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Presents a response by V. Schechner and co-authors to a letter to the editor about their article "Increased Red Blood Cell Adhesiveness/Aggregation Owing to Fibrinogen Elevation in Hypercholesterolaemic Patients and the Rationale of Fibrinogen-Lowering by LDL Apheresis," in the 2004 issue of "European Journal of Clinical Investigation."

Background Fatigue is commonly reported by patients with inflammatory bowel disease ( IBD), both in quiescent and active disease. Few fatigue scales have been tested in IBD. Aim To assess three fatigue assessment scales in IBD and to determine correlates of fatigue. Methods Potential participants ( n = 2131) were randomly selected from an IBD organisation's members' database; 605 volunteered and were posted three fatigue scales: Inflammatory Bowel Disease Fatigue scale, Multidimensional Fatigue Inventory and Multidimensional Assessment Fatigue scale and questionnaires assessing anxiety, depression, quality of life (QoL) and IBD activity. The questionnaires were tested for stability over time with another group ( n = 70) of invited participants. Internal consistency was measured by Cronbach's alpha and test-retest reliability by the intraclass correlation coefficient ( ICC). Results Four hundred and sixty-five of 605 (77%) questionnaires were returned; of 70 invited, 48/70 returned test (68.6%) and 41/70 (58.6%) returned retest. The three scales are highly correlated ( P < 0.001). Test-retest suggests reasonable agreement with ICC values between 0.65 and 0.84. Lower age, female gender, IBD diagnosis, anxiety, depression and QoL were associated with fatigue ( P < 0.001) on univariable analysis. However, on multivariable analysis only depression and low QoL were consistently associated with fatigue, while female gender was associated on most scales. IBD diagnosis, age and other factors were not consistently associated with severity or impact of fatigue once other variables were controlled for. Conclusions All three fatigue scales are likely to measure IBD fatigue adequately. Responsiveness to change has not been tested. Depression, poorer QoL and probably female gender are the major associations of fatigue in IBD. [ABSTRACT FROM AUTHOR]

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common cause of elevated alanine aminotransferase (ALT). NAFLD is associated with insulin resistance and hepatic inflammation. Similarly, patients with depression exhibit insulin resistance and increased inflammatory markers. However, no study has shown a clear association between elevated ALT and the development of depression. The aim of the study was to test whether elevated ALT, a surrogate marker for NAFLD, predicts the development of depression.MethodThe present prospective cohort study investigated 12 180 employed adults referred for health examinations that included fasting blood tests and anthropometric measurements between 2003 and 2010. Exclusion criteria were: baseline minor/major depression, excessive alcohol consumption and other causes for ALT elevation. Depression was evaluated by the eight-item Patient Health Questionnaire (PHQ-8) score.ResultsThe final cohort included 5984 subjects [69.4% men, aged 45.0 (s.d. = 10.24) years]. The incidence rate of minor and major depression was 3.8% and 1.4%, respectively. Elevated ALT was a significant independent predictor for the occurrence of minor [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.40–2.92] and major (OR 3.132, 95% CI 1.81–5.40) depression after adjusting for age, gender, body mass index, education level, serum levels of lipids, glucose, smoking and physical activity. Adding subjective health and affective state parameters (sleep disturbances, self-rated health, anxiety and burnout) as potential mediators only slightly ameliorated the association. Persistently elevated ALT was associated with the greatest risk for minor or major depression as compared with elevation only at baseline or follow-up (p for trend < 0.001).ConclusionsElevated ALT was associated with developing depressive symptoms, thus suggesting that NAFLD may represent an independent modifiable risk factor for depression. [ABSTRACT FROM PUBLISHER]

Background and purpose Polymorphic paraoxonase ( PON1) variants can variably prevent low- and high-density lipoprotein oxidation, but their role in provoking atherosclerosis remained unclear. We addressed this issue by profiling PON1 polymorphisms and enzymatic activities, and assessing atherosclerosis and cerebral arteriosclerosis severity in post-stroke patients. Methods Carotid artery intima-media-thickness ( IMT), cerebral white matter lesions ( WML), serum PON1 -108 C/ T, Q192 R and L55 M polymorphisms, and PON and acetylcholinesterase (AChE) enzyme activities were determined in 237 patients. Results Genetic variation at the PON1 locus showed a strong influence on PON1 activity in ischaemic stroke patients, but lacked direct influence on IMT. Stroke patients with PON1 QQ192 or MM55 genotypes demonstrated lower PON and arylesterase activities at both Day 1 and 12 months post-stroke than patients with either RQ/ RR192 or LM/ LL55 genotypes ( P < 0.001). Furthermore, patients with carotid atherosclerosis and/or cerebral arteriosclerosis expressed as IMT, carotid plaques and WML had lower 12 months PON1 activity than patients without ( P = 0.02, P = 0.027 and P = 0.001, respectively), and PON and AChE hydrolysis rates were more tightly correlated in patients carrying the PON1 192 R compared with the 192 QQ allele, in a gene dose-dependent manner ( P < 0.001). Conclusion Our findings show inverse PON1 activity-carotid atherosclerosis and -cerebral arteriosclerosis association in stroke patients: the lower the PON1 activity the more progressed is the atherosclerotic process and the weaker is the association with AChE activity. Extending previous PON1 genetic studies in stroke populations, our study emphasizes the PON1 activity as a potential anti-atherogenic element and proposes involvement of cholinesterase activities in its effects. [ABSTRACT FROM AUTHOR]

Background The diagnosis of irritable bowel syndrome (IBS) is symptom-based. Although considered a functional disease, accumulating evidence supports a low-grade gut inflammation as an element of its pathophysiology. Thus, high-sensitivity C-reactive protein (hs-CRP), a marker of micro inflammation, may be elevated in IBS. Our aim was to assess whether hs-CRP is higher in IBS patients compared to healthy controls (HC) and does it differ among the IBS clinical subgroups and correlate with disease severity. Methods A diagnostic case control study was conducted in two gastroenterology departments. Eighty-eight IBS patients who were recruited prospectively answered the Rome III diagnostic questionnaire. They all completed the Functional Bowel Disorder Severity Index (FBDSI), dietary, and general health questionnaires. All patients underwent blood sampling for hs-CRP levels. Each IBS patient was matched to four HC by age, gender, and BMI. Blood samples were obtained from the HC at a periodic health survey. Key Results The mean hs-CRP level in the IBS group was significantly higher than in HC (1.17 ± 1.26 mg L−1 vs 0.72 ± 0.91 mg L−1 respectively, P = 0.001). Hs-CRP levels were highest in patients with diarrhea-predominant IBS and in patients with greater disease severity. A cut-off value of 1.08 mg L−1 had a sensitivity of 60.2% and a specificity of 68% for differentiating IBS from HC. Conclusions & Inferences Hs-CRP levels are higher in IBS patients than HC, but still in the normal laboratory range. This may reflect the low-grade gut inflammation believed to occur in IBS and support its existence. [ABSTRACT FROM AUTHOR]

Background Early biomarkers for survival in an acute ischaemic stroke/transient ischaemic attack might serve as a useful tool for the clinician. Several studies have highlighted the role of inflammatory biomarkers as an early signal for acute ischaemic stroke prognosis. Aims This study examines the potential advantage of using high-sensitivity interleukin-6 as a possible biomarker at the early stages of acute stroke for identifying patients at a high risk for 12-month mortality. Methods Inflammatory biomarkers and neurological scores were determined in 250 patients following mild to moderate acute ischaemic stroke within 24 h of hospital admission. Outcome data on mortality were collected after 12 months. The signal detection methodology was used to identify subgroups that were at a high risk for 12-month mortality. Results Twelve months following the event, 234 of the 250 stroke patients survived. Signal detection identified predictors that distinguished individuals likely to die from those with a better recovery prediction. Plasma interleukin-6 concentration emerged as the optimal predictor, with a cut point of 6·47 pg/ml, χ2 (l, N=250)=20·5, P<0·001. Interleukin-6 above 6·47 pg/ml during the acute phase predicted subsequent non-survival ( P=0·006, odds ratio 8·0). Conclusions This study demonstrates the clinical potential of using high-sensitivity interleukin-6 as an early signal for acute ischaemic stroke survival and suggests a clear cut point for patients at a high risk who might benefit from closer clinical surveillance and/or administration of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objective and background: To explore the possibility that increased resting heart rate (HR) is associated with a microinflammatory response. Such an association could explain, at least in part, the recently described worse cardiovascular prognosis in individuals with increased HR. Methods: Concentrations of fibrinogen and high-sensitivity C-reactive protein, as well as the absolute number of polymorphonuclear leucocytes, were analysed in a cohort of 4553 apparently healthy men and in those with atherothrombotic risk factors. Results: Following adjustment for age and body mass index, lipid profile and cardiovascular risk factors, a significant (p<0.001) difference was noted between individuals in the first quintile of HR (⩽58 beats/min) and those in the fifth quintile (⩾79 beats/min) regarding all the above-mentioned inflammatory biomarkers, the respective mean values being 7.38 and 8.11 µmol/l, 1.12 and 1.61 mg/I, and 4.23 and 4.74×109/l. Conclusions: Resting HR is associated with a micromnflammatory response in apparently healthy men and in those with atherothrombotic risk factors. Sympathetic activation might be a common factor explaining such an association, if confirmed in additional studies, this association might be a relevant target for therapeutic manipulations. [ABSTRACT FROM AUTHOR]

Background – Carotid intimal medial thickening (c-IMT) is an established surrogate marker for atherosclerosis. There have been sporadic reports about an increase of c-IMT on the left carotid artery among populations with a mean age of ±50 years. Objective – The purpose of this study was to evaluate whether there is a difference in c-IMT between the two carotid arteries in a group of young healthy adults. Methods – Ninety-eight healthy adults with a mean age of 28 years underwent blood tests to evaluate various cardiovascular risk factors as well as automated ultrasonic measurements of their c-IMT on both carotid arteries. Results – No significant difference was noted between c-IMT on both sides. In fact, the c-IMT on left carotid artery in men ( n = 52) was 0.625 ± 0.078 mm while on the right carotid it was 0.626 ± 0.075 mm ( P = 0.884). The values for women ( n = 46) were 0.615 ± 0.059 mm and for men 0.622 ± 0.0618 mm ( P = 0.582), respectively. Conclusion – As opposed to a noted increase of c-IMT on the left carotid artery in older individuals, we did not find this difference in a group of young and relatively healthy adults. It is possible that if mechanical stress forces contribute to an enhanced left c-IMT, it takes a relatively long time to become evident. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) increases following an acute stroke/transient ischemic attack (TIA), but the increment level varies among patients. We analyzed CRP concentrations during an acute stroke/TIA in relation to the CRP gene −717A>G polymorphism. Six months following an acute ischemic stroke/TIA, basal concentrations of CRP were measured in 507 controls and 219 patients and were found to be unassociated with the CRP −717A>G polymorphism. However, during the acute phase of stroke/TIA, individuals with the AG/GG genotype had significantly elevated CRP concentrations as opposed to those with the AA genotype (2.02 ± 1.59 vs. 1.73 ± 1.69 mg/l, P = 0.027). In addition, significant 3.22-fold increments in CRP concentrations was noted in individuals carrying the −717G allele when comparing the acute phase with the basal state of each patient and averaging the results. CRP −717A>G polymorphism is associated with triggered CRP concentrations during acute stroke/TIA. These findings might shed more light on the mechanisms of CRP elevation in acute ischemic stroke/TIA. [ABSTRACT FROM AUTHOR]

Objective – To compare the recently introduced wide-range C-reactive protein (wr-CRP) with the widely used high-sensitivity Behring Dade method (hs-CRP) in acute stroke/transient ischemic attack (TIA) patients. Materials and methods – A total of 119 consecutive patients admitted to a tertiary medical center with acute ischemic stroke/TIA were included in the study. Venous blood was obtained for both assays during the first 24 h, 3–5 days, as well as 3–6 months thereafter. Results – A highly significant correlation ( r = 0.994, P < 0.0001) was found between the two methods even when analyzed at three different time points. In addition, a similar correlation was noted between these two assays and other commonly used biomarkers, including white blood cell count, Westergren's sedimentation rate and quantitative fibrinogen. Conclusion – Real-time, on-line and low-cost wr-CRP assay is a reasonable alternative to the Behring Dade hs-CRP method in acute stroke/TIA patients. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have suggested the insulin resistance might be accompanied by enhanced erythropoiesis. We have examined this association in individuals with the metabolic syndrome (MS) who in addition to insulin resistance harbor a chronic low grade inflammation. This study is relevant because chronic inflammation might have a suppressive effect on erythropoiesis. 280 and 554 non-smoking women and men with respective age of 46.4±9.3 (mean±S.D.) and 44.0±11.0 years are included. A significant correlation was noted between the numbers of the components of the MS and the inflammatory biomarkers including the white blood cell count, high sensitivity C-reactive protein, fibrinogen concentrations and the erythrocyte sedimentation rate. In addition, a significant correlation (r =0.157, p =0.008) was noted between the number of components of the MS and the number of red blood cells in the peripheral blood in women. The same was true for men (r =0.192, p &#60;0.0005). We conclude that enhanced erythropoiesis could be a new, hitherto unrecognized component of the MS. The enhanced erythropoiesis could give an erroneous impression of general “good” health in these individuals. [Copyright &y& Elsevier]

OBJECTIVE:To clarify the role of body mass index (BMI, kg/m2) adjustment in predictive models for cardiovascular events that add high-sensitivity C-reactive protein (hs-CRP) to the 10-y Framingham Coronary Heart Disease Risk Score (FCRS).DESIGN:A cross-sectional study in a group of apparently healthy individuals.SUBJECTS:In all, 1512 apparently healthy individuals (955 men and 557 women) at a respective age of 49.7±10.6 and 50.6±9.6 y.RESULTS:The Pearson correlation between hs-CRP and the calculated 10-y FCRS was lower when adjusted for BMI. This reduction was especially noted in women where it dropped from 0.247 to 0.09. The dominant role of hs-CRP concentrations was also noted in a linear regression model, again, especially noted in women (drop of the standardized coefficient from 0.517 for BMI to 0.08 for the FCRS).CONCLUSIONS:The correlation between hs-CRP and the 10-y FCRS is partly related to the presence of obesity. We raise the possibility that the addition of BMI to the predictive model of FCRS might attenuate the cost-effectiveness of CRP measurements for this specific risk assessment.International Journal of Obesity (2005) 29, 772–777. doi:10.1038/sj.ijo.0802939 Published online 29 March 2005 [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Enhanced red blood cell (RBC) aggregation has an adverse effect on microcirculatory blood flow and tissue oxygenation. It has been previously shown that obesity is associated with increased RBC aggregation. The objectives of the present study were to further characterize obesity-related RBC aggregation and to examine whether the enhanced aggregation is a plasma- or cellular-dependent process. METHODS:: Obese (body mass index (BMI)=40±6.3?kg/m2, n=22) and nonobese (BMI=24±3.4?kg/m2, n=18) individuals were evaluated for inflammation markers and aggregation parameters. Aggregation parameters were derived from the distribution of RBC population into aggregate sizes, and from the variation of the distribution as a function of flow-derived shear stress, using a cell flow properties analyzer. To differentiate plasmatic from cellular factors, we determined the aggregation in the presence of autologous plasma or dextran-500kDa and calculated the plasma factor (PF) in the obese group. PF ranges from 0 to 1. When the PF=1, the aggregation is all due to plasmatic factors, when PF=0, the altered aggregation depends entirely on cellular factors, whereas 0

BACKGROUND: Many theories regarding the pathophysiology leading to ovarian hyperstimulation syndrome (OHSS) have been proposed and tested. Increased erythrocyte aggregation is associated with capillary slow flow and tissue hypoxaemia. We performed this study in order to assess the degree of erythrocyte aggregation in the peripheral blood of individuals with OHSS and undergoing controlled ovarian stimulation (COH). METHODS: Twenty women with severe OHSS, 20 women undergoing COH under IVF protocol, and 20 healthy matched controls were recruited for this prospective study. Blood samples were drawn for determination of erythrocyte aggregation as well as haematological indices. The percentage of slide covered by the cells (‘erythrocyte percentage’: EP) was determined using a simple slide test and image analysis. Lower EP values correspond to higher degrees of aggregation. RESULTS: The respective measures of EP were 59.2 ± 3.0, 42.0 ± 3.0 and 35.0 ± 2.4% µm for the controls, women with COH and OHSS (P < 0.01 between controls and the two stimulation groups). CONCLUSIONS: The degree of erythrocyte aggregation is enhanced in the peripheral venous blood of patients with both COH and OHSS. This finding, known to cause capillary leak, may contribute to the pathophysiology of the OHSS. [ABSTRACT FROM AUTHOR]

Anuk T, Assayag EB, Rotstein R, Fusman R, Zeltser D, Berliner S, Avitzour D, Shapira I, Arber N, Bornstein NM. Prognostic implications of admission inflammatory profile in acute ischemic neurological events. Acta Neurol Scand 2002: 106: 196–199. © Blackwell Munksgaard 2002. Objective – To reveal the potential prognostic implications of admission inflammatory markers in patients with acute ischemic neurological events. Patients and methods – Sixty patients with an acute ischemic neurological event who were examined within 24 h from the appearance of symptomatology. We determined the high-sensitive C-reactive protein (hs-CRP) concentrations, erythrocyte sedimentation rate (ESR), fibrinogen concentrations and degree of erythrocyte adhesiveness/aggregation. Results – A significant correlation was noted between baseline hs-CRP concentrations, ESR as well as adhesiveness/aggregation and the outcome of the ischemic neurological event as determined by the modified Rankin scale 8–12 months following the insult. Conclusion – Admission inflammatory markers have long-term prognostic implications in patients with acute ischemic neurological events. These findings are relevant in view of the new therapeutic interventions now available for reducing the inflammatory response. [ABSTRACT FROM AUTHOR]

Summary We have developed a simple slide test and image analysis to reveal the state of erythrocyte adhesiveness/aggregation in the peripheral blood of patients with various degrees of the humoral acute phase response. The significant correlation between the results of the erythrocyte adhesiveness/aggregation test (EAAT), the erythrocyte sedimentation rate and fibrinogen concentration support the notion that it is possible to use the EAAT as a marker for the intensity of the acute phase response. Within a group of 860 individuals, we were able to differentiate effectively between groups of patients with a different intensity of humoral acute phase response. The present study confirms previous observations that support the applicability of the EAAT to routine clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Aims To determine whether increased red blood cell adhesiveness/aggregation in diabetic patients is related to the extent of their metabolic control. Methods We measured erythrocyte adhesiveness/aggregation in a group of 85 adult patients with diabetes mellitus by using citrated venous whole blood and a simple slide test. The erythrocyte adhesiveness/aggregation was determined by measuring the size of the spaces that are formed between the aggregated erythrocytes. We divided the patients into those with either low or high erythrocyte adhesiveness/aggregation values. Results The erythrocyte adhesiveness/aggregation values of the two groups differed significantly in terms of their fibrinogen concentration, erythrocyte sedimentation rate, high sensitive C-reactive protein (CRP), total cholesterol and triglyceride concentrations. There was no difference between the two groups regarding the concentrations of HbA1c . Logistic regression was applied to construct a model to predict the belonging of a patient in the low or high erythrocyte adhesiveness/aggregation group. A linear regression was applied to construct a model to predict the erythrocyte adhesiveness/aggregation values. Both models turned out to include gender, age, fibrinogen, triglyceride, retinopathy, coronary artery disease and age and gender interaction. Neither HbA1c nor CRP entered the models. Conclusions The degree of erythrocyte adhesiveness/aggregation and several variables of the acute-phase response in patients with diabetes mellitus are not directly related to the degree of metabolic control as evaluated by means of HbA1c concentration. Diabetic patients might benefit from rheological or anti-inflammatory interventions regardless of their metabolic control. [ABSTRACT FROM AUTHOR]

Presents information on a study which identified clinically relevant parameters of red blood cell aggregation. Methodology; Results of the study; Discussion.

The article discusses the procalcitonin (PCT) in the elderly. Bacterial infections are an important cause of morbidity and mortality in the elderly population. A number of acute-phase reactants are used in the diagnosis of acute infections. One substance that has been widely investigated is procalcitonin, a glycopeptide consisting of 116 amino acids produced by the C cells of the thyroid gland and a precursor of calcitonin. In previous studies, PCT levels were measured in children and in non-elderly adults. Since only one previous study specifically investigated the usefulness of PCT for identifying illness in the elderly.

Purpose: C-reactive protein (CRP) is a common proxy of inflammation, but accurate characterizations of its dynamics during acute infections are scant. The goal of this study was to examine C-reactive protein (CRP) trajectories in hospitalized patients with viral infections, confirmed bacteremia (stratified by Gram-negative or Gram-positive bacteria), and non-bacteremic infections/inflammations, considering antibiotic treatment., Methods: Electronic medical records from Tel Aviv Sourasky Medical Center (July 2007-May 2023) were analyzed. Patients with blood cultures or positive viral tests were included. CRP levels were modeled using generalized additive mixed-effects models (GAMMs) and observed up to 150 h after initial infection diagnosis. Patients with initial CRP levels > 31.9 were excluded, to remove individuals already in a highly active inflammatory process. The shapes of the CRP curves were characterized and peak CRP as well as area under the CRP curve were the primary variables of interest., Results: Viral infections had the lowest and flattest CRP curves. Non-bacteremic infections showed intermediate levels, while bacteremia (especially Gram-negative under antibiotic treatment) had the highest CRP peaks. For instance, peak CRP ranged from 15.4 mg/L in viral infections without antibiotics to 140.9 mg/L in Gram-negative bacteremia with antibiotics., Conclusions: CRP trajectories significantly differ based on infection type and antibiotic treatment. Frequent CRP measurement could be a valuable diagnostic and risk stratification tool in hospitalized patients., (© 2024. The Author(s).)

Background: Serum ferritin is usually measured in the presence of anemia or in suspected iron overload syndromes. Ferritin is also an acute-phase protein that is elevated during systemic inflammation. However, the prognostic value of routinely measuring ferritin upon admission to a medical facility is not clear. Therefore, we examined the association between ferritin concentrations measured at the time of hospital admission with 30-day and long-term mortality., Methods: We obtained routine ferritin measurements taken within 24 hours of admission in 2859 patients hospitalized in an internal medicine department. Multiple clinical and laboratory parameters were used to assess the association between ferritin and overall mortality during a median follow-up of 15 months (interquartile range [IQR] 8-22)., Results: Ferritin levels were associated with increased 30-day mortality rates (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.03-1.06) for each 100 ng/mL increase. Patients with intermediate (78-220 ng/mL) and high (>221 ng/mL) ferritin concentrations (2nd and 3rd tertiles) had higher 30-day mortality rates even after adjustment for age, sex, and existing comorbidities (OR 2.05, 95% CI 1.70-2.5). Long-term overall mortality rates demonstrated a similar pattern across ferritin tertiles (hazard ratio [HR] 1.54, 95% CI 1.39-1.71)., Conclusions: Routine admission ferritin concentrations are linearly and independently correlated with excess mortality risk in hospitalized patients, even those with apparently "normal" ferritin concentrations (<300 mg/mL). Thus, low-grade ferritinemia might not be an innocent finding in the context of the inflammatory response. Its potential biological and therapeutic implications warrant future research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Acute kidney injury associated with the underlying inflammatory process of an acute bacterial infection affects patient morbidity and mortality. Clinicians use creatinine and estimated glomerular filtration rate (EGFR) to assess this renal injury, however, these measures may lag behind and change only once significant kidney injury has occurred. Neutrophil gelatinase-associated lipocalin (NGAL) is up-regulated by inflammation and infection and may serve as an early detection biomarker of kidney injury., Methods: Patients hospitalized with bacterial infections were assessed demographically, clinically and had their creatinine levels, EGFR and inflammatory biomarker levels, including urinary NGAL measured. Findings were compared between controls and patients across different EGFRs., Results: Fifty-one participants were included in the study. Among this cohort, 31 suffered bacterial infection. Inflammatory biomarkers including urinary NGAL were found to be higher in the infection group compared to the control group. Urinary NGAL level was significantly higher across all EGFRs of patients diagnosed with infection, including those with normal EGFR., Conclusion: Urinary NGAL identifies early kidney damage associated with bacterial infection even at normal EGFR and alerts the treating physician to undertake the necessary measures to mitigate the renal injury., Competing Interests: The authors declare no conflict of interest., (© 2024 Levinson et al.)

The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults. This study aims to investigate the association between eCRPv and bacterial etiologies among pediatric patients with very elevated CRP levels. We conducted a retrospective analysis of patients under 18 years of age who had been admitted to our Pediatric Emergency Department from 2018 to 2020 with a fever and CRP levels ≥ 150 mg/L. Bacterial and non-bacterial etiologies were determined from hospital discharge diagnoses, which were monitored independently by three physicians from the research team. The records of 495 suitable patients (51.2% males, median age 3.2 years) were retrieved of whom 444 (89.7%) were eventually diagnosed with bacterial infections. The mean CRP levels were significantly higher for bacterial etiologies compared with other causes (209.2 ± 59.8 mg/L vs. 185.6 ± 35.8 mg/L, respectively, p < .001), while the mean eCRPv values did not differ significantly (p = .15). In a time course analysis, we found that specifically in patients presenting ≥ 72 h after symptom onset, only a eCRPv1 level > 1.08 mg/L/h was an independent predictor of bacterial infection (aOR = 5.5 [95% CI 1.7-17.8], p = .004).   Conclusion: Pediatric patients with very high CRP levels and fever mostly have bacterial infections. eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset, warranting further prospective investigations into CRP kinetics in pediatric patients. What is Known: • The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. • Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults, but data on CRP kinetics in pediatric patients is sparse. What is New: • eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset in pediatric patients with remarkably elevated CRP levels., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The C-reactive protein (CRP)-troponin-test (CTT) comprises simultaneous serial measurements of CRP and cardiac troponin and might reflect the systemic inflammatory response in patients with acute coronary syndrome. We sought to test its ability to stratify the short- and long-term mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI)., Methods: We examined 1,675 patients diagnosed with NSTEMI on discharge who had at least two successive measurements of combined CRP and cardiac troponin within 48 h of admission. A tree classifier model determined which measurements and cutoffs could be used to best predict mortality during a median follow-up of 3 years [IQR 1.8-4.3]., Results: Patients with high CRP levels ( > 90th percentile, >54 mg/L) had a higher 30-day mortality rate regardless of their troponin test findings (16.7% vs. 2.9%, p < 0.01). However, among patients with "normal" CRP levels ( < 54 mg/L), those who had high troponin levels ( > 80th percentile, 4,918 ng/L) had a higher 30-day mortality rate than patients with normal CRP and troponin concentrations (7% vs. 2%, p < 0.01). The CTT test result was an independent predictor for overall mortality even after adjusting for age, sex, and comorbidities (HR = 2.28 [95% CI 1.56-3.37], p < 0.01 for patients with high troponin and high CRP levels)., Conclusions: Early serial CTT results may stratify mortality risk in patients with NSTEMI, especially those with "normal" CRP levels. The CTT could potentially assess the impact of inflammation during myocardial necrosis on the outcomes of patients with NSTEMI and identify patients who could benefit from novel anti-inflammatory therapies., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) is associated with significant morbidity and mortality. C-reactive protein (CRP) is a useful inflammatory biomarker for patients admitted with an infection. This study aimed to compare CRP level as an indicator of inflammation severity between SARS-CoV-2 and common respiratory viral infections. A cross-sectional study of all adult patients hospitalized in the internal medicine department, geriatric department, or internal intensive care unit between 02/2012 and 06/2021 with laboratory-confirmed respiratory viral infection was performed. SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus (RSV) were studied. Patients with laboratory-confirmed concurrent viral or bacterial infections were excluded. Patients with malignancy were also excluded. Age, gender, comorbidities, and CRP level upon admission were compared between groups. Univariate and multivariable analyses were applied. Among 1124 patients, 18.2% had SARS‑CoV‑2, 48.3% influenza A, 18.9% RSV, and 14.6% influenza B. SARS‑CoV‑2 patients were significantly younger (median 69.4 vs. ≥ 76 years) and had lower Charlson score (median 3 vs. ≥ 4 in other groups) compared to patients with other viral pathogens. After adjustment for patients' age, gender and comorbidities, SARS‑CoV‑2 patients had a higher probability (OR = 1.84-2.02, p < 0.01) of having CRP values in the upper quartile (> 117 mg/L) compared to all other viral pathogens while between all others there was no significant difference. To conclude, a higher CRP level upon admission is approximately twice more common among SARS-CoV-2 patients compared to other widespread respiratory viruses which may demonstrate the higher intensity of inflammation caused by SARS-CoV-2., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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.)

Background: Pressure overload of the right heart (pulmonary hypertension [PH]) can be an acute or a chronic process with various pathophysiologic changes affecting the dimensions of the heart chambers. The automatic four-chamber volumetric analysis tool is now available to measure the volume of the cardiac chambers in patients undergoing a computed tomography pulmonary angiogram (CTPA)., Purpose: To characterize the volumetric changes that occurred in response to increased systolic pulmonary arterial pressures (sPAP) in acute events, such as acute pulmonary embolism (APE), compared with other etiologies., Material and Methods: Consecutive patients who underwent CTPA and echocardiography within 24 h between 2011 and 2015 were included. Differences in cardiac chamber volumes were investigated in correlation to the patients' sPAP., Results: The final cohort of 961 patients included 221 (23%) patients diagnosed with APE. The right (RV) to left (LV) ventricular volume ratio (VVR) was higher, while the left atrial (LA) volume index was smaller ( P  < 0.001) in the patients with APE. A decision tree for the prediction of APE showed that an RV to left VVR >2.8 was characteristic of APE, whereas an LA volume index >37.5 mL/m² was more compatible with PH due to other etiologies ( P  < 0.001)., Conclusion: The combination of VVR and LA volume index may help in differentiating between APE and chronic PH. CTPA-based volumetric information may be used to help clarify the underlying etiology of the dyspnea.

Introduction: The global prevalence of metabolic syndrome and its association with increased morbidity and mortality has been rigorously studied. However, the true prevalence of "metabolic health", i.e. individuals without any metabolic abnormalities is not clear. Here, we sought to determine the prevalence of "metabolically healthy" individuals and characterize the "transition phase" from metabolic health to development of dysfunction over a follow-up period of 5 years., Methods: We included 20,507 individuals from the Tel Aviv Sourasky Medical Center Inflammation Survey (TAMCIS) which comprises apparently healthy individuals attending their annual health survey. A second follow-up visit was documented after 4.8 (± 0.6) years. We defined a group of metabolically healthy participants without metabolic abnormalities nor obesity and compared their characteristics and change in biomarkers over time to participants who developed metabolic impairment on their follow-up visit. The intersections of all metabolic syndrome components and elevated high sensitivity C-reactive protein (hs-CRP) were also analyzed., Results: A quarter of the cohort (5379 individuals, (26.2%) did not fulfill any metabolic syndrome criteria during their baseline visit. A total of 985 individuals (12.7% of returning participants) developed metabolic criteria over time with hypertension being the most prevalent component to develop among these participants. Individuals that became metabolically impaired over time demonstrated increased overlap between metabolic syndrome criteria and elevated hs-CRP levels. The group that became metabolically impaired over time also presented higher delta values of WBC, RBC, liver biomarkers, and uric acid compared with participants who were consistently metabolically impaired. LDL-C (low-density lipoprotein cholesterol) delta levels were similar., Conclusions: Roughly one-quarter of apparently healthy adults are defined as "metabolically healthy" according to current definitions. The transition from health to metabolic dysfunction is accompanied with active inflammation and several non-metabolic syndrome biomarkers. Aggressive screening for these biomarkers, blood pressure and hs-CRP might help identify apparently healthy individuals at increased risk of developing metabolic syndrome over time., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The parasympathetic system and its main neurotransmitter, acetylcholine, contributes to homeostasis of inflammation. Cholinergic dysregulation is thought to contribute to the pathogenesis of inflammatory rheumatic diseases. Cholinesterase activity in patients with psoriatic arthritis (PsA) has not been investigated., Objectives: To compare the cholinesterase activity in patients with PsA and immunocompetent controls and to explore the correlation between cholinergic status (CS) and PsA disease activity., Methods: Serum acetylcholinesterase (AChE) and total cholinesterase activity were measured in patients with PsA (n=88) and matched controls (n=84). Cholinergic activity before and 3-6 months after the initiation of a biologic treatment was evaluated in seven patients with PsA., Results: The levels of AChE and CS were similar in both PsA patients and controls. PsA patients treated with biologics had significantly lower levels of AChE and CS compared to patients treated with non-biologics: 447.4 vs. 526 substrate hydrolyzed/min/ml, P = 0.005, and 1360.9 vs. 1536, P = 0.029, respectively. We found an association between C-reactive protein levels, AChE activity (r = 0.291, P = 0.008), and cholinergic status (r = 0.247, P = 0.026) in patients with PsA but not in controls. No correlation between AChE activity, cholinergic status, and the indices of PsA disease activity was found. After initiating or switching biologic treatment in 7 patients, AChE levels remained stable., Conclusions: We demonstrated similar cholinesterase activity in patients with psoriatic arthritis and controls, highlighting a potential effect of biologic treatment on cholinergic activity in patients with PsA.

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new "inflammatory stamp".

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.)

Background: C-reactive protein (CRP) is a marker of inflammation and infection. The main proinflammatory cytokine that leads to CRP gene expression is IL-6. The study aimed to compare CRP level between patients who were treated with Tocilizumab (TCZ), an il-6 receptor blocker, and other advanced anti-inflammatory treatments (AAIT), as well as with other admitted and non-admitted populations., Methods: A cross-sectional study of all patients (≥18 years) hospitalized at tertiary medical center between December 2009 and February 2020 and treated before hospitalization with (AAIT). Only the first hospitalization of each patient was included. Women admitted to obstetrics department were excluded. Demographic data, first blood tests results, and comorbidities were collected., Results: The study included 563 patients treated with AAIT (2.5% received TCZ). Patients treated with TCZ were older (median 75 vs. 50 years, p < 0.001), had higher Charlson score (median 5 vs. 1, p < 0.001) and more infectious diseases at admission (50% vs. 23.4%, p = 0.05). Patients treated with TCZ had lower CRP levels (median 0.5 vs. 25 mg/l, p < 0.001) and more common normal values (64.3% vs. 20.8%, p < 0.001) compared to patients treated with other AAIT.CRP level in patients treated TCZ (median 0.5 mg/l) was lower than that of 58,548 patients admitted to the hospital between 2010 and 2020 (median 12.55 mg/l, p < 0.001) and not statistically different from 140 non-admitted randomly selected individuals without acute disease (1.33 mg/l, p = 0.294)., Conclusion: Tocilizumab is associated with lower levels of CRP in patients admitted to acute care hospital. This finding must be considered by treating physician to avoid misinterpretation of CRP results., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Purpose: To investigate the effect of change in body mass index (BMI) on intraocular pressure (IOP) in a large cohort of apparently healthy volunteers who underwent an annual comprehensive screening examinations., Methods: This study included individuals who were enrolled in the Tel Aviv Medical Center Inflammation Survey (TAMCIS) and had IOP and BMI measurements at their baseline and follow up visits. Relationships between BMI and IOP and the effect of change in BMI on IOP were investigated., Results: A total of 7,782 individuals had at least one IOP measurement at their baseline visit, and 2,985 individuals had ≥2 visits recorded. The mean (SD) IOP (right eye) was 14.6 (2.5) mm Hg and mean (SD) BMI was 26.4 (4.1) kg/m2. IOP positively correlated with BMI levels (r = 0.16, p<0.0001). For individuals with morbid obesity (BMI≥35 kg/m2) and ≥2 visits, a change in BMI between the baseline and first follow-up visits correlated positively with a change in the IOP (r = 0.23, p = 0.029). Subgroup analysis of subjects who had a reduction of at least 2 BMI units showed a stronger positive correlation between change in BMI and change in IOP (r = 0.29, p<0.0001). For this subgroup, a reduction of 2.86 kg/m2 of BMI was associated with a reduction of 1 mm Hg in IOP., Conclusions: BMI loss correlated with reduction in IOP, and this correlation was more pronounced among morbidly obese individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Coster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: We aimed to examine the relationships between body mass index (BMI) and metabolic syndrome (MS) components as a function of age and gender across weight categories., Methods: This cross-sectional study included 19,328 subjects who participated in a health-screening program. We analyzed 14,093 apparently healthy subjects with a BMI ≥ 18.5 kg/m 2 (ranging from 18.5 to 46 kg/m 2 )., Results: At a BMI of 18.5 kg/m 2 , 16% of subjects had one or more MS components (MS ≥ 1). The number of MS components increased linearly with BMI. The most prevalent components for MS1-4 were hypertension (in men) and increased waist circumference (in women). Among 6391 non-obese subjects with MS = 0, there was a linear increase in blood pressure, glucose, and triglycerides, as well as a decline in high-density lipoprotein cholesterol, as BMI increased. In 2087 subjects with a BMI ≥ 30 kg/m 2 , a true normometabolic state (MS = 0) was observed in only 7.5%, declining to less than 1% at a BMI ≥ 36 kg/m 2 (ATP criteria). Women were metabolically protected relative to men between the ages of 30 and 50 years., Conclusions: (A) MS components increase linearly with BMI from the lowest normal BMI and continue to increase with age and BMI; (B) metabolically healthy obesity is rare in subjects with a high BMI and declines with age; (C) hypertension is the most common component in men; and (D) in women, MS components are seen at older ages than in men for the same BMI. Metabolic health declines with age and BMI in nearly all subjects with obesity.

Objectives: To assess the correlation between inflammatory markers (IM) and hearing loss (HL) in a large cohort of apparently healthy individuals., Design: A cross sectional study., Setting: Tel-Aviv Medical Center (a tertiary referral center) Inflammatory Survey Participants Individuals who attended the Tel-Aviv Medical Center Inflammatory Survey (TAMCIS) for a routine annual health check., Results: Out of 2,500 individuals included in the final study cohort, 1,170 (47.3%) had some hearing impairment. Those with a hearing loss in 1 or both ears had significantly higher levels of neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and red blood cell counts. There was a difference between low- and high- frequencies losses associated with the inflammatory status., Conclusions: IM levels were associated with the presence of a HL, supporting a link between inflammatory changes and hearing loss., (© 2022 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Purpose: Differentiating between acute viral and bacterial infection is challenging due to the similarity in symptom presentation. Blood tests can assist in the diagnosis, but they reflect the immediate status and fail to consider the dynamics of an inflammatory response with time since symptom onset. We applied estimated C-reactive protein (CRP) velocity (eCRPv), as derived from the admission CRP level divided by time from symptom onset, in order to better distinguish between viral and bacterial infections., Methods: This cross-sectional study included patients admitted to the emergency department with a confirmed viral (n = 83) or bacterial (n = 181) infection. eCRPv was defined as the ratio between the absolute CRP level upon admission to time from symptom onset (in hours). Absolute CRP and eCRPv values were compared between the 3 groups., Results: Bacterial patients presented with higher CRP levels (133 mg/L) upon admission compared to viral patients (23.31 mg/L) (P < 0.001). Their median value of eCRPv velocity was 4 times higher compared to the viral patients (1.1 mg/L/h compared 0.25 mg/L/h, P < 0.001). Moreover, in intermediate values of CRP (100-150 mg/L) upon admission, in which the differential diagnosis is controversial, high eCRPv is indicative of bacterial infection, eCRPv >4 mg/L/h represents only bacterial patients., Conclusions: During an acute febrile illness, the eCRPv value can be used for rapid differentiation between bacterial and viral infection, especially in patients with high CRP values. This capability can potentially expedite the provision of appropriate therapeutic management. Further research and validation may open new applications of the kinetics of inflammation for rapid diagnosis of an infectious vs. a viral source of fever., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Largman-Chalamish et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Pericardial effusion may present clinically as pleuritic chest pain, dyspnea, or hemodynamic compromise and is a frequent finding in computerized tomographic pulmonary angiography (CTPA) exams. We hypothesized that CTPA-based analysis of the cardiac chamber volumes can be used to predict the hemodynamic significance of pericardial effusion (HsPE) as compared with echocardiography., Methods: Retrospective analysis of consecutive patients who underwent CTPA and echocardiography between January 2009 and November 2017 that ruled-out acute pulmonary embolism was included. Differences in cardiac chamber volumes were investigated in correlation to echocardiographic evidence of HsPE., Results: The final cohort included 208 patients, of whom 22 (11%) were diagnosed with HsPE. The HsPE patients had much smaller right cardiac chamber volumes (Median 78.8 ml (IQR 72.4-89.1)) than patients without HsPE (Median 115.1 ml (IQR 87.4-150). A decision tree for the prediction of HsPE showed multiple cutoff values. Right atrium (RA) volume had the best accuracy (area under the curve 0.851, 95% confidence interval 0.776-0.925, p < .001) for predicting the presence of HsPE. An RA volume ≤86 ml yielded a sensitivity of 95.5%, a specificity of 64%, and a NPV of 99.2% for the presence of HsPE., Conclusion: CTPA-based volumetric information with focus on the RA volume may help predict the presence of HsPE., Advances in Knowledge: Pericardial effusion is a frequent finding in CTPA exams. Our study shows that CTPA-based volumetric information can predict the presence of HsPE with RA volume as the best indicator.

Background: Patients who are admitted to the Department of Internal Medicine with apparently normal C-reactive protein (CRP) concentration impose a special challenge due the assumption that they might not harbor a severe and potentially lethal medical condition. Methods: A retrospective cohort of all patients who were admitted to the Department of Internal Medicine with a CRP concentration of ≤31.9 mg/L and had a second CRP test obtained within the next 24 h. Seven day mortality data were analyzed. Results: Overall, 3504 patients were analyzed with a mean first and second CRP of 8.8 (8.5) and 14.6 (21.6) mg/L, respectively. The seven day mortality increased from 1.8% in the first quartile of the first CRP to 7.5% in the fourth quartile of the first CRP (p < 0.0001) and from 0.6% in the first quartile of the second CRP to 9.5% in the fourth quartile of the second CRP test (p < 0.0001), suggesting a clear relation between the admission CRP and in hospital seven day mortality. Conclusions: An association exists between the quartiles of CRP and 7-day mortality as well as sepsis related cause of death. Furthermore, the CRP values 24 h after hospital admission improved the discrimination.

Background: Several biomarkers and models have been proposed to predict in-hospital mortality among COVID-19 patients. However, these studies have not examined the association in sub-populations. The present study aimed to identify the association between the two most common inflammatory biomarkers in the emergency department and in-hospital mortality in subgroups of patients. Methods: A historical cohort study of adult patients who were admitted to acute-care hospital between March and December 2020 and had a diagnosis of COVID-19 infection. Data on age, sex, Charlson comorbidity index, white blood cell (WBC) count, C-reactive protein (CRP), and in-hospital mortality were collected. Discrimination ability of each biomarker was observed and the CHAID method was used to identify the association in subgroups of patients. Results: Overall, 762 patients (median age 70.9 years, 59.7% males) were included in the study. Of them, 25.1% died during hospitalization. In-hospital mortality was associated with higher CRP (median 138 mg/L vs. 85 mg/L, p < 0.001), higher WBC count (median 8.5 vs. 6.6 K/µL, p < 0.001), and higher neutrophil-to-lymphocyte ratio (NLR) (median 9.2 vs. 5.4, p < 0.001). The area under the ROC curve was similar among all biomarkers (WBC 0.643, NLR 0.677, CRP 0.646, p > 0.1 for all comparisons). The CHAID method revealed that WBC count was associated with in-hospital mortality in patients aged 43.1−66.0 years (<11 K/µL: 10.1% vs. 11+ K/µL: 27.9%), NLR in patients aged 66.1−80 years (≤8: 15.7%, >8: 43.3%), and CRP in patients aged 80.1+ years (≤47 mg/L: 18.8%, 47.1−149 mg/L: 43.1%, and 149.1+: 71.7% mortality). Conclusions: WBC, NLR, and CRP present similar discrimination abilities. However, each biomarker should be considered as a predictor for in-hospital mortality in different age groups.

Elevated concentrations of C-reactive protein (CRP) early during an acute coronary syndrome (ACS) may reflect the magnitude of the inflammatory response to myocardial damage and are associated with worse outcome. However, the routine measurement of both CRP and cardiac troponin simultaneously in the setting of ST-segment myocardial infarction (STEMI) is not used broadly. Here, we sought to identify and characterize individuals who are prone to an elevated inflammatory response following STEMI by using a combined CRP and troponin test (CTT) and determine their short- and long-term outcome. We retrospectively examined 1186 patients with the diagnosis of acute STEMI, who had at least two successive measurements of combined CRP and cardiac troponin (up to 6 h apart), all within the first 48 h of admission. We used Chi-Square Automatic Interaction Detector (CHAID) tree analysis to determine which parameters, timing (baseline vs. serial measurements), and cut-offs should be used to predict mortality. Patients with high CRP concentrations (above 90th percentile, >33 mg/L) had higher 30 day and all-cause mortality rates compared to the rest of the cohort, regardless of their troponin test status (above or below 118,000 ng/L); 14.4% vs. 2.7%, p < 0.01. Furthermore, patients with both high CRP and high troponin levels on their second measurement had the highest 30-day mortality rates compared to the rest of the cohort; 21.4% vs. 3.7%, p < 0.01. These patients also had the highest all-cause mortality rates after a median follow-up of 4.5 years compared to the rest of the cohort; 42.9% vs. 12.7%, p < 0.01. In conclusion, serial measurements of both CRP and cardiac troponin might detect patients at increased risk for short-and long-term mortality following STEMI. We suggest the future use of the combined CTT as a potential early marker for inflammatory-prone patients with worse outcomes following ACS. This sub-type of patients might benefit from early anti-inflammatory therapy such as colchicine and anti-interleukin-1ß agents.

Purpose: The presence of a microinflammatory response is one of the possible pathological mechanisms related to the development of nonarteritic anterior ischemic optic neuropathy (NAAION), a common cause of optic neuropathy in old age.We tested whether individuals with NAAION harbor a heightened microinflammatory response compared to controls., Methods: We measured the erythrocyte sedimentation rate (ESR) and high sensitivity C-reactive protein (hs-CRP) in NAAION patients during hospital admission and in four matched controls for each patient, retrieved from a large cohort of 20,000 apparently healthy individuals., Results: We included 128 NAAION patients and 512 controls. No significant differences were found between patients and controls regarding the inflammatory biomarkers., Conclusions: This is the first report showing a lack of difference in ESR and hs-CRP levels between NAAION patients and matched controls, suggesting NAAION is not associated with a heightened inflammatory response, such as the one associated with multiple atherothrombotic risk factors.

The COVID-19 pandemic has been spreading worldwide since December 2019, presenting an urgent threat to global health. Due to the limited understanding of disease progression and of the risk factors for the disease, it is a clinical challenge to predict which hospitalized patients will deteriorate. Moreover, several studies suggested that taking early measures for treating patients at risk of deterioration could prevent or lessen condition worsening and the need for mechanical ventilation. We developed a predictive model for early identification of patients at risk for clinical deterioration by retrospective analysis of electronic health records of COVID-19 inpatients at the two largest medical centers in Israel. Our model employs machine learning methods and uses routine clinical features such as vital signs, lab measurements, demographics, and background disease. Deterioration was defined as a high NEWS2 score adjusted to COVID-19. In the prediction of deterioration within the next 7-30 h, the model achieved an area under the ROC curve of 0.84 and an area under the precision-recall curve of 0.74. In external validation on data from a different hospital, it achieved values of 0.76 and 0.7, respectively., (© 2022. The Author(s).)

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.)