Search Results (5,139)

Background: Xinshubao tablet (XSB), a traditional Chinese medicine (TCM) formula composed of five medicinal herbs, is used clinically to alleviate cardiovascular diseases. This study aimed to investigate the coronary vasodilatory effects of XSB and its individual herbs, exploring its active constituents and the underlying mechanisms. Methods: The vasorelaxant effects of XSB and its individual herbal intestinal absorption solutions (IASs) were evaluated by ex vivo coronary artery ring assays. The chemical constituents of the best active herbal IAS were qualitatively identified using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC–Q-TOF-MS). Molecular docking and ex vivo assays were used to predict and validate the bioactive constituents and mechanisms responsible for coronary vasorelaxation. Results: Vasodilation experiments revealed that XSB-IAS and its individual herb IAS exhibited varying degrees of vasodilatory effects, in the range of 0.8–18 g raw materials/mL. At 6, 12, and 18 mg of raw materials/mL, Crataegus pinnatifida Bge (Shanzha) exhibited vasodilation rates of 26.45% ± 1.8%, 36.57% ± 3.5%, and 45.16% ± 6.3%, which were obviously higher than those of the other individual herbs. Fifty constituents in Shanzha IAS were identified by UPLC-Q-TOF-MS. Vasodilation-related protein–protein interaction (PPI) network revealed NOS3 as a core regulatory target. Molecular docking demonstrated that among the identified constituents, isochlorogenic acid B, betulin, etc., displayed binding affinity to NOS3. Isochlorogenic acid B was further validated to exhibit vasodilatory effects in the ranges of 0.05–2.5 mM. Mechanistic results showed that isochlorogenic acid B improved vasodilation by inhibiting Ca²⁺ influx through both voltage-dependent and receptor-operated Ca²⁺ channels, activating K⁺ channels, and exhibiting endothelium-dependent vasorelaxation. Conclusions: This study provides insights into the material basis and mechanisms underlying the vasorelaxant effects of XSB. Isochlorogenic acid B was firstly found to exert the coronary vasodilatory effect. This study can also contribute to the identification of efficacy-related quality markers in TCM. Full article

Background/Objectives: Coronary artery disease (CAD) remains the leading cause of mortality worldwide, with South Asia bearing a disproportionately high and rising burden, particularly at younger ages. The present study aimed to investigate genetic variants associated with premature coronary artery disease (PCAD) using whole-genome sequencing (WGS). Methods: WGS was conducted on 12 people (five PCAD cases, seven matched controls) to assess feasibility and methodology for future large-scale research. High-quality genomic DNA was sequenced at a minimum read depth of 10× with a quality threshold of Q30. Variant calling with stringent quality control identified single-nucleotide polymorphisms (SNPs), followed by annotation against gnomAD for allele frequencies and ClinVar for pathogenicity. Protein-coding variants were filtered, and candidate genes were prioritized for comparative analysis between cases and controls. Results: An average of over 8.8 million SNPs per individual was identified, with comparable overall variant distributions between cases and controls. Initial analyses revealed 120 SNPs exclusively present in PCAD cases. All protein-coding variants were rare (allele frequency < 0.0001), and none were previously classified as pathogenic in ClinVar. After filtration, 87 candidate genes were prioritized. Enriched or unique variants in PCAD cases are mapped to genes involved in lipid metabolism, endothelial dysfunction, inflammatory signaling, immune regulation, thrombosis, vascular remodeling, and metabolic processes. Additional variants were identified in genes related to smooth muscle proliferation, oxidative stress, and other biological pathways. Conclusions: This WGS pilot study provides an initial overview of the genomic landscape of PCAD in a South Asian cohort, highlighting rare variants across multiple biological pathways implicated in atherosclerosis that need validation in a large-scale study. Full article

Transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) are central regulators of vascular inflammation and remodeling in coronary artery disease. However, their cell-type-specific and context-dependent effects in primary human coronary artery endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) remain incompletely defined. Primary human coronary artery endothelial cells (pHCAECs) and smooth muscle cells (pHCASMCs) were stimulated with TGF-β1 (10 ng/mL), TNF-α (100 ng/mL), or their combination. Canonical SMAD2/3 activation, Krüppel-like factor 11 (KLF11) expression, cytoskeletal and junctional remodeling, vascular cell adhesion molecule-1 (VCAM-1) expression, migration dynamics (wound healing and confluent assays), and endothelial tube formation were assessed using immunofluorescence microscopy, live-cell imaging, and quantitative trajectory analysis. Both cytokines were associated with increased nuclear pSMAD2/3 signal in ECs and VSMCs, consistent with functional interplay between inflammatory and TGF-β-related signaling pathways. In pHCAECs, TNF-α robustly induced VCAM-1 functional expression and disrupted VE-cadherin continuity, whereas TGF-β1 primarily promoted cytoskeletal remodeling without strong inflammatory activation. TGF-β1 increased endothelial migration velocity and accumulated distance. In contrast, TNF-α preferentially enhanced Euclidean displacement and directional persistence, shifting the migratory pattern toward more directed movement most evident under combined TGF-β1 + TNF-α stimulation. Notably, TGF-β1 significantly reduced endothelial tube formation, indicating impaired network organization rather than proangiogenic activity. In pHCASMCs, TGF-β1 enhanced migratory activity, particularly in confluent monolayers, whereas TNF-α enhanced directional displacement. KLF11 was induced by TGF-β1 in both pHCAECs and pHCASMCs. In pHCAECs, TNF-α also increased KLF11 and co-stimulation promoted nuclear enrichment, whereas in pHCASMCs TNF-α alone was not effective and combined treatment amplified the TGF-β1 response, supporting cell-type-specific integration of inflammatory and TGF-β-dependent signals. TGF-β1 and TNF-α differentially regulate the inflammatory activation and migration of primary human coronary vascular cells in a cell-type- and structural-context-dependent manner. TGF-β1 enhances migratory force generation, whereas TNF-α reinforces directional polarization, and their integration determines effective vascular repair dynamics. Canonical SMAD2/3 activation does not uniformly predict functional outcome, and KLF11 was identified as a context-sensitive transcription-associated factor showing differential nuclear localization in response to cytokine stimulation, representing a hypothesis-generating observation for future mechanistic studies. Full article

Background and Objectives: The presence of comorbidities in both the pre- and post-diagnostic periods is a critical consideration in the diagnosis and management of patients with cancer. This study aimed to investigate the prevalence and burden of pulmonary and extrapulmonary comorbidities in patients diagnosed with lung cancer (LC) and malignant pleural mesothelioma (MPM). Materials and Methods: The data were obtained from official patient records of the Turkish Ministry of Health. Patients diagnosed with either lung cancer (LC) or malignant pleural mesothelioma (MPM) between 2015 and 2018 were included in the study. Comorbidities were classified as pulmonary or extrapulmonary. Results: A total of 74,835 patients with LC and 1678 patients with MPM were included. The burden of comorbid conditions increased significantly in the post-diagnostic period in both males and females across both cancer types. When the two cancer groups were compared with respect to diagnostic periods, comorbidities such as hypertension (HT), phlebitis/venous thrombosis/thrombophlebitis, pulmonary embolism, pneumothorax, and pleural effusion were significantly more prevalent in the MPM group (p < 0.05). Compared with the pre-diagnostic period, the comorbidity risk in LC was highest for pulmonary embolism, ARF, and pneumonia in the post-diagnostic period, whereas renal failure was the most frequent comorbidity in the MPM group (p < 0.001 and p = 0.024). When comparing changes in comorbidity burden between sexes in the lung cancer group, male patients had higher frequencies of pulmonary embolism, pneumonia, pneumothorax, and coronary artery disease than females. In contrast, in the female lung cancer group, the prevalence of chronic renal failure was higher than in males (OR = 2.14 vs. 2.00), whereas acute renal failure was more prominent in the male patient group (OR = 2.64 vs. 1.94). In gender-based comparison of comorbid conditions among patients with MPM, the risk of renal failure was higher in females than in males (CRF and ARF respectively: OR = 2.63 vs. 2.16 and OR = 6.80 vs. 5.44). Additionally, increased rates of COPD were observed in male patients within this group (OR = 1.93 vs. 1.81). Conclusions: Patients with LC and MPM are burdened not only by their primary malignancies but also by a wide spectrum of comorbidities, particularly in the post-diagnostic period. Comprehensive knowledge of comorbid conditions is essential for clinicians to guide clinical decision-making, anticipate disease progression, and optimize treatment strategies, thereby informing national healthcare policies. Future studies incorporating matched control groups or longitudinal designs with standardized surveillance protocols may help conduct better research. Full article

Background: Lipoprotein(a) [Lp(a)] is an inherited cardiovascular risk factor, but its relationship with coronary anatomical complexity, plaque phenotype, and outcomes after percutaneous coronary intervention (PCI) remains incompletely defined. Methods: We conducted a systematic review and meta-analysis of studies evaluating the association between circulating Lp(a) levels and coronary disease characteristics, post-PCI clinical outcomes, stent-related adverse outcomes, and aortic valve disease. Results: Twenty-six studies were included. Elevated Lp(a) levels were associated with greater coronary anatomical complexity and a higher risk of major adverse cardiovascular events after PCI (HR 1.4, 95% CI 1.2–1.7). The strongest associations were observed for stent-related adverse outcomes, including restenosis (OR 3.23, 95% CI 2.2–4.8) and target vessel revascularization (OR 2.6, 95% CI 1.6–4.4). Higher Lp(a) levels were also associated with vulnerable plaque features and aortic valve calcification. Conclusions: Elevated Lp(a) is associated with greater coronary disease complexity and adverse outcomes after PCI. Elevated Lp(a) may represent a biological marker identifying high-risk patients and providing additional insight for personalized risk stratification and procedural decision-making in patients undergoing PCI. Full article

Background: Moderate-to-severe coronary calcification is associated with worse outcomes following percutaneous coronary intervention (PCI). We aimed to assess the safety and efficacy of optical coherence tomography (OCT) compared with conventional angiography in PCI guidance of moderate-to-severe calcified coronary artery lesions. Methods: Multiple databases were systematically searched for outcomes of OCT- versus angiography-guided PCI in calcified lesions. Study selection and data extraction were conducted in accordance with the PRISMA guidelines. The primary endpoint was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and ischemia-driven target vessel revascularization (ID-TVR). Secondary endpoints included clinical (i.e., TVF components, stent thrombosis, and 30-day major adverse cardiovascular events [MACEs]), imaging, and procedural outcomes. Results: Four randomized controlled trials involving 3186 participants were included. Compared with angiography, OCT was associated with a significant reduction in TVF (risk ratio [RR] = 0.66; 95% confidence interval [CI]: 0.52–0.82), cardiac death (RR = 0.39; 95% CI: 0.22–0.70), TV-MI (RR = 0.63; 95% CI: 0.42–0.94), and stent thrombosis (RR = 0.24; 95% CI: 0.08–0.72). However, there were no significant changes in ID-TVR (RR = 0.77; 95% CI: 0.55–1.08) or 30-day MACEs (RR = 0.50; 95% CI: 0.16–1.61). Most procedural outcomes varied across studies and showed significant heterogeneity. Conclusions: OCT-guided PCI was associated with better clinical outcomes compared with angiography-guided PCI in this patient population. However, larger randomized trials are needed to confirm these results. Full article

Background: Acute type A aortic dissection (ATAAD) is a life-threatening condition that may be complicated by malperfusion, particularly in patients with prior aortic interventions such as Thoracic Endovascular Aortic Repair (TEVAR). Management becomes increasingly complex when the dissection involves supra-aortic branches and compromises previously placed stents. Methods: We report the case of a 58-year-old male presenting with ATAAD and left lower limb paralysis, with a history of prior TEVAR. Imaging demonstrated an entry tear in the ascending aorta with extension into the distal left main and supra-aortic branches, resulting in a dissection flap obstructing the proximal end of the TEVAR stent. The patient underwent emergency surgical intervention including a Bentall procedure, coronary artery bypass grafting (CABG), and deployment of a small Ascyrus Medical Dissection Stent (AMDS) distally within the TEVAR stent. Pre-operatively, the patient had severe lower limb ischemia due to near-complete obstruction of distal flow. Results: Following surgical intervention, there was restoration of true lumen perfusion with resolution of malperfusion. The patient was successfully weaned from cardiopulmonary bypass, extubated on post-operative day 4, and discharged on day 7 with stable hemodynamics and intact bilateral lower limb perfusion. Post-operative computed tomography (CT) demonstrated a well-seated AMDS with no evidence of ongoing false lumen perfusion. At 30-day follow-up, there was no clinical or biochemical evidence of organ malperfusion. Conclusions: The use of an AMDS deployed within a pre-existing TEVAR stent may represent an effective strategy for managing complex ATAAD with malperfusion, particularly in cases requiring combined surgical interventions. Full article

Background/Objectives: This study aimed to assess complications after endoscopic radial artery harvest, evaluate patient satisfaction, and assess the feasibility of a questionnaire interview. The primary aim was to assess neurological damage after endoscopic radial artery harvest (ERAH), and the secondary aim was to assess the feasibility of a newly constructed questionnaire in Danish. Methods: From June 2010 through October 2012, 108 patients underwent endoscopic radial artery harvest for coronary artery bypass grafting (CABG) at our institution. A total of 100 patients were interviewed by phone between one and two years after the operation. The interviews included questions about infection, bleeding, neurological damage, vascular perfusion of the hand, re-intervention, and general satisfaction with the procedure. Results: The described cohort was mainly male (88.9% 95% confidence interval (CI) 90.5–98.4%) with a mean age of 60.8 years (standard deviation (SD) 9.0). The self-reported incidence of postoperative antibiotic treatment was 7.0% (95% CI 3.1–14.4%), sensory deficit 18.0% (95% CI 11.3–27.2%), pain 8.0% (95% CI 3.8–15.6%), motoric deficit 4.0% (95% CI 1.3–10.5%) and cold or pale fingers 9.0% (95% CI 4.5–16.8%). At a follow-up time with a mean of 1.40 years (range 0.97–2.37 years, SD 0.36), all incisions were healed satisfactorily, 12.0% (95% CI 6.6–20.4%) reported sensory deficit, 7.0% (95% CI 3.1–14.4%) reported pain, 2.0% (95% CI 0.3–7.7%) reported motoric deficit, and none had a tendency towards cold fingers. The mean duration of antibiotic treatment was 8.7 days ± 2.3. When asked to rate the endoscopic procedure points of satisfaction from 0 (worst) to 10 (best), the mean was 9.7 ± 0.7. Conclusions: This study reports the occurrence of surgical complications immediately after ERAH, with an occurrence of self-reported neurological deficits of 18%. A questionnaire was feasible in a cohort of postoperative patients receiving radial artery harvest. Full article

Background: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogenous clinical syndrome in which aetiologies range from “true” ischemic mechanisms to non-ischemic mimics (e.g., myocarditis and Takotsubo syndrome). Cardiac magnetic resonance (CMR) plays a central role in the diagnostic pathway. Recent advances in parametric mapping (native T1, T2, and extracellular volume ECV) and evolving AI/radiomic methods promise to further improve diagnostic accuracy and prognostic stratification. This review aims to evaluate the current CMR evidence in MINOCA, while highlighting parametric mapping advances and future directions in the sphere of AI and radiomics. Methods: A systematic literature search of PubMed and the Directory of Open Access Journals (DOAJ) was performed. We included original prospective and retrospective CMR studies of MINOCA and MINOCA-like presentations in adults. Data were extracted into a master dataset and synthetised thematically into five subsections: (1) diagnostic yield, (2) reclassification rate), (3) timing of CMR, (4) prognosis, and (5) future directions. Results: Twenty-two studies met the inclusion criteria. CMR diagnostic yield varied by protocol and timing but was consistently substantial. CMR consistently reclassified initial MINOCA diagnoses (ischemia or alternative non-ischemic diagnoses). Parametric mapping provided incremental diagnostic and prognostic information. Across studies, early imaging (ideally within the first 1–2 weeks) increased diagnostic yield, while delayed CMR reduced detectability of transient lesions. Early AI and radiomics work show promise for LGE-based classification and for predicting post-contrast findings from non-contrast data, but current models require larger, multicentre training and robust external validation. Conclusions: CMR increases diagnostic yield and reclassification rates in MINOCA, particularly when performed early and with standardised T1/T2/ECV mapping. Mapping not only improves detection of inflammatory and diffuse injuries but also contributes to prognostic stratification. High-resolution LGE, OCT, and AI/radiomics are promising future refinements but need prospective validation in large, early, mapping-inclusive cohorts. Full article

Background: Patients with coronary artery disease (CAD) and severely reduced left ventricular ejection fraction (LVEF) ≤ 30% represent a high-risk group for coronary artery bypass grafting (CABG). Outcomes are of significant concern; therefore, real-world outcome data and predictors of early mortality remain important for perioperative decision-making. Aim: This study aims to evaluate early and mid-term outcomes in patients with severe ischemic cardiomyopathy (LVEF ≤ 30%) undergoing isolated CABG and to identify independent predictors of in-hospital mortality. Methods: We conducted a retrospective single-centre cohort analysis including patients with preoperative LVEF ≤ 30% undergoing isolated CABG (2017–2021). Early outcomes included in-hospital and 30-day mortality. The mid-term outcome was all-cause mortality up to 36 months. Multivariable logistic regression was used to identify independent predictors of in-hospital mortality. A predefined subgroup comparison was performed for LVEF ≤ 20% versus LVEF 20–30%. Results: The study comprised 147 patients with LVEF ≤ 30% undergoing isolated CABG. Overall, in-hospital mortality was 21.1%, and 30-day mortality was 23.8%. Cumulative all-cause mortality was 31.3%, 37.4%, and 42.9% at 12, 24 and 36 months respectively. Patients with LVEF ≤ 20% showed significantly higher early mortality (in-hospital 37.2% vs. 14.4%; 30-day 41.9% vs. 16.3%) and 36-month mortality (58.1% vs. 36.5%) compared with those with LVEF at 20–30%. Independent predictors of in-hospital mortality included preoperative hemodynamic instability, elevated operative risk scores, emergency status, prolonged cardiopulmonary bypass time, and major postoperative complications (all p < 0.05). Conclusions: CABG in patients with LVEF ≤ 30% is associated with substantial early mortality, while mid-term survival remains acceptable. Severely reduced LVEF identifies a particularly high-risk subgroup requiring careful perioperative risk stratification. Full article

Bisphenols may negatively impact human health, including the heart and circulatory system. It is crucial to determine the presence of these xenobiotics in biological samples, including pericardial fluid. Pericardial fluid was collected from patients with acute coronary syndromes (ACS), and with coronary artery disease during coronary artery bypass surgery. Bisphenol residues were identified and quantified in samples from 15 patients. Quantitative analysis of bisphenols in the samples was performed by LC–MS/MS on a triple quadrupole (QqQ) mass spectrometer and electrospray ionization (ESI−/ESI+) was applied in the negative and positive ion modes, respectively. The procedure was successfully applied to the biomonitoring of free forms of 14 bisphenols in pericardial fluid. After statistical examination of the relationships between the selected variables, it was concluded that while male subjects demonstrated higher Body Mass Index (BMI), longer procedural times, and earlier troponin release, female subjects exhibited later but more pronounced increases in CK and TrI, suggesting differences in kinetics and physiological response. Full article

Background and Clinical Significance: Revascularization of the circumflex territory remains technically challenging because of its anatomical position and the frequent need for distal branch grafting. Case presentation: We report the case of a 76-year-old man in whom the proximal circumflex trunk was used as the target for an in situ right internal thoracic artery routed through the transverse sinus during combined coronary and ascending aortic surgery. This approach allowed antegrade perfusion of the circumflex territory while avoiding multiple distal anastomoses. In this selected anatomical setting, the technique proved feasible and was associated with excellent intraoperative flow and 1-year radiological patency. Conclusions: Direct grafting of the circumflex trunk is not a new concept, but this case revisits it using a contemporary total arterial revascularization strategy. This approach may represent a useful adjunctive option in carefully selected patients with favorable circumflex anatomy. Full article

Background/Objectives: Coronary artery disease (CAD) remains the leading cause of death worldwide. Traditional cardiovascular risk assessment is based on chronological age and other clinical factors, with inherent limitations and poor accuracy. Objective was to estimate the artificial intelligence (AI)-enhanced biological cardiovascular age calculation derived from coronary computed tomography angiography (CTA) reports using a large language model (LLM), in predicting major adverse cardiovascular events (MACE). Methods: Coronary CTA reports were analyzed using a LLM (ChatGPT-4.0v, OpenAI), from symptomatic patients with suspected CAD who underwent coronary CTA for clinical indications. Patients in which the LLM successfully analyzed the key metrics (1) coronary artery calcium (CAC) score and (2) coronary CTA reports (coronary stenosis severity (CAD-RADS), high-risk anatomy, non-calcified plaque, cardiac function (LVEF and others) were included. Results: 386 CTA reports were uploaded, and 346 (89.6%) included. The mean biological age (bioAGE) was 57.2 ± 10.9 and the chronological 58.5 ± 10.8 years. 137 (39.6%) were women. The intra-individual deviation in bioAGE was high (median: 8.8; IQR 9.98). BioAGE exceeded chronological age in 45.4% patient and was lower or equal in 54.6%) MACE rate was 8.7% comprising 2 deaths, 5 myocardial infarctions, and 22 late revascularizations. The accuracy for prediction of MACE was higher for bioAGE (c = 0.768; 95% CI: 0.681–0.855, p < 0.001) compared to chronological age (c = 0.590; 95% CI: 0.492–0.689, p = 0.102) Conclusions: Biological age calculation from coronary CTA reports using LLM is feasible, yet intra-individual deviations are high. The accuracy for prediction of MACE is improved by bioAGE compared to chronological. Full article

Background: Left ventricular (LV) thrombosis after blunt trauma is uncommon and is most often attributed to traumatic coronary artery injury; however, it can also arise from severe myocardial contusions. Here, we report a case of LV thrombosis due to severe myocardial contusion without coronary artery injury. Case Presentation: A 36-year-old man struck by industrial fan fragments presented with hemorrhagic shock. Focused Assessment with Sonography for Trauma revealed cardiac tamponade. An emergent sternotomy was performed under cardiopulmonary bypass via the femoral vessels, which exposed severe contusion-associated hemorrhage with epicardial–myocardial dissection at the LV apex. On postoperative day (POD) 5, transthoracic echocardiography showed apical akinesia with mural thrombi; prophylactic anticoagulation was escalated and later transitioned to warfarin. Coronary computed tomography on POD 21 and invasive angiography at 6 months revealed negative findings. The thrombi resolved within 3 months; however, apical akinesia persisted. After discontinuing anticoagulation, a transient ischemic event occurring at 9 months prompted direct oral anticoagulant therapy. Apical akinesia persisted for over 7 years without recurrent thrombosis. Conclusion: This case underscores the importance of vigilance for intracardiac thrombosis in severe contusions, as well as the value of stepwise imaging (contrast echocardiography) and cautious, individualized discontinuation of anticoagulation when regional dysfunction persists. Full article

Endothelial dysfunction (ED) arises in multiple pathologies, and its severity correlates with disease progression. Common ED biomarkers could provide prognostic value for associated complications. This study aims to identify shared ED biomarkers and assess their prognostic significance. Endothelial cells in culture (human microvascular endothelial cells, HMEC-1) were exposed to sera from patients in five disease groups (n = 20 patients/group)—liver cirrhosis with portal hypertension, idiopathic pulmonary arterial hypertension, placental disorders such as intrauterine growth restriction, coronary artery disease with acute myocardial infarction, and chronic kidney disease—or matched controls, in the absence/presence of anti-inflammatory (apixaban) and antioxidant (EUK134) compounds. We explored changes in: VCAM-1, ICAM-1, eNOS, VWF, extracellular matrix thrombogenicity, and reactive oxygen species (ROS). In serum samples, proteomics and metabolomics analyses (including lipids, amino acids, and polar metabolites) were performed through an extraction protocol to identify common ED biomarkers. Expression of VCAM-1, ICAM-1, VWF, platelet adhesion, and ROS increased in most groups versus controls (p < 0.05). Both drugs decreased all biomarker levels except eNOS (n = 6 for in vitro experiments). For serum ED biomarkers, 18 metabolites and 24 proteins showed AUC-ROC and hit rates >77.5%, and six metabolites were associated with event-free survival. These diseases share ED driven by systemic inflammatory, oxidative, and metabolic stress, are partially reversible in vitro, and are linked to biomarkers associated with clinical outcomes. Overall, ED emerges as a modifiable pathological axis with potential prognostic value. Full article