Prognostic Marker In Patients Research Articles

Breathing pattern and pulmonary gas exchange in elderly patients with and without left ventricular dysfunction-modification with exercise-based cardiac rehabilitation and prognostic value.

Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure. To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE). In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up. In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE. Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.

ADAM12 promotes the resistance of lung adenocarcinoma cells to EGFR-TKI and regulates the immune microenvironment by activating PI3K/Akt/mTOR and RAS signaling pathways.

Lung adenocarcinoma (LUAD) is a malignant respiratory disease, resulting in a heavy social burden. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance and tumor immune microenvironment are important directions in the treatment of LUAD. In this study, we confirmed the role of ADAM metallopeptidase domain 12 (ADAM12) in LUAD development and progression. Our bioinformatic analysis was conducted to screen ADAM12 was correlated with EGFR-TKI and immune infiltration in LUAD patients. Our results showed that the transcription and post-transcription level of ADAM12 is significantly increased in tumor samples compared to normal samples, and ADAM12 correlated with poor prognosis in LUAD patients. High level of ADAM12 accelerated the LUAD progression via promoting proliferation, cell cycle, apoptosis escaping, immune escaping, EGFR-TKI resistance, angiogenesis, invasion and migration based on experiment validation in vitro and in vivo, which could be attenuated by ADAM12 knockdown. Further mechanistic studies suggested that the PI3K/Akt/mTOR and RAS signaling pathways were activated after ADAM12 knockdown. Therefore, ADAM12 might be validated as a possible molecular therapy target and prognostic marker for patients with LUAD.

Temporal muscle thickness has no prognostic relevance in patients with high-grade glioma compared to functional scales.

GBM research is constantly assessing potential valuable prognostic biomarkers to better understand the disease and prognosticate future outcomes. Measuring temporal muscle thickness (TMT) has appeared to be a promising new surrogate marker for skeletal muscle mass and sarcopenia, which further indicates frailty and predicts overall survival (OS). The aim of this study was to determine its usefulness as a prognostic marker in patients with high-grade glioma compared to functional status scales. TMT was measured in preoperative axial T1-weighted contrast-enhanced magnetic resonance images in 277 patients who received surgical treatment of newly diagnosed WHO III and IV gliomas in our institution between 2015 and 2020. Clinical Frailty Scale (CFS) and Karnofsky Performance Scale (KPS) were assessed preoperatively and during a follow-up visit. Female gender has shown significant correlation with TMT, while TMT did not correlate with preoperative and follow-up functional scores, age, WHO classification, IDH mutation, MGMT promoter methylation, EGFR and ATRX expression, or 1p/19q co-deletion. No significant prognostic value of TMT could be shown in 6, 12, and 24 months OS, while changes in CFS and KPS proved to have a significant impact. Only female gender, but no other clinical, histological, or molecular marker showed any interrelation with TMT. Functional scores outclass measuring TMT as a reliable prognostic factor for predicting OS in patients with high-grade glioma.

The Diagnostic and Prognostic Roles Played by Homocysteine and Other Aminothiols in Patients with Chronic Kidney Disease.

We examined standard clinical and laboratory biochemical parameters, as well as the levels of aminothiols in the blood and urine (homocysteine (Hcy), cysteine (Cys), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH)) via capillary electrophoresis in patients with CKD at stages II-V. Patient outcomes were assessed after five years. To complete forecasting, correlation and ROC analysis were performed. It was found that the levels of Cys and Hcy in blood plasma were earlier markers of CKD starting from stage II, while the levels of SAM and SAM/SAH in urine made it possible to differentiate between CKD at stages II and III. Blood plasma Hcy and urinary SAM and SAM/SAH correlated with mortality, but plasma Hcy concentrations were more significant. Thus, plasma Hcy, urine SAM, and SAM/SAH can be considered to be potential diagnostic and prognostic markers in patients with CKD.

248. SYSTEMIC INFLAMMATORY MARKERS AS PROGNOSTIC FACTORS IN ESOPHAGEAL CANCER: A MEXICAN PERSPECTIVE

Abstract Background Esophageal cancer (EC) represents the eighth most commonly diagnosed cancer, and sixth cause of cancer-related deaths worldwide. Several studies have demonstrated an association between systemic inflammation, anti-cancer immunity, and poor oncological outcomes in patients with EC. Biomarkers including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) may reflect the balance between pro-cancer inflammation and anti-cancer immune response and have prognostic implications in Mexican esophageal cancer patients. Methods A retrospective review of a prospectively collected database of all EC patients from 2011–2022 was performed. Baseline pre-treatment NLR, LMR and PLR was collected. The date of last follow-up or death was ascertained from medical records. ROC curves were used to calculate cut-off values for NLR and PLR, while the median-value was used for LMR. Serum albumin of <3.5 g/dL was considered malnutrition. Kaplan–Meier (univariate) and Cox regression (multivariate) were performed to evaluate survival against prognostic factors. Results 498 patients were included during the study period, 80.1% men and 19.9% women, median age 60 (±12.2) years old. Adenocarcinoma (49.8%) was the most common histological subtype, followed by squamous cell carcinoma (31.7%). Clinical stage included: I (3%), IIA-B (11.8%), III (37.6%), IVA (2.6%), and IVB (44.2%). Neoadjuvant chemoradiotherapy was the predominant initial therapy (50.4%), followed by chemotherapy (41.7%). ROC curves revealed the following cut-off value: 2.92 for NLR, 174 for IPL, and 3.5 for LMR. In the univariate analysis, four prognostic factors were significant for overall survival (NLR, PLR, LMR, albumin) (Table 1), while in the multivariate analysis only NLR and albumin remained independent factors for survival (Table 2). Conclusion In our population, low NLR and high albumin can be considered independent prognostic markers in patients with esophageal cancer. These common pretreatment biomarkers can serve to identify patients with good prognostic factors, contributing to an improved consent process and therapeutic decision making. Further research should focus on more accurate cut-off values for survival prognostication.

Value of Chromogranin A as a Prognostic Marker in Cirrhotic Patients with HCC before and after Radiofrequency

Abstract Background The majority of HCC cases are undetected until advanced stage owing to lack of symptoms and the absence of sensitive and convenient screening procedures. The overall AFP performance in this field has been inadequate in terms of its poor specificity and sensitivity. Various prior studies found an elevated serum Cg-A concentrations in HCC patients. Radiofrequency ablation (RFA) is the preferred approach for small sized lesion. Therefore, the aim of this study was to highlight the value of determination of CgA serum levels in monitoring patients with cirrhosis for early detection of HCC and its significance as a prognostic marker in patients with very early/early stage of HCC before and after radiofrequency. Subjects and methods The present study enrolled 30 cirrhotic patients with very early/early stage of HCC, 15 cirrhotic patients without HCC, and 15 healthy controls. Serum AFP & Cg-A levels were estimated in all patients before intervention and 1 month after radiofrequency ablation in the HCC group. Results Serum Cg-A was significantly higher in HCC cases compared to healthy subjects and cirrhotic patients (P = 0.001). At a cut off value of 250 (ng/ml), serum Cg-A had a 96.7% sensitivity and a 93.3% specificity for detecting HCC while AFP at 3.736 ng/ml had 93.3% sensitivity and 86.7% specificity. Furthermore, the selected cut-off values to distinguish HCC patients who have better (improved) outcome from those with bad outcome was 375 (ng/ml) with 96.7% sensitivity and 76.7% specificity (for Cg –A) and 17 (ng/ml) with 73.3% sensitivity and 70% specificity (for AFP). Conclusion Cg-A can act as valuable diagnostic as well as prognostic biomarkers for liver cirrhosis and HCC as it was significantly higher in HCC patients than in cirrhotic patients and controls and it had higher sensitivity, specificity than AFP for HCC diagnosis.

Exploring the role of m6A methylation regulators in glioblastoma multiforme and their impact on the tumor immune microenvironment.

Although the role of N6-Methyladenosine (m6A) methylation factors has been established in multiple cancer types, its involvement in glioblastoma multiforme (GBM) remains limited. This study aims to explore the involvement of m6A regulators in GBM and examine their association with the tumor immune microenvironment (TIME). A comprehensive set of 24 candidate m6A RNA regulators was procured. Consensus clustering was performed based on these regulators to identify distinct GBM clusters. PD-L1 and PD-1 levels, immune cell infiltration, and immune scores were evaluated between two clusters. Prognostic signatures and correlation analysis with TIME were analyzed using Lasso and Spearman's analysis. GBM tissue was collected to verify the correlations. Eighteen m6A regulators (WTAP, YTHDF2, HNRNPC, CAPRIN1, YTHDF3, METTL14, GNL3, ZCCHC4, HNRNPD, YTHDF1, RBM15, PCIF1, RBM27, KIAA1429, MSI2, FTO, ALKBH5, and METTL3), PD-L1, and PD-1 were significantly upregulated in GBM tissue. These regulators were divided into two distinct molecular subtypes (clusters 1 and 2). Cluster 2 exhibited a significant increase in immune score, monocytes, M1 macrophages, activated mast cells, and eosinophils. HNRNPC, YWHAG, and ALKBH5 were significantly associated with TIME and positively correlated with PD-L1. Immune cell invasiveness profiles dynamically changed with copy number changes of these three m6A regulators. Finally, YWHAG and ALKBH5 were found to be independent prognostic indicators of GBM through risk analysis and were experimentally verified with clinical samples. YWHAG and ALKBH5 may be used as prognostic markers for patients with GBM. m6A methylation regulators may play an important role in regulating PD-L1/PD-1 expression and immune infiltration, thus having a significant impact on GBM TIME.

Nonspecific intraventricular conduction delay predicts the prognosis of dilated cardiomyopathy

PurposeLeft bundle branch block (LBBB) has been confirmed to be independently associated with adverse outcomes in dilated cardiomyopathy (DCM). However, prognostic data on nonspecific intraventricular conduction delay (NSIVCD) are still limited and conflicting. We aimed to evaluate the prognosis of DCM with NSIVCD.MethodsA total of 548 DCM patients who underwent cardiovascular magnetic resonance imaging (CMR) from January 2016 to December 2017 were consecutively enrolled. The cohort was divided into four groups: 87 with LBBB, 27 with RBBB, 61 with NSIVCD, and 373 without intraventricular conduction delay (IVCD). After a median follow-up of 58 months (interquartile range: 47–65), 123 patients reached the composite endpoints, which included cardiovascular death, heart transplantation, and malignant arrhythmias. The associations between different patterns of IVCD and the outcomes of DCM were analysed by Kaplan‒Meier analysis and Cox proportional hazards regression analysis.ResultsOf 548 DCM patients, there were 398 males (72.6%), and the average age was 46 ± 15 years, ranging from 18 to 76 years. In Kaplan‒Meier analysis, patients with NSIVCD and LBBB showed higher event rates than patients without IVCD, while RBBB patients did not. By multivariate Cox regression analysis, LBBB, NSIVCD, NYHA class, left ventricular ejection fraction (LVEF), indexed left ventricular end-diastolic diameter (LVEDDI), percentage of late gadolinium enhancement mass (LGE%), and global longitudinal strain (GLS) were found to be independently associated with the outcomes of DCM.ConclusionsIn addition to LBBB, NSIVCD was an unfavourable prognostic marker in patients with DCM, independent of LVEDDI, NYHA class, LVEF, LGE%, and GLS.

Clinicopathologic Significance of Heat Shock Protein 60 as a Survival Predictor in Colorectal Cancer.

The role of heat shock protein 60 (HSP60), a mitochondrial chaperone, in tumor progression or its anti-tumor effects remains controversial. This study aimed to confirm the possibility of using HSP60 as a prognostic marker in patients with colorectal cancer (CRC), considering TNM classification for precise prediction. HSP60 expression increased with differentiation and p53 mutations in patients. However, compared to patients with high HSP60 expression, patients with low HSP60 expression had event-free survival and disease-specific survival hazard ratios (HRs) of 1.42 and 1.69, respectively. Moreover, when the survival rate was analyzed by combining TNM classification and HSP60 expression, the prognosis was poor, particularly when HSP60 expression was low in the late/advanced stage. This pattern was also observed with HSP family D member 1, HSPD1, the gene that encodes HSP60. Low HSPD1 expression was linked to lower overall survival and relapse-free survival rates, with HRs of 1.80 and 1.87, respectively. When TNM classification and HSPD1 expression were considered, CRC patients with low HSPD1 expression and advanced malignancy had a poorer prognosis than those with high HSPD1 expression. Thus, HSPD1/HSP60 can be a useful biomarker for a sophisticated survival prediction in late- and advanced-stage CRC, allowing the design of individualized treatment strategies.

Extensive versus focal lymphovascular invasion in squamous cell carcinoma of the cervix: A comprehensive international, multicenter, retrospective clinicopathologic study

ObjectiveWe evaluated clinicopathologic parameters of patients with cervical squamous cell carcinoma (SCC) who were treated with initial surgical management and assessed their relation to survival outcomes. Specifically, we evaluated the relation between extent of lymphovascular invasion (LVI) and survival outcomes. MethodsAll available tumor slides from patients with initially surgically treated cervical SCC were collected from 10 institutions and retrospectively analyzed. Standard clinicopathological parameters, tumor stroma, and extent of LVI were assessed (focal: <5 spaces, extensive: ≥5 spaces). PFS and OS were evaluated using Kaplan–Meier methodology. Univariable and multivariable Cox proportional hazards models were created to determine prognostic survival-related risk factors. ResultsA total of 670 tumor samples were included in the analysis. Median age at diagnosis was 47 years (IQR: 38–60), 457 patients (72%) had a 2018 International Federation of Gynecology and Obstetrics (FIGO) stage I tumor, and 155 tumors (28%) were flat and/or ulcerated. There were 303 nonkeratinizing tumors (51%), 237 keratinizing tumors (40%), and 356 histologic grade 2 tumors (61%). Quantifiable LVI was present in 321 cases (51%; 23% focal and 33% extensive). On multivariable analysis for PFS, extensive and focal LVI had worse outcomes compared to negative LVI (HR: 2.38 [95% CI: 1.26–4.47] and HR: 1.54 [95% CI: 0.76–3.11], respectively; P = 0.02). The difference did not reach statistical significance for OS. ConclusionPresence of LVI is a prognostic marker for patients with cervical SCC. Quantification (extensive vs. focal vs. negative) of LVI may be an important biomarker for oncologic outcome.

Use of NUTrition Risk in the Critically Ill and Modified NUTrition Risk in the Critically Ill with C-Reactive Protein Scores as a Prognostic Indicator in COVID-19 Patients

Objective: This study aimed to investigate the applicability of the NUTrition Risk in the Critically Ill and modified NUTrition Risk in the Critically Ill with C-reactive protein scores for assessing nutritional risks and predicting outcomes of these critically ill coro- navirus disease 2019 patients. Methods: This retrospective study included 246 adult patients admitted to the intensive care unit between March 15, 2020, and August 15, 2021, diagnosed with coronavirus disease 2019 which was confirmed with real-time-polymerase chain reaction, and who received invasive mechanical ventilation. Treatments in the intensive care unit and clinical outcomes of the patients were recorded. The nutritional risk for each patient was assessed using both the NUTrition Risk in the Critically Ill and the modified NUTrition Risk in the Critically Ill with C-reactive protein scores. If the NUTrition Risk in the Critically Ill and modified NUTrition Risk in the Critically Ill with C-reactive protein scores were ≥6, and the nutritional risk was considered to be high. Results: The median age was 68 (21-93) years, and 61% of them were male. The median duration of invasive mechanical ven- tilation was 9 (1-62) days, the median length of stay in intensive care unit was 15 (1-65) days, and the mortality rate in 28 days was 77.2%. Most of the patients had low nutritional risk according to NUTrition Risk in the Critically Ill score (75.2%) and modi- fied NUTrition Risk in the Critically Ill with C-reactive protein score (69.1%). High NUTrition Risk in the Critically Ill and modified NUTrition Risk in the Critically Ill with C-reactive protein scores were not significantly associated with the duration of invasive mechanical ventilation, length of stay in intensive care unit, and mortality at 28 days. Conclusion: It was shown that NUTrition Risk in the Critically Ill and modified NUTrition Risk in the Critically Ill with C-reactive protein scores were not correlated with the duration of invasive mechanical ventilation, length of stay in intensive care unit, and 28-day mortality in critically ill coronavirus-19 patients. NUTrition Risk in the Critically Ill score was not an appropriate nutrition risk assessment tool as a prognostic marker in patients with severe acute respiratory syndrome coronavirus 2 infection, which is correlated to interleukin-6 and C-reactive protein levels.

Assessing Pulmonary Tuberculosis Using Bandim Tuberculosis and Karnofsky Performance Scale Scores with Serum Adenosine Deaminase Levels.

Elevated pulmonary serum adenosine deaminase (ADA) levels signify lung tissue damage and severe tuberculosis (TB). Serum ADA assays can be used as an additional criterion for assessing TB treatment response and as a prognostic marker in patients with pulmonary TB. The Bandim TB and Karnofsky Performance Scale (KPS) scores were developed based on available clinical data and investigations to allow physicians to evaluate disease treatment and response. This study examined the use of a clinical scoring system (Bandim TB and KPS scores) in the context of serum ADA activity. Forty adults (aged >18 years) diagnosed with pulmonary TB by Ziehl-Neelsen staining for acid-fast bacilli and/or cartridge-based nucleic acid amplification test were recruited. Standardized questionnaires were used to record Bandim TB and KPS scores. Serum ADA levels were estimated using a commercial kit. The Bandim TB score was positively associated (ρ=0.74, P≤0.001) and the KPS score was negatively associated (ρ=-0.69, P≤0.001) with serum ADA levels. Subjective and objective clinical scores of pulmonary TB were strongly correlated with serum ADA levels. Knowledge of clinical scores corresponding to serum ADA levels could help physicians understand stage and progression of the disease which may aid in early detection and better management, and reduce disease transmission in a TB-endemic country.

Loss of hepatic FTCD promotes lipid accumulation and hepatocarcinogenesis by upregulating PPARγ and SREBP2

Exploiting key regulators responsible for hepatocarcinogenesis is of great importance for the prevention and treatment of hepatocellular carcinoma (HCC). However, the key players contributing to hepatocarcinogenesis remain poorly understood. We explored the molecular mechanisms underlying the carcinogenesis and progression of HCC for the development of potential new therapeutic targets. The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and Genotype-Tissue Expression (GTEx) databases were used to identify genes with enhanced expression in the liver associated with HCC progression. A murine liver-specific Ftcd knockout (Ftcd-LKO) model was generated to investigate the role of formimidoyltransferase cyclodeaminase (FTCD) in HCC. Multi-omics analysis of transcriptomics, metabolomics, and proteomics data were applied to further analyse the molecular effects of FTCD expression on hepatocarcinogenesis. Functional and biochemical studies were performed to determine the significance of loss of FTCD expression and the therapeutic potential of Akt inhibitors in FTCD-deficient cancer cells. FTCD is highly expressed in the liver but significantly downregulated in HCC. Patients with HCC and low levels of FTCD exhibited worse prognosis, and patients with liver cirrhosis and low FTCD levels exhibited a notable higher probability of developing HCC. Hepatocyte-specific knockout of FTCD promoted both chronic diethylnitrosamine-induced and spontaneous hepatocarcinogenesis in mice. Multi-omics analysis showed that loss of FTCD affected fatty acid and cholesterol metabolism in hepatocarcinogenesis. Mechanistically, loss of FTCD upregulated peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element-binding protein 2 (SREBP2) by regulating the PTEN/Akt/mTOR signalling axis, leading to lipid accumulation and hepatocarcinogenesis. Taken together, we identified a FTCD-regulated lipid metabolic mechanism involving PPARγ and SREBP2 signaling in hepatocarcinogenesis and provide a rationale for therapeutically targeting of HCC driven by downregulation of FTCD. Exploiting key molecules responsible for hepatocarcinogenesis is significant for the prevention and treatment of HCC. Herein, we identified formimidoyltransferase cyclodeaminase (FTCD) as the top enhanced gene, which could serve as a predictive and prognostic marker for patients with HCC. We generated and characterised the first Ftcd liver-specific knockout murine model. We found loss of FTCD expression upregulated peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element-binding protein 2 (SREBP2) by regulating the PTEN/Akt/mTOR signalling axis, leading to lipid accumulation and hepatocarcinogenesis, and provided a rationale for therapeutic targeting of HCC driven by downregulation of FTCD.

Absolute eosinophil count is a reliable prognostic marker in patients with liver cirrhosis: a cross-sectional study at rural central India

BackgroundVarious laboratory parameters like C-reactive protein (CRP), Cortisol, and Von Willebrand factor antigen have been evaluated independently in foreseeing outcomes of cirrhotic patients. As these parameters lack cost-effectiveness in a rural setup, there is a need for a cost effective and feasible prognostic marker for cirrhotic patients. The present study was aimed at evaluating the role of Absolute Eosinophil Count (AEC) as a prognostic marker in cirrhotic patients.MethodsThis cross-sectional study was conducted at a rural tertiary care teaching hospital in central India from August 2019 to September 2021. AEC was measured from counter report as a part of automated complete blood counts. Child-Turcotte-Pugh (CTP) score and Model for end stage liver disease (MELD) score were calculated at the time of admission. AEC levels on admission were correlated with mortality and with CTP score and MELD score.ResultsA total of 110 patients were enrolled with mean age of 46.37 ± 11.6 years. AEC was the significant predictor of mortality at cut off point of ≤ 120 with 80.30% (AUC 0.803; 95% CI: 0.716 to 0.873). AEC was the significant predictor of CTP score ≥ 11 at cut off point of ≤ 148 (AUC 0.726; 95% CI: 0.633 to 0.807). AEC was the significant predictor of MELD score ≥ 25 at cut off point of ≤ 136 (AUC 0.74; 95% CI: 0.647 to 0.819). Significant negative correlation was seen between AEC with Child–Pugh score and MELD score with correlation coefficient of -0.257 and -0.258.ConclusionLow level of AEC on admission fairly predicted raised CTP score and MELD score on admission. Low AEC levels predicted increased mortality in cirrhotic patients making it a cheap and reliable prognostic marker in a rural setup.

A Novel Method Using Fine Needle Aspiration from Tumor-Draining Lymph Nodes Could Enable the Discovery of New Prognostic Markers in Patients with Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell cancer (cSCC) is the second most common form of skin cancer, characterized by abnormal, accelerated growth of squamous cells. When caught early, most cSCCs are curable. About 5 percent of the cSCC cases have advanced to such an extent, generally metastatic, that they are far more dangerous, with very poor prognosis and challenging to treat. All efforts to find biomarkers, in blood or in the tumor itself, for early identification of patients with a risk for metastasis have so far failed. The present study describes a novel method that enables the identification of lymphocyte markers in tumor-draining lymph nodes. Six patients with advanced cSCC were analyzed using a combination of a sentinel lymph node biopsy (SLNB) protocol, fine needle aspiration (FNA), and flow cytometry. Immunological results from the sentinel nodes were combined with corresponding data from peripheral blood and unfixed tumor tissues. The result demonstrates a striking difference between the subsets of T-cells from the three compartments. Our interpretation of this first pilot study is that the ability to follow specific immunological markers on lymphocytes in tumor-draining lymph nodes will enable the identification of novel prognostic biomarkers not detectable in material from blood and tumor tissues.

Left ventricular torsion as a prognostic marker in patients with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular (LV) torsion is the wringing motion of the ventricle around its long axis induced by contracting obliquely oriented myofibers in the LV wall and it predicts functional capacity more appropriately than LV ejection fraction (EF). Purpose This study was intended to evaluate reduced LV torsion as a potential marker of disease severity and a predictor of hospitalization for worsening heart failure in patients with non-ischemic dilated cardiomyopathy (DCM). Methods This was a single center prospective observational study wherein 127 patients with a diagnosis of non-ischemic DCM with a LVEF &amp;lt;50% were enrolled. In addition, 48 age and sex matched healthy individuals without any prior history of cardiovascular diseases and normal LVEF were enrolled as controls. All these patients underwent detailed clinical assessment including symptomatology, NYHA function class evaluation and routine blood investigations including CPK-MB levels. In addition, all enrolled subjects underwent 2D transthoracic echocardiography along with speckle tracking imaging to determine the LV global longitudinal strain (LV-GLS), LV twist and LV torsion. Based on the measurement of LV torsion, patients were stratified into two groups: preserved LV torsion (&amp;gt;0.59 degrees/cm) and reduced LV torsion (&amp;lt;0.59 degrees/cm). These patients were followed up for six months in terms of MACE events. Results Reduced LV torsion was reported in 52/127 (40.9%) patients with DCM. These patients had significantly lower LVEF, altered LV geometry (base-apical distance) and higher levels of CPK-MB. Additionally, patients with reduced LV torsion had a worsened functional class and a greater frequency of hospital admissions (34 vs 6; P&amp;lt;0.001) over 6 months of follow-up as compared to those with preserved LV torsion. Multivariate logistic regression reported reduced LV torsion to be an independent predictor of MACE events over six months of follow-up (OR:4.20; P=0.001). Conclusion Findings from our study suggested that LV torsion can serve as an additional prognostic marker in patients with non-ischemic DCM.

Computed tomography-derived myocardial extracellular volume in patients with severe aortic stenosis: correlation with markers of ventricular dysfunction

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial fibrosis is a potential adverse prognostic marker in patients with severe aortic stenosis (AS) and can be quantified using non-invasive imaging measures, such as the extracellular volume fraction (ECV). Although computed tomography (CT) for transcatheter aortic valve replacement (TAVR) planning was originally developed to assess the aortic valve complex and access routes, it has evolved to include the measurement of ECV for myocardial tissue characterization. Aim This study aimed to determine associations between CT-derived ECV (ECVCT) and clinical and echocardiographic markers of ventricular function in patients with severe AS referred for TAVR-planning CT. Methods Single-center prospective study enrolling all consecutive patients with severe symptomatic AS referred for TAVR-planning CT between April and November 2022. CT was performed on a 192-slice dual-source 3rd generation scanner (Siemens Somatom Force) and ECVCT was acquired during TAVR-planning using an additional 5-minute post-contrast low-radiation-dose prospective acquisition. ECVCT was calculated as the ratio of change in CT attenuation (Hounsfield units [HU]) of the septal myocardium and the left ventricle (LV) blood pool before and after contrast administration, according to the equation: ECVCT = (1 – hematocrit) x (DHUmyo/DHUblood) – Figure 1A. Results A total of 102 patients were included (mean age 81 ± 7 years; 46% male; mean valvular transaortic gradient 51 ± 14 mmHg; mean aortic valve area 0.7 ± 0.2 cm2; mean LV ejection fraction (EF) by 2D echocardiogram 57 ± 11%). No patient had a clinical diagnosis of cardiac amyloidosis. Overall, the mean ECVCT value was 33.4 ± 7.0%. Myocardial ECVCT values significantly differed between AS subtypes, with higher values in patients with low-gradient AS (n=13, 13%; ECVCT 40.3 ± 4.8% vs 32.4 ± 6.7%, p&amp;lt;0.001) - Figure 1B. Additionally, myocardial ECVCT values correlated with markers of LV and right ventricular (RV) dysfunction, including lower LV EF (r = -0.354, p&amp;lt;0.001), worse LV global longitudinal strain (r = 0.420, p = 0.002), reduced TAPSE (r = -0.230, p = 0.043) and RV S wave by tissue doppler imaging (r = -0.321, p = 0.010) and higher NT-proBNP values (r = 0.347, p = 0.002). Conclusions In patients with severe AS scheduled for TAVR-planning CT, ECVCT values are significantly higher in those with low-gradient AS and correlated with several measures of biventricular dysfunction. This CT parameter may be useful to identify a subgroup of patients with higher risk of adverse prognosis.

Dark papillary muscles sign: a novel prognostic marker for cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background the prognostic role of left ventricular (LV) papillary muscle abnormalities in patients with preserved LV systolic ejection fraction (LVEF) is unknown. Aim to evaluate the prevalence and the clinical and prognostic impact of papillary muscle abnormalities by CMR in patients with ventricular arrhythmias, preserved LVEF with no cardiac disease. Methods 391 patients with &amp;gt;500/24h premature ventricular complexes and/or with non-sustained ventricular tachycardia (NSVT), preserved LVEF and no cardiac disease, were enrolled. Different features of LV papillary muscles were considered: supernumerary muscles, papillary thickness, the attachment, late gadolinium enhancement (LGE). The end-systolic hypointensity was defined when its measured signal intensity (SI) was lower than the SI of the septum in early post-contrast cine CMR images. Dark-Paps was defined when both the main papillary muscles had systolic hypointensity. Mitral valve prolapse, mitral annular disjunction (MAD), myocardial LGE were considered. The outcome of hard cardiac events was define as a composite of cardiac death, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) shock, sustained ventricular tachycardia (lasting ≥30 s at ≥100 beats/min). Results Dark-Paps was found in 79 (20%) patients and was more frequent in females. It was associated with higher prevalence of mitral valve prolapse and MAD. During a median follow-up of 2534 days, 22 hard cardiac events occurred. At Kaplan-Meier curve (Figure) analysis patients with Dark-Paps were at higher risk of events than those without (p&amp;lt;0.0001). Dark-Paps was significantly associated with hard cardiac events in all the multivariate models performed. Dark-Paps improved prognostic estimation when added to NSVT (p = 0.0006), to LGE (p = 0.005) and to a model including NSVT+LGE (p = 0.014). Dark-Paps allowed a significant net reclassification when added to NSVT (NRI 0.30, p =0.03), to LGE (NRI 0.25, p =0.04), and to NSVT + LGE (NRI 0.32, p =0.02). Conclusions Dark-Paps sign could be considered a novel imaging prognostic marker in patients with ventricular arrhythmias and preserved ejection fraction.

#3249 BLOOD UREA NITROGEN TO CREATININE RATIO IS ASSOCIATED WITH HIGH MORTALITY IN ELDERLY PATIENTS STARTING HEMODIALYSIS: A KSGN RETROSPECTIVE COHORT

Abstract Background and Aims Previous studies have shown that increased blood urea nitrogen to creatinine ratio (BCR) is a poor prognostic marker in patients with some chronic diseases or in the general population. However, the clinical implication of BCR in elderly dialysis patients is unknown. The purpose of this study was to verify the association of BCR with the risk of death in elderly patients starting hemodialysis. Method The Korean Society of Geriatric Nephrology Retrospective Cohort consists of patients who started maintenance hemodialysis from January 1, 2010 to December 31, 2017 at 17 nephrology centers in Korea. After excluding patients with malignancy or estimated glomerular filtration rate 30 ml/min/1.73 m2 or greater, we retrospectively analyzed 2,183 patients. The main predictor was patients BCR at the time of hemodialysis initiation and subjects were divided into four groups according to their BCR quartile. The main outcome was all-cause mortality. Results During 7,545 person-years of follow-up, 1,382(63.3%) patients died. Patients in the high BCR group died more (60.9%, 59.3%, 62.5% and 70.5% for the 1st to 4th BCR quartiles, respectively, P=0.001). In multivariate Cox proportional hazard model, BCR increase by one was associated with increased risk of death (HR 1.01; 95% CI, 1.01-1.02). This model was adjusted for age, sex, body mass index, cause of renal disease, hypertension, diabetes, ischemic heart disease, cerebrovascular disease, congestive heart failure, eGFR, hemoglobin, albumin, calcium and phosphorus. Compared to 3rd quartile of BCR group, 4th quartile group was associated with increased risk of death (HR, 1.30; 95% CI, 1.12-1.51). Conclusion High BCR is a predictor of high mortality in elderly patients starting hemodialysis. This result suggests that more attention should be paid to elderly patients starting hemodialysis with high BCR.

Assessment of the Peradeniya Organophosphorus Poisoning Scale as a Severity and Prognostic Marker in Patients With Acute Organophosphorus Poisoning Presenting to an Emergency Medicine Department.

Background Organophosphorus (OP)compound poisoning is the most common toxicological medical emergency in India, where the majority of the population lives on agriculture. The Peradeniya Organophosphorus Poisoning (POP) scale can be a simple and effective system to determine the need for ventilatory support early in the course of admission. The objective of this study was to evaluate the prognostic value of the clinical parameters of the POP scale in predicting the severity of organophosphorus compound poisoning, by comparing early predicted patient prognosis evaluated by the POP scale on admission with the patient outcome. Methods This was a prospective observational study of acute organophosphorus compound poisoning presenting to the emergency department of Sir Sayajirao General (SSG) Hospital and Medical College, Baroda. We included patients over 12 years of age with a history of, or symptoms suggestive of, acute OP poisoning. The patients receivedinitial resuscitation according to airway, breathing, circulation, disability, and exposure simultaneously with decontamination and gastric lavage by Ryle's tube. They also received the standard antidotes of atropine and pralidoximeimmediately. We appliedthe POP scale to each patient uponadmission and graded the poisoning severity as mild (a POP scale score of 0-3), moderate (4-7), or severe (8-11). This scale assessed the patients' need for mechanical ventilation and ICU management and their final clinical outcome. Results We enrolled 60 patients in the study. Most of themwere under 20 years of age, and 65% of them were male. Social laborers were the major population, and most of them had suicidal intention. Monocrotophos was the most commonly consumed OP compound. Most of the patients were brought to the hospital within two to sixhours of consumption. Vomiting and profuse secretions were the primary presenting symptoms. A majority of the patients (47) fell into the mild POP scale range. None of the patients had severe poisoning. Out of 60 patients, 49 patients improved and 11 patients died. Seven patients (15%) with mild POP scale scores and four patients (31%) with moderate scores died. Overall, 61.7% of patients with mild POP scale scores and 100% of patients with moderate scores needed mechanical ventilation. Conclusion The POP scale is an effective tool to measure severity and make a prognosisin patients with acute OP compound exposure. It may be asimple, inexpensive tool that may help predict the need for ventilatory support at admission. Early identification of danger signs may help in the reduction of mortality and morbidity when resources are limited. However, we found incorporating other clinical parameters and biochemical markers provides better prognostication than using the POP scale alone.