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Background: Despite its widespread use, the precise dynamics of CRP response in clinical practice remain poorly defined. We employed a novel quadratic model to explore the time-course analysis of CRP values in trauma patients with known precise time of injury., Methods: Relevant data on all adult patients admitted to our hospital following traumatic incidents between January 1st 2010 to December 31, 2020 were retrospectively collected. Those with a documented time of injury and who underwent CRP evaluation within the first 24 h since injury were studied., Results: Based on the findings from our annual health check-up center, we established a reference upper normal CRP value of 12.99 mg/L. Within the first 7 h after injury, the CRP levels of 8-9% of the 1545 study patients exceeded the reference threshold. The proportion of patients with CRP levels > 12.99 mg/L increased to 18.5% at 8-9 h later and rose sharply to 91.6% at 22-24 h later. Our quadratic model yielded the equation: CRP = 5.122-0.528xTime + 0.139xTime 2 . It accounted for > 40% of the variance in CRP levels (R 2  = 42.4%)., Conclusions: Clear and prominent CRP elevations following atraumatic event are detected only 9-12 h following the insult. This novel finding has crucial implications for accurate CRP assessment of inflammatory responses to physical injuries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Examiningthe usefulness of C-reactive protein velocity (CRPv) as an early biomarker for the presence of bacteraemia in patients presenting to the Department of Emergency Medicine with acute infection/inflammation and suspected bacteraemia., Methods: A retrospective study examining a cohort of patients who presented to the E.R and in whom blood cultures were taken. CRPv was calculated as the difference in mg/hour/litter between two consecutive CRP tests performed within 12 h., Results: 256 patients were included in the cohort. Using CRPv in patients who at first presented with a relatively low (17.9 ≤ mg/L 1stquartile) CRP concentration, we found an AUC of 0.808 ± 0.038 (p < 0.001) for the presence of positive versus negative blood cultures (what is AUC?). This was better than the AUC that was obtained when the WBC for the same purpose., Conclusions: CRPv may be a useful biomarker in the identification of patients with suspected bacteremiaand a low CRP-a challenging situation for clinicians who may underestimate the severity of illness in this patient group., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population worldwide, and its prevalence is anticipated to increase globally. While most NAFLD patients are asymptomatic, NAFLD may progress to fibrosis, cirrhosis, cardiovascular disease, and diabetes. Research reports, with daunting results, show the challenge that NAFLD's burden causes to global population health. The current process for identifying fibrosis risk levels is inefficient, expensive, does not cover all potential populations, and does not identify the risk in time. Instead of invasive liver biopsies, we implemented a non-invasive fibrosis assessment process calculated from clinical data (accessed via EMRs/EHRs). We stratified patients' risks for fibrosis from 2007 to 2017 by modeling the risk in 5579 individuals. The process involved time-series machine learning models (Hidden Markov Models and Group-Based Trajectory Models) profiled fibrosis risk by modeling patients' latent medical status resulted in three groups. The high-risk group had abnormal lab test values and a higher prevalence of chronic conditions. This study can help overcome the inefficient, traditional process of detecting fibrosis via biopsies (that are also medically unfeasible due to their invasive nature, the medical resources involved, and costs) at early stages. Thus longitudinal risk assessment may be used to make population-specific medical recommendations targeting early detection of high risk patients, to avoid the development of fibrosis disease and its complications as well as decrease healthcare costs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Detection of an eventful course in the early days of sepsis treatment is clinically relevant. The white blood cell count (WBCC) and C-reactive protein (CRP) are used in daily practice to monitor the intensity of the inflammatory response associated with sepsis. It is not entirely clear which of the two might better discriminate the outcomes of patients with sepsis., Methods: 30-day mortality was assessed in a cohort of patients who were hospitalized with sepsis in the departments of Internal Medicine in a tertiary medical center. Admission and 72-hour time points were analyzed to discriminate between patients with increased versus decreased 30 days mortality risk., Results: The study included 195 patients. Higher 72 h CRP, WBCC, neutrophil counts and neutrophils to lymphocyte ratio were associated with increased mortality (p < 0.02). Baseline WBCC and CRP failed to discriminate between patients who died and those who survived (AUC = 0.551, 0.479). In multivariate analysis of the 72 h tests, higher WBCC count (OR = 1.12, 95%CI 1.05-1.20, p = 0.001), was associated with increased mortality whereas CRP was not (OR = 1.004, 95%CI 0.998-1.01, p = 0.146)., Conclusion: Patients who presented a 72-hour leukocyte descent had a better outcome and in this regard, WBCC was superior to 72-hour CRP in predicting 30 days mortality., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: Parasympathetic dysfunction is associated with increased risk for major adverse cardiovascular events (MACE). However, clinically validated biomarkers that reflect parasympathetic activity are not yet available. We sought to assess the ability of serum cholinesterase activity to predict long term survival in patients undergoing coronary angiography., Methods: We prospectively followed 1002 consecutive patients undergoing clinically indicated coronary angiography (acute coronary syndrome or stable angina). We measured blood acetylcholinesterase (AChE) activity using the acetylcholine analog acetylthiocholine. Mortality rates were determined up to 10 years of follow-up. We divided our cohort into 3 groups with low, intermediate and high AChE activity by a Chi-square automatic interaction detection method (CHAID)., Results: Patients with lower than cutoff levels of AChE (<300 nmol/min/ml) had higher mortality rates over 10 years of follow-up, after adjusting for conventional risk factors, biomarkers, clinical indication, and use of medications (HR = 1.6, 95% CI 1.1-2.5, p = 0.02). Patients with intermediate levels of AChE (300-582 nmol/min/ml) were also at increased risk for death (HR = 1.4, 95% CI 1.1-1.9, p = 0.02). AChE was inversely correlated with C-reactive protein, troponin I, fibrinogen and neutrophil/lymphocyte ratio levels., Conclusions: Patients presenting for coronary angiography with low levels of serum AChE activity are at increased risk for death during long term follow-up., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Previously we found that cardiac chambers' volumes correlate with estimated glomerular filtration rate (eGFR) of hospitalized patients. Currently we aimed to demonstrate this relation among apparently healthy individuals., Methods: Ambulatory participants who underwent electrocardiography-gated cardiac computed tomography angiography (CCTA) were included. Subjects with an eGFR<60 ml/min/1.73m 2 , cardiovascular risk factors, and co-morbidities or medications which may influence cardiac chambers' volumes were excluded. Chambers' sizes were obtained by automatic four chamber volumetric analysis of the CCTAs, and calcium score was assessed using the Agatston score., Results: The cohort consisted of 89 apparently healthy individuals, mostly of male gender (70%), with a mean age of 51 years and a mean eGFR of 79.5 ml/min/1.73m 2 . A low calcium score (≤10HU) was found in 67.4%(n = 60) of the cohort. After adjustment for baseline characteristics, renal function was associated exclusively with the volume of the left atrium (LA; b-coefficient-0.15, 95%CI -0.3- -0.01, p = .041). A 15.9% (95%CI 0.3-33.9%, p = .045) increase in LA volume index (LAVI) was found among participants with eGFR of 80-90 when compared to those with eGFR>90 ml/min/1.73m 2 . Participants with a low calcium score showed an increase in LAVI only when eGFR was reduced from normal (>90 ml/min/1.73m 2 ) to 70-80 ml/min/1.73m 2 (and not to 80-90 ml/min/1.73m 2 ), revealing a percentage increase of 24.7% (95%CI 5.5-47.4%, p = .011)., Conclusions: Renal function is closely related to LA volume even in the absence of overt renal failure, demonstrating that minor changes in eGFR instigate an increase in volumes. Risk factors for this interaction should be identified and treated prior to the development of cardio-renal syndrome., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: C-reactive protein (CRP) is considered a marker of inflammation. We sought to evaluate the association between CRP level and commonly use blood tests in apparently healthy population., Methods: A cross-sectional study of all visits in a routine health examination center between 1/2002 and 7/2018. CRP, complete blood count and chemistry blood panel were evaluated in each visit. Visits of individuals who had CRP above the 99th percentile or use statins were excluded. Correlation between CRP and blood tests was evaluated in the whole cohort as well as in sub-populations., Results: Blood parameters of 33,261 visits were included. Moderate positive correlation between CRP and white blood cells count (r = 0.269), neutrophils count (r = 0.275), triglycerides (r = 0.275), alkaline phosphatase (r = 0.221) and gamma glutamyl transpeptidase (r = 0.220) was evaluated. Correlation with triglycerides was stronger in female then in males (r = 0.38 vs. 0.25). Uric acid was positively correlated in females and males. In participants under 30 years, inverse correlation with hemoglobin, creatinine and albumin levels and positive correlation with cholesterol were documented., Conclusion: Significant moderate association between CRP and several blood tests was evaluated in apparently healthy population. This information should be used for further studies of the relationship between inflammation and biological processes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The importance of the inflammatory processes and C-reactive protein (CRP) evaluation was observed. Only few studies used cut-off value <1 mg/L. We sought to evaluate the association between very low CRP (vlCRP) and health status, to describe the repetition of vlCRP and to identify predictors for repetition., Methods: A historical cohort study of all participants who underwent a routine annual check-up between January 2002 and July 2018 at the Tel Aviv Sourasky medical center. CRP test was evaluated in all participants. Individuals who use statins or with CRP >10 mg/L were excluded. CRP ≤0.12 mg/L was considered as vlCRP., Results: The final study cohort included 14,161 individuals. Of them, 5065 were females and mean age was 43.4 years (SD 10.6). vlCRP at first check-up was observed in 1299 (9.2%) of the participants. In multivariable analysis, older age, hyperlipidemia, hypertension and smoking were significantly associated with lower probability of vlCRP. At the second check-up, 50.1% vlCRP repetition was observed with no significant predictor from previous visit., Conclusion: vlCRP is associated with younger age, non-smoking, and absence of hyperlipidemia and of hypertension. However, it may also be part of the individual physiology., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Lung function is inversely associated with coronary heart disease and cardiovascular disease. High-sensitive cardiac troponin T (hs-cTnT) was recently found to represent early subclinical cardiac disease even in healthy individuals. We explored the inter-relationship between lung function and hs-cTnT and the changes over time in these two measurements., Methods: Lung function test and hs-cTnT were determined in apparently healthy individuals from the Tel Aviv Medical Center Inflammatory Survey. Participants with normal lung function were followed up for 5 years in order to evaluate the effect of lung function deterioration on hs-cTnT levels. The correlation between annual Forced vital capacity (FVC) % predicted decline and hs-cTnT levels were analyzed., Results: A 5-year follow-up of 2,618 participants with normal lung function at baseline revealed a mean annual FVC deterioration of 31.9 (±91.3) ml/year. Lung function decline >5% was associated with an increased risk of having hs-cTnT >5 ng/L (Exp. β = 1.55 1.20-1.99, p = 0.001). Delta FVC between two consecutive visits was inversely correlated with an increase of hs-cTnT (r = -0.24, p < 0.001)., Conclusions: Deterioration of lung function predicts elevated troponin levels and may be a sign of early subclinical cardiac disease., (Copyright © 2019. Published by Elsevier Ltd.)

Albuminuria is a prognostic factor for mortality and cardiovascular events, even at low levels. Changes in albumin excretion are associated with end-stage renal disease and hypertension (HTN) in cohorts including high-risk participants. We aimed to investigate the evolvement of albumin excretion in healthy individuals with normal kidney function and normoalbuminuria, and possible associations with HTN and metabolic outcomes. The study cohort consisted of 1967 healthy adults with normal kidney function (estimated glomerular filtration rate ≥ 90 mL/min/1.73 m 2 ; urine albumin to creatinine ratio [ACR] < 30 mg/g). Delta ACR slope was calculated as ACR difference between two consecutive visits divided by the time interval. During a mean follow-up period of 93.8 months, mean delta ACR slope was 0.27 ± 3.29 mg/g/year and was higher in participants with age >40 years, obesity, a high waist circumference, higher baseline ACR, HTN, prediabetes, and metabolic syndrome. Delta ACR slopes in the upper quartile predicted diabetes (OR = 1.31, P = .027) and albuminuria (4.34, P < .001). Upper quartile of ACR slopes correlated with a higher risk for new-onset HTN (1.249, P = .031). Delta systolic and diastolic blood pressures were associated with ACR slopes in addition to age, body mass index, and baseline ACR. In conclusion, accelerated change in ACR correlates with HTN and diabetes in healthy individuals with normal kidney function and normoalbuminuria., (Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac chamber size was previously studied by echocardiography, among patients with progressive kidney disease only. We aimed to explore the relations between all heart chamber volumes as assessed by CT pulmonary angiography and renal function, throughout all ranges., Methods: Using a novel technology for automatic four-chamber volumetric analysis, we analyzed CT pulmonary angiography results for 748 consecutive patients (between January 1 and December 31, 2014) without pulmonary embolism, and correlated the chamber volumes, indexed to body surface area, with the estimated glomerular filtration rates (eGFRs)., Results: After adjustment for age, all cardiac chamber volumes aside from that of the left ventricle inversely correlated with the eGFR. For every 10-unit decrease in eGFR, the volume indices of the left atrium, right atrium, and right ventricle were larger by 3.1%, 2.3%, and 1.5% (P < .001, P = .003, P = .007), respectively. There was a significant correlation between left atrial volume index and eGFR (r = -0.43; P < .001). In a categorical comparison, patients with even minimal renal dysfunction (eGFR, 60 to 90 mL/min/1.73 m 2 ) had a 10.3% larger left atrial volume index (95% CI, 3.1-17.9; P = .004) compared to patients with an eGFR > 90 mL/min/1.73 m 2 ., Conclusions: A simple concomitant volumetric analysis of all four cardiac chambers by CT pulmonary angiography demonstrated that differences in volume correlate with renal function even within the normal range spectrum. The difference was most evident in the left atrium. This finding may be the first clue to evolving cardiorenal syndrome and may serve as a target for early therapeutic interventions., Trial Registry: ClinicalTrials.gov; Clinical Trials registration number (Helsinki Committee): 0603-15-TLV; URL: www.clinicaltrials.gov., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Emergency department (ED) revisit might be partially preventable. C-reactive protein (CRP) is an inflammatory biomarker which is commonly used as screening tool in the ED. We sought to evaluate the association between CRP level in patients visiting emergency department and 7 days revisit after discharge., Methods: A historical cohort study of all patients who visited the internal division of the emergency department between June 2007 and July 2017 and had a CRP test. New ED visit was defined when neither any emergency department visit nor any hospital admission was recorded in our files during the previous 90 days. Univariate and multivariate models were used to evaluate the association between CRP and 7 days ED revisit., Results: The study included 135,476 patients with 173,443 new visits. In 101,181 (58.3%) visits the patients were released and 7077 (7%) of them were revisited in 7 days. Even mild elevated CRP (5-25 mg/L) was independently associated with significant risk for revisit (OR 1.27, 95% CI 1.20-1.35)., Conclusion: CRP is an independent predictor for 7 days ED revisit and should be considered at the time of discharge. Prediction models for ED revisit should include CRP as a potential predictor in their models., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Evaluations of patients with pulmonary hypertension (PH) commonly include chest CT imaging. We hypothesized that cardiac chamber volumes calculated from the same CT scans can yield additional information to distinguish PH related to left-sided heart disease (World Health Organization group 2) from other PH subtypes., Methods: Patients who had PH confirmed by right heart catheterization and contrast-enhanced chest CT studies were enrolled in this retrospective multicenter study. Cardiac chamber volumes were calculated using automated segmentation software and compared between group 2 and non-group 2 patients with PH., Results: This study included 114 patients with PH, 27 (24%) of whom were classified as group 2 based on their pulmonary capillary wedge pressure. Patients with group 2 PH exhibited significantly larger median left atrial (LA) volumes (118 mL vs 63 mL; P < .001), larger median left ventricular (LV) volumes (90 mL vs 76 mL; P = .02), and smaller median right ventricular (RV) volumes (173 mL vs 210 mL; P = .005) than did non-group 2 patients. On multivariate analysis adjusted for age, sex, and mean pulmonary arterial pressure, group 2 PH was significantly associated with larger median LA and LV volumes (P < .001 and P = .008, respectively) and decreased volume ratios of RA/LA, RV/LV, and RV/LA (P = .001, P = .004, and P < .001, respectively). Enlarged LA volumes demonstrated a high discriminatory ability for group 2 PH (area under the curve, 0.92; 95% CI, 0.870-0.968)., Conclusions: Volumetric analysis of the cardiac chambers from nongated chest CT scans, particularly with findings of an enlarged left atrium, exhibited high discriminatory ability for identifying patients with PH due to left-sided heart disease., (Copyright © 2017. Published by Elsevier Inc.)

Background: High sensitivity C-reactive protein (hsCRP) has become a routine assessment tool to discriminate between patients at low, intermediate or high risk for cardiovascular events using the threshold values of 1 and 3mg/L, respectively. Over the past years, several studies have proposed the wide range C-reactive protein (wrCRP) as an alternative to the hsCRP in various clinical scenarios. However, the potential use of wrCRP in assessing the cardiovascular risk has not yet been evaluated., Methods: Both wrCRP and hsCRP were evaluated in 15,780 apparently healthy individuals who underwent a routine annual checkup in the Tel Aviv Sourasky Medical Center. Individuals with CRP levels >5mg/L were excluded. Agreement between the two methods was observed using the Bland-Altman method and the concordance correlation coefficient. Deming regression was used to build a calibration equation. Reclassification of individuals' risk level was observed and Cohen's kappa was used to evaluate risk agreement., Results: A high correlation (r=0.98) along with a significant difference (p<0.001) between hsCRP and wrCRP raised the need for calibration. A simple calibration equation (Adjusted wrCRP=0.3136+0.8803×wrCRP) led to high agreement which enabled 8.4% reclassification of the risk group. A change in the intermediate risk threshold value from 1 to 0.9mg/L led to an almost perfect agreement (kappa=0.87, p<0.001) and a low reclassification rate (7.6%), with under 0.05% of the population undergoing a major reclassification (from high to low risk or vice versa)., Conclusions: In the era of limited financial resources, wrCRP assay may be used as a reasonable routine assay to evaluate the cardiovascular risk in patients undergoing a routine annual checkup., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Preliminary reports suggest that a small left atrium (LA) is associated with severe acute pulmonary embolism (PE). This study used data derived from volumetric analyses of computed tomographic pulmonary angiography (CTPA) to investigate whether a reduced LA volume can predict adverse outcome in a large series of patients with acute PE., Methods: We retrospectively analyzed 756 consecutive patients who received a diagnosis of acute PE by nongated CTPA between January 2007 and December 2010. Each CTPA was investigated with volumetric analysis software that automatically provides the volumes of the LA, right atrium, right ventricle, and left ventricle. A classification tree divided the cardiac chamber volumes and ratios into categories according to mortality. Cox regression assessed the association between these categories and 30-day mortality after adjustment for age, sex, and clinical background., Results: The final study group consisted of 636 patients who had successful volumetric segmentation and complete outcome data. Eighty-four patients (13.2%) died within 30 days of PE diagnosis. There was a higher mortality rate among patients with an LA volume ≤62 mL compared with those with an LA volume >62 mL (19.6% vs 8.9%, respectively; HR, 2.44; P < .001), a left ventricle volume ≤67 mL (16.4% vs 8.3%; HR, 1.8; P = .024) and a right atrium/LA volume ratio >1.2 (17% vs 9.4%; HR, 2.1; P = .002). A reduced LA volume was the best predictor of adverse outcome., Conclusions: Decreased LA volume is associated with higher mortality and is the first among the various cardiac compartments to predict mortality in patients with acute PE., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Neutrophil/lymphocyte ratio (NLR) is a novel biomarker that can single out individuals at risk for vascular events. We assessed whether NLR provides additive prognostic value in patients with ST-elevation myocardial infarction (STEMI)., Methods: NLR was computed from the absolute values of neutrophils and lymphocytes from the complete blood count of patients who underwent primary coronary angioplasty for STEMI. The cohort was divided into 2 groups according to NLR (NLR ≥ 6.5%, NLR < 6.5%) using χ(2) automatic interaction detection. The association between NLR and in-hospital clinical complications and left ventricular ejection fraction (EF) was assessed using logistic regression. The association between NLR, 30-day and 5-year all-cause mortality were analyzed using Cox regression models, adjusting for potential clinical, metabolic, and inflammatory confounders., Results: In a group of 538 consecutive STEMI patients, high NLR (NLR ≥ 6.5%) was independently associated with increased 30-day and 5-years mortality rates (odds ratio, 15.8; 95% confidence interval, 1.6-154; P = 0.018; and hazard ratio, 2.2; 95% confidence interval, 1.04-4.8; P = 0.039, respectively). High NLR was also independently associated with lower EF (49 ± 8 vs 46 ± 8; P < 0.001) and fewer hospital complications., Conclusions: In patients presenting with STEMI, high NLR was independently associated with lower EF, fewer hospital complications, and higher mortality rates up to 5 years. NLR value appears additive to conventional risk factors and commonly used biomarkers., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The "Slow Coronary Flow" (SCF) phenomenon in the presence of angiographically normal coronaries is attributed to microvascular and endothelial dysfunction. The microcirculation can be non-invasively assessed by measuring retinal blood flow velocity. The aim of the present study was to evaluate the efficacy of the "Retinal Functional Imager" (RFI) device as a noninvasive method of diagnosing patients with slow coronary flow., Methods: Coronary blood flow velocity assessed by corrected TIMI Frame Count and retinal arterioles blood flow assessed by RFI were measured in 28 consecutive patients with normal coronary arteries. The patients were divided into 2 groups: a slow coronary flow (SCF) and a normal coronary flow (NCF) groups., Results: Inverse correlation was found between retinal and coronary blood flows so that higher retinal arterial flow velocity was observed in the SCF group (3.8 ± 1.1 mm/s vs. 2.9 ± 0.61 mm/s, respectively, p = 0.022). RFI provided 73% sensitivity and 77% specificity for diagnosing SCF using ROC analysis. Additionally, patients with SCF had higher values of serum LDL cholesterol (104.7 ± 18.93 mg/dl vs. 81.55 ± 14.62 mg/dl in NCF, p = 0.005), Glucose (96.9 ± 23.0 mg/dl vs. 83.55 ± 9.7 mg/dl in NCF, p = 0.024), and lower percentage of statin consumption (40.0% vs. 76.9% in NCF, p = 0.049)., Conclusions: Slow coronary blood flow can be non-invasively diagnosed with Retinal Functional Imager. Patients with normal coronary arteries and slow coronary blood flow have high retinal arteriolar blood flow. Early non-invasive diagnosis of SCF might help detect individuals who are at higher risk to develop coronary atherosclerosis, and to provide them with early preventive measures., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Anemia on admission and during hospitalization is associated with poor short and long term prognosis among patients with acute coronary syndrome (ACS). Our objective was to examine the prognostic implications of longitudinal hemoglobin (Hb) levels following a first acute myocardial infarction (AMI)., Methods: We utilized data obtained from the computerized database of a large community based health care maintenance organization to identify patients who survived for at least 6 months following a first AMI, during the years 2003-2010. Hazard ratios were calculated using Cox proportional regression models with various Hb measurements as dependent variables, and net reclassification improvement (NRI) was applied to evaluate the prognostic usefulness of these Hb measurements., Results: Last Hb measurement during a 6-24 month follow-up period was found to have the highest prognostic power. In males, Hb levels below 13 g/dL were gradually associated with a higher risk of events, reaching a HR of 4.13 at Hb levels <11 g/dL. In females, only Hb levels lower than 11 g/dL were significantly associated with a higher event rate (HR=2.42, p=0.003). Hb decrease was significantly associated with an increased risk in both genders, even among non-anemic patients at baseline., Conclusions: Anemia and Hb decrement following a first AMI are associated with worse prognosis and elevated risk of combined all cause mortality and recurrent cardiac events., (© 2013.)

Background: Estimated glomerular filtration rate (eGFR) predicts major adverse cardiovascular events (MACE) in patients with chronic kidney disease (CKD), though the effect of eGFR on MACE and vascular disease extent among individuals with normal or mildly impaired renal function requires definition. Our aim was to examine the prognostic implications of eGFR and its effect on atherosclerosis burden in individuals without CKD undergoing vascular imaging studies., Methods: The study enrolled 2746 consecutive patients undergoing clinically-driven coronary angiography who had an eGFR > 60 mL/min/1.73 m(2) and no history of CKD. Same-day carotid duplex results were available for 317 patients. Patients were followed for up to 3 years for the occurrence of all-cause mortality, myocardial infarction, and stroke., Results: After adjustment for potential clinical and biochemical confounders, eGFR was found to be independently associated with coronary artery disease extent in the entire study population and among patients with normal renal function (n = 1170; eGFR > 90 mL/min/1.73 m(2)): odds ratio (OR) = 1.16 (95% confidence interval [CI], 1.09-1.24) and OR = 1.25 (95% CI, 1.11-1.4) per 10 mL/min decrements in eGFR, respectively. Similarly, eGFR was independently associated with carotid artery stenosis in the entire cohort (OR, 1.86 [95% CI, 1.12-3.1]). By Cox regression analysis, eGFR was an independent predictor of the composite MACE end point (hazard ratio, 1.16 [95% CI, 1.04-1.28]), and all-cause mortality (hazard ratio, 1.38 [95% CI, 1.19-1.60])., Conclusions: eGFR is an independent predictor of atherosclerotic vascular disease extent and MACE rates in patients with normal or mildly impaired renal function., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: White blood cell count is an independent predictor of cardiovascular events and mortality. Neutrophil/lymphocyte ratio (NLR) is a biomarker that can single out individuals at risk for vascular events., Objective: To evaluate whether NLR adds additional information beyond that provided by conventional risk factors and biomarkers for coronary artery disease (CAD) severity and adverse outcome, in a large cohort of consecutive patients referred for coronary angiography., Materials and Methods: NLR was computed from the absolute values of neutrophils and lymphocytes from the complete blood count of 3005 consecutive patients undergoing coronary angiography for various indications. CAD severity was determined by an interventional cardiologist unaware of the study aims. The association between NLR and CAD severity was assessed by logistic regression and the association between NLR and 3-years outcome were analyzed using Cox regression models, adjusting for potential clinical, metabolic, and inflammatory confounders., Results: The cohort was divided into 3 groups according to the NLR value (<2, 2-3, and >3). NLR was independently associated with CAD severity and it contributed significantly to the regression models. Patients with NLR >3 had more advanced obstructive CAD (OR = 2.45, CI 95% 1.76-3.42, p < 0.001) and worse prognosis, with a higher rate of major CVD events during up to 3 years of follow-up (HR = 1.55, CI 95% 1.09-2.2, p = 0.01)., Conclusion: Neutrophil/lymphocyte ratio is independently associated with CAD severity and 3-years outcome. NLR value appears additive to conventional risk factors and commonly used biomarkers., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Anemia is associated with an unfavorable outcome in acute myocardial infarction (AMI). An acute phase response could contribute to the development of anemia in AMI patients., Methods: We have performed a cross-sectional analysis on prospectively collected data at a tertiary hospital catheterization laboratory. Multi-adjusted linear regression models were fitted for hemoglobin as the dependent variable. ANOVA tests were used to determine interactions between time cutoffs of the respective hemoglobin and the concentrations of two inflammatory proteins, namely C-reactive protein and fibrinogen. Anemia indices were analyzed in a subgroup of 138 male AMI patients for whom frozen serum samples were available., Results: Enrolled were 1017 patients (340 with unstable angina pectoris [UAP] and 677 with AMI). Correlates of hemoglobin in the AMI group included age, male gender, the inflammatory proteins, as well as time from symptom onset to angiography (r(2)=0.47; p<0.001). A significant decrease in the concentration of hemoglobin with a parallel increase in the inflammatory proteins was observed between the time cutoff from symptom onset to angiography only in the AMI group for males and females, respectively. A pattern suggestive of anemia of inflammation including higher ferritin, lower transferring, lower transferrin saturation, and lower serum iron concentrations has been observed in anemic AMI patients ( all p<0.05)., Conclusions: Inflammation-sensitive proteins are associated with lower hemoglobin concentrations in AMI patients. We therefore suggest the possibility that at least part of the hemoglobin drop in AMI prior to angiography is related to the anemia of inflammation., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: There are multiple lines of evidence to suggest the role of erythrocyte aggregation (EA) in microcirculatory dysfunction during conditions of very slow flow. Such conditions might develop in the myocardium of patients with acute coronary syndromes (ACS)., Methods: EA as a function of shear stress was evaluated by using a cell flow properties analyzer (CFA) in a cohort of 91 ACS patients and in 36 patients with non specific chest pain or heart failure at the time of cardiac catheterization., Results: The ACS group included 34 patients with acute myocardial infarction and 57 patients with unstable angina. In addition, we examined 36 patients who underwent angiography for non specific chest pain or heart failure. A significant (r=0.44, p<0.0005) correlation was found between the concentration of fibrinogen and the average aggregate size (AAS) only when using conditions of very slow flow and applying relatively low (0.15 dyn/cm(2)) shear stress in the ACS group. This correlation decreased and became insignificant when applying shear stress forces of 1 dyn/cm(2) and more. This correlation was nonsignificant for all the 5 shear stress forces (between 0.15 and 4 dyn/cm(2)) in the samples obtained from the non-ACS group., Conclusion: Erythrocytes that are suspended in autologous plasma obtained from patients with ACS tend to aggregate in conditions of very slow flow. These findings might be detrimental in terms of microcirculatory flow in ACS patients and might open new therapeutic options such as the use of low dose thrombolysis following PCI., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Early identification by computed tomography pulmonary angiography (CTPA) of patients with acute pulmonary embolism (PE) who have signs associated with a high embolic burden would be highly desirable., Objectives: To investigate whether an increased obstruction of the pulmonary vasculature is associated with reduced left atrial (LA) and increased right atrial (RA) areas., Methods: We retrospectively analyzed a consecutive series of CTPA studies of 137 patients with acute PE and 38 controls without PE between October 2004 and March 2006. Left and right atrial areas and longitudinal and short axis diameters were measured and correlated with the pulmonary arterial obstruction index (PAOI) divided into tertiles (obstruction of < 12.5%, 12.5%-42.5% and ≥ 42.5%)., Results: There was a significant negative age- and gender-adjusted correlation between the PAOI and LA measurements, particularly the LA area (r = -0.259) and the LA short axis diameter (r = -0.331). All RA measurements had positive correlations (RA area, r = 0.279; RA short axis diameter, r = 0.313). The LA/RA area ratio correlated negatively with the PAOI (r = -0.447). All above-mentioned correlations had P < 0.002. All the LA measurements were the largest in the controls and gradually decreased with higher PAOIs. A receiver operating characteristic curve analysis demonstrated that the RV/LV diameter, LA/RA area and LA/RA short axis diameter ratios had comparable discriminative ability for higher PAOI tertiles., Conclusions: The higher the clot load in the pulmonary arteries, the smaller the LA area and the larger the RA area. Atrial area measurements by CTPA may serve as a real-time parameter in assessing the severity of PE upon diagnosis., (© 2011 International Society on Thrombosis and Haemostasis.)

Background: The exact cause of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress is one of the factors implicated in the etiology of ALS as well as in that of other neurodegenerative diseases. Uric acid is an important natural antioxidant that may reduce oxidative stress. The objective of this study was to prospectively determine the serum uric acid levels in ALS patients and allegedly healthy individuals and to correlate those values with measures of ALS disease progression among the patients., Methods: The ALS patients and well-matched controls underwent blood tests for serum uric acid levels which were then correlated with the patients' disability status, as expressed by the ALS Functional Rating Scale (ALSFRS-R)., Results: Eighty-six ALS patients and 86 well-matched controls participated. The ALS patients' mean+/-SD uric acid level was significantly lower (4.78+/-1.3 mg/dl) than that of the controls (5.76+/-1.26 mg/dl) (p<0.0001). The findings were similar for a second examination performed after an interval of at least 6 months. There was a correlation between the relative decrease of serum uric acid levels among patients (the difference between the patients' level and the controls' level) and the rate of disease progression (ALSFRS-R decline) (p<0.0001, r=0.624)., Conclusions: ALS patients had lower serum uric acid levels than healthy individuals. The decreased uric acid levels were correlated to the rate of disease progression (ALSFRS-R decline), further demonstrating the possible role of oxidative stress in the induction and propagation of the disease.

Background: Recent exposure to air pollution has a decremental effect on pulmonary function. This short-term effect has only been studied for up to a few days postexposure. Our objective was to analyze the effect of air pollution on spirometric parameters in varying lag times of up to 1 week from the time of exposure., Methods: Healthy subjects, never smokers, who were participants in the Tel Aviv Sourasky Medical Center Inflammation Survey held between 2002 and 2007, were included if residing within an 11-km range to the nearest air pollution monitoring station. Linear regression models were applied to each lung function variable [first second of exhalation (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC] against air pollutant variables (particulate matter under 10 microns in diameter, sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone) for increasing lag periods of up to 7 days, and they were adjusted for possible confounders that affect air pollution and spirometric measurements., Results: The study population comprised 2380 individuals. We found a statistically significant negative correlation between air pollutants, mainly SO(2), and between FEV(1) and FVC. This effect was significant from days 3 to 6, with a maximal effect noted for the fifth day and for the 7-day average before pulmonary function measurement. No significant change was found for FEV(1)/FVC ratio., Conclusions: Air pollution has a decremental effect on lung function parameters for up to 6 days after exposure in healthy adults. SO(2) emerged as the most significant air pollutant affecting short-term lung function parameters.

Objective: To explore the possibility that mild inflammatory changes exist in asymptomatic adults during bouts of acute respiratory tract infections in the general population, and may mediate atherothrombotic events., Methods: An epidemiological study that enrolled 5315 males and 2795 females attending a routine screening health program between the years 2003 and 2007. We correlated the concentrations of high sensitivity C-reactive protein (hs-CRP) and quantitative fibrinogen in completely asymptomatic and non-inflamed adults to the weekly epidemiological data for the incidence of acute respiratory tract infections in the community., Results: Significant seasonal variations in the inflammatory variables were found for both genders. The population's weekly rates of acute respiratory tract infection had a significant epidemiological influence on the inflammatory biomarkers in the asymptomatic cohort. The magnitude of this influence could reach as much as 12% (3-22%) in hs-CRP concentrations in women and 0.30 micromol/L (0.20-0.41) in fibrinogen concentrations in men, for the change between the mean August and the mean January population's respiratory illness burden., Conclusion: Increase in the concentrations of two inflammation-sensitive biomarkers can occur in completely asymptomatic adults at times of increased burden of acute respiratory tract infection in the general population. The possibility exists that these inflammatory changes represent occult and asymptomatic infections that could by themselves trigger acute atherothrombotic events.

Objective: To investigate whether fast grading of reflux of contrast to the inferior vena cava (IVC) on computerized tomographic pulmonary angiography (CTPA) is a potential biomarker for real-time risk stratification., Methods: We retrospectively identified 343 patients investigated for possible pulmonary embolism (PE) by CTPA at our medical center between September 2004 and March 2006. A total of 145 consecutive patients with PE (age 67 +/- 19 years) and 168 consecutive ones with negative CTPAs (age 64 +/- 20 years) fulfilled entry criteria. CTPAs were evaluated for retrograde reflux of contrast to the IVC by fast visual grading from 1 to 6 using the original axial images. Pulmonary obstruction index, the diameters of right and left ventricles and pulmonary artery, and patient survival data were recorded as well., Results: Twenty-nine (20.0%) patients with positive CTs and 23 (13.7%) patients with negative CTs had substantial degrees (>or=4) of reflux of contrast to the IVC (P = 0.14). The Kaplan-Meier 30-day survival curves demonstrated significant reduction in survival in individuals with PE and grade >or=4 reflux of contrast to the IVC compared with lower grades (P = 0.008), but not in patients with grade >or=4 and no PE on CTPA (P = 0.26). The other cardiovascular parameters showed no significant correlation with survival in patients with and without PE., Conclusion: Substantial grades of reflux of contrast to the IVC during CTPA could predict early mortality in patients with acute PE. Rapid grading of reflux of contrast from the original axial CTPA images can be used for real-time risk stratification in patients with acute PE.

Background: Ethnic origin affects spirometric prediction values. Our aims were to investigate the effect of ethnic origin on prediction equations in an immigrant-based society, identify possible deviations from commonly used prediction equations and analyze the effect of miscalculation in a large cohort of apparently healthy individuals., Methods: Healthy never-smokers participants from a large Israeli survey underwent lung function testing and were divided into two major ethnic groups: Ashkenazi Jews (AJ) and Sephardic Jews (SJ). Data were analyzed by multiple linear regressions. Forced vital capacity (FVC), forced expiratory volume in 1s (FEV1) and the FEV1/FVC ratio were measured according to ERS-ATS guidelines., Results: The study population comprised 3150 individuals (AJ=1817; SJ=1333). AJ tended to be older and taller than SJ (all p<0.005). Ethnicity entered as a significant regression variable for FVC for both genders and for FEV1 for females only. The final regression model for both FVC and FEV1 had R2=0.71 and the standard error of the estimate (SEE) for FVC and FEV1 were 0.54 and 0.43 L, respectively. The regression model for the FEV1/FVC ratio has less statistical strength (R2=0.06, SEE=6.15%). We found statistically significant underestimates of predicted lung volumes from the commonly used prediction equation for each ethnic group., Conclusions: Ashkenazi and Sephardic Jews have different ranges of normal pulmonary function values. Lung function prediction equations in an immigrant-based society should be based on local and not previously reported regional equations and adjusted for ethnic attributed variance.

Background: C-reactive protein (CRP) has been tested in patients with systolic heart failure (HF) and mixed results have been obtained with regards to its potential predictive value. However, the role of C-reactive protein (CRP) in patients with diastolic HF is not established. We studied the predictive role of high sensitivity CRP (hsCRP) in patients with diastolic HF., Methods: HsCRP levels were measured in a cohort of CHF outpatients, 77 patients with diastolic HF and 217 patients with systolic HF. Concentrations were compared to a large cohort of healthy population (n=7701) and associated with the HF admissions and mortality of the patients., Results: Levels of hsCRP did not differ between patients with systolic and diastolic HF and were significantly elevated compared to the cohort of healthy subjects even after adjustment to various clinical parameters (p<0.0001). In patients with diastolic HF, hsCRP levels associated with New York Heart Association functional class (NYHA-FC) (r=0.31 p=0.01). On univariate Cox regression model hsCRP levels independently predicted hospitalizations in patients with systolic but not diastolic HF (p=0.047)., Conclusion: HsCRP concentrations are elevated in patients with diastolic HF and correlate with disease severity; their prognostic value in this patient population should be further investigated.

Objectives: To evaluate the effect of short-term exposure to air pollutants on inflammation-sensitive biomarkers in apparently healthy individuals., Methods: We enrolled all participants from The Tel-Aviv Sourasky Medical Center inflammation survey held between 2003 and 2006, excluding participants with an acute or chronic inflammatory disease, pregnancy, steroidal or nonsteroidal treatment, or a recent invasive procedure. Additional subjects were excluded for living more than 11km from the nearest air pollution monitoring station. Analysis was performed separately for men and women. Linear regression models were fitted for each inflammatory variable against air pollutant variables (particulate matter under 10microm, sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone) for increasing lag times of up to 7 days, and adjusted for all possible and known confounding parameters., Results: The study population comprised 3659 individuals (2203 males and 1456 females). We found a statistically significant negative correlation in the male population between air pollutants, mainly NO2, SO2, and CO, and fibrinogen in several lag days. A positive correlation was found for PM10 at day 7. No such correlation was found for CRP and WBC, or for the female population., Conclusion: Our findings do not support the potential link between short-term exposure to air pollution and enhanced inflammation as a possible explanation for increased cardiovascular morbidity. Additional large-scale population-based studies with good methodological design are needed in order to clarify this issue.

Background: The determination of low grade inflammation in apparently healthy individuals (microinflammation) has prognostic significance in terms of future vascular events and accelerated atherothrombotic disease., Methods: We compared the Bayer wide range (wr)-C-reactive protein (CRP) immunoturbidometric assay on the ADVIA 1650 system to the Dade Behring high sensitivity (hs)-CRP on the BNII Nephelometer in 1446 apparently healthy individuals having a relatively low (<10 mg/l) concentration. The correlation between the 2 assays was also analyzed in relation to other commonly used microinflammatory biomarkers., Results: A significant (p<0.0005) correlation was noted between the hs-CRP and the wr-CRP for the entire cohort (r=0.99) as well as for both women (r=0.99 n=483) and men (r=0.99 n=963). The mean difference between the measures (hs-CRP minus wr-CRP) was -0.039 (SD 0.317). The Deming regression results for the entire cohort showed a slope of 1.112+/-0.004 and an intercept of -0.263+/-0.01., Conclusions: The Bayer wr-CRP assay performed presents a reasonable alternative to the Behring Dade hs-CRP assay. The advantages of the wr-CRP assay are its online and real time availability as well as lower costs.

Objective: To find the relative contribution of various inflammation-sensitive proteins including fibrinogen, immunoglobulins (IgG, IgM and IgA), ceruloplasmin and high sensitivity C-reactive protein (hs-CRP) to the induction and/or maintenance of enhanced erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors., Methods: The degree of erythrocyte adhesiveness/aggregation was determined by a simple slide test and image analysis. In addition, we measured various inflammation-sensitive protein levels including fibrinogen, ceruloplasmin, immunoglobulins and hs-CRP in a group of 234 individuals with atherothrombotic risk factors and healthy ones. Pearson partial correlations and multiple linear regression analysis were performed., Results: Fibrinogen was found to be the major protein contributing to the enhanced erythrocyte adhesiveness/aggregation, explaining 30% of the model. Fibrinogen and IgG together explained 32.4% of the model. Other inflammation-sensitive proteins did not reach statistical significance and were excluded from the model., Conclusions: Among inflammation-sensitive proteins measured in our cohort, fibrinogen is the dominant contributor to erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with atherothrombotic risk factors and healthy ones. These findings may pave the way for the development of therapeutic strategies directed at the attenuation of erythrocyte aggregability in individuals with atherothrombosis.

Aims: To clarify whether individuals with low concentrations of highly sensitive C-reactive protein (hs-CRP) are free of atherothrombotic risk factors or low-grade inflammation., Methods and Results: This cross-sectional study included 1266 individuals with risk factors (diabetes, hypertension, hyperlipidemia, smoking, obesity). Eighty percent of women and the same percentage of men with a low concentration (0.8 +/- 0.4 mg/l) of hs-CRP had at least one atherothrombotic risk factor. About one-fourth of the females and a one-third of the males with a low concentration of hs-CRP had at least one laboratory marker of chronic inflammation (erythrocyte sedimentation rate (ESR), white blood cell count (WBCC) or fibrinogen concentration) in the upper 75th percentile., Conclusion: Individuals presenting with low concentrations of hs-CRP are not necessarily free of atherothrombotic risk factors. One-fourth of the females and a third of the males in this group presented laboratory evidence of a low-grade inflammation as detected by increased erythrocyte sedimentation rate, white blood cell count or fibrinogen concentration.

Background and Purpose: Factor XI (FXI) contributes to thrombin generation thereby affecting fibrin formation and to down regulation of fibrinolysis by activation of thrombin-activatable fibrinolysis inhibitor (TAFI). The purpose of this study was to evaluate whether patients with severe FXI deficiency are protected against acute myocardial infarction (AMI)., Methods: The incidence of AMI in patients with severe FXI deficiency (FXI activity less than 15 U dL(-1)) whose age was 35 years or more was compared to the incidence of AMI in age and gender matched persons of the general population. Atherosclerotic risk factors were assessed in FXI deficient patients and blood was tested for prothrombotic parameters such as FV Leiden, prothrombin G20210A, lupus anticoagulant, and platelet membrane polymorphisms. The common mutations causing FXI deficiency in Jews were also examined., Results: Of 96 patients with severe FXI deficiency (55 women and 41 men) 16 had a history of AMI (6 women and 10 men). The median age at the time of AMI was 64.5 for women and 58 for men. The calculated annual rate of AMI in men was similar to the expected in the general Israeli population, whereas in women it was almost 2-fold higher, but this difference did not reach statistical significance. One or more atherosclerotic risk factors were observed in 13 of 16 patients (81.3%) with AMI compared to 44 of 79 patients (55.7%) without AMI (P < 0.001). The frequency distributions of platelet polymorphisms and of prothrombotic polymorphisms were not different between patients with severe FXI deficiency who experienced or not an AMI. None of the patients had lupus anticoagulant. The common genotypes which cause FXI deficiency in Jews were similarly distributed in patients with and without AMI., Conclusions: Severe FXI deficiency does not confer protection against AMI.

Background: Multiple acute phase proteins and atherosclerotic risk factors increase the aggregability of erythrocytes., Methods and Results: We used a simple slide test and image analysis to determine the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of 222 women and 221 men with no, one, two or more atherosclerotic risk factors. The degree of erythrocyte adhesiveness/aggregation correlated significantly with the concentration of commonly used variables of the acute phase response. We also showed that individuals with low erythrocyte adhesiveness/aggregation tend to be younger and to have fewer risk factors for atherosclerosis, including diabetes mellitus, hypertension, hyperlipidemia and smoking., Conclusions: The association between increased erythrocyte adhesiveness/aggregation, higher concentrations of acute phase proteins, and increased atherosclerotic risk factors points to a possible clinical applicability of the erythrocyte adhesiveness/aggregation test (EAAT) to reveal the presence of both low-grade subclinical smoldering inflammation and morbid biology in individuals with risk factors for atherosclerosis.

Objectives: To determine whether the increased aggregability of both white and red blood cells previously reported in acute myocardial infarction (aMI) correlates with each other., Design: Cross-sectional study comparing two groups of patients and a group of healthy controls., Setting: A tertiary university affiliated hospital (Intensive Cardiac Care Unit and Department of General Internal Medicine)., Patients: Consecutive patients with aMI, patients with chest pain and no infarction, and healthy controls., Measurements and Results: We adapted a simple slide test and image analysis to reveal the state of both leukocyte and erythrocyte adhesiveness/aggregation in the peripheral blood of patients with aMI. A significant (P=0.0001) increment in the aggregation of both cellular populations was noted in 48 patients with aMI as opposed to the 141 patients with ischemic heart disease and no infarction and in 45 matched controls. In addition, a significant correlation was noted between the various variables of the leukocyte and erythrocyte adhesiveness/aggregation tests., Conclusions: The significant correlation between the aggregability of white and red blood cells in patients with aMI is suggestive of there being a commonly shared adhesive protein(s). The prompt identification of patients with increased aggregation might have clinical and therapeutic implications.

Background: Previous articles have reported the appearance of leukopenia after the administration of high-dose intravenous gamma-globulins., Methods: A simple slide test was used to reveal the state of leukocyte aggregation (LA) in the peripheral blood as well as the absolute number of leukocytes in the slides., Results: A significant (P < 0.00001) increment was noted in the state of LA, from 9 +/- 6% before to 25 +/- 11% after gamma-globulin administration. This was accompanied by a significant (P < 0.0004) reduction in the number of white blood cells in the peripheral blood (from 8433 +/- 3905 to 6550 +/- 3252 cells/mm3) but no significant change in the absolute number of the cells as determined by the leukocyte count per high power field in the peripheral slides., Conclusions: We raise the possibility that the leukopenia reported in some patients after the intravenous administration of high dose gamma-globulin is explained in part by the agglutination effect of the drug.

The inflammatory response during thermal injury increases the adhesiveness of white blood cells. A direct slide test was used to compare the state of leucocyte adhesiveness/aggregation (LAA) in the peripheral blood of mice subjected to a thermal injury with the findings in control animals. The state of LAA in the peripheral blood increased from baseline values of 1.1 +/- 1.1 per cent to 6.5 +/- 1.3 per cent within 1 h and to 11.0 +/- 1.2 per cent and 14.8 +/- 4 per cent after 3 and 6 h respectively following thermal injury. The respective leucocyte counts were 3075 +/- 277/mm3 (baseline), 3871 +/- 359, 3840 +/- 687 and 6395 +/- 1152 cells/mm3. The LAA values had subsided by 5 days following burning and correlated with the degree of pulmonary leukostasis. Our study suggests that the LAA is an early and sensitive marker of inflammation and that it can be used as a marker for the presence of pulmonary leukostasis during thermal injury.

Leukocyte aggregation is involved in the generation of vascular damage during various inflammatory conditions. So far, in vitro leukocyte aggregation has been studied by mixing patients' plasma or serum with leukocytes of a normal donor in a platelet aggregometer. We evaluated the leukergy phenomenon, that is, the occurrence of aggregated leukocytes in peripheral blood of patients with inflammatory disorders, as an alternative tool to the former method. Leukocyte aggregation could be induced by zymosan-activated plasma, phorbol myristate acetate, and formyl-methionyl-leucyl-phenylalanine, as well as by the calcium ionophore A23187 in vitro in whole human blood. This aggregation was blocked by various lipoxygenase and cyclooxygenase pathway inhibitors. Leukergy was diagnosed in peripheral blood of patients with inflammatory disorders and was generally not associated with elevated concentrations of immune complexes, lactoferrin, C3a des Arg, or C5a des Arg. To the best of our knowledge, this is the first report on leukocyte aggregation studies performed in whole blood. Such study permits evaluation of the aggregation phenomena of leukocytes in their natural milieu. Furthermore, it is possible with this method to obtain direct visualization of leukocytic aggregates in the peripheral blood of patients. The significance of our results and their possible implications are discussed in light of the pertinent literature.