Category: 3. Business

Introduction

Acute type A aortic dissection (ATAAD) is a critical cardiovascular emergency defined by a tear in the inner layer of the aorta, allowing blood to enter the middle layer and create a false channel.¹ Epidemiological data indicate that, without timely surgical intervention, the mortality risk increases by 1% to 2% each hour, with more than half of patients dying within 48 hours.^1–4Emergency surgical repair is currently the only effective treatment.^5,6 However, despite advances in surgical techniques, recent studies report that 30-day postoperative mortality remains high, highlighting the urgent need for effective preoperative risk assessment.^7–9

ATAAD pathobiology involves a surge of systemic inflammation, endothelial injury, tissue hypoperfusion, and ischemia–reperfusion during surgery.^10,11 Pro-inflammatory mediators such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) amplify matrix degradation, impair microcirculatory flow, and increase the risk of mortality.^10,11 Concomitantly, catabolic stress and hepatic reprioritization of protein synthesis depress serum albumin,¹² while neuroendocrine stress leads to stress-induced lymphopenia, reflecting impaired cellular immunity.^13,14 Each of these processes has been individually linked to adverse outcomes after aortic surgery. Based on this, we prespecified that lower CALLY would be associated with a higher risk of postoperative in-hospital mortality.

The C-reactive protein–albumin–lymphocyte (CALLY) index is a composite biomarker integrating inflammatory, nutritional, and immunologic status and has gained attention in cardiovascular research. Multiple prospective cohorts have shown an inverse association between CALLY and both all-cause and cardiovascular mortality in cardiovascular disease populations.^15–17 In NHANES V, each 1-unit increase in CALLY was associated with an 18% lower risk of all-cause mortality.¹⁷ In coronary revascularization, patients in the lowest CALLY quartile had a 2.3-fold higher 5-year mortality than those in the highest quartile.¹⁵ However, whether CALLY predicts mortality in surgically managed acute type A aortic dissection (ATAAD) remains unknown.

Compared with traditional single-dimension inflammatory ratios such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), CALLY combines CRP, albumin, and lymphocyte counts to capture complementary biology and has shown superior discrimination in other diseases while relying on routine laboratory tests.^18,19 Notably, current ATAAD risk stratification paradigms often rely on postoperative or late-presenting biomarkers (eg, D-dimer >5 mg/L, lactate >4 mmol/L),²⁰ which do not meet the time-sensitive needs of emergency preoperative triage. In contrast, CALLY provides a multidimensional snapshot of preoperative pathophysiology.

Accordingly, this study aimed to: (1) assess the association between preoperative CALLY and postoperative in-hospital mortality (POIM) in surgically treated ATAAD; and (2) develop a preoperative risk prediction model incorporating CALLY to enable early identification of high-risk patients and inform perioperative decision-making.

Materials and Methods

Study Population

This retrospective cohort study analyzed 522 consecutive ATAAD patients diagnosed at Union Hospital affiliated to Fujian Medical University between October 2015 and July 2024. Patients hospitalized between October 2015 and July 2022 were included in the training cohort, while those hospitalized between August 2022 and July 2024 were included in the external validation cohort. A predictive model was constructed, and a nomogram was plotted based on the training cohort. Internal validation was performed using the K-fold cross-validation technique, and external validation was conducted using regression equations developed from the training cohort.²¹

Data Collection

Diagnosis was confirmed by computed tomography angiography (CTA) and/or magnetic resonance imaging (MRI) according to the 2022 ESC Guidelines on Aortic Diseases. Clinical data were extracted from electronic medical records using a standardized case report form, including:

Demographics: Age, sex, pre-existing hypertension (defined as systolic BP ≥140 mmHg or antihypertensive use).Emergency Department Workup: Blood samples collected via antecubital venipuncture within 30 minutes of admission for:Hematological profiling: White blood cell (WBC), neutrophil, monocyte, platelet, and lymphocyte counts (Sysmex XN-9000 analyzer) Biochemical profiling: Random glucose, troponin I (TNI; ARCHITECT STAT assay), creatine kinase (CK),CRP; immunoturbidimetry, albumin (bromocresol green method), D-dimer (immunofluorescence), uric acid (UA; enzymatic colorimetry), fibrinogen (Clauss method), serum creatinine (modified Jaffe method).

The CALLY index was calculated as:

CALLY Index=Albumin x lymphocyte count/(CRP x 10)

Inclusion criteria included adult patients 18 years of age and older who underwent ATAAD surgery. The exclusion criteria for this study were as follows: (1) patients with diseases that affect initial counts of blood cell populations and/or in-hospital mortality, such as malignancies, hematological disorders, and infectious diseases; (2) patients with severe organ dysfunction, such as hepatic or renal failure; (3) patients taking medications that may affect the parameters of the complete blood count (eg, chemotherapeutic agents, such as cyclophosphamide, methotrexate, etc).; (4) patients with suspected subclinical myocardial involvement (eg, chronic inflammation or history of acute infection); (5) patients using intra-aortic balloon counterpulsation pumps (IABP); and (6) patients with incomplete clinical data. The study was approved by the Ethics Committee of Fujian Medical University Affiliated Union Hospital (2020 KY 082).Ultimately, a total of 522 patients were enrolled in the study. Medical records were used to collect basic clinical characteristics, imaging manifestations, surgical data, and clinical outcomes of the subjects. Consent was obtained from all subjects and their legal guardians after providing them with relevant information. This study was a retrospective observational analysis of informed consent based on the principles outlined in the Declaration of Helsinki. We guaranteed the confidentiality and anonymity of all patient data, which were used only for data analysis purposes. Figure 1 illustrates the procedure for inclusion of patients.

Figure 1 Flowchart of Patient Enrollment.

Primary Endpoint

The primary endpoint was POIM, defined as all-cause death occurring during the index hospitalization following surgery, including patients discharged against medical advice due to irreversible clinical deterioration.

Surgical Protocol

All patients underwent standardized surgical management:

Cardiopulmonary Bypass (CPB) Establishment:Median sternotomy with bicaval venous cannulation (24–28Fr).Arterial inflow via femoral artery (18–20Fr) and right axillary artery (12–14Fr) cannulation.Myocardial Protection:Direct antegrade delivery of cold blood cardioplegia (4:1 blood:crystalloid ratio, 4°C) into coronary ostia.Maintenance of myocardial temperature <15°C via topical cooling.Circulatory Arrest Management:Initiation of hypothermic circulatory arrest (HCA) at nasopharyngeal temperature 25–28°C.Unilateral antegrade cerebral perfusion (uACP) via right axillary artery (10 mL·kg⁻¹·min⁻¹ at 20°C).Intermittent bilateral cerebral perfusion during frozen elephant trunk deployment:Left common carotid artery cannulation (8Fr) via side graft.Flow maintenance >800 mL/min with cerebral oximetry monitoring.

Aortic Reconstruction:Open distal anastomosis using quadrifurcated graft (26–30mm Gelweave).Frozen elephant trunk implantation (Cronus^® stent-graft, 26–34mm diameter).Proximal reconstruction with mechanical valve conduit (St. Jude Medical 25–29mm).Reperfusion Strategy: Gradual rewarming (<0.5°C/min) during graft deairing.Modified ultrafiltration (MUF) for inflammatory mediator removal.

Statistical Methods

Statistical analysis was performed using IBM SPSS^® 26.0 and R version 4.2.3. Continuous variables that followed a normal distribution were expressed as mean ± standard deviation (mean ± SD), while non-normally distributed data were expressed as median (P25, P75). Count variables are expressed as frequencies or percentages.Student’s t-tests were used to compare regularly distributed continuous variables between groups, whereas Mann–Whitney U-tests were used to examine information on continuous variables that did not conform to a normal distribution. The chi-square test or Fisher’s exact test was used to compare count data between groups. This was done by calculating the subject’s work characteristic curve (ROC) and selecting the threshold that maximized the sum of sensitivity and specificity.We adopted a prespecified stepwise adjustment strategy to clarify the independent association between the CALLY index and in-hospital mortality. The set of potential confounders was defined a priori based on clinical relevance and literature. We used LASSO regression analysis to identify independent predictors of all-cause mortality (P<0.2) and constructed column-line plots. Logistic regression models were used to evaluate the predictive efficacy of the CALLY index for mortality. Furthermore, we evaluated the predictive performance of the nomogram by calculating the area under ROC curve AUC in the training cohort. Internal validation was performed using 5-fold cross-validation, while external validation utilized the same formula applied to the validation cohort over a time period. Calibration curves were used to assess the consistency between predicted probabilities and observed outcomes.Statistical significance was defined as P<0.05.

Results

Baseline Characteristics of the Study Population

After excluding ineligible patients, 522 surgically treated ATAAD patients (395males and 127 females) were enrolled between October 2015 and July 2024 (Figure 1). The cohort had a mean age of 52.24 years (standard deviation [SD] 11.94). During hospitalization, 55 patients experienced in-hospital mortality. A comprehensive summary of baseline characteristics stratified by CALLY quartiles is presented in Table 1. The CALLY index was categorized into four groups based on quartile thresholds: Q1: <0.187; Q2: 0.187–0.580; Q3: 0.580–0.905; and Q4: ≥0.905.

Table 1 Baseline Characteristics of Patients by CALLY Quartile Groups

Association Between CALLY Index and in-Hospital Outcomes

Table 2 presents the in-hospital outcomes stratified by preoperative CALLY index quartiles. There were no significant differences in length of hospital stay among the four CALLY quartile groups (P=0.073). However, significant differences were observed in the incidence of gastrointestinal hemorrhage, acute kidney injury (AKI), and POIM across the quartiles. Patients in the lowest CALLY quartile (Q1) had the highest incidences of gastrointestinal hemorrhage (11.45%), AKI (32.82%), and POIM (26.72%), whereas those in the highest quartile (Q4) had the lowest incidences (2.31%, 9.23%, and 1.54%, respectively; All P<0.001). No significant difference in length of stay across CALLY quartiles.

Table 2 In-Hospital Outcomes Stratified by Preoperative CALLY

Preoperative CALLY Index Shows Superior Predictive Performance for Mortality vs Individual Biomarkers

ROC curves were utilized to evaluate the predictive performance of preoperative CALLY index, lymphocyte count, albumin, and CRP for POIM. The results demonstrated significant predictive capacity of all analyzed parameters for postoperative mortality. Notably, the CALLY index exhibited the highest discriminative power for mortality prediction (AUC = 0.820,P<0.001), outperforming individual biomarkers (Figure 2).

Figure 2 ROC Curve Analysis Evaluating the Predictive Value of Lymphocyte Count, CRP, Albumin, and the CALLY Index for Postoperative In-Hospital Mortality in ATAAD Patients. The ROC curves compare the discriminative ability of individual biomarkers and the composite CALLY score for predicting postoperative in-hospital mortality. The x-axis represents 1-specificity (false positive rate) and the y-axis represents sensitivity (true positive rate). Each curve demonstrates the trade-off between sensitivity and specificity at different threshold values. The area under the curve (AUC) values are shown in parentheses: CALLY score (blue line, AUC=0.820), C-reactive protein (red line, AUC=0.744), albumin (green line, AUC=0.587), and lymphocyte count (purple line, AUC=0.683). The diagonal grey line represents the line of no discrimination (AUC=0.500), equivalent to random chance. The CALLY score demonstrated superior discriminative performance compared with individual biomarkers, with an AUC significantly greater than 0.5 (P<0.05). AUC values closer to 1.0 indicate better discriminative ability, while values closer to 0.5 suggest poor discrimination.

Subgroup Analysis

To validate the consistency of the association between CALLY and in-hospital mortality, subgroup analyses were performed. Interaction analyses revealed no significant interactions between subgroups stratified by age, sex, BMI, hypertension, diabetes, coronary heart disease, Systolic Blood Pressure(SBP), Diastolic Blood Pressure(DBP), smoking, and alcohol consumption (P>0.05 for all variables, including sex, smoking status, drinking habits, age groups, hypertension, and diabetes). The results are shown in Table 3. In conclusion, the CALLY index can serve as an effective predictor of mortality in patients undergoing surgery for type A aortic dissection, with consistent clinical predictive significance across various clinical subgroups.

Table 3 Subgroup Analysis of the Associations Between Preoperative CALLY and in-Hospital Mortality

CALLY Index Serves as an Independent Predictor of Postoperative Mortality in ATAAD Patients

To avoid multicollinearity, albumin, lymphocyte count, and CRP were excluded from the analysis. The final LASSO-derived model included prehospital emergency care, PT, urea, CK, TNI, lactate, and the CALLY index. Univariate logistic regression revealed that prehospital emergency care (OR = 5.737, 95% CI: 1.808–18.208, P=0.003) and CALLY index (OR = 0.131, 95% CI: 0.110–0.199, P<0.001) were associated with significantly reduced mortality risk, whereas PT (OR = 1.226), urea (OR = 1.175), TNI (OR = 1.136), CK (OR = 1.000), and lactate (OR = 1.252) significantly increased mortality risk (all P< 0.05). In multivariate analysis adjusted for potential confounders, only prehospital emergency care (OR = 4.707, 95% CI: 0.947–23.386, P=0.058), lactate (OR = 1.225, 95% CI: 1.133–1.324, P<0.001), and the CALLY index (OR = 0.048, 95% CI: 0.014–0.162, P<0.001) retained statistical significance, confirming their roles as independent predictors (Table 4).

Table 4 Univariate and Multivariate Logistic Regression Analyses of POIM and Clinical Candidate Predictors

The CALLY index demonstrated a robust inverse association with mortality risk across multivariate logistic regression models. In the unadjusted model (Model 1), the OR for CALLY was 0.131 (95% CI: 0.110–0.199, P<0.001). After partial adjustment for demographic variables (age, sex, BMI, height, weight) in Model 2, the OR increased to 0.091 (95% CI: 0.019–0.428, P=0.002). Full adjustment in Model 3, incorporating heart rate, blood pressure, serum potassium, sodium, and left ventricular ejection fraction (LVEF), yielded a stable OR of 0.059 (95% CI: 0.01–0.336, P=0.001). Across all models, the CALLY index remained a protective factor against all-cause mortality (P<0.05) (Table 5).

Table 5 Association Analysis of the CALLY Index with in-Hospital Mortality Across Adjusted Models

Development of a CALLY Index-Based Nomogram

This study employed a multistage variable screening strategy to optimize the construction of the predictive model. First, univariate logistic regression analysis (with a lenient significance threshold of α=0.2) was performed for preliminary screening of predictors, identifying 31 potential variables, including sex, age, LVEF, height, weight, length of hospital stay, platelet count, white blood cell count, PT, N-terminal pro-B-type natriuretic peptide (NT-proBNP), lactate dehydrogenase (LDH), urea, CK, TN, lactate, and the CALLY index. Subsequently, the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm was applied for feature selection. The LASSO regression model achieved optimal performance when the regularization parameter λ was set to 0.031 (based on the minimum criteria of cross-validated error), ultimately retaining seven critical variables: prehospital emergency care,PT, urea, CK, TNI, lactate, and the CALLY index (Figure 3A and B).

Figure 3 LASSO regression analysis for variable selection in acute type A aortic dissection (ATAAD) patients. (A) Cross-validation curve for LASSO regression model. The x-axis shows log(λ) and the y-axis the mean binomial deviance (red dots) with ±1 SE error bars (gray). The numbers along the top indicate the count of non-zero coefficients at each λ. Two vertical dotted lines mark the cross-validated choices: λ.min (the value yielding the lowest mean deviance) and λ.1se (the most regularized model whose deviance is within one standard error of the minimum). In this study, we prioritized discrimination and selected the optimal penalty as λ.min=0.0308. (B) Variable coefficient trajectory plot. Each colored trajectory corresponds to one candidate variable and depicts how its standardized coefficient changes as log(λ) increases. As the penalty strengthens, coefficients shrink toward zero; variables whose coefficients reach zero at a given λ are excluded from the model. The sign of each path indicates the direction of association with the outcome, and earlier shrinkage to zero suggests weaker or more redundant signals. The vertical dotted lines match those in Panel A. At λ.min=0.0308, the model retained 7 predictors (non-zero coefficients), which were subsequently entered into the multivariable logistic model and the nomogram.

A POIM prediction nomogram was developed using predictors selected by LASSO regression: prehospital emergency care, PT, urea, TNI, Lac, CK, and the CALLY index (Figure 4). Each predictor was assigned a score on the “Points” axis proportional to its regression coefficient. For example, lactate >4 mmol/L contributed 25 points, whereas a CALLY index <0.1 contributed 40 points. The total score—obtained by summing all individual scores—maps to the “Probability of Mortality” axis, yielding predicted probabilities from 0% to 90%.

Figure 4 Nomogram Based on the CALLY Index for Discrimination of All-Cause Mortality. The nomogram integrates multiple clinical variables to provide individualised risk prediction for all-cause mortality. To use the nomogram, locate the patient’s value for each variable on the corresponding axis and draw a vertical line upward to the “Points” axis to determine the points assigned for that variable. The points for all variables are summed to obtain the “Total Points” score, which corresponds to the predicted probability of death shown on the bottom scale. The variables included are: out-of-hospital emergency care (dichotomous: Yes/No), prothrombin time (PT, seconds), urea (mmol/L), troponin I (TNI, ng/mL), lactate (Lac, mmol/L), creatine kinase (CK, U/L), and CALLY score (0–18 points). The total points range from 0 to 160, corresponding to death probabilities ranging from 0.2 to 0.8. Higher total point scores indicate increased risk of mortality.

To provide an overall assessment of predictive performance and to benchmark modeling strategies, we subsequently compared the nomogram based on conventional variable screening with a CALLY-guided model using ROC analysis (Figure 5). Model 1 included variables with P<0.05 in univariable analyses and showed good discrimination, with a smoothed ROC AUC of 0.81 (95% CI, 0.75–0.88). Building on this, Model 2 treated the CALLY index as a core predictor and applied LASSO regularization for automated selection among all candidate variables. The ROC curve for Model 2 consistently exceeded that of Model 1, with an AUC of 0.85 (95% CI, 0.79–0.91). Across most false-positive-rate ranges, Model 2 achieved higher sensitivity at comparable FPRs, indicating that the CALLY-guided LASSO approach better integrates heterogeneous information while limiting overfitting, thereby providing stronger overall discrimination and enhanced clinical utility.

Figure 5 Discrimination performance of two modelling strategies: Univariable-screened Multivariable Model Versus CALLY-guided LASSO Model. ROC curves are displayed after loess smoothing for two prespecified models: the multivariable model derived by entering predictors with P<0.05 in univariable analyses (Model 1, blue), which includes the following variables: tricuspid regurgitation, urea, D-dimer index (DDI), hemoglobin, international normalized ratio (INR), aid, N-terminal pro b-type natriuretic peptide (NT-proBNP), total protein, age, TNI, and CRP; and the CALLY-guided model obtained via LASSO regularization across all candidate predictors (Model 2, red). The smoothed lines depict the trend of sensitivity (true positive rate) over the full range of 1–specificity (false positive rate); the grey dashed diagonal denotes no discrimination. AUC values with 95% confidence intervals are shown within the panel: Model 1, AUC 0.811 (95% CI 0.747–0.876); Model 2, AUC 0.849 (95% CI 0.792–0.907). Across most false positive rate ranges, the CALLY-guided LASSO model demonstrates higher sensitivity at comparable false positive rates, indicating superior overall discrimination.

Nomogram Validation

A 5-fold internal cross-validation was conducted 400 times in the training cohort and revealed an average AUC value of 0.849 (95% CI: 0.792–0.907) for internal validation, as shown by the red ROC curve in Figure 5. The external validation yielded an AUC value of 0.869 (95% CI: 0.808–0.929) demonstrating the robust accuracy of the model across different cohorts (Figure 6). These results highlight the model’s effectiveness in predicting outcomes reliably. Figure 7 display the results of the Hosmer-Lemeshow (H-L) test, yielding P-values of 0.42 and 0.498, respectively, neither of which reached statistical significance. This indicates that the predicted probabilities are consistent with the actual probabilities, suggesting good model fit and reliability. This consistency further supports the model’s effectiveness in clinical application, enhancing predictive accuracy for POIM.

Figure 6 ROC curve for external validation of the predictive model. The curve illustrates the relationship between sensitivity (true positive rate) and 1-specificity (false positive rate). AUC is reported as 0.869 with a 95% confidence interval of 0.808 to 0.929, indicating robust discriminatory performance of the model in identifying high-risk patients. The diagonal dashed line represents the line of no discrimination (AUC = 0.5).

Figure 7 Calibration curves for the nomogram with Hosmer-Lemeshow (H-L) test. (A) Training cohort; (B) validation cohort. The X-axis shows the predicted probability of in-hospital mortality, and the Y-axis shows the observed outcomes. H-L tests show good consistency in both two cohorts, with p values of 0.420 and 0.498, respectively.

Discussion

ATAAD is a critical cardiovascular emergency with high POIM rates. Although many studies have examined postoperative outcomes in ATAAD patients,^22,23 this is the first to assess the relationship between the CALLY index and POIM. We retrospectively analyzed data from 522 patients who underwent emergency surgery for ATAAD at our institution. The results of this study indicate that the CALLY index is a good predictor for identifying high-risk POIM patients with ATAAD. ROC curve analysis revealed that CALLY is a better predictor of in-hospital mortality compared to lymphocyte count, C-reactive protein, or albumin alone. Patients with ATAAD and lower preoperative CALLY levels had an increased risk of in-hospital mortality, consistent with previous studies.^15–17 Furthermore, after adjusting for potential confounders, lower preoperative CALLY in ATAAD patients was associated with an increased risk of in-hospital mortality. Subgroup analysis showed no significant interactions between patient subgroups. Finally, a preoperative risk assessment nomogram model was constructed based on these indicators. We divided the database into a training cohort and a time-period validation cohort according to the patients’ admission dates (2015 to 2022 compared to 2022 to 2024). This approach aligns with a large-sample study, enhancing the predictive capability of the nomogram.²¹ Furthermore, the nomogram underwent rigorous validation through various methods, including K-fold cross-validation, confirming its robustness.

The CALLY index is a composite biomarker that integrates inflammatory burden (C-reactive protein), nutritional status (albumin), and immune competence (lymphocyte count). Prior studies have shown that it outperforms several traditional inflammatory markers in prognostic discrimination for malignancies such as hepatocellular carcinoma and gastric cancer.^16,19 Zhu et al¹⁶ reported inverse associations between the CALLY index and all-cause, cardiovascular, and cancer-specific mortality among patients with cancer, indicating that lower values are linked to higher mortality risk. Consistently, studies in colorectal cancer have demonstrated that higher CALLY values are associated with longer overall survival.¹⁹ In the cardiovascular domain, the CALLY index has been validated as an important prognostic indicator in patients with coronary artery disease undergoing percutaneous coronary intervention; Ji et al¹⁵ found that higher CALLY values were protectively associated with both short- and long-term major adverse cardiovascular events (MACE) after primary PCI for ST-elevation myocardial infarction, and that greater values correlated with less severe coronary lesions. Moreover, beyond oncology and cardiology, the CALLY index is inversely associated with all-cause mortality in patients receiving maintenance hemodialysis, supporting its utility for mortality risk stratification in this population.²⁴

This study demonstrates that a higher CALLY index independently protects against POIM in ATAAD. By combining CRP, albumin, and lymphocyte count, CALLY captures concurrent disturbances in inflammation, nutrition, and immunity more comprehensively than any single marker.Mechanistic evidence supports this association. Albumin is tightly linked to hepatic synthesis, systemic metabolism, and vascular function.^25,26 It maintains colloid osmotic pressure, exerts antioxidant and anti-inflammatory effects, and modulates platelet activation, thereby mitigating inflammation, ischemia–reperfusion injury, and vascular dysfunction.^27,28 Its redox-active Cys-34 residue scavenges reactive oxygen and nitrogen species.^25,26 In ATAAD, low albumin (<32 g/L) inversely correlates with aortic wall oxidative damage, likely because exposure of medial collagen and elastin promotes ROS release and accelerates albumin degradation.¹³ CRP, an acute-phase protein, amplifies complement activation, phagocytosis, leukocyte function, and inflammatory signaling.^29,30 Intimal tearing exposes the vessel wall to circulating blood, rapidly recruiting monocytes and neutrophils that release IL-6, IL-8, and TNF-α, sustaining a cytokine cascade.^11,31,32 Lymphocytes provide layered defense via cellular and humoral immunity; in ATAAD, Th1/Th17 subsets may aggravate injury, whereas regulatory T cells and selected B-cell subsets may restrain progression.³³

ATAAD pathobiology magnifies CALLY’s prognostic value. Dissection-induced mechanical stress activates NF-κB and increases IL-6 five- to eight-fold versus stable coronary disease; downstream JAK2/STAT3 signaling accelerates CRP synthesis while suppressing albumin transcription.^12,34 The resulting inflammatory surge (often CRP >20 mg/L) coexists with hypoalbuminemia, and systemic inflammatory response syndrome further reduces hepatic albumin synthesis and increases catabolism.^3,6 This pattern reflects uncontrolled inflammation, endothelial dysfunction, and evolving multiorgan injury, enhancing CALLY’s discrimination.^35,36 Lymphopenia adds prognostic information by indicating stress glucocorticoid-induced apoptosis and IL-6-mediated myelosuppression, which raise infection risk.^37–39

CALLY complements routine clinical indicators. Elevated lactate signals perfusion crisis and gut ischemia with endotoxin translocation and TLR4/MyD88-mediated SIRS.^40–42 Prolonged prothrombin time denotes coagulopathy and portends adverse cardiovascular outcomes.⁴³ Higher urea reflects metabolic stress and renal hypoperfusion and is associated with poor prognosis.⁴⁴ Together, these variables delineate the coagulation–metabolic–immune axis underlying organ failure. Compared with traditional markers, CALLY captures multisystem compensatory capacity—albumin as hepatic reserve,⁴⁵ lymphocytes as stress hematopoiesis,⁴⁶ and CRP as inflammatory intensity —thereby identifying decompensation thresholds and suggesting actionable targets. Potential strategies include albumin support for hypoalbuminemia and selective IL-6 inhibition for hyperinflammation; resistin may exacerbate endothelial permeability via p38 MAPK and compound capillary leak.⁴⁷

Practically, we integrated CALLY into a preoperative nomogram using only readily available variables, enabling rapid risk stratification in emergency settings. Limitations include the retrospective single-center design and modest sample size.

Overall, CALLY encapsulates ATAAD’s acute inflammatory, nutritional, and immune derangements and independently predicts POIM. Combined with standard clinical data, it offers a timely, low-cost tool for preoperative decision-making and a coherent framework for targeted perioperative care.

Conclusion

This study demonstrates that the preoperative CALLY index exhibits strong predictive efficacy for POIM in ATAAD patients. The constructed nomogram model provides a valuable tool for preoperatively identifying high-risk individuals. The clinical significance lies in its capacity to en able rapid risk stratification of multi-organ injury through routine laboratory parameters, thereby guiding time-sensitive surgical decision-making in emergency settings, which may ultimately reduce in-hospital mortality rates.

Data Sharing Statement

Full data set available from the corresponding author. However, reanalysis of the full data need be approved by Fujian Medical University Union Hospital.

Ethics Statement

The investigation conformed with the principles outlined in the Declaration of Helsinki and was approved by the Ethics Committee of Fujian Medical University Affiliated Union Hospital (2020 KY082) Informed consent was obtained from patients before this study.

Acknowledgments

The authors appreciate all subjects who participated in this study. We would also like to thank the hospital for supporting the data collection of this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by grants from the Fifth Batch of Hospital Key Discipline Construction Projects (2022YYZDXK01).

Disclosure

The authors report no conflicts of interest in this work.

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Latest innovation builds on the firm’s Aon Broker Copilot and Risk Analyzers to deliver greater speed, insight and value in claims resolution and analytics

DUBLIN, 11 Nov. 2025 – Aon plc (NYSE: AON), a leading global professional services firm, today announced the launch of Aon Claims Copilot, a single, integrated digital platform designed to enhance client outcomes through advanced analytics, automation, globally consistent claims management and the specialized expertise of Aon’s claims advocates.  

Aon Claims Copilot reflects the firm’s commitment to delivering outstanding claims services to clients when it matters most. The new platform supports every stage of the claim’s lifecycle – from the occurrence of a claim to advocacy and negotiation and resolution with advanced analytics. It enables global consistency, data-led performance evaluation and tailored insight to support each client’s risk capital strategy, with additional AI-driven capabilities to come in the first half of 2026. Clients are equipped with access to claims analytics, while Aon colleagues benefit from advanced digital tools to deliver faster, more effective claims outcomes.

“Aon Claims Copilot represents an exciting step forward in Aon’s commitment to deliver better information, advice and solutions to clients through technology,” said Joe Peiser, CEO of Commercial Risk at Aon. “It empowers our professionals to turn insight into action, helping clients achieve faster claims resolution, maximize recoveries and make better informed risk and coverage decisions.”

The platform will launch in Germany first, then expand to North America, Asia Pacific and EMEA in 2026 with full global implementation by the end of 2027.

Aon Claims Copilot enhances how Aon’s 1,800-strong team of Claims professionals – operating in more than 50 countries – deliver proactive advocacy and technical expertise across 20+ product lines. Its capabilities include:  

• Analytics and Risk Insights: Real-time dashboards and analytics provide visibility into claims trends, portfolio performance and peer benchmarking.
• Carrier Performance Evaluation: Enables data-driven feedback on carrier responsiveness, claim closure efficiency and outcomes.
• Client Transparency: Allows clients to securely track claim progress and status through a dedicated portal.
• Process Optimization: Automation and seamless integrations improve speed and accuracy throughout the end-to-end claims process.

“Expert advocacy combined with AI-driven analytics will give our clients superior visibility and control over their claims,” said Mona Barnes, global chief claims officer for Commercial Risk at Aon. “Aon Claims Copilot empowers our teams, amplifying their expertise and maximizing claim payouts for our clients. It also creates a powerful feedback loop with our brokers, ensuring we place business with market partners that consistently deliver the best results.”

Aon Claims Copilot equips professionals with tools to prepare and present complex claims, help clients maximize recoveries and reduce the lifecycle of a claim. It supports the firm’s broader goal of providing distinct claims-related services that strengthen clients’ overall risk mitigation strategies.

The launch of Aon Claims Copilot follows Aon’s recent technology innovations including AI-powered Aon Broker Copilot and the firm’s Risk Analyzers, underscoring the firm’s continued investment in technology that enhances decision-making and resilience in an increasingly volatile world.

About Aon

Aon plc (NYSE: AON) exists to shape decisions for the better — to protect and enrich the lives of people around the world. Through actionable analytic insight, globally integrated Risk Capital and Human Capital expertise, and locally relevant solutions, our colleagues provide clients in over 120 countries with the clarity and confidence to make better risk and people decisions that protect and grow their businesses.

Follow Aon on LinkedIn, X, Facebook and Instagram. Stay up-to-date by visiting Aon’s newsroom and sign up for news alerts here.

Media Contact

mediainquiries@aon.com

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BANGKOK — Asian shares were mostly lower on Tuesday as the recent rebound fueled by buying of technology shares lost steam.

Markets showed little reaction to the latest step toward ending the U.S. shutdown, after the Senate passed legislation to reopen the government.

U.S. futures were little changed and oil prices slipped.

Shares have been bouncing on criticism that tech share prices have shot too high due to the mania for artificial intelligence, which some have likened to the 2000 dot-com bubble that ultimately burst.

In Tokyo, the Nikkei 225 lost 0.5% to 50,675.92.

The U.S. dollar climbed to 154.15 against the Japanese yen, from 154.14 yen, near its highest since February. Expectations that the government will push back its schedule for trimming Japan’s huge national debt and boost spending have helped to weaken the yen.

The euro inched up to $1.1563 from $1.1557.

Chinese shares also declined. Hong Kong’s benchmark Hang Seng index fell 0.2% to 26,595.97 and the Shanghai Composite index shed 0.4% to 4,002.06.

South Korea’s Kospi, recovering from last week’s fell below the 4,000 level, initially rose more than 1% but finished up 0.4% at 4,087.56.

Australia’s S&P/ASX 200 dropped 0.2% to 8,818.80.

Taiwan’s Taiex fell 0.3%, while the Sensex in India shed 0.4%.

On Monday, Big Tech and other superstars of the U.S. stock market got back to rallying, and Wall Street recovered most of its loss from last week.

The S&P 500 climbed 1.5% to 6,832.43, while the Dow Jones Industrial Average rose 0.8% to 47,368.63.

The Nasdaq composite rallied 2.3% to 23,527.17.

Nvidia was by far the strongest force lifting the market and leaped 5.8%. It was a powerful rebound after Nvidia and other winners of the frenzy around artificial-intelligence technology led last week’s drop. Critics say their stock prices shot too high and too fast in the AI mania, drawing comparisons to the 2000 dot-com bubble that ultimately burst.

Drops for several health insurers helped keep the market’s gains in check. They fell as uncertainty remains about whether Washington will extend expiring health care tax credits, a sticking point on Capitol Hill that’s created the longest-ever shutdown for the U.S. government.

Elsewhere on Wall Street, Berkshire Hathaway slipped 0.4% as its CEO, famed investor Warren Buffett, warned shareholders that many other companies will fare better in the decades ahead because of Berkshire Hathaway’s massive size. Buffett, 95, is set to step down in January.

Tyson Foods climbed 2.3% after the seller of chicken, beef and pork reported a stronger profit for the latest quarter than analysts expected.

Roughly four out of every five companies in the S&P 500 that have so far reported their results for the summer have also topped analysts’ profit expectations, according to FactSet. Companies usually beat analysts’ estimates each quarter, but the pressure was high this time around because they needed to justify the big moves upward for their stock prices since April.

Delivering bigger profits is one of the easier ways companies can quiet criticism that their stock prices have become too expensive.

In other dealings early Tuesday, U.S. benchmark crude oil lost 25 cents to $59.88 per barrel. Brent crude, the international standard, shed 25 cents to $63.81 per barrel.

___

AP Business Writers Stan Choe and Matt Ott contributed.

Unemployment in the UK has risen by more than expected to the highest level in four years, official figures show, amid a worsening slowdown in the jobs market before Rachel Reeves’s autumn budget.

With under three weeks to go before the chancellor’s tax and spending statement, figures from the Office for National Statistics (ONS) show the headline unemployment rate rose to 5.0% in the three months to the end of September, up from 4.8% in the previous quarter.

City economists had forecast an increase to 4.9%. The official headline unemployment rate was last higher in the first quarter of 2021, during the height of the Covid pandemic.

Liz McKeown, the ONS director of economic statistics, said: “These figures point to a weakening labour market.”

The ONS’s figures are based on its widely criticised labour force survey, which has suffered from collapsing response rates. Experts have argued this leaves policymakers “flying blind”, risking decisions being taken based on flawed data.

However, separate data suggests the jobs market has slowed sharply, as employers come under pressure from tax increase, stubborn inflation, elevated borrowing costs and a sluggish growth outlook.

Figures from HMRC published on Tuesday showed the number of workers on company payrolls fell by 32,000 in October, compared with September.

Reeves is expected to raise taxes in the budget to plug a shortfall in the government finances of up to £30bn. However, business leaders have warned doing so could hit jobs and growth.

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• GCP launches at COP30 as the world’s first global voluntary framework for measuring, managing, and communicating circularity impacts.  
• Developed by WBCSD and One Planet Network (hosted by UNEP) with 150+ experts and 80+ organizations. 
• Empowers companies to cut waste, reduce emissions, boost accountability and improve business performance. 
• Impact analysis: up to 120 billion tonnes of material savings and 76 gigatons CO₂ can be avoided by 2050. 
• Piloted by industry leaders, the GCP sets a new benchmark for credible, comparable circularity reporting. 

Belém, 11 November 2025: The World Business Council for Sustainable Development (WBCSD) and One Planet Network (hosted by UNEP) have announced the official launch of the Global Circularity Protocol for business (GCP) at COP30, marking a major milestone in the global transition to a circular economy. 

Developed in partnership with over 150 experts from more than 80 organizations – including leading businesses, policymakers, and scientific advisors – the GCP is the world’s first voluntary science-based, globally harmonized framework designed to help companies of all sizes measure, manage, and communicate their circular performance and impacts across value chains. 

A new era for corporate performance and accountability 

The GCP empowers businesses to move beyond linear, wasteful models by providing practical, standardized steps and metrics for reducing waste, cutting emissions, and creating value for people and planet while delivering business value for all. By aligning with leading global standards, the Protocol enables credible, comparable reporting and supports companies in meeting rising regulatory and stakeholder expectations.

The Global Circularity Protocol for Business sets a new benchmark for corporate performance and accountability. Circularity is no longer optional – it is a strategic necessity for the resilience of business and the health of our planet. The GCP provides companies with standardized, science-based metrics and a clear roadmap for measurable action, enabling leaders to drive tangible progress, build resilience, and deliver long-term value to both business and planet. The scale of the opportunity is significant. Our analysis has revealed that by 2050, widespread adoption of the GCP could save up to 120 billion tonnes of materials – equivalent to one year’s current global consumption – and avoid up to 76 gigatons of CO₂ emissions – equivalent to one and a half times current global annual emissions. I encourage business leaders and policymakers alike to adopt the GCP as a practical foundation for accelerating the shift to a just, circular, and regenerative economy.

– Peter Bakker, President and CEO, WBCSD

Real-world impact and global collaboration 

Piloted by industry leaders and a cohort of GCP Front Runners, the GCP is already delivering results – helping companies identify circularity hotspots and opportunities to drive innovation, and build resilient, future-fit value chains. The Protocol’s collaborative development process ensures it is robust, practical, and adaptable for diverse sectors and geographies. 

The GCP is a powerful catalyst for value chain transformation. It enables companies to map material flows, identify circularity hotspots, and collaborate with partners at every stage – unlocking efficiencies, reducing risk, and scaling impact beyond individual operations. Launching the GCP at COP30 is no coincidence. We’re here on the international stage because the GCP is a truly global solution – it responds to some of the most pressing global risks, including resource scarcity, supply chain volatility, and climate change.

– Diane Holdorf, Executive Vice President, WBCSD

A game changer for credible circularity 

The sustainability professionals, policy makers, and academics that contributed to develop the GCP are calling it “a game-changer for credible circularity,” “the missing link between ambition and action,” and “a roadmap for business value and accountability.” Their feedback continues to shape the Protocol as it evolves to meet the needs of a rapidly changing world. 

The GCP delivers what the circular economy has long lacked: a globally harmonized framework to help companies measure, manage, and disclose circularity impacts. This collaborative effort reflects the multilateral ambitions of the Stockholm+50 Action Agenda and of the Global Strategy for Sustainable Consumption and Production launched by the United Nations in 2022.

– Jorge Laguna-Celis, Head, One Planet Network (hosted by UNEP)

At Philips, circularity is a powerful lever to reduce material use and our overall impact on climate and nature, while driving customer value and business success. Healthcare is a material-intensive industry. Embedding circular practices and innovations can help hospitals with reducing their environmental footprint while improving healthcare resilience and patient outcomes. That’s why we collaborated and co-championed the Global Circularity Protocol. GCP1.0 offers a clear and unified approach to set ambitious and adequate goals for circularity – a much-needed step towards a sustainable and healthy future.

– Harald Tepper, Global Lead Circularity, Philips

The GCP is important to TOMRA because it provides a common framework for businesses to measure progress on circularity initiatives. This is vital for ensuring that change can occur at scale, supporting circularity targets and policymaking going forward.

– Tove Andersen, President and CEO, Tomra

The Global Circularity Protocol (GCP) is a strategic enabler for resource-intensive sectors like mining to contribute meaningfully to global sustainability and energy transition goals. At Vale, advancing circularity means transforming extraction and processing systems to maximize material recovery, reduce environmental impact, and accelerate the shift toward low-carbon, circular production models that will deliver the ‘mining of the future’ we are aiming at.

–  Bruno Pelli, Global Director in Mining Technical Services, Vale 

Time to turn circular ambition into measurable business impact 

The launch of the GCP at COP30 is a call to action for business leaders, sustainability professionals and policy makers to adopt the GCP and join the growing community of leading businesses that are accelerating the transition to a circular economy.

We invite all stakeholders – from pioneering organizations and policymakers, to researchers and financial experts – to contribute ideas, pilot methodologies and share lessons learned, as this first version of the GCP is just the starting point of a dynamic, multi-year journey working for a resilient, regenerative economy that benefits people and planet. 

Discover the GCP and help your organization turn circular ambition into measurable business impact. 

The launch was co-hosted by the Ministry of the Environment Government of Japan (MOEJ), the World Business Council for Sustainable Development (WBCSD), and UNEP One Planet network at the COP30 Japan Pavilion. 

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Notes

The potential impact of the GCP 

Source: World Business Council for Sustainable Development, & One Planet Network. (2024). Global Circularity Protocol for Business: Impact Analysis on Climate, Nature, Equity and Business Performance. Link 

• The GCP could enable 100-120 billion tonnes of cumulative material savings by 2050 – equivalent to one year’s current global material consumption. 

• Adoption of the GCP could deliver 67-76 gigatons of CO₂ equivalent avoided by 2050, or about 1.3–1.5 times current annual global emissions. 

• The GCP can double the pace at which businesses reach advanced circularity maturity levels, accelerating the benefits of circular business models by more than a decade. 

• The protocol is expected to drive 11-12% annual reductions in PM2.5 air pollution between 2026 and 2050, contributing to significant public health gains. 

• By 2050, the GCP could reduce arable land occupation by up to 2.9% (0.7-1.1 million km²) – comparable to the size of Ethiopia. 

• Circularity, enabled by the GCP, could unlock $4.5 trillion in economic growth and create 6 million new jobs through activities such as recycling, repair, renting, and remanufacturing. 

• These figures underscore the GCP’s potential to deliver measurable, system-wide benefits for business, society, and the environment – making it a critical tool for the global transition to a circular economy.