taxonomy provides clinically meaningful stratification of CRC patients and may support personalised risk assessment. This accessible approach may facilitate early identification of high-risk individuals, although validation in prospective studies is required. Full article

Background/Objectives: To identify clinical, biochemical, and psychological factors associated with metabolic syndrome (MS) in climacteric women and to determine independent predictors of MS across menopausal stages. Methods: A cross-sectional study was conducted in 225 women (perimenopausal, n = 75; early postmenopausal, n = 75; late postmenopausal, n = 75). Anthropometry, clinical history, and fasting laboratory tests were obtained. Psychological measures included perceived stress (Perceived Stress Scale, PSS), anxiety symptoms (Short Health Anxiety Inventory, SHAI-18), and depressive symptoms (Hamilton–Bech–Rafaelsen Scale). Results: Perimenopausal women had higher BMI than both postmenopausal groups (33 ± 5 vs. 30 ± 5 and 29 ± 4 kg/m²; F = 13.39, p < 0.001). Waist/hip ratio showed a modest group effect (F = 6.34, p = 0.002), being higher in perimenopause versus late postmenopause (p = 0.001). Significant group differences were observed in lipid and glucose profiles across menopausal stages. Total cholesterol (F = 4.86, p = 0.009), HDL cholesterol (F = 7.12, p = 0.001), and non-HDL cholesterol (F = 8.13, p < 0.001) differed significantly, as confirmed by post hoc Tukey HSD tests, with higher total and non-HDL cholesterol levels in early and late postmenopausal women compared with the perimenopausal group, and higher HDL cholesterol levels in early postmenopausal women compared with the perimenopausal group. Fasting glucose showed a significant difference (H = 9.89, p = 0.007, Kruskal–Wallis test), with higher median levels in perimenopausal (127 mg/dL) than in early postmenopausal women (97 mg/dL, p = 0.003, Mann–Whitney U). Perceived stress was highest in early postmenopause (61.3%) compared with late postmenopause (48.0%) and perimenopause (34.7%), χ² = 10.68, p = 0.0048, while anxiety and depression did not differ. Logistic regression analyses identified perceived stress and depressive symptoms as significant predictors of metabolic syndrome under different diagnostic definitions. Higher perceived stress was inversely associated in the psychological model (aOR = 0.62; 95% CI 0.43–0.88; p = 0.008) but positively related in the clinical model including fasting glucose and blood pressure (aOR = 1.54; 95% CI 1.07–2.22; p = 0.021). In the combined model, both fasting glucose and perceived stress remained independent predictors (p < 0.05), under-scoring the contribution of psychological factors to metabolic risk. Conclusions: Among climacteric women, perceived stress and cardiometabolic factors (systemic arterial hypertension, Type 2 DM, and elevated fasting glucose) are independent predictors of metabolic syndrome. Early identification and integrated management of stress and metabolic risks may help reduce the burden of metabolic syndrome across menopausal stages. Full article