Biomarker For Mortality In Patients Research Articles

Abstract 6123: Validating cancer modulated allostatic load as a composite biomarker for mortality in patients with cancer

Abstract Allostatic load (AL) is the cumulative burden of chronic stress and life events typically measured by lab and vital values routinely collected during standard care. AL has been associated with adverse socioenvironmental stressors and increased mortality rates including risk of cancer death. Despite modifications of AL as a result of progressing cancer and anti-cancer treatments, AL may serve as a valuable biomarker for cancer outcomes, and highlight similar disparities across sociodemographic groups agnostic of a history of cancer diagnosis. Recent investigations have shown associations of AL with overall mortality rates in patients with non-small cell lung cancer (NSCLC) and breast cancer, as well as various social determinants of health. The impact of AL on different malignancies, particularly in the context of genetic variations identified through genomic profiling, is yet to be thoroughly investigated. We identified a pan-cancer cohort of 29,433 patients sequenced with the MSK-IMPACT targeted panel sequencing assay, and collected clinical, genomic, and lab data. We first studied the association of AL with patient and tumor characteristics such as tumor type, stage, cancer genomics, comorbidities, social deprivation defined by the Yost index, and genetic ancestry. We derived AL using 10 standard biomarkers across cardiovascular, metabolic, renal, and immune systems, and created a composite AL summary score with a range between 0 and 10. Composite AL summary score into quartiles for comparisons. We found that AL was increased with higher cancer stage, older age, smoking, multiple comorbidities, African ancestry, and Yost index. Multivariate logistic regression analysis showed that AL was correlated with mutations e in KRAS and anti-correlated with EGFR mutations (FDR<0.02). Next, we investigated AL as a biomarker for mortality in patients with cancer and compared its prognostic value to other biomarkers. Using a Cox proportional hazard model we found that AL was significantly associated with shorter overall survival, controlling for stage and socioeconomic variables (HR=1.7, 2.2, 2.7 in AL Quartiles 2-4 respectively). Finally, we decomposed AL into its individual markers to quantify the most important features driving outcomes. Using a Random Survival Forest model with a focus on NSCLC patients, we found that albumin and alkaline phosphatase were the strongest features of shorter survival in our AL composite model. Our findings suggest that elevated AL is associated with a poorer prognosis across multiple cancer types, a trend observable across different stages of cancer. The association between AL and clinically actionable mutations highlights the importance of understanding the relationship between somatic alterations and social/environmental factors. The study underscores the utility of AL as a powerful prognostic tool that can be routinely collected in a clinical setting. Citation Format: Christopher J. Fong, Kaicheng U, Cheryl Phua, Xuechun Bai, Michele Waters, Tom Fu, Kanika Arora, Tomin Perea-Chamblee, Devika Jutagir, Michael Berger, Nikolaus Schultz, Adam Schoenfeld, Francesca Gany, Justin Jee, Jian Carrot-Zhang. Validating cancer modulated allostatic load as a composite biomarker for mortality in patients with cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6123.

Prognostic Biomarkers of Mortality in Older Patients Without Cancer in Home Healthcare.

Introduction The number of patients without cancer who receive home healthcare is increasing; however, prognostic prediction is challenging among them. This study aimed to investigate the prognostic value of generic biomarkers for mortality in patients without cancer who receive home healthcare. Materials and methods The multicenter retrospective cohort study included 114 older patients without cancer, of which 12 (10.5%) died during the study period. The median (interquartile range (IQR)) of the study observation period was 181 (49-293) days. Generic biomarkers included hemoglobin (Hb), albumin (Alb), C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). A multivariate-adjusted Cox proportional hazard model on all-cause mortality was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) for each biomarker. The cut-off values of each biomarker were calculated by receiver operating characteristic curve analysis. Theperformance of cut-off values was evaluated by time-dependent area under the curves (AUCs). Results The median (IQR) of AST was 13 (10-21) U/L. The biomarkers significantly predictive of mortality were Hb (fully adjusted HR: 0.41; 95% Cl: 0.25 - 0.70), Alb (HR: 0.41; 95% Cl: 0.02 - 0.69), and AST (HR: 1.09; 95% Cl: 1.00 - 1.18), along with male sex (HR: 4.07; 95% Cl: 1.15 - 14.35). The AUC of a cut-off value of AST (> 31 U/L) at 360 days was 0.72 (95% CI 0.71 - 0.72; p < 0.01), which outperformed the AUCs for Hb and Alb. Conclusion AST, in addition to Hb and Alb, may be useful for predicting the prognosis of older patients without cancer, who had a normal-to-mild increased level of AST, in home healthcare settings. Larger-sampleand longer follow-up studies will be warranted.

Predictive biomarkers of mortality in patients with severe COVID-19 hospitalized in intensive care unit.

This study was performed to identify predictive markers of worse outcomes in patients with severe COVID-19 in an intensive care unit. Sixty patients with severe COVID-19, hospitalized in the Intensive Care Unit (ICU) between March and July 2021, were stratified into two groups according to the outcome survivors and non-survivors. After admission to the ICU, blood samples were collected directly for biomarker analysis. Routine hematological and biochemical biomarkers, as well as serum levels of cytokines, chemokines, and immunoglobulins, were investigated. Lymphopenia, neutrophilia, and thrombocytopenia were more pronounced in non-surviving patients, while the levels of CRP, AST, creatinine, ferritin, AST, troponin I, urea, magnesium, and potassium were higher in the non-surviving group than the survival group. In addition, serum levels of IL-10, CCL2, CXCL9, and CXCL10 were significantly increased in patients who did not survive. These changes in the biomarkers evaluated were associated with increased mortality in patients with severe COVID-19. The present study confirmed and expanded the validity of laboratory biomarkers as indicators of mortality in severe COVID-19.

Targeting the TWEAK-Fn14 pathway prevents dysfunction in cardiac calcium handling after acute kidney injury.

Heart and kidney have a closely interrelated pathophysiology. Acute kidney injury (AKI) is associated with significantly increased rates of cardiovascular events, a relationship defined as cardiorenal syndrome type 3 (CRS3). The underlying mechanisms that trigger heart disease remain, however, unknown, particularly concerning the clinical impact of AKI on cardiac outcomes and overall mortality. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are independently involved in the pathogenesis of both heart and kidney failure, and recent studies have proposed TWEAK as a possible therapeutic target; however, its specific role in cardiac damage associated with CRS3 remains to be clarified. Firstly, we demonstrated in a retrospective longitudinal clinical study that soluble TWEAK plasma levels were a predictive biomarker of mortality in patients with AKI. Furthermore, the exogenous application of TWEAK to native ventricular cardiomyocytes induced relevant calcium (Ca2+ ) handling alterations. Next, we investigated the role of the TWEAK-Fn14 axis in cardiomyocyte function following renal ischaemia-reperfusion (I/R) injury in mice. We observed that TWEAK-Fn14 signalling was activated in the hearts of AKI mice. Mice also showed significantly altered intra-cardiomyocyte Ca2+ handling and arrhythmogenic Ca2+ events through an impairment in sarcoplasmic reticulum Ca2+ -adenosine triphosphatase 2a pump (SERCA2a ) and ryanodine receptor (RyR2 ) function. Administration of anti-TWEAK antibody after reperfusion significantly improved alterations in Ca2+ cycling and arrhythmogenic events and prevented SERCA2a and RyR2 modifications. In conclusion, this study establishes the relevance of the TWEAK-Fn14 pathway in cardiac dysfunction linked to CRS3, both as a predictor of mortality in patients with AKI and as a Ca2+ mishandling inducer in cardiomyocytes, and highlights the cardioprotective benefits of TWEAK targeting in CRS3. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Nucleated red blood cells are a predictor of mortality in patients under extracorporeal membrane oxygenation

BackgroundThe presence of Nucleated Red Blood Cells (NRBCs) in critically ill patients is associated with higher mortality and poor prognosis. Although patients on extracorporeal support such as veno-venous or veno-arterial extracorporeal membrane oxygenation (VV/VA-ECMO) are severely ill, NRBCs have rarely been investigated regarding their predictive value so far.MethodsAs part of a retrospective study, we examined all cardiothoracic surgery patients from July 2019 to September 2020 who received ECMO treatment during their inpatient stay. The aim of this study was to investigate the occurrence of NRBCs during ECMO support in terms of their predictive value for mortality.ResultsIn total 30 patients (age at admission: 62.7 ± 14.3 year; 26 male; ECMO duration: 8.5 ± 5.1 days; ICU duration: 18.0 ± 14.5 days) were included. 16 patients (53.3%) died during their inpatient stay. There were no significant differences in demographic characteristics between VA- or VV- ECMO patients. NRBCs occurred in all patients while under ECMO support. NRBC value was significant higher in those who died (2299.6 ± 4356.6 µl) compared to the surviving patients (133.6 ± 218.8 µl, p < 0.001). Univariate analysis found that patients with a cutoff value of ≥ 270 NRBCs/µl during ECMO support were 39 times more likely to die (OR 39.0, 95% CI 1.5–997.5, p < 0.001). 12 out of 13 patients (92.3%) with ≥ 270 NRBCs/µl died. The area under the curve (AUC) of the receiver operating characteristic curve was 0.85 (95% CI 0.69–0.96) with a sensitivity of 75.0% and a specificity of 92.9%.ConclusionNRBCs appear to be an accurate biomarker for mortality in patients with ECMO support. They may be helpful in deciding if therapy becomes futile.Trial registration DRKS00023626 (December 20th 2020).

Transcriptomics unveils immune metabolic disruption and a novel biomarker of mortality in patients with HBV-related acute-on-chronic liver failure

HBV-related acute-on-chronic liver failure (HBV-ACLF) is a complex syndrome associated with high short-term mortality. This study aims to reveal the molecular basis and identify novel HBV-ACLF biomarkers. Seventy patients with HBV-ACLF and different short-term (28 days) outcomes underwent transcriptome sequencing using peripheral blood mononuclear cells. Candidate biomarkers were confirmed in two external cohorts using ELISA. Cellular composition analysis with peripheral blood mononuclear cell transcriptomics showed that the proportions of monocytes, T cells and natural killer cells were significantly correlated with 28-day mortality. Significant metabolic dysregulation of carbohydrate, energy and amino acid metabolism was observed in ACLF non-survivors. V-set and immunoglobulin domain-containing 4 (VSIG4) was the most robust predictor of patient survival (adjusted p= 1.74×10-16; variable importance in the projection= 1.21; AUROC= 0.89) and was significantly correlated with pathways involved in the progression of ACLF, including inflammation, oxidative phosphorylation, tricarboxylic acid cycle and T-cell activation/differentiation. Plasma VSIG4 analysis externally validated its diagnostic value in ACLF (compared with chronic liver disease and healthy groups, AUROC= 0.983). The prognostic performance for 28-/90-day mortality (AUROCs= 0.769/0.767) was comparable to that of three commonly used scores (COSSH-ACLFs, 0.867/0.884; CLIF-C ACLFs, 0.840/0.835; MELD-Na, 0.710/0.737). Plasma VSIG4 level, as an independent predictor, could be used to improve the prognostic performance of clinical scores. Risk stratification based on VSIG4 expression levels (>122μg/ml) identified patients with ACLF at a high risk of death. The generality of VSIG4 in other etiologies was validated. This study reveals that immune-metabolism disorder underlies poor ACLF outcomes. VSIG4 may be helpful as a diagnostic and prognostic biomarker in clinical practice. Acute-on-chronic liver failure (ACLF) is a lethal clinical syndrome associated with high mortality. We found significant immune cell alterations and metabolic dysregulation that were linked to high mortality in patients with HBV-ACLF based on transcriptomics using peripheral blood mononuclear cells. We identified VSIG4 (V-set and immunoglobulin domain-containing 4) as a diagnostic and prognostic biomarker in ACLF, which could specifically identify patients with ACLF at a high risk of death.

Mean Platelet Volume-to-Lymphocyte Ratio Is a Biomarker of 1-Year Mortality in Patients With Diabetic Foot Infections.

We aimed to evaluate the value of 2 peripheral blood cell ratios, the mean platelet volume-to-lymphocyte ratio (MPVLR) and the neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers of mortality in patients with diabetic foot infections (DFIs). We conducted a prospective observational study consisting of a cohort of 200 patients with moderate to severe DFIs consecutively recruited from our Diabetic Foot Unit, Hospital San Juan de Dios, San José de Costa Rica, Costa Rica from October 15, 2020, to December 15, 2021. We studied the variables associated with one-year all-cause mortality using a multivariate backward Cox's regression model. Nonparametric Spearman Rho was used to study the linear correlation between NLR and MPVLR and other inflammatory markers. The variables associated with all-cause mortality were retinopathy (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.22-5.33, P = .01), estimated glomerular filtration rate (HR: 0.979, 95% CI: 0.969-0.990, P < .001), HbA1c (HR: 0.825, 95% CI: 0.702-0.969, P = .01), and MPVLR (HR: 1.093, 95% CI: 1.020-1.172, P = .01). NLR showed a strong correlation with white blood cell count (r = 0.60 [<0.001]) and c-reactive protein (r = 0.63 [<0.001]), and a weak correlation with erythrocyte sedimentation rate (r = 0.33 [<0.001]), though it was not associated with mortality. In conclusion, apart from other risk factors of mortality, we have for the first time demonstrated that the increasing value of MPVLR is a factor associated with one-year mortality in patients with DFIs.

Association between serum calcium and in-hospital mortality in critical patients with multiple myeloma: a cohort study

ABSTRACT Background Elevated serum calcium levels may serve as a useful clinical biomarker of mortality in patients with multiple myeloma(MM). However, the clinical significance of the relationship between serum calcium levels and in-hospital mortality in MM patients admitted to the Intensive Care Unit (ICU) remains unclear. Objectives This study aimed to explore the association between serum calcium levels and in-hospital mortality in patients with MM in the ICU. Methods Patients with MM were identified from the Medical Information Mart for Intensive Care IV(MIMIC-IV) database. The outcome was in-hospital mortality. Multivariable-adjusted Cox regression analysis, curve fitting, and threshold effects analysis were used to assess the relationship between serum calcium levels and in-hospital mortality in patients with MM in the ICU. Results Our study included 262 patients with MM with a mean age of 72.3 ± 11.0 years, 63.4% of whom were male. The in-hospital mortality was 19.5% (51/262). The relationship between serum calcium levels and in-hospital mortality was nonlinear. The effect size on the left and right sides of the inflection point, were 0.270 (HR: 0.270, 95% CI 0.106-0.687, P < 0.05) and 2.104 (HR: 2.104, 95% CI 1.069-4.142, P < 0.05), respectively. The results of the sensitivity analysis remained stable. Conclusion Our findings show that a nonlinear relationship exists between serum calcium levels and in-hospital mortality in critically ill patients with MM. A serum calcium level of approximately 8.40 mg/dL was associated with the lowest risk of in-hospital mortality, which increases with rising serum calcium levels, and should be of concern to ICU physicians.

Prognostic value of glucose-to-lymphocyte ratio in critically ill patients with acute respiratory distress syndrome: A retrospective cohort study.

BackgroundThere is need to identify biomarkers for prognosis of acute respiratory distress syndrome (ADRS). This may allow early and accurate identification of patients with high‐risk ARDS to guide adjustment of clinical treatment and nursing intervention, which would ultimately improve prognosis of patients with ARDS. Biomarkers based on a combination of fasting glucose and lymphocyte counts to predict prognosis in critically ill patients with ARDS remain undefined. In this study, we investigated the association between glucose‐to‐lymphocyte ratio (GLR) and in‐hospital mortality.MethodsThe study obtained data from Medical Information Mart for Intensive Care‐IV (MIMIC‐IV Version 1.0) database. We defined the GLR as fasting glucose/lymphocyte count and the patient in‐hospital mortality was considered as the outcome. In addition, we employed linear and logistic regression models for analysis.ResultsIn total, 1,085 patients with ARDS were included in this study. The eligible participants included 498 female and 587 males, with a mean age of 64.2 ± 17.5 years. Logistic regression analysis demonstrated that higher GLR was an independent risk factor for all‐cause mortality (OR =1.67, 95% CI: 1.26–2.22) after adjusting for age, sex, anion gap, white blood cell count, congestive heart failure, sequential organ failure assessment (SOFA), SBP, DBP, and respiratory rate in both the dichotomized group and subgroups. We also analyzed the in‐hospital mortality to ROC curves by comparing the value between SOFA + GLR and SOFA. The area under the curve (AUC) was 0.6991 for the SOFA + GLR (95% CI: 0.6634–0.7348), and 0.6613 for the SOFA (95% CI: 0.6238–0.6988).ConclusionOur data showed that the GLR was an independent predictor of in‐hospital mortality for patients with ARDS. The GLR is an integrated, readily available clinical biomarker for mortality in patients with ARDS.

Hepatocyte growth factor and soluble cMet levels in plasma are prognostic biomarkers of mortality in patients with severe acute kidney injury.

BackgroundHepatocyte growth factor (HGF)/cMet pathway is necessary for repair and regeneration following acute kidney injury (AKI). We evaluated the clinical potential of plasma HGF and soluble cMet as prognostic biomarkers for severe AKI requiring continuous renal replacement therapy (CRRT).MethodsOne hundred thirty-six patients with severe AKI who participated in the VENUS (volume management under body composition monitoring in critically ill patients on CRRT) trial between 2017 and 2019 were enrolled in this study. We investigated associations between plasma HGF and cMet concentrations and all-cause mortality.ResultsPlasma HGF and soluble cMet levels were positively correlated. Patients were divided into three groups based on their HGF and soluble cMet concentrations. The day D 0, D2, and D7 highest concentration HGF groups had significantly higher in-hospital mortality after adjusting for sex, body mass index, Acute Physiology and Chronic Health Evaluation II, and age-adjusted Charlson comorbidity index score, especially on D7 (hazard ratio, 4.26; 95% confidence interval, 1.71–10.62; p = 0.002). D7 soluble cMet level was also associated with mortality. Receiver operating characteristic curve analysis indicated that D7 HGF and soluble cMet levels were best at predicting mortality. Addition of plasma HGF and soluble cMet to conventional prognostic indices significantly improved the predictive value for mortality on D7. However, plasma HGF and soluble cMet were not associated with fluid status.ConclusionPlasma HGF and soluble cMet levels were significant predictors of the outcomes of severe AKI patients undergoing CRRT. There was no correlation between plasma HGF and soluble cMet levels and fluid balance.

OPG/TRAIL ratio as a predictive biomarker of mortality in patients with type A acute aortic dissection

Following hospital discharge, patients with type A acute aortic dissection (TA-AAD) may present an increase in mortality risk. However, little is known about specific biomarkers associated with post-discharge survival, and there is a paucity of prognostic markers associated with TA-AAD. Here, we identify nine candidate proteins specific for patietns with TA-AAD in a cross-sectional dataset by unbiased protein screening and in-depth bioinformatic analyses. In addition, we explore their association with short-term and long-term mortality in a derivation cohort of patients with TA-AAD, including an internal (n = 300) and external (n = 236) dataset. An elevated osteoprotegerin (OPG)/tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) ratio was the strongest predictor of overall, 30-day, post-30-day mortality in both datasets and was confirmed to be a strong predictor of mortality in an independent validation cohort (n = 400). Based on OPG/TRAIL ratio-guided risk stratification, patients at high risk (>33) had a higher 1-year mortality (55.6% vs. 4.3%; 68.2% vs. 2.6%) than patients at low risk (<4) in both cohorts. In Conclusion, we show that an elevated OPG/TRAIL ratio is associated with a significant increase in short-term and long-term mortality in patients with TA-AAD.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Predict Mortality in Patients with Diabetic Foot Ulcers Undergoing Amputations.

PurposeElevated platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with poor outcomes in various diseases. The objectives of this study were to explore the utility of PLR and NLR in predicting all-cause mortality in patients with diabetic foot ulcers (DFU) undergoing amputations.Patients and MethodsA retrospective observational study was performed that included a total of 348 DFU patients undergoing amputations. The primary end-point was all-cause death. According to the PLR and NLR cut-off values, patients were divided into two groups and Kaplan–Meier survival curves were constructed. Multivariable Cox regression was conducted to test the independent predictors of mortality in the study cohort.ResultsAll-cause mortality was significantly higher in patients with a high PLR/NLR compared to those with a low PLR/NLR. In the low NLR group, the overall survival (OS) rates at 1, 3, and 5 years after amputation were 96.8%, 84% and 80.1%, respectively (p=0.001). In the high NLR group the corresponding OS rates at 1, 3, and 5 years were 85.2%, 58.6% and 23.9% (p<0.001). According to the multivariate analysis, age (HR 1.074, 95% CI 1.045–1.104, p<0.001), Wagner classification (HR 2.274, 95% CI 1.351–3.828, p=0.002), PLR (HR 1.794, 95% CI 1.014–3.174, p=0.045), NLR (HR 2.029, 95% CI 1.177–3.499, p=0.011), creatinine (HR 1.003, 95% CI 1.001–1.004, p<0.001) and direct bilirubin (HR 1.154, 95% CI 1.081–1.232, p<0.001) were independent predictors of mortality following amputation.ConclusionPostoperative PLR and NLR values may be reliable predictive biomarkers of mortality in patients following amputation for DFU. Considering the high mortality in those patients, the patients with elevated PLR/NLR should be given more intensive in clinical practice.

Biomarkers of Mortality in Patients With Sickle Cell Disease

Biomarkers of Mortality in Patients With Sickle Cell Disease

Leucocyte ratios are biomarkers of mortality in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

In patients with cirrhosis, progression to acute decompensation (AD) and acute-on-chronic liver failure (ACLF) has been associated with poor prognosis. Differential leucocyte ratios might predict mortality in systemic inflammatory conditions. To evaluate differential leucocyte ratios as prognostic biomarkers in patients with cirrhosis. Patients with AD and ACLF were recruited from four centres in three countries. Peripheral blood differential leucocytes were measured (three centres using flow cytometry) on hospital admission and at 48 hours. Ratios were correlated to model for end-stage liver disease (MELD), chronic liver failure-sequential organ failure (CLIF-SOFA), suspected/culture-positive bacterial infection and survival. Nine hundred twenty-six patients (562 (61%) male, median age 55 (25-94) years) were studied. Overall, 350 (37%) did not survive to hospital discharge. Neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) were elevated in patients with AD and ACLF who died during their hospital stay. On multivariate analysis NLR retained statistical significance independently of CLIF-SOFA or MELD. NLR >30 was associated with an 80% 90-day mortality in patients with ACLF but not AD. On sensitivity analysis for subgroups (alcohol-related liver disease and suspected sepsis), NLR and MLR retained statistically robust accuracy for the prediction of mortality. Significant predictive accuracy was only observed in centres using flow cytometry. Leucocyte ratios are simple and robust biomarkers of outcome in ACLF, which are comparable to CLIF-SOFA score but dependent on leucocyte quantification method. NLR and MLR may be used as screening tools for mortality prediction in patients with acutely deteriorating cirrhosis.

Evaluation of usefulness in surfactant protein D as a predictor of mortality in myositis-associated interstitial lung disease.

Surfactant protein D (SP-D) is considered a serum biomarker of various forms of interstitial lung disease (ILD). In this study, we examined the utility of SP-D as a predictive biomarker for mortality in patients with ILD associated with polymyositis/dermatomyositis (PM/DM) using large-scale multicentre cohort data. We enrolled 381 patients with incident PM/DM-associated ILD in a multicentre retrospective cohort based on the availability of serum SP-D at the baseline. Demographic and clinical characteristics as well as the presence of autoantibodies to melanoma differentiation-associated gene 5 (MDA5) and aminoacyl tRNA synthetase were measured at the time of diagnosis, and follow-up survival data were collected prospectively. Seventy-eight patients died during the median observation period of 18 months, and the majority of patients died of ILD. The SP-D levels at baseline were significantly lower (P = 0.02) in a non-survivor subset than in a survivor subset among the entire enrolled patients. However, the SP-D levels were higher in the non-survivor subset than in the survivor subset based on the stratification by anti-MDA5-positive, anti-ARS-positive and, double-negativity, although there was an only statistically significant difference (P = 0.01) in the double-negative group. Surprisingly, the SP-D levels were within the upper limit of normal, 110 ng/mL, in 54 (87%) of 62 anti-MDA5-positive patients who died. In the double-negative group, the mortality rates were significantly higher (P = 0.002) in a subset with SP-D ≥127.6 ng/mL, the cut-off value for mortality calculated by the receiver operating characteristic curve, than the other subset. All of patients with SP-D <127.6 ng/mL survived. Serum SP-D levels behave differently among patients with stratified by anti-MDA5 antibody, anti-ARS antibody and both negativity in PM/DM-associated ILD. Its use in clinical practice should be applied with caution on the basis of the presence or absence of anti-MDA5 antibody or anti-ARS antibody.

New prognostic biomarkers of mortality in patients undergoing liver transplantation for hepatocellular carcinoma.

The outcome prediction of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) was classically established using various macromorphological factors and serum alpha-fetoprotein levels prior to LT. However, other biomarkers have recently been reported to be associated with the prognosis of HCC patients undergoing to LT. This review summarizes clinical data on these new biomarkers. High blood levels of malondialdehyde, total antioxidant capacity, caspase-cleaved cytokeratin-18, soluble CD40 ligand, substance P, C-reactive protein, and vascular endothelial growth factor, increased neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in blood, high peripheral blood expression of human telomerase reverse transcriptase messenger ribonucleic acid, and high HCC expression of dickkopf-1 have recently been associated with decreased survival rates. In addition, high blood levels of des-gamma-carboxy prothrombin, and high HCC expression of glypican-3, E-cadherin and beta-catenin have been associated with increased HCC recurrence. Additional research is necessary to establish the prognostic role of these biomarkers in HCC prior to LT. Furthermore, some of these biomarkers are also interesting because their potential modulation could help to create new research lines for improving the outcomes of those patients.

Cardiac troponin elevation as an evidence of neurogenic myocardial dysfunction in patients with head trauma

Background: cardiac dysfunction is frequently observed after severe traumatic brain injury (sTBI), however its significance is poorly understood. Our study sought to elucidate the association of cardiac troponin I (cTnI) elevation with all cause in-hospital mortality following isolated sTBI (brain AIS ≥ 3 and admission GCS ≤ 8, no AIS ≥3 to any other bodily regions). Patients and methods: After approval of this study from local ethical committee, and obtaining written informed consent from relatives, head trauma patients will be enrolled in this observational prospective study. study was conducted in the 10-bed trauma-surgical ICU in Sohag university hospital , Fifty patients with isolated TBI , were consecutively included between January 2015 and February 2017. Results: our study validated cTnI as a novel biomarker and independent predictor of all cause in-hospital mortality in patients with TBI. these findings have several implications. First, cTnI assay should be considered in patients with sTBI even in absence high suspicion of cardiac injury. Second, cTnI is a sufficiently prognostic biomarker of mortality in patients with sTBI. Third, cTnI elevation in patients with sTBI must be treated with caution. Conclusion: cTnI level was a significant indicator for stress cardiomyopathy , severity of trauma calculated by RTS had no relation with incidence of stress cardiomyopath . Our study provided important insights to the heart-brain interactions following TBI and possible schemes for subsequent optimization of management of these patients.

Mid-Regional Proadrenomedullin as a Prognosis Biomarker of Mortality in Patients Treated with Non-Invasive Ventilation in the Emergency Room

Mid-Regional Proadrenomedullin as a Prognosis Biomarker of Mortality in Patients Treated with Non-Invasive Ventilation in the Emergency Room

CRP velocity and short-term mortality in ST segment elevation myocardial infarction

Context: There is a known association between C-reactive protein (CRP) levels and adverse outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). The optimal time frame to measure CRP for risk stratification is not known.Objective: The aim of the current study was to evaluate the relation between the change in CRP velocity (CRPv) and 30-d mortality among STEMI patients.Material and methods: We included consecutive patients with a diagnosis of STEMI who presented to Tel-Aviv Medical Center between 2008 and 2014 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 h after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements.Results: The study population comprised of 492 patients, mean age was 62 ± 14, 80% were male. CRPv was significantly higher among patients who died within 30 d of admission (1.42 mg/l versus 0.18 mg/l, p < 0.001). In a multivariate regression model adjusted to multiple confounders, CRPv was independently associated with 30-d mortality (OR 1.39, 95% CI: 1.20–1.62, p < 0.001).Conclusion: CRPv might be an independent and rapidly measurable biomarker for short-term mortality in patients presenting with STEMI.

Siglec-7 as a Novel Biomarker to Predict Mortality in Decompensated Cirrhosis and Acute Kidney Injury.

Patients with decompensated cirrhosis have high morbidity and are commonly hospitalized with acute kidney injury. We examined serum levels of Siglec-7, a transmembrane receptor that regulates immune activity, as a biomarker for mortality in patients with cirrhosis and acute kidney injury. Serum Siglec-7 was measured in hospitalized patients with cirrhosis and acute kidney injury, as well as in reference groups with acute liver injury/acute kidney injury, cirrhosis without acute kidney injury, and sepsis without liver disease. Clinical characteristics and subsequent outcomes were examined using univariate and multivariable analyses according to initial Siglec-7 levels. Primary outcome was death by 90days. One hundred twenty-eight subjects were included, 92 of which had cirrhosis and acute kidney injury and were used in the primary analysis. Average Model for End-Stage Liver Disease (MELD) score was 24 [95% CI 23, 26], and serum creatinine was 2.5 [2.2, 2.8] mg/dL at the time Siglec-7 was measured. After adjusting for age and MELD score, high serum Siglec-7 level predicted mortality with a hazard ratio of 1.96 [1.04, 3.69; p=0.04]. There was no difference in Siglec-7 levels by etiology of AKI (p=0.24). Addition of serum Siglec-7 to MELD score improved discrimination for 90-day mortality [category-free net reclassification index=0.38 (p=0.04); integrated discrimination increment=0.043 (p=0.04)]. Serum Siglec-7 was associated with increased mortality among hospitalized patients with cirrhosis and acute kidney injury. Addition of Siglec-7 to MELD score may increase discrimination to predict 90-day mortality.