Surrogate Markers Of Inflammation Research Articles

Postoperative prognostic nutrition index predicts survival in patients with small bowel adenocarcinoma after surgical resection.

Surgical resection (SR) is the main treatment for small bowel adenocarcinoma (SBA), but it increases metabolic demand, systemic inflammation, and digestive dysfunction, resulting in major impacts on the postoperative outcomes of patients. This study, we aimed to investigate the role of the postoperative prognostic nutritional index (PNI), a surrogate marker of inflammation and nutrition, in patients with SBA after resection. From June 2014 to March 2022, 44 consecutive patients who underwent SR for SBA in Taipei Veterans General Hospital were retrospectively reviewed. Factors associated with survival including PNI were analyzed. PNI decreased in patients after SR for SBA (median change: -1.82), particularly in those who underwent Whipple operation or developed postoperative pancreatic fistula. Postoperative PNI < 45.2 best predicted overall survival (OS) (AUROC: 0.826, p = 0.001). Patients with lower postoperative PNI had significantly worse OS compared to those higher postoperative values (median OS: 19.3 months vs. not reached, p < 0.001). Low postoperative PNI (hazard ratio [HR]: 11.404, p = 0.002), tumoral lymphovascular invasion (HR: 8.023, p = 0.012), and adjuvant chemotherapy (HR: 0.055, p = 0.002) were independent risk factors for OS. Postoperative PNI also significantly predicted recurrence-free survival independent of lymphovascular invasion and adjuvant chemotherapy (HR: 6.705, p = 0.001). PNI commonly decreases in patients with SBA who undergo Whipple surgery or develop postoperative pancreatic fistula. Postoperative PNI independently predicts survival and may serve as a clinical marker to optimize patient outcomes.

Malnutrition: muscle wasting, inflammation, RDW, and their relation with adverse outcomes.

The objective of the study was to explore red cell distribution width (RDW) as a surrogate marker of inflammation, alone and in conjunction with muscle wasting to predict malnutrition-related adverse outcomes. This was a single-center observational study including adult hospitalized patients. Demographic variables, malnutrition criteria, and RDW were captured within 24 hours of hospital admission. Correlation tests and regression models were performed between these variables (RDW and muscle wasting) and adverse outcomes (in-hospital mortality and unplanned transfer to critical care areas (CCA). Five hundred and forty-five patients were included in the final analysis. Muscle wasting showed an independent association with adverse outcomes in every regression model tested. RDW alone showed fair predictive performance for both outcomes' significance and the adjusted model with muscle wasting showed association only for unplanned transfer to CCA. RDW did not improve the prediction of adverse outcomes compared to muscle wasting assessed by physical examination and simple indexes for acute and chronic inflammation. Malnourished patients presented higher RDW values showing a possible metabolic profile (higher inflammation and lower muscle). It is still unknown whether nutrition support can influence RDW value over time as a response marker or if RDW can predict who may benefit the most from nutritional support.

Preoperative Serum Albumin as Predictor of Outcomes After Thyroidectomy.

Albumin is considered to be a surrogate marker for inflammation and nutritional status. Levels usually decrease after surgery but little is known about the predictive value of preoperative albumin levels in patients undergoing thyroidectomy. This study aimed to investigate the 30-day incidence of postoperative outcomes in thyroidectomy patients with and without preoperative hypoalbuminemia. Retrospective cohort study. TriNetX Database. TriNetX, a federated deidentified database, was retrospectively queried to identify patients who underwent thyroidectomy. Postoperative outcomes within 30 days of thyroidectomy, based on International Classification of Disease, 10th Revision and Current Procedural Terminology codes, in patients with preoperative hypoalbuminemia (≤3.4 g/dL) (cohort 1) were analyzed and compared to patients without hypoalbuminemia (cohort 2). After propensity score matching, 2398 patients were identified in each cohort. Hypoalbuminemia patients were more likely to have postoperative pneumonia (odds ratio, OR: 3.472, 95% confidence interval, CI [2.016-5.978]), acute renal failure (OR: 3.872, 95% CI [2.412-6.217]), venous thromboembolism (OR: 1.766, 95% CI[1.016-2.819]), and surgical site infection (OR: 2.353, 95% CI [1.282-4.32]). Rates of recurrent laryngeal nerve injury were comparable between cohorts. Patients undergoing thyroidectomy with preoperative hypoalbuminemia have a higher prevalence of postoperative complications compared to patients without preoperative hypoalbuminemia. While not routinely assessed, preoperative evaluation of serum albumin levels may help guide expectations and optimal management of thyroidectomy patients.

Gamma-Glutamyl Transferase as a prognostic risk factor in complex coronary disease: a serendipitous (re)discovery of machine learning in the SYNTAXES?

Abstract Background/Introduction Over the last decade, epidemiology and pathology studies have suggested that gamma-glutamyl transferase (GGT) has an independent role in the pathogenesis and clinical evolution of cardiovascular diseases associated with atherosclerosis. Recently, machine learning (ML) algorithms have identified pre-procedural GGT as a significant predictor of long-term mortality after coronary revascularization in the SYNTAX trial. Purpose The aim of this study is to investigate the impact of pre-procedural GGT on 10-year all-cause mortality in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) following revascularization. Methods The SYNTAX trial was a randomized trial comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in 1,800 patients with complex CAD. The present report is a post-hoc sub-analysis of the SYNTAXES study, an investigator-driven extended 10-year follow-up of the SYNTAX trial. Before revascularization, blood samples were taken for GGT as well as other biological markers and analyzed by an independent central chemistry laboratory. The primary endpoint was all-cause mortality at 10-years. The changes in hazard for all-cause mortality in GGT over time were modelled using restricted cubic spline functions in a Cox regression model adjusted by age and sex. Subsequently, we compared survival in four groups defined by gender specific GGT thresholds of &amp;lt;32 IU and ≥32 IU for females and &amp;lt;64 IU and ≥64 IU for males, in accordance with prior studies. Results Out of 1,800 patients enrolled in the SYNTAX study, 167 (9.3%) did not have a GGT available at baseline and 1,633 (90.7%) patients were included in the present study. The mean values of GGT for males and females were 43.5±48.5 and 36.4±46.1 U/L, respectively. In the overall population a 10 U/L increase in GGT was significantly associated with 10-year all-cause death (adjusted hazard ratio [HR] 95% confidence interval [CI]: 1.03 [1.02–1.04], p &amp;lt;0.001, Figure A). For Kaplan–Meier analysis, patients were stratified into four groups according to previously reported sex related GGT thresholds. Ten-year mortality was numerically higher in males (adjusted HR 1.31, 95% CI: 0.90–1.91), and significantly higher in females (adjusted HR 1.88, 95% CI: 1.16–3.05) among patients with higher versus lower GGT (Figure B). Furthermore, GGT was significantly associated with CRP, a surrogate-marker of inflammation, as well as established cardiovascular risk biomarkers such as TG, total cholesterol, and glucose. Conclusions Preprocedural GGT is an independent predictor of 10-year mortality following coronary revascularization in patients with 3VD and/or LMCAD. This long-term association has been identified using ML algorithms and should be corroborated using data from large biobanks.Figure AFigure B

Glucose indices as inflammatory markers in children with acute surgical abdomen: a cross-sectional study

Background Glycaemic dysregulation potentiates the pro-inflammatory response and increases oxidative injury; therefore, preoperative hyperglycaemia is linked to increased mortalities. In addition, inflammation is accompanied by higher glycated haemoglobin (HbA1c) levels, and the relationship between this and random blood sugar (RBS) could be non-linear. Methods This is a cross-sectional study. Non-diabetic paediatric patients with acute surgical abdomen, presenting to the emergency surgical services were enrolled, over a period of 6 months. They were all screened for their random blood sugar and HbA1c levels. Results Fifty-three cases were studied. The prevalence of glycaemic dysregulation in the enrolled children was high. Abnormal HbA1c was observed in 66% of the study group. Stress hyperglycaemia was observed in 60% of the enrolled children. There was a significant correlation (r = 0.770, p-value: < 0.001) between RBS and the total leucocytic count (TLC). The TLC cutoff value for predicting stress hyperglycaemia was 13,595 cells/mm3. The cutoff value of RBS for predicting leukocytosis was 111.5 mg/dl. Median RBS level was significantly higher in complicated appendicitis (169.5 mg/dl), compared to uncomplicated appendicitis (118.0 mg/dl). Conclusion HbA1c and RBS could be used as inflammatory markers for surgical acute abdomen and its degree of severity, respectively. HbA1c rises in a considerable number of cases with surgical acute abdomen, irrespective of the disease stage. However, as the disease progresses, the random blood sugar rises due to stress hyperglycaemia, thus becoming a surrogate inflammatory marker.

Neutrophil-to-lymphocyte ratio and prognosis in patients undergoing percutaneous coronary intervention for acute coronary syndrome

ObjectiveThe purpose of this study was to characterize Acute Coronary Syndrome (ACS)-associated inflammation by investigating correlates of the neutrophil-to-lymphocyte ratio (NLR), a surrogate marker of inflammation, and its relation to 1-year mortality in a cohort of patients undergoing percutaneous coronary intervention (PCI) for ACS at a single institution. MethodsWe performed a single-institution, retrospective, observational study of all-comer ACS patients who underwent PCI and were discharged home before the COVID-19 pandemic between September 23, 2011 and July 31, 2017 for who outcomes data were available. ResultsNLRhigh group tended to be older, white patients, less likely to smoke, more likely to have a history of heart failure and cardiac arrest, higher creatinine values, lower LVEF, and higher CK-MB (a surrogate for infarct size). Linear regression model demonstrated a strong correlation between increasing NLR and white race (B = 1.103, p = 0.001, hemoglobin (B = −0.30, p < 0.001), peak CK-MB (B = 0.004, p = 0.02), LVEF (B = −0.048, p < 0.001), and serum creatinine (B = 0.47, p = 0.03). There were a total of 87 deaths at one year. NLR > 3.4 was associated with worse one-year survival post-PCI (91.4 % vs. 95.4 %, log-rank p < 0.004), which was confirmed on multivariate analysis. ConclusionOur data confirm the independent prognostic significance of inflammation to mortality after ACS and may provide some insight into the putative benefits of inflammation modulation.

Coronary CT angiography for the assessment of atherosclerotic plaque inflammation: postmortem proof of concept with histological validation.

To evaluate the diagnostic utility of multiphase postmortem CT angiography (PMCTA) to detect plaque enhancement as a surrogate marker of inflammation, using fatal coronary plaques obtained from autopsies following sudden cardiac death. In this retrospective study, we included 35 cases (12 women, 34%; median [IQR] age, 52 [11] years), with autopsy-proven coronary thrombosis, histological examination, and multiphase PMCTA. Two radiologists blinded towards histological findings assessed PMCTA for plaque enhancement of the culprit lesion in consensus. Two forensic pathologists determined the culprit lesion and assessed histological samples in consensus. Cases with concomitant vasa vasorum density increase and intraplaque and periadventital inflammation were considered positive for plaque inflammation. Finally, we correlated radiology and pathology findings. All 35 cases had histological evidence of atherosclerotic plaque disruption and thrombosis; 30 (85.7%) had plaque inflammation. Plaque enhancement at multiphase PMCTA was reported in 21 (60%) and resulted in a PPV of 95.2% (77.3-99.2%) and an NPV of 28.6% (17-43.9%). Median histological ratings indicated higher intraplaque inflammation (p = .024) and vasa vasorum density (p = .032) in plaques with enhancement. We found no evidence of a difference in adventitial inflammation between CT-negative and CT-positive plaques (p = .211). Plaque enhancement was found in 2/3 of fatal atherothrombotic occlusions at coronary postmortem CT angiography. Furthermore, plaque enhancement correlated with histopathological plaque inflammation and increased vasa vasorum density. Plaque enhancement on multiphase CT angiography could potentially serve as a noninvasive marker of inflammation in high-risk populations. Phenotyping coronary plaque more comprehensively is one of the principal challenges cardiac imaging is facing. Translating our ex vivo findings of CT-based plaque inflammation assessment into clinical studies might help pave the way in defining high-risk plaque better. • Most thrombosed coronary plaques leading to fatality in our series had histological signs of inflammation. • Multiphase postmortem CT angiography can provide a noninvasive interrogation of plaque inflammation through contrast enhancement. • Atherosclerotic plaque enhancement at multiphase postmortem CT angiography correlated with histopathological signs of plaque inflammation and could potentially serve as an imaging biological marker of plaque vulnerability.

Elevated serum polyclonal immunoglobulin free light chains in patients with severe asthma.

Background: Inflammation plays a pivotal role in the pathophysiology of asthma. Free light chains (FLC) can cause inflammation by mast cell antigen-activation. Serum immunoglobulin (Ig) FLC κ, but not λ, were shown elevated in adult males with asthma. We sought to investigate if serum Ig FLC concentrations are affected by asthma severity and their relationships with inflammatory outcomes. Methods: By using immunoassays, we measured serum κ and λ Ig FLCs in 24 severe persistent asthma patients, 15 patients with moderate persistent asthma, 15 steroid-naïve mild persistent asthma patients and 20 healthy control subjects in a cross-sectional observational study. Total and specific serum IgE concentrations, fractional exhaled nitric oxide (FENO), lung function, peripheral blood eosinophils and neutrophils, and C reactive protein (CRP) were also measured. Results: Serum κ FLC concentrations were elevated in severe asthma patients compared mild asthma patients (p < 0.05) and healthy subjects (p < 0.05). Serum λ FLCs were higher in severe asthma patients than in healthy subjects (p < 0.05) and correlated with blood eosinophil counts (percentage, κ: r = 0.51, p = 2.9678-6; λ: r = 0.42, p = 1.7377-4; absolute values, κ: r = 0.45, p = 6.1284-5; λ: r = 0.38, p = 7.8261-4), but not with total or specific serum IgE. In severe asthma patients, serum Ig FLC correlated with serum CRP (κ: r = 0.33; p = 0.003; λ: r = 0.38, p = 8.8305-4) and blood neutrophil cell counts (percentage, κ: r = 0.31; p = 0.008; λ: r = 0.29, p = 0.01; absolute values, κ: r = 0.40; p = 3.9176-4; λ: r = 0.40, p = 4.5479-4), were elevated in subjects with blood eosinophilia (≥300 cells/µL) (n = 13) compared with non-eosinophilic subjects (n = 10) (κ: 19.2 ± 1.2mg/L versus 12.1 ± 1.3mg/L, p < 0.001; λ: 27.2 ± 2.6mg/L versus 16.8 ± 2.5mg/L, p < 0.01), but were similar in atopic (n = 15) versus nonatopic subjects (n = 9) (κ: p = 0.20; λ: p = 0.80). Serum FLC were negatively correlated with lung function tests, including forced expiratory volume in one second (FEV1) (κ: r = -0.33; p = 0.0034; λ: r = -0.33; p = 0.0035), and FEV1/forced vital capacity ratio (κ: r = -0.33; p = 0.0034; λ: r = -0.33; p = 0.0036). Conclusion: Serum Ig FLCs are elevated in severe asthma adults and might represent new surrogate markers of inflammation. The pathophysiological implications of these findings require further research. This study was approved by the ethics committee of the University Hospital Agostino Gemelli Foundation and Catholic University of the Sacred Heart (approval number P/1034/CE2012).

Three‐dimensional multispectral facial imaging to monitor actinic damage treated with 5‐fluorouracil

AbstractBackgroundStandardised therapeutic monitoring of field skin cancerisation is challenging. 5‐fluorouracil (5‐FU) is a common topical therapy for ultraviolet radiation (UV) and actinic keratosis (AK) but is often accompanied with adverse side effects. Monitoring of patients following treatment can be improved with novel imaging technologies.ObjectivesThis case series used new, improved facial imaging technology in assessing topical 5‐FU treatment for actinic damage.MethodsA case series followed 18 participants treated with topical 5‐FU over 2 weeks, with facial imaging at baseline, at the end of treatment and at Week 12 posttreatment. Skin characteristics were automatically measured across selected treatment areas using the VISIA three‐dimensional (3D) multispectral facial imaging system.ResultsVISIA analysis recorded sharp increases in erythema, UV‐spots and skin roughness at Week 2 followed by reduction of erythema, UV‐spots and skin roughness at 12 weeks posttreatment compared to baseline. Skin hyper‐ and hypopigmentation was observed across treatment areas at Week 2 returning to baseline levels by Week 12. Participants demonstrated improved skin texture indicating smoother skin and significantly diminished UV‐spots.Conclusions3D, multispectral facial imaging can facilitate topical treatment monitoring of field cancerisation. 5‐FU treatment of field cancerisation as observed in VISIA images and data are consistent with clinical experience. 3D, multispectral imaging was efficient, noninvasive and objective in monitoring treatment of actinic damage, for example, by measurement of erythema as a surrogate marker for inflammation. For clinical trials of new treatment modalities for facial photodamage and field cancerisation, 3D multispectral imaging features new tools for analysis of skin characteristics, including objective quantification of erythema, skin texture, UV‐spots and other inflammation‐related changes triggered by 5‐FU treatment.

Blood count derangements after sepsis and association with post-hospital outcomes.

Predicting long-term outcomes in sepsis survivors remains a difficult task. Persistent inflammation post-sepsis is associated with increased risk for rehospitalization and death. As surrogate markers of inflammation, complete blood count parameters measured at hospital discharge may have prognostic value for sepsis survivors. To determine the incremental value of complete blood count parameters over clinical characteristics for predicting 90-day outcomes in sepsis survivors. Electronic health record data was used to identify sepsis hospitalizations at United States Veterans Affairs hospitals with live discharge and relevant laboratory data (2013 to 2018). We measured the association of eight complete blood count parameters with 90-day outcomes (mortality, rehospitalization, cause-specific rehospitalizations) using multivariable logistic regression models. We identified 155,988 eligible hospitalizations for sepsis. Anemia (93.6%, N=142,162) and lymphopenia (28.1%, N=29,365) were the most common blood count abnormalities at discharge. In multivariable models, all parameters were associated with the primary outcome of 90-day mortality or rehospitalization and improved model discrimination above clinical characteristics alone (likelihood ratio test, p<0.02 for all). A model including all eight parameters significantly improved discrimination (AUROC, 0.6929 v. 0.6756) and reduced calibration error for the primary outcome. Hemoglobin had the greatest prognostic separation with a 1.5 fold increased incidence of the primary outcome in the lowest quintile (7.2-8.9 g/dL) versus highest quintile (12.70-15.80 g/dL). Hemoglobin and neutrophil lymphocyte ratio provided the most added value in predicting the primary outcome and 90-day mortality alone, respectively. Absolute lymphocyte count added little value in predicting 90-day outcomes. The incorporation of discharge complete blood count parameters into prognostic scoring systems could improve prediction of 90-day outcomes. Hemoglobin had the greatest prognostic value for the primary composite outcome of 90-day rehospitalization or mortality. Absolute lymphocyte count provided little added value in multivariable model comparisons, including for infection- or sepsis-related rehospitalization.

Pitfalls in the interpretation of blood tests used to assess and monitor micronutrient nutrition status.

Assessment of micronutrient (MN) status is of particular importance in patients who require medical nutrition therapy, especially those requiring parenteral nutrition. Blood testing is generally the only tool available in clinical settings to assess MN status. However, using plasma or serum concentration faces pitfalls mainly because of the impact of inflammation that diverts the MNs from the circulating compartment. This review aims to review the blood tests that are useful and provide information about how to integrate functional markers of status to reach a clinically relevant diagnosis. Most impacted, with a significant and proportional decrease in plasma concentrations, are iron, selenium, zinc, thiamin, folic acid, cobalamin, and vitamins A, C, and D; copper is the only MN for which the plasma concentration increases. Therefore, a surrogate marker of inflammation, C-reactive protein, must always be determined simultaneously. Validated intracellular and functional tests are proposed to improve status assessment. A protocol is suggested for tests required both on commencing and during nutrition support. A timely turnaround of analysis is essential for results to be clinically useful. In some cases, the appropriate provision of MNs should be commenced before results have been obtained to confirm the clinical assessment. Laboratory tests of MN status are an area prone to misuse and misinterpretation. The appropriate use and interpretation of such tests are essential to ensure the correct management of nutrition problems.

18F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease.

Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neuropathophysiological mechanism driving Parkinson’s disease (PD). We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [18F]NOS radiotracer to measure neuroinflammation in idiopathic PD. Ten adults consisting of 6 PD patients and 4 healthy controls (HC) underwent one hour of dynamic [18F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [18F]NOS whole brain distribution volume (VT) in PD patients compared to age-matched healthy controls (p < 0.008) via a 1-tissue compartment (TC) model. The rate constant K1 for transport from blood into tissue did not differ between groups (p = 0.72). These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD and indicate that [18F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation.

The Impact of Dietary Fiber as a Prebiotic on Inflammation in Children with Obesity.

Background: Obesity is associated with dysbiosis, contributing to inflammation and insulin resistance. Inulin might reduce inflammation by manipulating intestinal microbiota. Objective: We aimed to determine the effects of inulin supplementation on inflammation and assess the relationships of inflammatory cytokines with adiposity and insulin resistance in obese Thai children. Design: Obese Thai children ages 7–15 years were randomly assigned to inulin (intervention), maltodextrin (placebo), and dietary fiber advice groups. All participants received monthly follow-up and identical advice on lifestyle modification for six visits. Body composition was evaluated using bioelectrical impedance analysis. IL-1β, IL-6, TNF-α, and fecal calprotectin were analyzed by ELISA technique at baseline and the final visit. Spearman correlation was used to assess the associations between inflammation and other clinical outcome variables. Results: A total of 155 obese children completed the study (mean age: 10.4 ± 2.2 years, 59% male). All groups showed a significant decrease in BMI z-score, fat mass index (FMI), percent body fat, and trunk FMI. A generalized estimating equation (GEE) model showed significantly decreased IL-1β and TNF-α of 34.8% and 25.8%, (p < 0.0001) but increased IL-6 (21.5%, p = 0.006) in all groups. There were no significant differences in inflammatory cytokines and fecal calprotectin between groups. Mean IL-6 was higher in obese children with acanthosis nigricans (p = 0.048). Only IL-6 was positively correlated with body fat percentage and FMI (r = 0.29, p = 0.008 and r = 0.25, p = 0.049, respectively). Conclusions: Intensive behavioral modification and frequent follow-up visits were effective methods to reduce BMI and adiposity leading to decreased inflammatory cytokines. The additional benefits of inulin on inflammation could not be demonstrated due to the Hawthorne effect. Among the three cytokines, IL-6 was the most likely mediator relating FM and insulin resistance at baseline; therefore, it could be used as a surrogate marker of inflammation in obese children who are at risk for insulin resistance and metabolic syndrome.

Neutrophil-to-Lymphocyte Ratio and Cut-off Values as Predictor of Severity and Mortality in COVID-19 Patients in Millennium COVID-19 Care Center, Addis Ababa, Ethiopia.

BackgroundEarly identification of patients at high risk of poor clinical outcomes is the key to success in saving the lives of patients with coronavirus disease 2019 (COVID-19). Neutrophil to Lymphocyte Ratio (NLR) is an easily available and cheap surrogate inflammatory marker, its baseline NLR role in African COVID-19 patients remains to be investigated. The objective of the study aimed to evaluate the role of NLR as a predictor of severity and mortality of COVID-19 patients admitted at the Millennium COVID 19 care center in Addis Ababa, Ethiopia.MethodsA cross-sectional study was conducted on patients with COVID-19 admitted to the Millennium COVID-19 care center from August 1 to October 30, 2021. Receiver Operating Characteristic curve analysis was used to calculate the area under the curve to assess the predictive capacity of NLR on mortality and severity. Multivariable logistic regression analysis was done to identify the association between independent variables and disease outcomes with an Adjusted Odds Ratio (AOR), P-value, and 95% CI for AOR were used for testing significance.ResultsThe NLR of 9.47 was identified as the optimal cut-off value for predicting mortality with a sensitivity of 88.7% and a specificity of 95.4% (Area Under the Curve (AUC):0.95, 95% CI 0.92–98; P<0.001) and the NLR of 5.86 was an effective threshold value in predicting the severity of disease with a sensitivity of 92.2% and a specificity of 75% (AUC:0.85, 95% CI 0.800–0.905; P<0.001). In multivariable logistic regression analysis, after adjusting for confounding factors, NLR of more than 9.47 and 5.86 was significantly associated with all‐cause of in‐hospital mortality (AOR=4.73, 95% CI, 1.19–33.68; P<0.02), and severity of disease (AOR=12.98, 95% CI 3.85–43.80; P=0.001), respectively.ConclusionNLR greater than 9.47 and 5.86 effectively predict mortality and severity of the disease, respectively. It provides an objective input for early decision-making in inpatient management especially in resources limited area.

Surrogate Inflammatory Markers and Some Correlates in Pre-dialysis Chronic Kidney Disease Patients: a cross-sectional study

Objective: Chronic kidney disease is characterized by a state of chronic inflammation which is associated with poor cardiovascular disease outcomes. The study determined the prevalence of elevated neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as surrogate markers of inflammation and their association with some cardiovascular risk factors among pre-dialysis CKD patients. Method: This was a cross-sectional study to determine and compare the prevalence of elevated NLR and PLR. The correlation between these surrogate inflammatory markers and some cardiovascular risk factors was determined. Data were analyzed using SPSS version 21 software. P-value of &lt; 0.05 was taken as significant. Results: This study involved 51 pre-dialysis CKD patients and 51 controls with mean ages of 50.96±11.42 years and 48.31±9.83 years, respectively. The prevalence of elevated NLR was significantly higher in the CKD group (35.3% vs13.7%; P=0.010). In the CKD group, there was significant negative correlation between NLR and eGFR (r= -0.393; P=0.004), hemoglobin concentration (r= -0.543; P=&lt;0.001) and HDL (r= -0.292; P=0.037). There was significant positive correlation between NLR and PLR (r=0.669; P=&lt;0.001), TC:HDL (r=0.334; P=0.017), AIP(r=0.289; P=0.042) and LDL:HDL (r=0.320; P=0.020). There was significant positive correlation between PLR, NLR (r=0.695; P=&lt;0.001) and AIP (r=0.283; P=0.047). There was significant negative correlation between PLR and estimated GFR (r=- 0.448; P=0.001), hemoglobin concentration (r= -0.596; P=&lt;0.001), serum albumin (r= -0.388; P=0.005), serum HDL-C (r= -0.387; P= 0.005). Conclusion: NLR and PLR were significantly higher in pre-dialysis CKD patients and were associated with cardiovascular risk. They should be routinely used to identify those with high cardiovascular risk.

Exploring the Path of Mediterranean Diet, Non-Alcoholic Fatty Liver Disease (NAFLD) and Inflammation towards 10-Year Cardiovascular Disease (CVD) Risk: The ATTICA Study 10-Year Follow-Up (2002-2012).

Background: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease, affecting ~30% of the population and increasing CVD. This study aimed to explore the direct, indirect and combined effects of Mediterranean diet, NAFLD and inflammation on the 10-year CVD risk in a healthy adult population. Methods: Using baseline and 10-year follow-up data from the ATTICA study, adherence to Mediterranean diet was measured using MedDietScore, and presence of NAFLD at baseline was assessed using the fatty liver index (FLI). Participants’ 10-year CVD outcomes were recorded and C-reactive protein (CRP) was used as a surrogate marker for inflammation. The direct and indirect roles of these factors were explored using logistic regression models and the pathways between them were analysed using a structural equation model (SEM). Results: NAFLD prevalence was 22.9% and its presence was 17% less likely for every unit increase in MedDietScore. NAFLD presence at baseline was associated with increased 10-year CVD incidence (39.4% vs. 14.5%, p = 0.002), but when adjusted for MedDietScore, NAFLD was not an independent predictor of 10-year CVD risk. MedDietScore was an independent protective factor of 10-year CVD risk (OR = 0.989, 95% CI: 0.847, 0.935), when adjusted for NAFLD at baseline, age, gender, sedentary lifestyle and other confounders. Further exploration using SEM showed that MedDietScore was associated with CVD risk directly even when inflammation as CRP was introduced as a potential mediator. Conclusion: FLI as a proxy measure of NAFLD is a strong predictor of 10-year CVD risk, and this prognostic relationship seems to be moderated by the level of adherence to Mediterranean diet. Adherence to Mediterranean diet remained an independent and direct CVD risk factor irrespective of NAFLD status and CRP.

Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) has phenotypic variability only partially explained by established biomarkers that do not readily assess pathologically important factors of inflammation and kidney fibrosis. We evaluated asymptomatic pyuria (AP), a surrogate marker of inflammation, as a biomarker for disease progression. We performed a retrospective cohort study of adult patients with ADPKD. Patients were divided into AP and no pyuria (NP) groups. We evaluated the effect of pyuria on kidney function and kidney volume. Longitudinal models evaluating kidney function and kidney volume rate of change with respect to incidences of AP were created. There were 687 included patients (347 AP, 340 NP). The AP group had more women (65% versus 49%). Median ages at kidney failure were 86 and 80 years in the NP and AP groups (log rank, P=0.49), respectively, for patients in Mayo Imaging Class (MIC) 1A-1B as compared with 59 and 55 years for patients in MIC 1C-1D-1E (log rank, P=0.02), respectively. Compared with the NP group, the rate of kidney function (ml/min per 1.73 m2 per year) decline shifted significantly after detection of AP in the models, including all patients (-1.48; P<0.001), patients in MIC 1A-1B (-1.79; P<0.001), patients in MIC 1C-1D-1E (-1.18; P<0.001), and patients with PKD1 (-1.04; P<0.001). Models evaluating kidney volume rate of growth showed no change after incidence of AP as compared with the NP group. AP is associated with kidney failure and faster kidney function decline irrespective of the ADPKD gene, cystic burden, and cystic growth. These results support AP as an enriching prognostic biomarker for the rate of disease progression.

Neutrophil-Lymphocyte Ratio in Patients with Hypertriglyceridemic Pancreatitis Predicts Persistent Organ Failure

Background The neutrophil–lymphocyte ratio (NLR) has been proposed as a surrogate marker of inflammation with prognostic value in various diseases. Our objective was to investigate the predictive value of the NLR as an indicator of persistent organ failure (POF) in patients with hypertriglyceridemic pancreatitis (HTGP). Methods We retrospectively reviewed the data from patients with HTGP between 2016 and 2019. The NLR was obtained at admission. The diagnostic performance of the NLR for POF was evaluated by the area under the receiver operator characteristics curve (AUROC). Multivariate logistic regression determined whether elevated NLR was independently associated with POF. Results Of the 446 patients enrolled, 89 (20.0%) developed POF. Patients with POF showed a significantly higher NLR than those without POF (P < 0.001). A positive trend for the association across increasing NLR quartiles and the incidence of POF was observed (Ptrend < 0.001). The AUROC of NLR to predict POF was 0.673 (95% confidence interval, 0.627-0.716). With a cut-off of NLR > 6.56, the sensitivity and specificity were 73.0% and 55.7%, respectively. Multivariate analysis suggested that high NLR (>6.56) was independently associated with POF (odds ratio, 2.580; 95% confidence interval, 1.439-4.626; P = 0.001). Patients with a high NLR (>6.56) had a worse overall clinical course in HTGP. Conclusion Elevated NLR was significantly associated with an increased risk of developing POF and could be an early independent predictor of POF in patients with HTGP.

A170 SERUM ALBUMIN AS A MEASURE OF INFLAMMATION OR MALNUTRITION IN INFLAMMATORY BOWEL DISEASE: A CROSS SECTIONAL STUDY

BackgroundAlbumin may be both a marker of malnutrition and a marker of inflammation in various disease states but there has been little study of the precise etiology of hypoalbuminemia in patients with Crohn’s disease (CD). Malnutrition, a common complication of active CD, can lead to hypoalbuminemia. Inflammation can also lead to low albumin levels, and previous literature in other inflammatory diseases has suggested that inflammation may be more likely than malnutrition to be a primary driver of hypoalbuminemia.AimsIn order to investigate the association between serum albumin and disease activity in individuals with Crohn’s disease, we proposed the following research question:1. In Crohn’s disease, what is the association between serum albumin and two factors – (1) inflammation and (2) malnutrition, and;2. Is serum albumin an appropriate diagnostic measure of one or both of these factors in patients with CD.MethodsThis study was a single centre cross sectional study of patients with Crohn’s disease in St. John’s, NL. A total of 45 patients with Crohn’s disease were enrolled in the study. Serum albumin was compared with the subjective global assessment (SGA) for nutritional status, the Crohn’s disease activity index (CDAI), and C- Reactive Protein (CRP), a marker of inflammation.ResultsSimple correlation found negative relationships between albumin and inflammation (r = -0.44, p = 0.002) and between albumin and nutritional status (r = -0.406, p = 0.006). Multiple linear regression confirmed independent effect of both inflammation and malnutrition in the model. Participants who were both malnourished and had active inflammation had a mean serum albumin that was 5.32 g/L lower than those who were malnourished but had no active inflammation (p = 0.009) and 4.3 g/L lower than those who had active inflammation but were well-nourished (p = 0.005).ConclusionsIn our study, hypoalbuminemia was independently associated with both malnutrition and inflammation in patients with Crohn’s disease but was most profound in subjects with both malnutrition and active inflammation. These results suggest that although a low serum albumin in Crohn’s disease may be a marker of either malnutrition or active disease, the lowest levels will be seen in patients with both. There are limitations to most surrogate markers of inflammation and malnutrition in inflammatory bowel disease. Serum albumin is a nonspecific marker in this setting but hypoalbuminemia in patients with Crohn’s disease should prompt further investigation with both inflammation and malnutrition in mind.Funding AgenciesNone

The prognostic value of reduced global longitudinal strain (GLS) on cardiac outcomes in patients on peritoneal dialysis: a prospective study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction This study aims to evaluate the capacity of left ventricular global longitudinal strain (GLS) in end stage renal failure patients on peritoneal dialysis (PD) to predict cardiovascular mortality and major adverse cardiac events (MACE). GLS has been an established parameter in detecting subclinical left ventricular systolic dysfunction in the setting of preserved ejection fraction (EF &amp;gt; = 50%). We hypothesized that reductions of GLS (i.e. less negative value) are associated with adverse cardiovascular outcome. Methods We prospectively recruited a total of 60 PD patients from a single dialysis center in a tertiary hospital. GLS was determined by two-dimensional speckle-tracking echocardiography, under Philips QLab system. A less negative value reflects underlying subclinical LV dysfunction. The primary outcome was 4-point MACE, which was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for heart failure. Surrogate markers of inflammation (C-reactive protein [CRP], tumor necrosis factor [TNF]-alpha), nutrition (serum albumin), arterial stiffness (pulse wave velocity [PWV]), and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) were also measured. Results 16 (26.7%) and 34 (56.7%) PD patients had reduced GLS (≥ -18.3%) and left ventricular hypertrophy (LVH) respectively. In 12-month follow up, 4-point MACE occurred in 13.6% and 59.8% of normal and compromised GLS patients respectively (log-rank, P = 0.004), as illustrated by Kaplan-Meier curves (Fig 1). Patients with reduced GLS had higher proportion of uncontrolled blood pressure and higher prevalence of coronary artery disease. Their EF were significantly lower (53.6 ± 7.4% vs. 61.3 ± 4.1%, P= 0.001) compared with patients with normal GLS. In addition, GLS correlated with EF (r = -0.57, P &amp;lt;0.0001) and PWV (r= 0.33, P = 0.01). There was a trend towards an association between GLS and ln(CRP) (r= 0.25, P = 0.057), and ln(NT-proBNP) (r = 0.22, P= 0.09), respectively. Conclusions Subclinical LV systolic dysfunction was present in one-fourth of peritoneal dialysis patients despite having preserved EF. Reduced GLS (less negative than 18.3%, illustrated in Fig 2) is a strong predictor of poor cardiovascular prognosis among PD population. Abstract Figure 1 Abstract Figure 2