Marker For Risk Stratification Research Articles

An oral microbiota-based deep neural network model for risk stratification and prognosis prediction in gastric cancer

ABSTRACT Background This study aims to develop an oral microbiota-based model for gastric cancer (GC) risk stratification and prognosis prediction. Methods Oral microbial markers for GC prognosis and risk stratification were identified from 99 GC patients, and their predictive potential was validated on an external dataset of 111 GC patients. The identified bacterial markers were used to construct a Deep Neural Network (DNN) model, a Random Forest (RF) model, and a Support Vector Machine (SVM) model for predicting GC prognosis. Results GC patients with <3 years of survival showed a higher abundance of Aggregatibacter and diminished abundances of Filifactor and Moryella than those who survived ≥3 years. The Boruta algorithm unearthed Leptotrichia as another significant marker for GC prognosis. Consequently, a DNN model was constructed based on the relative abundances of these bacteria, predicting 3-year and 5-year survival in GC patients with Area Under Curve of 0.814 and 0.912, respectively. Notably, the DNN model outperformed the TNM staging system, SVM and RF models. The prognostic value of these bacterial markers was further reinforced by external validation. Conclusion The oral microbiota-based DNN model may advance GC prognosis. The biological functions of these oral bacterial markers warrant further investigation from the perspective of GC progression.

Quantifying Tumor Budding: Implications for Prognosis in Gastric Adenocarcinoma.

The mechanism of tumor budding (TB) in gastric adenocarcinoma (GAC) and its relationship with biological indicators and prognostic significance, remains unclear. In this study, we conducted a comprehensive analysis using whole-slide imaging to evaluate TB in 75 cases of GAC. Our findings revealed the risk factors associated with TB in GAC and their impact on patient prognosis. The results indicate that the majority of cases exhibited a TB grade exceeding 10 (n=41), followed by 6-10 (n=15). Histologic grade (R=0.26, P=0.06), pT stage (R=0.56, P=0.00), neural invasion (R=0.29, P=0.01), marginal zone growth pattern (R=0.25, P=0.02), and basal zone growth pattern (R=0.38, P=0.001) are associated with TB in GAC. Logistic regression analysis revealed that the infiltrative growth pattern in both the marginal zone (odds ratio=5.90, 95% CI: 1.04-33.44, P=0.05) and basal zone (odds ratio=12.80, 95% CI: 2.03-80.68, P=0.01) were identified as risk factors for TB in GAC. Univariate analysis demonstrated a negative correlation between TB and TB grade with overall survival and progression-free survival in GAC patients. Furthermore, the multivariate COX analysis revealed that TB and TB grade, along with American Joint Committee on Cancer stage, lymph node metastasis, and pT stage, independently influenced the prognosis of GAC patients. In conclusion, a comprehensive evaluation of TB could serve as a significant histologic marker for risk stratification in GAC.

Coronary Plaque Characteristics Assessed by Optical Coherence Tomography and Plasma Lipoprotein(a) Levels in Patients With Acute Coronary Syndrome.

Lipoprotein(a) [Lp(a)] is associated with increased cardiovascular risk, but its influence on plaque characteristics at optical coherence tomography (OCT) evaluation is not fully understood. This study seeks to explore the impact of Lp(a) levels on plaque morphology as assessed by OCT in a very high-risk subset of patients. Consecutive patients admitted for acute coronary syndrome (ACS) and undergoing OCT-guided percutaneous coronary intervention (PCI) at a large tertiary care center between 2019 and 2022 were deemed eligible for the current analysis. The overall population was categorized into two subgroups according to baseline Lp(a) levels: (1) lower Lp(a) (Lp(a) ≤ 300 mg/L) and (2) elevated Lp(a) (Lp(a) 300 mg/L). Predictors of lipid-rich plaques were identified using multivariable logistic regression with stepwise selection of candidate covariates. A total of 202 patients were included in this study. OCT findings revealed that patients with elevated Lp(a) had a higher prevalence of lipid-rich plaques, a significantly greater mean lipid arc, along with increased macrophage infiltration and thin-cap fibroatheroma (TCFA). In contrast, calcific plaque prevalence was higher in the lower Lp(a) group. Multivariable regression analysis identified low-density lipoprotein cholesterol ≥ 70 mg/dL, and elevated Lp(a) as strong predictors of lipid-rich plaques at OCT. In this observational study including ACS patients undergoing OCT-guided PCI, those with elevated Lp(a) levels exhibited a higher prevalence of lipid-rich plaques, increased macrophage infiltration, and TCFA, thereby indicating a more vulnerable plaque phenotype. Additionally, elevated Lp(a) levels and LDL-C levels ≥ 70 mg/dL were each independently associated with lipid enrichment of coronary plaques. These findings suggest Lp(a), beyond other well-known risk factors, as a key marker for risk stratification, potentially informing optimal medical management strategies.

Improved survival of patients with newly diagnosed oligometastatic prostate cancer through intensified multimodal treatment

Background and objectivesThe standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT), novel antihormonal therapies (NHT) and/or chemotherapy. Patients with newly diagnosed oligometastatic prostate cancer (omPCa) represent a distinct subgroup of mHSPC, for which the optimal treatment, particularly the role of radical prostatectomy (RP) and metastasis-directed therapy (MDT), is currently under debate.Materials and methodsIn this single center, retrospective analysis, 43 patients with newly diagnosed omPCa were included. All patients underwent RP as part of a multimodal, personalized treatment approach. Other treatments included ADT, NHT, MDT (surgery or radiotherapy), adjuvant radiotherapy (prostatic fossa and/or pelvic lymph nodes) or chemotherapy in various combinations. Clinical endpoints were progression free and cancer specific survival (PFS, CSS).ResultsNo patient with omPCa died from prostate cancer during an up to ten years follow-up period after intensified multimodal treatment i.e., RP, ADT, adjuvant radiation therapy and MDT (n=13). In contrast, patients requiring chemotherapy (n=10) showed a significantly worse PFS (p&amp;lt;0.001) and CSS (p&amp;lt;0.001). Patients receiving various combinations (&amp;lt;4 therapeutic modalities; n=20) showed a more favorable outcome than patients receiving chemotherapy, but differences in PFS and CSS were not statistically significant compared to patients receiving an intensified multimodal treatment.ConclusionsAn intensified, multimodal treatment approach including RP can lead to excellent survival outcomes in patients with newly diagnosed omPCa. Patients requiring chemotherapy have most likely a more aggressive disease and therefore a more rapid tumor progression. Future studies to identify markers for risk stratification in patients with omPCa are therefore needed.

Monocyte to high-density lipoprotein cholesterol ratio predicts restenosis of drug-eluting stents in patients with unstable angina pectoris

Several studies have shown that the monocyte count to high-density lipoprotein cholesterol ratio (MHR) serves as a predictive marker for in-stent restenosis (ISR) of bare-metal stents (BMSs). However, the ability of the MHR to predict ISR in patients with drug-eluting stents (DESs) remains uncertain. This study aimed to investigate the predictive value of the MHR for ISR in patients with unstable angina pectoris who have undergone primary DES implantation. A total of 474 consecutive patients with unstable angina pectoris who underwent successful DES-based percutaneous coronary intervention (PCI) from 01-12-2014 to 01-12-2022 were enrolled in the study. Patients were divided into the ISR group and the non-ISR group on the basis of the follow-up results of coronary angiography. The demographic and clinical characteristics of the patients were documented. The MHR was calculated via the following formula: . Multivariate logistic regression models were developed to evaluate the predictive value of the MHR for DES-ISR. The baseline MHR was notably greater in the ISR group than in the non-ISR group (P < 0.001). After adjusting for confounding factors, the MHR emerged as an independent predictor of ISR (OR = 1.244; 95%CI 1.171–1.321). Receiver operating characteristic (ROC) curve analysis revealed that MHR for predicting ISR had an AUC of 0.752 (95% CI 0.708–0.796). For a MHR > 7.32, the sensitivity was estimated to be 59.8% (95% CI 47.2-66.5%) and the specificity was 81.2% (95% CI 71.2-86.4%). Including the MHR in the predictive model for ISR improved the area under the curve (0.698 vs. 0.782, P < 0.001), categorical net reclassification improvement (0.703; 95%CI 0.536–0.871), and integrated discrimination improvement (0.121; 95%CI 0.092–0.151). The MHR can be used to predict DES-ISR in patients with unstable angina pectoris, indicating that the MHR may serve as a valuable marker for risk stratification and prognosis in individuals undergoing DES implantation.

Effects of Cognitive Behavior Therapy on Heart Rate Variability among Medical Students at a Teaching Institution in Jaipur, India

Abstract Introduction: Heart rate variability (HRV) is the variation in the time interval between heartbeats. It is controlled by the autonomic nervous system, which also regulates many other vital body functions. HRV has been used as a noninvasive marker of cardiac autonomic activity and cardiovascular risk stratification. The present study aimed to investigate the effect of cognitive behavior therapy (CBT) on different domains of HRV and their correlation at baseline and after 3 months of intervention. Methods: After obtaining institutional ethical clearance, the study was conducted from July to October 2022 among 140 1st-year Bachelor of Medicine and Bachelor of Surgery students at a medical college in Jaipur, Rajasthan, India. Linear component, i.e., time and frequency domain, and nonlinear components, i.e., Poincare plot of HRV assessed at baseline and after the 3 months of CBT. Results: Findings show that there was a significant decrease in linear components, i.e., time domain and frequency domain parameters (P &lt; 0.001) and nonlinear components Poincare plot standard deviation (SD) 1/SD2 (P &lt; .0.001) after 3 months of CBT. Linear and nonlinear components of HRV were positively correlated (P &lt; 0.01). Conclusion: The study indicates that after 3 months of CBT, the autonomic nervous system shifted toward parasympathetic dominance, which was assessed by linear components, time domain and frequency domain parameters, and nonlinear components, i.e., Poincare plot (SD1/SD2) of HRV.

RV-PA uncoupling is associated with increased mortality in transthyretin amyloid cardiomyopathy treated with tafamidis.

The right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload. In case of transthyretin amyloid cardiomyopathy (ATTR-CM), impaired RV-PAc can result from increased left ventricular diastolic stiffness due to fibril deposition. While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unknown. We sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM. In this multicentre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with a TTR stabilizer. The primary outcome was all-cause mortality. Within a median time of 1.52 [IQR 0.72-2.56] years after diagnosis, 49 (11.7%) patients died. In multivariate Cox regression analysis impaired RV-PAc was a strong independent predictor of mortality (Hazard Ratio (HR) 2.16, 95% Confidence Interval (CI) 1.14-4.07, p=0.018). RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382mm/mmHg (area under the curve (AUC) 0.73, 95% CI 0.65-0.81). Patients with RV-PAc ratio ≤ 0.382mm/mmHg exhibited significantly lower survival (HR 4.17, 95% CI 2.21-7.87, p<0.001) within 3years of follow up than those with RV-PAc ratio above the cut-off (Graphical Abstract). Impaired adaptation of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality. Therefore, the determination of RV-PAc could improve risk stratification for ATTR-CM patients.

Gene Co-Expression Network Analysis Associated with Endometrial Cancer Tumorigenesis and Survival Outcomes.

Endometrial cancer (EC) presents a substantial health challenge, with increasing incidence and mortality rates. Despite advances in diagnosis and treatment, understanding the molecular underpinnings of EC progression remains unknown. In this study, we conducted a comprehensive investigation utilizing The Cancer Genome Atlas (TCGA-UCEC n = 588) data to analyze gene co-expression patterns, elucidate biological process pathways, and identify potential prognostic and diagnostic biomarkers for EC, using weighted gene co-expression network analysis (WGCNA), differential gene expression, survival analysis, and functional analysis, respectively. We determined that the Green module (M5) was significantly correlated with patient survival. Functional analysis of the genes in module M5 indicates involvement in cell cycle regulation, mitotic spindle assembly, and intercellular signaling. TPX2, BUB1, and ESPL1 were among the top differentially expressed genes in the Green module, suggesting their involvement in critical pathways that contribute to disease progression and patient survival outcomes. The biological and clinical assessments of our findings provide an understanding of the molecular landscape of EC and identified several potential prognostic markers for patient risk stratification and treatment selection.

YKL-40 as a risk stratification marker in acute pancreatitis: a prospective study

Background/objectives. Increased systemic concentrations of YKL-40 are seen in various inflammatory conditions. We explored the relationship between the serum YKL-40 concentrations and subsequent disease severity in patients with acute pancreatitis (AP). MethodsConsecutive adults with AP were prospectively enrolled, and classified as having mild, moderate or severe disease. On admission and 48 hours later, C-reactive protein (CRP), YKL-40, interleukin-6 and 8 (IL-6, IL-8), and tumor necrosis factor alpha (TNF-α) concentrations were measured. Patients were also classified as those with low (<50 ng/mL, in the range seen in 30 age and sex-matched non-AP subjects), high (≥190 ng/mL, seen in most of the other inflammatory conditions), and intermediate YKL-40 (50-189 ng/mL). ResultsIncidence of mild, moderate and severe AP among the 150 enrolled patients was 80 (53.3%), 59 (39.3%), and 11 (7.4%), respectively. Both on admission and 48 hours later, high YKL-40 (vs. intermediate or low) was strongly associated with higher odds of a more severe AP, independently of the concurrent IL-8 and TNF-α concentrations (OR around 3.5-4.0, or higher). On admission, the association was independent also of the concurrent CRP, whereas the association between the later concentrations and the outcome was conditional on CRP – uncertain at low, strong at high CRP. The high YKL-40 – outcome association at both time-points was conditional on concurrent IL-6: uncertain if IL-6 was low, strong if IL-6 was high. ConclusionsSerum YKL-40 is a plausible candidate for further evaluation as an early biochemical indicator of subsequent AP severity, particularly if considered jointly with CRP and/or IL-6.

Estimated aortic pulse wave velocity predicts adverse events in females with thoracic aortic aneurysms

Abstract Introduction Despite being more common in males, thoracic aortic aneurysms (TAAs) have worse prognosis in females. Females with TAA are 3x more likely to experience acute aortic syndromes, and 40% more likely to die than their male counterparts, but mechanisms underlying this paradox are incompletely understood. The estimated aortic pulse wave velocity (e-PWV) is a marker of aortic stiffness that can be used widely due to its simplicity, as it does not require specialized equipment. We have previously shown that e-PWV was independently associated with faster TAA growth,(1) and that this association was twice as strong in females than males, but the role of e-PWV as a predictor of adverse outcomes in TAA remains unknown. Purpose We sought to evaluate the sex-specific association of e-PWV with adverse outcomes in patients with TAA. Methods We performed a prospective study of 102 males and 48 females with TAA. e-PWV was calculated according to validated equations utilizing age, mean arterial pressure, and presence/absence of cardiovascular risk factors.(2) The primary outcome was a composite of acute aortic syndromes, death, or elective aortic surgery. We used a Cox proportional hazard model to determine the independent association of e-PWV with the primary outcome, adjusted for age, BSA, aneurysm size and location, hypertension, and pulse pressure. Sex-specific models were performed if the interaction of sex*e-PWV was significant (P≤0.05). Univariate logistic regression models were performed to determine the c-statistic for e-PWV in predicting adverse outcomes, and the best e-PWV cutoff for this prediction was established based on sensitivity and specificity. Kaplan-Meier curves were performed using this cut-off. Results A summary of study design and results is presented in Picture 1. Mean age was 62±12 years, 70 (47%) had degenerative etiology, baseline aneurysm size was 46.3±4.3mm, and e-PWV was 9.5±1.9 m/s (not different between sexes, P&amp;gt;0.07 for each). Mean follow-up was 4.6±2.4 years in females and 5.5±2.3 years in males, P=0.031. The primary outcome occurred in 37 (25%) participants (3 dissections, 3 intramural hematomas, 1 aortic rupture, 22 elective surgical repairs and 11 deaths - 3 of which followed surgery). The interaction term sex*e-PWV was significant (P=0.0001), so sex-specific models were performed. e-PWV independently predicted the primary outcome in females (HR for 1m/s increase in e-PWV: 3.4; 95% confidence interval (CI): 1.1-14.7, P=0.033), but not in males (HR: 0.87; 95% CI: 0.50-1.51, P=0.622). In females, e-PWV had a c-statistic of 0.860 for the detection of the primary outcome, with a best e-PWV cutoff of 11.58 m/s (73% sensitivity, 92% specificity). Kaplan-Meier curves for the primary outcome in females using this cutoff are shown in Picture 2. Conclusion e-PWV independently predicts adverse outcomes in females with TAA, highlighting a novel marker for risk stratification and therapeutic targeting.Study summaryKaplan-Meier curves

A novel marker of cardiovascular risk stratification: the role of total cardiovascular calcium score using cardiac CT

Abstract Introduction It is widely accepted that coronary and valve calcification measured by cardiac CT, individually, are associated with cardiovascular events and mortality. However, the role of an encompassing marker of cardiovascular atherosclerosis could be more representative of the real cardiovascular risk. Objectives To determine the prognostic value of a combined coronary, valvular and aortic calcium score to predict long-term major adverse cardiac and cerebrovascular events (MACCE). Methods We conducted a single center study on 316 consecutive patients who underwent cardiac CT scan between January 2018 and December 2019. We excluded patients with poor imaging quality, constrictive pericarditis, prosthetic valves and/or devices. The calcium score of coronary arteries (CA), mitral valve (MV), aortic valve (AoV), ascending aorta (AAo) and aortic arch (AAc) were calculated from non-contrast ECG-gated CT using the Agatston method and were combined to derive a valvular (VA=MV+AoV), total cardiac (TC=CA+VA) and total cardiovascular (TCV=TC+AAo+AAc) calcium scores (Fig.1A). The primary endpoint was a composite of MACCE, defined as all-cause death, stroke, myocardial infarction and hospital admission for heart failure. Results A total of 275 CT scans were suitable for analysis. Mean age was 59.6±12.3 years, 48.4% were female. A total of 183 (66.7%) patients presented calcification in at least one location. Patients with calcification on any of the prespecified locations had higher prevalence of hypertension, dyslipidemia and type 2 diabetes mellitus (DM) than those without any calcium (p&amp;lt;0.05). After a median follow-up of 3.18 [IQR 2.84-3.69] years, 40 (14.5%) patients had met the primary endpoint. Regression analyses demonstrated that all CA, VA, TC and TCV scores were independent predictors of MACCE (p&amp;lt;0.05 for all). The best prediction models included calcium score (all combinations), age, sex, type 2 DM and smoking status (Fig.1B). The model with TCV score was the most powerful predictor of MACCE (χ2 47.8), followed by TC score (χ2 43.1). Of interest, the model with CA score had the poorest performance (χ2 35.4). Conclusion Coronary calcium score is a quick way to stratify risk in clinical practice, but its performance is too focused on coronary events. Total cardiovascular calcium score, however, is more encompassing, also quick to measure, and a more truthful depiction of the patient’s cardiac and cerebrovascular risk, potentially allowing a more tailored and timely approach to risk factors in clinical practice.

RV-PA uncoupling is a strong predictor of 3-year all-cause mortality in transthyretin amyloid cardiomyopathy

Abstract Background Right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload which, in case of transthyretin amyloid cardiomyopathy (ATTR-CM), can result from increased left ventricular diastolic stiffness due to fibril deposition. While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unclear. This study sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM. Methods In this two-centre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with TTR stabilizer. The primary outcome was all-cause mortality. Receiver operation curves and Youden’s J analysis were applied to identify an optimal cut-off value of RV-PAc ratio. Results Within a median time of 631 (IQR 361-983) days after diagnosis, 14.4% of patients died. RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382mm/mmHg (area under the curve (AUC) 0.746, 95% CI 0.68-0.82). Patients with RV-PAc ratio ≤0.382mm/mmHg (impaired RV-PAc, n=158) exhibited significantly lower survival (HR 4.07, 95% CI 2.26-7.33, p&amp;lt;0.001) within 3 years of follow up than those with RV-PAc ratio &amp;gt; 0.382mm/mmHg. In multivariate Cox regression analysis, incorporating a range of known prognostic variables, reduced RV-PAc was a strong echocardiographic predictor of mortality (Hazard Ratio (HR) 2.99, 95% Confidence Interval (CI) 1.63-5.51, p &amp;lt;0.001). Conclusion Impaired adaption of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality within three years after diagnosis. Therefore, determination of RV-PAc could improve risk stratification for ATTR-CM patients.Figure_1_Kaplan-Meier curves

Prognostic value of reticulocyte production ability in patients with chronic heart failure

Abstract Background Anaemia is frequently observed in patients with chronic heart failure (CHF), and many studies have elucidated the association between anaemia and mortality in patients with CHF. The quality of erythropoiesis is an intrinsic aspect of pathophysiology of anaemia, and the ability of reticulocyte production would be one of the pivotal factors in the quality of erythropoiesis. Purpose We sought to investigate whether the reticulocyte production ability is associated with clinical outcomes, and clarify the pathophysiology of reticulocyte production in patients with CHF. Methods We prospectively examined 1,328 symptomatic CHF patients (median age 71 [IQR 65-82] years, mean left ventricular ejection fraction 50 ± 16%, median NT-proBNP 743 [IQR 360–1710] pg/mL) in a multicentre registry with 27 Japanese sites between January 2020 and October 2023. The reticulocyte production ability was evaluated by calculating the reticulocyte production index (RPI) using reticulocyte counts and serum haematocrits. Patients were divided into four groups according to the presence or absence of WHO defined anaemia and the median value of RPI. The primary outcome was a composite of all-cause death and hospitalisation for worsening HF. Results During a median follow-up period of 551 (IQR 321–712) days, the primary outcome occurred in 219 (17%) patients. The group with anaemia and high RPI (≥0.978, the median) showed the highest incidence of the primary outcome among the groups (P &amp;lt; 0.001) (Figure 1). Multivariable regressions showed that higher RPI was independently associated with the higher risk of the primary outcome, even after adjustment for NT-proBNP, sodium, haemoglobin, serum iron, erythropoietin, and MAGGIC risk score (HR 1.41, 95% CI 1.09–1.82). Erythrocyte counts were significantly increased in patients with higher RPI compared to those with lower RPI in the groups without anaemia (P &amp;lt; 0.001)whereas there were no significant differences on erythrocyte counts between the groups with anaemia (P = 0.90) (Figure 2A). Patients with higher RPI had higher log erythropoietin levels compared to those with lower RPI in either anaemic or non-anaemic group (Figure 2B). In addition, serum iron levels and transferrin saturation did not significantly differ between the RPI groups in either anaemic or non-anaemic group (Figures 2C and D). Furthermore, in patients without anaemia, erythrocyte counts positively correlated with RPI (R = 0.27, P &amp;lt; 0.001) whereas there was very weak correlation between erythrocyte counts and RPI in those with anaemia (R = 0.07, P = 0.045). Conclusions Higher RPI was independently associated with worse clinical outcomes, suggesting RPI could be a surrogate marker for risk stratification in patients with CHF, especially in anaemic population. Higher reticulocyte production ability might reflect the impaired maturation of reticulocytes to erythrocytes independent of iron parameters.

The Association of Neutrophil to Lymphocyte Ratio and Other Complete Blood Count Parameters with Global Registry of Acute Coronary Events Risk Score in Patients with Non-ST Segment Elevation - Acute Coronary Syndrome: A Single-Center Study.

The involvement of inflammation in the start and advancement of atherosclerotic plaques in acute coronary syndrome has been clarified. White blood cell count and its differential are key inflammatory markers in cardiovascular disease, with the neutrophil-to-lymphocyte ratio (NLR) emerging as a marker of inflammation and a predictor of mortality in patients with acute coronary syndrome. The study aims to investigate the utility of neutrophil to lymphocyte ratio and other complete blood count parameters as a risk stratification tool and independent predictor of Global Registry for Acute Coronary Events (GRACE) risk score in Non-ST segment elevation acute coronary syndrome (NSTE-ACS). This was a cross-sectional retrospective single-center study conducted in Baghdad Teaching Hospital. A total of 110 patients diagnosed with NSTE-ACS were enrolled in this study. Demographic data and components that determine the GRACE risk score were recorded at admission to the emergency department alongside risk factors for coronary artery disease. Venous blood for relevant laboratory analysis was obtained from all patients. Patients were categorized into three risk groups according to the GRACE risk score. The study results were statistically analyzed using the one-way Analysis of Variance (ANOVA) test and the Kruskal Wallis test. Spearman test and multiple linear regression analysis were used for correlation and identification of independent predictors respectively. The mean age of patients was 59.4 years with a standard deviation of 21.1 years. The majority of them were males (61.8%). The predominant portion (102) had non-ST elevation myocardial infarction (NSTEMI). The mean total white blood cell count, absolute neutrophil count, absolute lymphocyte count, and neutrophil to lymphocyte ratio of the patients were 11.1 ×103/ml, 8.7 ×103/ml, 1.7 ×103/ml, and 5.9 respectively. The mean admission left ventricle ejection fraction (LV EF) of the patients was 52.5 % with a standard deviation of 9.6 %. There is a significant positive correlation between NLR and GRACE risk score (r = 0.339, P < 0.001) and a statistically significant negative correlation between NLR and LV EF (r = -0.385, P = 0.005). This study showed a statistically significant association and positive correlation between neutrophil-to-lymphocyte ratio (NLR) and Global Registry of Acute Coronary Events (GRACE) risk score, so neutrophil-to-lymphocyte ratio (NLR) is a valuable marker for risk stratification and prognosis in NSTE-ACS patients, serving as an independent predictor of the GRACE risk score.

Cardiac MRI in infarct-like myocarditis: transmural extension of late gadolinium enhancement is associated with worse outcomes

ObjectivesTo assess the prognostic value of cardiac MRI (CMR) parameters for the occurrence of major adverse cardiac events (MACE) in patients with infarct-like myocarditis.MethodsIn this retrospective single-center study, patients with CMR-confirmed acute myocarditis with infarct-like presentation were identified (2007–2020). Functional and structural parameters were analyzed including late gadolinium enhancement (LGE). The primary endpoint was the occurrence of MACE up to 5 years after discharge.ResultsIn total, 130 patients (mean age, 40 ± 19 years; 97 men, 75%) with infarct-like myocarditis were included. CMR was conducted a median of 3 days (interquartile range [IQR], 1–5) after symptom onset. MACE occurred in 18/130 patients (14%) during a median follow-up of 19.3 months (IQR, 4.5–53). The median extent of LGE was 7% (IQR, 4–10). LGE affected the subepicardium in 111/130 patients (85%), the midwall in 45/130 patients (35%), and both the subepicardium and midwall in 27/130 patients (21%). Transmural extension of non-ischemic LGE lesions was observed in 15/130 patients (12%) and septal LGE in 42/130 patients (32%). In univariable Cox regression analysis, a significant association was found between the occurrence of MACE and both, quantified LGE extent and transmural LGE pattern. In multivariable analysis, transmural extension of LGE was an independent predictor for MACE (hazard ratio, 6.34; 95% confidence interval: 2.29–17.49; p < 0.001). Patients with the transmural extension of LGE had a shorter event-free time on Kaplan–Meier analysis (log-rank p < 0.001).ConclusionsMACE occurred in 14% of patients with infarct-like myocarditis during follow-up. A transmural extension of non-ischemic LGE was associated with a worse long-term prognosis.Critical relevance statementCMR-based assessment of transmural extension of non-ischemic LGE holds the potential to serve as an easily assessable marker for risk stratification in patients with infarct-like myocarditis.Key PointsThe prognostic value of CMR was studied in patients with infarct-like myocarditis.The extent of LGE and transmural extension were linked to adverse cardiac events.Transmural non-ischemic LGE can serve as an easily assessable prognostic marker.Graphical

Impact of Hypoalbuminemia on Outcomes Following Hepatic Resection: A NSQIP Retrospective Cohort Analysis of 26,394 Patients

Background/Objectives: Efforts to preoperatively risk stratify and optimize patients before liver resection allow for improvements in postoperative outcomes, with hypoalbuminemia being increasingly researched as a surrogate for nutrition, overall health and functional status. Given the paucity of studies examining the relationship between hypoalbuminemia and liver resection, this study aims to determine the impact of hypoalbuminemia on outcomes following liver resections using a large multicenter database. Methods: The American College of Surgeons–National Surgical Quality Improvement Program (2017–2021) database was used to extract the data of patients who underwent a hepatic resection. Two cohorts were defined; those with hypoalbuminemia (HA; &lt;3.0 g/L) and those with normal albumin levels (≥3.0 g/L). Both baseline characteristics and 30-day postoperative complication rates were compared between the two cohorts. Multivariable logistic regression models were used to assess the independent effect of HA on various outcomes. Area under curve–receiver operating characteristic (AUC-ROC) curves were used to identify optimal albumin thresholds for both serious complications and mortality. Results: We evaluated 26,394 patients who underwent liver resections, with 1347 (5.1%) having preoperative HA. The HA patients were older (62.3 vs. 59.8; p &lt; 0.001) and more likely to be of an ASA class ≥ 4 (13.0% vs. 6.5%; p &lt; 0.001). The patients with HA had significantly more complications such as an increased length of stay, readmission, reoperation, sepsis, surgical site infection, bile leak, and need for transfusion. After controlling for demographics and comorbidities, HA remained a significant independent predictor associated with both 30-day serious complication rates (aOR 2.93 [CI 95% 2.36–3.65, p &lt; 0.001]) and mortality (aOR 2.15 [CI 95% 1.38–3.36, p = 0.001]). The optimal cut-off for albumin with respect to predicting serious complications was 4.0 g/dL (sensitivity 59.1%, specificity 56.8%, AUC-ROC 0.61) and 3.8 g/dL (sensitivity 56.6%, specificity 68.3%, AUC-ROC 0.67) for mortality. Conclusions: In this large, retrospective database analysis, preoperative HA was significantly associated with 30-day morbidity and mortality rates following hepatic resection. Preoperative albumin may serve as a useful marker for risk stratification in conjunction with pre-existing calculators. Future studies evaluating the risk mitigation impact of nutrition and exercise prehabilitation in these patients and its capacity to modify hypoalbuminemia would be beneficial.

Age-Related Macular Degeneration and Its Genetic Risk: A Population-based Study

Purpose Specific genetic factors might serve as markers for risk stratification of AMD progression, but their association with key features of AMD has not been fully elucidated. Thus, we investigated the association between overall and pathway-specific genetic risk scores (GRS) and lead loci (ARMS2, CFH) with AMD stages and features of high-risk nonlate AMD, including reticular pseudodrusen (RPD) and large drusen area (LDA). Methods We performed a cross-sectional analysis of data from the Rhineland Study, a population-based study in Bonn, Germany. We included 4016 individuals aged 50 years and older of European descent. GRS and pathway-specific subscores were constructed based on a large genome-wide association study of AMD. Subscores were generated based on gene-pathways associations (complement, extracellular matrix remodeling (ECM) and lipid metabolism). Associations were assessed using logistic and multinomial regression. Results The mean age of participants was 63.36 years and 1813 (45.1%) were men. The GRS was positive in 48.1% of individuals and increased, but did not fully overlap, across AMD stages. Pathway-specific subscores increased across AMD stages except for the ECM subscore, which only showed a trend for increasing in late AMD. Increasing overall GRS was associated with RPD and LDA (OR [95%CI] for RPD: 1.70 [1.33–2.15], for LDA: 1.64 [1.29–2.07]) among individuals with AMD. Similarly, higher complement and ECM subscores was associated with RPD, while for LDA, only an association with complement subscore was observed. Conclusions In a population-based setting, we confirmed higher genetic risk to be associated with more severe AMD and identified associations with high-risk features of intermediate AMD. Conjoint analyses suggested that high-risk features and late AMD might be differentially associated with genetic architecture in AMD, such as ECM remodeling. Incorporation of genetic information such as GRSs might improve AMD risk prediction strategies.

A comprehensive meta-analysis of tissue resident memory T cell shaping non-small-cell lung cancer immune microenvironment and patient prognosis.

210 Background: Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Methods: Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. A machine learning model was developed to prognosticate survival, tested in multiple independent NSCLC cohorts. Model performance was corroborated through Kaplan-Meier survival plots, receiver operating characteristic (ROC) curves, principal component analysis, and t-SNE analyses. Results: We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the TCGA dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Conclusions: Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification. Keywords: Tissue resident memory T cell, non-small-cell lung cancer, prognosis, tumor immune microenvironment, machine learning.

Preoperative anemia is a risk factor for worse 30-day outcomes in both open and endovascular repair of non-ruptured infrarenal abdominal aortic aneurysm.

Anemia is a highly prevalent condition potentially linked to chronic inflammation. Preoperative anemia is an independent risk factor across many surgical fields. However, the relationship between anemia and abdominal aortic aneurysm (AAA) repair outcomes remains unclear. This study aimed to examine the effects of preoperative anemia on 30-day outcomes of non-ruptured infrarenal AAA repair. Patients who underwent open surgical repair (OSR) and endovascular aneurysm repair (EVAR) for infrarenal AAA were identified in National Surgical Quality Improvement Program (NSQIP) targeted databases from 2012 to 2021. Anemia was defined as preoperative hematocrit less than 39% in males and 36% in females. Multivariable logistic regression was used to compare 30-day perioperative outcomes between anemic and non-anemic patients, adjusting for demographics, comorbidities, indications, aneurysm extents, operation time, and surgical approaches. There were 408 (22.13%) anemic and 1436 (77.88%) non-anemic patients who underwent OSR for non-ruptured AAA, while 3586 (25.20%) patients with and 10,644 (74.80%) without anemia underwent EVAR. In both OSR and EVAR, anemic patients had higher risks of bleeding requiring transfusion (OSR, aOR = 2.446, p < .01; EVAR, aOR = 3.691, p < .01), discharge not to home (OSR, aOR = 1.385, p = .04; EVAR, aOR = 1.27, p < .01), and 30-day readmission (OSR, aOR = 1.99, p < .01; EVAR, aOR = 1.367, p < .01). Also, anemic patients undergoing OSR had higher pulmonary events (aOR = 2.192, p < .01), sepsis (aOR = 2.352, p < .01), and venous thromboembolism (aOR = 2.913, p = .01), while in EVAR, anemic patients had higher mortality (aOR = 1.646, p = .01), cardiac complications (aOR = 1.39, p = .04), renal dysfunction (aOR = 1.658, p = .02), and unplanned reoperation (aOR = 1.322, p = .01). Moreover, in both OSR and EVAR, anemic patients had longer hospital length of stay (p < .01). In OSR and EVAR, preoperative anemia was independently associated with worse 30-day outcomes. Preoperative anemia could be a useful marker for risk stratification for patients undergoing infrarenal AAA repair.

Association of Systemic Inflammation Level on Admission with Total and Cardiovascular‑Specific Death in Heart Failure with Preserved Ejection Fraction: A Large Multi‑Center Retrospective Longitudinal Study.

Heart failure with preserved ejection fraction (HFpEF) is inherently a complex inflammatory syndrome, and heightened inflammation is strongly associated with an increased risk of death. However, the association of systemic inflammation levels with total and cardiovascular death among patients with HFpEF remains unknown. We aimed to investigate the prognostic impact of systemic inflammation on all-cause and cardiovascular death among patients with HFpEF. Patients with HFpEF were included in this study. Systemic inflammation response index (SIRI) is defined as the multiplication of neutrophil and monocyte divided by lymphocyte count, and patients were divided into four groups based on SIRI quartiles. Cox regression models and competing risk models were used to examine the relationships between SIRI and total and cardiovascular‑specific mortality, respectively. 9,986 patients with HFpEF were included in five tertiary hospitals. During a median follow-up period of 4.4 years, a total of 2004 patients died, of which 965 were cardiovascular deaths. After fully adjusting for confounders, elevated SIRI level was significantly related to the increased risk of all-cause death (Q2, Q3, Q4: adjusted hazard ratio (aHR) [95 confidence interval (CI)%] =1.17[1.01-1.35], 1.31[1.13-1.52], 1.51[1.30-1.76], respectively; P for trend <0.001). The elevated quartile of SIRI showed higher risks of cardiovascular death, but there was no statistically significant increased risk of cardiovascular death across the lower SIRI quartile (model 3: Q2, Q3, Q4: aHR [95CI%] =1.22[0.99-1.51], 1.50[1.20-1.86], 1.73[1.37-2.18], respectively; P for trend <0.001). Elevated systemic inflammation level on admission was correlated with an increased risk of all-cause and cardiovascular death among patients with HFpEF. The SIRI may serve as a promising marker of risk stratification for patients with HFpEF.