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To assess the correlation between inflammatory markers (IM) and hearing loss (HL) in a large cohort of apparently healthy individuals.A cross sectional study.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.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.IM levels were associated with the presence of a HL, supporting a link between inflammatory changes and hearing loss. more...

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. more...

Background Elevated concentrations of C-reactive protein (CRP) early after 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 using the CRP Troponin test (CTT) and determine their short- and long-term outcome. Material and methods We retrospectively examined 1,186 patients with the diagnosis of acute STEMI, who had at least two successive measurements of combined CRP and cardiac troponin (up to 6 hours apart), all within the first 48 hours 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. Results Patients with high CRP concentrations (above 90th percentile, >33mg/L) had higher 30 day- and all-cause mortality rates regardless of their troponin test status (above or below 118,000 ng/L); 14.4% vs 2.7%, p Conclusions 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 CRP Troponin-test (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-IL-1β agents. Funding Acknowledgement Type of funding sources: None. more...

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.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).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.Patients presenting for coronary angiography with low levels of serum AChE activity are at increased risk for death during long term follow-up. more...

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 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/1.73m2. 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/1.73m2. Participants with a low calcium score showed an increase in LAVI only when eGFR was reduced from normal (>90 ml/min/1.73m2) to 70-80 ml/min/1.73m2 (and not to 80-90 ml/min/1.73m2), 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. more...

PURPOSE The purpose of this study was to evaluate the association between small left atria (LA) according to computed tomography pulmonary angiography (CTPA) and mortality among individuals without pulmonary embolism, and to examine which volumes begin to portend adverse outcomes. MATERIALS AND METHODS Left atrial volume indices (LAVIs) of 752 consecutive patients who underwent CTPA, in which pulmonary embolism were ruled out, were measured retrospectively using an automatic 4-chamber volumetric analysis software. Groups of 5 percentiles within the lower quartile were investigated, and the interquartile range (25th to 75th percentiles) was regarded as the control group. RESULTS Patients within the lower 25th LAVI percentiles ( more...

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, p2) 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, p2 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. more...

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/m2 (ranging from 18.5 to 46 kg/m2). Results: At a BMI of 18.5 kg/m2, 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/m2, a true normometabolic state (MS = 0) was observed in only 7.5%, declining to less than 1% at a BMI ≥ 36 kg/m2 (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. more...

The challenge of survival prediction is ubiquitous in industry and medicine. Few methods are available for survival prediction of time varying data. Here we propose a novel method for this problem, using a random forest of survival trees for left truncated and right-censored data. We demonstrated the advantage of our method on prediction of breast cancer and prostate gland cancer risk among healthy individuals by analyzing routine laboratory measurements, vital signs and age. We analyzed electronic medical records of 20,317 healthy individuals who underwent routine checkups and identified those who later developed cancer. In cross-validation, our method predicted future prostate and breast cancers six months before diagnosis with an area under the ROC curve of 0.62±0.05 and 0.6±0.03 respectively, outperforming standard random forest, Cox-regression model and a single survival tree. Our results suggest that computational analysis of data on healthy individuals can improve the detection of those at risk of future cancer development. more...

Background To assess the utility of C-reactive protein (CRP) velocity to discriminate between patients with acute viral and bacterial infections who presented with relatively low CRP concentrations and were suspected of having a bacterial infection. Methods We analyzed a retrospective cohort of patients with acute infections who presented to the emergency department (ED) with a relatively low first CRP measurement (CRP1) ≤ 31.9 mg/L and received antibiotics shortly after. We then calculated C-reactive protein velocity (CRPv), milligram per liter per hour, for each patient based on CRP1 and the second CRP value (CRP2) measured within the first 24 h since admission. Finally, we compared CRPv between patients with bacterial and viral infections. Results We have presently analyzed 74 patients with acute bacterial infections and 62 patients with acute viral infections at the mean age of 80 and 66 years respectively, 68 male and 68 female. CRP1 did not differ between both groups of patients (16.2 ± 8.6 and 14.8 ± 8.5 for patients with viral and bacterial infections respectively, p value = 0.336). However, the CRP2 was significantly different between the groups (30.2 ± 21.9 and 75.6 ± 51.3 for patients with viral and bacterial infections respectively, p-value Conclusion CRPv and CRP2 are useful biomarkers that can discriminate significantly between patients who present with acute bacterial and viral infections, and relatively low CRP concentration upon admission who were suspected of having a bacterial infection. more...

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. more...

Differential diagnosis between acute viral and bacterial infection is an emerging common challenge for a physician in the emergency department. Serum C-reactive protein (CRP) is used to support diagnosis of bacterial infection, but in patients admitted with low CRP, its ability to discriminate between viral and bacterial infections is limited. We aimed to use two consecutive CRP measurements in order to improve differential diagnosis between bacterial and viral infection. A single-center retrospective cohort (n = 1629) study of adult patients admitted to the emergency department with a subsequent microbiological confirmation of either viral or bacterial infection. Trend of CRP was defined as the absolute difference between the first two measurements of CRP divided by the time between them, and we investigated the ability of this parameter to differentiate between viral and bacterial infection. In patients with relatively low initial CRP concentration ( more...

Background Resting heart rate (RHR) is an obtainable, inexpensive, non-invasive test, readily available on any medical document. RHR has been established as a risk factor for cardiovascular morbidity, is related to other cardiovascular risk factors, and may possibly predict them. Change in RHR over time (∆RHR) has been found to be a potential predictor of mortality. Methods In this prospective study, RHR and ∆RHR were evaluated at baseline and over a period of 2.9 years during routine check-ups in 6683 subjects without known cardiovascular disease from the TAMCIS: Tel-Aviv Medical Center Inflammation Survey. Multiple linear regression analysis with three models was used to examine ∆RHR. The first model accounted for possible confounders by adjusting for age, sex and body mass index (BMI). The 2nd model included smoking status, baseline RHR, diastolic blood pressure (BP), dyslipidemia, high-density lipoprotein (HDL) and metabolic equivalents of task (MET), and in the last model the change in MET and change in BMI were added. Results RHR decreased with age, even after adjustment for sex, BMI and MET. The mean change in RHR was − 1.1 beats/min between two consecutive visits, in both men and women. This ∆RHR was strongly correlated with baseline RHR, age, initial MET, and change occurring in MET and BMI (P Conclusions Our results highlight the need for examining individual patients’ ∆RHR. Reinforcing that a positive ∆RHR is an indicator of poor adherence to a healthy lifestyle. more...

Aims To assess whether hospitalization may assist in correcting errors in anticoagulant therapy among patients with atrial fibrillation (AF). Methods Our cohort included patients admitted to our institution with a history of AF between 2016 and 2018. We categorized patient's treatment upon admission and discharge as lacking (no treatment despite indication), inadequate (according to individual characteristics) or adequate. We assessed adequacy of treatment upon discharge and determined factors associated with correcting admission errors. Results Of 4427 patients admitted with a history of AF, the categorization to lacking, inadequate and adequate treatment was 1746 (39.4%), 1237 (27.9%) and 1444 (32.6%) patients, respectively. Of those with inadequate treatment, the most common types of errors were direct oral anticoagulant (DOAC) underdosing (n = 578; 46.7%), vitamin-K antagonists when DOAC was indicated (n = 258; 20.9%), DOAC despite contraindication to DOAC (n = 166; 13.4%) and DOAC overdosing (n = 124; 10%). Upon discharge 688 (18.6%, out of n = 3694) corrections but also 316 (8.6%) new mistakes were found. On multivariate logistic regression, the factors associated with correction of an error on admission were hospitalization due to AF (odds ratio [OR] 2.94 [2.39-3.61]), hospitalization in the neurologic or geriatric wards (OR 2.79 [2.04-3.80]), female sex (OR 1.34 [1.10-1.63]) and a history of stroke (OR 1.47 [1.17-1.86]), while the presence of a contraindication to DOAC decreased the chance of correction (OR 0.10 [0.06-0.18]). Conclusion Hospitalization for any reason may contribute to correction of errors in AC treatment in patients with AF. Unfortunately, a significant portion of patients remains inadequately treated by both outpatient and inpatient providers. more...

Background Family history of heart disease (FH‐HD) is associated with an increase drisk of subsequent HD. High sensitive cardiac troponin T (hs‐cTnT) is arecognized biomarker of myocyte injury even in HD free patients. We examined the association between FH‐HD and hs‐cTnT in apparently healthy individuals. Hypothesis FH‐HD is associated with elevated hs‐cTnT in apparently healthy individuals. Methods In a cross sectional study we analyzed data of apparently healthy individuals (n=3,821) recruited for the Tel‐Aviv Medical Center Inflammation Survey (TAMCIS). Blood samples were obtained for hs‐cTnT and high sensitive CRP (hs‐CRP) among other tests. FH‐HD was defined as first degree family member with HD diagnosis and classified as premature if the diagnosis was done before the age of 55 for men or 65 for women. Results Elevated hs‐cTnT (>14 ng/L) was more common in FH‐HD of any age, and in premature FH‐HD (FH‐P‐HD) participants than in participants without FH‐HD (4.4% vs 2.0%, p3 mg/L) increased the risk for elevated hs‐cTnT (OR=3.07, p=0.036 for FH‐HD and OR=3.25, p=0.053 for FH‐P‐HD). Conclusions FH‐HD and its interaction with elevated hs‐CRP levels were significantly associated with elevated hs‐cTnT in apparently healthy individuals suggesting that an inflammatory process may be involved in this association. more...

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. more...

Introduction C-reactive protein (CRP) is a marker commonly used in clinical practice as a reference for the inflammatory activity in vivo. Low levels are often associated with good health and lower risk for adverse outcomes. Patients and methods We examined medical records of the last 6 years, of all patients admitted for hospitalization in internal medicine wards who had the first CRP measurement below ≤ 0.03 mg/L (detection limit). Diagnosis criteria and 7 days’ survival were reviewed. Results Out of 61,590 total admissions to internal medicine wards, three hundred and thirteen patients had CRP equal to or lower than 0.03 mg/L (0.5%). Second CRP measurement revealed gradual increment up to 10.8 ± 35.4 mg/L. Four patients died within 7 days from admission. Discussion Presentation to the internal medicine department with a very low concentration of CRP is highly unusual, but it does not exclude the existence of significant acute morbidities. Clinicians should take additional CRP tests before any conclusion is considered regarding the presence or absence of an inflammatory response. more...

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. more...

Maintaining hemodynamic stability during the induction and maintenance of anesthesia is one of the challenges of the anesthesiologist. Patients with vascular disease are at increased risk of instability due to imbalance between the sympathetic and parasympathetic parts of the autonomic nervous system, a balance accessible by serum cholinesterase activity. We aim to characterize the dynamics of cholinesterase activity in patients undergoing general anesthesia (GA) and surgery. This was a prospective study of 57 patients undergoing ambulatory or vascular surgery under GA. Cholinesterase activity was measured before the induction of anesthesia, after 15 min and at the end of surgery by calculating the capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase to hydrolyze AcetylThioCholine. Data on atherosclerotic disease, anesthesia management were analyzed. Both AChE and total cholinergic status (CS) decreased significantly after GA induction at 15 min and even more so by the end of surgery. Vascular surgery patients had lower baseline cholinesterase activity compared to ambulatory surgery patients. Patients requiring intraoperative administration of phenylephrine for hemodynamic support (21.1%) had a significantly lower level of AChE and CS compared to untreated patients. Our findings serve as a mirror to the sympathetic/parasympathetic imbalance during GA, with a marked decrease in the parasympathetic tone. The data of a subgroup analysis show a correlation between low cholinesterase activity and an increase in the need for hemodynamic support. more...

AIM Increased ratio between the right and left ventricular (RV/LV) diameters ≥1 is considered an important imaging marker for risk stratification among patients diagnosed with acute pulmonary embolism (PE). Our goal was to assess the prevalence of RV/LV≥1 among consecutive patients undergoing computed tomography pulmonary angiography, and to compare the prevalence of RV/LV≥1 between patients with and without PE. METHODS Retrospective analysis of consecutive patients who underwent computed tomography pulmonary angiography due to clinical suspicion of PE between January 1, 2014 and December 31, 2014. The axial RV/LV diameters were measured. The prevalence of RV/LV ≥1 was compared between patients with and without PE and among PE patients, between those with central versus peripheral PE. RESULTS The final cohort included 862 patients. A total of 142 (16.5%) had PE. RV/LV ≥1 was found in 553 (64.1%) of all patients, of them in 453 (63%) patients without PE and in 100 (70.4%) patients with PE (P=0.117). On multivariate analysis, PE was not significantly associated with RV/LV ≥1 (odds ratio [OR]: 1.4; 95% confidence interval [CI]: 0.9-2.1; P=0.102). There was no significant difference in the prevalence of RV/LV ≥1 among patients with central versus peripheral PE distribution (79.5% vs. 67%, P=0.101). Older age (OR: 1.03; 95% CI: 1.02-1.04; P more...

Elevated C-reactive protein (CRP) was shown to be associated with an increased risk for new-onset atrial fibrillation (AF) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI); however, the optimal time frame to measure CRP for risk stratification is not known.To evaluate the relation between the change in CRP over time (CRP velocity [CRPv]) and new-onset AF among STEMI patients treated with primary PCI.We included 801 STEMI patients who underwent PCI between 2007 and 2017 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 hours after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements. Patient medical records were reviewed for occurrence of new-onset AF.New onset AF occurred in 45 patients (6%). Patients with new onset AF had significantly higher median CRPv (1.27 vs. 0.43 mg/l/h, P = 0.002). New-onset AF during hospitalization occurred in 3.4%, 4.5 %, and 9.1% of patients in the first, second and third CRPv tertiles, respectively (P for trend = 0.006). In a multivariable logistic regression, adjusting for clinical variables the odds ratios for new onset AF was 1.93 (95% confidence interval 1.0-3.59, P = 0.04) for patients in the third CRPv tertile.CRPv might be an independent and rapidly measurable biomarker for new-onset AF following primary PCI in STEMI patients. more...

Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results when accessing the patient with infectious disease while on TCZ. We conducted this study to report cases treated with tocilizumab who developed serious infections with special reference to levels of CRP and to review the literature on the effect of tocilizumab on acute phase response (APR) during infections. Methods: The files of RA and GCA patients hospitalized in the Tel Aviv medical center between 2009–2019 were reviewed. Cases of patients with RA and GCA treated with tocilizumab who were hospitalized due to severe infections were reviewed with special emphasis on the duration of treatment, type of infection, and APR. Results: We identified nine admissions. Seven patients were treated with tocilizumab for RA, two for GCA. The diagnosis was pneumonia in three cases, osteomyelitis in one, cellulitis in one, endocarditis due to Whipple disease in one, abscess of cervix uteri in one, meningitis in one, and perforated diverticulitis in one. The mean CRP levels on admission were 4.75 mg/L (normal range, up to 5 mg/L). All cases were diagnosed correctly on admission. Conclusions: CRP levels may not correctly reflect the severity of infectious diseases during tocilizumab treatment. Increased awareness of the masking effect of tocilizumab on the APR during infection is needed in order to avoid a delay in the diagnosis. more...

ObjectiveTo predict breast cancer (BC) and prostate gland cancer (PGC) risk among healthy individuals by analyzing routine laboratory measurements, vital signs and age.Materials and MethodsWe analyzed electronic medical records of 20,317 healthy individuals who underwent routine checkups, encompassing more than 600 parameters per visit, and identified those who later developed cancer. We developed a novel ensemble method for risk prediction of multivariate time series data using a random forest model of survival trees for left truncated and right-censored data.ResultsUsing cross-validation, our method predicted future PGC and BC 6 months before diagnosis, achieving an area under the ROC curve of 0.62±0.05 and 0.6±0.03 respectively, better than standard random forest, Cox-regression model and a single survival tree. Our method can complement existing screening tests such as clinical breast examination and mammography for BC, and help in detection of subjects that were missed by these tests.DiscussionComputational analysis of results of routine checkups of healthy individuals can improve the detection of those at risk of cancer development.ConclusionOur method may assist in early detection of breast and prostate gland cancer. more...

Atherosclerotic patients challenge the anesthesiologist as they display a significant instability between the two parts of the autonomic nervous system. We aimed to assess the effect of general anesthesia (GA) and surgery on serum cholinesterase activity. Prospective study of 57 patients undergoing ambulatory or vascular surgery under GA. Cholinesterase levels were measured before induction of anesthesia, 15 minutes thereafter and at the end of surgery by measuring the capacity of serum Acetylcholinesterase (AChE) and Butyrylcholinesterase to hydrolyze AcetylThioCholine. Data of atherosclerotic disease, anesthesia management were analyzed.Both AChE and total Cholinergic Status (CS) decreased significantly after GA induction at 15 minutes and furthermore by the end of surgery. Vascular surgery patients, presented lower baseline cholinesterase activity compared to patients for ambulatory surgery. In patients requiring intraoperative administration of phenylephrine for hemodynamic support (21.1%), a significant lower level of AChE and CS was observed compared to untreated patients. A positive correlation was found between the lowest temperatures measured and the AChE and CS change from the baseline values. Our findings serve as a mirror to the sympathetic/parasympathetic disbalance during GA with a marked decrease in the parasympathetic tone. Our data show that low cholinesterase activity increase the need for hemodynamic support. more...

Pulmonary hypertension (PH) is often diagnosed late in the disease course. As many patients may undergo computed tomography pulmonary angiography (CTPA) for exclusion of pulmonary embolism (PE), we aimed to create a model that can detect the existence of PH and grade its severity. Consecutive patients who underwent CTPA which was negative for PE, and echocardiography study within 24 h, were included. The CT parameters evaluated to assess PH were: the diameters of the main pulmonary artery (MPA), ascending aorta (AA), calculation of each heart chamber volume, and the severity of reflux of contrast material. Randomly, 70% of patients were included in the model creation group, and 30% were used to validate the model. The final study group included 740 patients, 268 male patients, median age 72 years. 374 patients (51%) had PH, of them 94 (13%) had severe PH on the echocardiography. Right atrium (RA) and Left atrium (LA) volume indices were the strongest parameter to indicate PH (area under the curve, AUC = 0.738 and 0.736, respectively), while Right ventricle (RV) and RA volume indices were the strongest parameter to identify severe PH (AUC = 0.735 and 0.715, respectively) with MPA diameter being the least influential indicator (AUC = 0.623). Using the patients age, gender, and multiple CTPA parameters, we created a model for predicting the existence of severe PH. After validation, the model demonstrated 91% sensitivity and a negative predictive value of 97%. Applying our models, CTPA can be used to identify severe PH immediately after the completion of CTPA exam. more...

Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease.To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE.We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results.Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT)81 msec (P = 0.04), stroke volume44 cc (P = 0.005), and RIMP0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function.Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE. more...

A first C-reactive protein (CRP) test, as often performed by clinicians during the presentation of patients with an acute bacterial infection, might be misleading. The aim of our study was to explore the dynamic between a second CRP test taken within 12 hours from admission CRP test in a cohort of patients diagnosed with acute bacterial infection in comparison to CRP in a control group of apparently healthy individuals. This was a historical cohort study comprised of all patients admitted to the Sourasky Tel-Aviv Medical Center, Israel, between July 2007 and March 2016. The study cohort included adult patients who were diagnosed as having an infection, assumed to be of bacterial etiology (cellulitis and erysipelas, pneumonia, cholecystitis, pyelonephritis, or septicemia), who had a CRP test during the first 6 hours of hospital admission (baseline CRP), and a successive CRP test up to 12 hours from the first one (recurrent CRP). The control group was of healthy subjects who attended our medical center for a routine annual check-up. The study included 950 patients. Baseline CRP ranged from 0.04 to 454 mg/L. The median CRP velocity was 0.53 mg/L/h. Patients were grouped by baseline CRP into 4 groups (CRP more...

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.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.We included 128 NAAION patients and 512 controls. No significant differences were found between patients and controls regarding the inflammatory biomarkers.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. more...

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.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.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).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. more...

Objective Subclinical myocardial dysfunction has been reported to occur early in systemic lupus erythematous (SLE). The study aim was to search for biomarkers of subclinical myocardial dysfunction which may correlate with disease activity in SLE patients. Methods This is a prospective, controlled, cross-sectional study of 57 consecutive patients with SLE and 18 controls. Serum samples were obtained to determine serum soluble ST2 (sST2), CXCL-10 and high-sensitivity troponin (hs-troponin) levels. All participants underwent an echocardiographic tissue Doppler study. Results sST2, CXCL-10 and hs-troponin levels were higher in patients with higher SLE disease activity (SLEDAI). sST2 and CXCL-10 levels were higher in patients with more disease damage as measured by the SLE damage index. Measures of diastolic dysfunction, as assessed by echocardiographic tissue Doppler negatively correlated with log CXCL-10: including E/A; E/e′lateral and E/e′septal, while E/e′ positively correlated with CXCL-10. Diastolic dysfunction parameters also correlated with log sST2 levels, a negative correlation was seen with E/e′lateral and a positive correlation was seen with E/e′. Systolic dysfunction parameters positively correlated with hs-troponin: LVED, LVES, IVS, LVMASS and LVMASS index. In a multivariate analysis, sST2 and CXCL-10 were found to be significantly different in SLE vs. healthy controls, independent of each other and independent of cardiovascular risk factors. Conclusions Soluble ST2 and CXCL-10 are markers of disease activity and accrued damage in SLE and may serve as sensitive biomarkers for detection of subclinical diastolic dysfunction, independent of traditional cardiovascular risk factors. more...

Low C-reactive protein in acute bacterial infections could convey the erroneous impression of a mild infection. We focussed on gram-negative bacteraemia, a phenomenon frequently seen at the emergency room.Of 2200 patients with gram-negative bacteraemia, 460 patients with first C-reactive protein30 mg/L and 460 patients with C-reactive protein187 mg/L were reviewed. Following exclusions, we finally investigated 229 and 289 patients with low and high C-reactive protein concentrations, respectively.The cohort was divided into low and high C-reactive protein groups. Median first C-reactive protein was 13.6 and 219.9 mg/L, respectively (interquartile range 6.4-21.6 and 195-270.1). Compared to patients with first high C-reactive protein, patients with first low C-reactive protein concentrations had a significant five-fold higher C-reactive protein level with their second test.Patients with gram-negative bacteraemia can present with C-reactive protein within the range of apparently healthy individuals. A second C-reactive protein might help to avoid an erroneous decision regarding the severity of the infection. more...

Background While chronic respiratory diseases are among the leading causes of mortality and morbidity worldwide, little is known about the effect of blood eosinophil levels on lung function trajectories among healthy individuals. Methods We analyzed data of apparently healthy individuals (n=18,089) recruited for the Tel Aviv Medical Center Inflammation Survey. Blood eosinophil levels were compared between participants with normal and those with abnormal lung function. Multivariate regression was used to assess the OR of forced expiratory volume in 1 second (FEV1) deterioration according to baseline eosinophils in subjects with normal lung function (n=4,141) during a follow-up period of 4 years. Results Participants with an abnormal, as opposed to a normal, pulmonary function test (PFT) (n=1,832, 10.1%) had significantly higher eosinophil levels, expressed as a percentage or count (2.99%±2.00% compared to 2.67%±1.88% and 0.2210e3/µL±0.163/µL compared to 0.1810e3/µL±0.183/µL, respectively; P more...

Background: Currently, normal values of the cardiac chambers' volumes are adjusted only for gender and body surface area (BSA). We aim to investigate the association between the heart rate and the volume of each of the four cardiac chambers using cardiac-gated computed tomography angiography (CCTA). Methods: A total of 350 consecutive patients without known cardiac diseases or significant (>50%) stenosis undergoing CCTA between January 2009 and June 2014 for suspected coronary artery disease were included. Cardiac chamber volumes adjusted to BSA were calculated using automated model-based segmentation analysis software of the CCTA data and correlated with patients' mean heart rate during the scan. Results: There were 240 men and 110 women, median interquartile range age was 55 years (47–61). Women were older 59.0 years (53.7–64) versus 52.0 years (45.0–59.0), had higher prevalence of hyperlipidemia, diabetes mellitus, anemia, and hypothyroidism, and higher median heart rates 64.0 (59.7–66.0) versus 60.0 (55.0–65.0) (p more...

Studies performed in controlled laboratory conditions have shown that environmental thermal application may induce various circulatory changes. We aimed to demonstrate the effect of local climate on hemodynamics according to echocardiography. Echocardiographic studies conducted in ambulatory patients, 18 yr of age or older, between January 2012 and July 2016, at our medical center, for whom climate data on the day of the echocardiogram study were available, were retrospectively included in case climate data. Discomfort index, apparent temperature, temperature-humidity index, and thermal index were computed. Echocardiograms conducted in hotter months (June–November) were compared with those done in colder months (December–May). The cohort consisted of 11,348 individuals, 46.2% women, and mean age of 57.9 ± 18.1 yr. Climate indexes correlated directly with stroke volume ( r = 0.039) and e′ (lateral r = 0.047; septal r = 0.038), and inversely with systolic pulmonary artery pressure (SPAP; r = −0.038) (all P values < 0.05). After adjustment for age and sex, echocardiograms conducted during June–November had a lower chance to show e′ septal < 7 cm/s (odds ratio 0.88, 95% confidence interval 0.78–0.98, P = 0.017) and SPAP > 40 mmHg (odds ratio 0.81, 95% confidence interval 0.67–0.99, P = 0.04) compared with those conducted in other months. The authors concluded that climate may affect hemodynamics, according to echocardiographic assessment in ambulatory patients. NEW & NOTEWORTHY In the present study, we examined 11,348 individuals who underwent ambulatory echocardiography. Analyses of the echocardiographic studies demonstrated that environmental thermal stress, i.e., climate, may affect hemodynamics. Most notably were the effects on diastolic function. Higher values of mitral e′, stroke volume, as well as ejection fraction, and lower values of systolic pulmonary artery pressure and tricuspid regurgitation were demonstrated on hotter days and seasons. more...

Aims To demonstrate the association between small left atria (LA) and outcome in a relatively large heterogeneous population of hospitalized patients. Methods and results In a single-centre retrospective study, all inpatients that underwent an echocardiographic assessment between 2011 and 2016 and had an available left atrial volume index (LAVI) measurement were included. The cohort consisted of 17 343 inpatients who had an available LAVI measurement, 288 with small LA (LAVI 45 mL/m2). Median follow-up time was 2.4 years. After adjustments for age, gender, and baseline characteristics with a P-value Conclusion Small LA are independently associated poorer short- and long-term mortality. LA volume should be referred to as J-shaped in terms of mortality. Helsinki committee approval number 0170-17-TLV. more...

Background Only few studies of living kidney donors have included controls that were similarly healthy, including excellent kidney function. Methods In this study, we aimed to estimate long term metabolic and renal outcome in a cohort of 211 living donors compared to two control groups: paired-matched controls, and another control group of 2534 healthy individuals with excellent kidney function. Results Donors presented with higher estimated Glomerular Filtration Rate (eGFR): (97.6 ± 15.2 vs 96.1 ± 12.2 vs 94.5 ± 12.4 ml/min/1.73m2) and lower urine albumin to creatinine ratio (UACR) (4.3 ± 5.9 vs 5.9 ± 6.1 vs 6.1 ± 6.9 mg/g) for donors, matched controls and healthy controls, respectively (p more...

Background Exercise induced albuminuria (EiA) is elevated in patients with metabolic dysfunction and diabetes, and may serve as an early biomarker for endothelial dysfunction and “kidney reserve”. However, the change in EiA levels over time and its interaction with metabolic dysfunction and glucose metabolism has never been studied. Therefore, we sought to determine EiA levels over time in a cohort of individuals attending a routine annual health survey. Methods We prospectively enrolled 412 patients attending an annual healthy survey at our Medical Center. We collected urine samples for albumin and creatinine measurements before and immediately after completing an exercise stress test, along with multiple physiologic and metabolic parameters. Participants returned to a second follow up visit after a mean follow up period of 3 years (± 1.7 SD). Results Patients with diagnosed diabetes and subjects with HbA1c ≥ 6.5% significantly increased their EiA over time (median [IQR] change between visits = 19.5 [− 10.4–56.1] vs. − 1.1 [− 12.7–4.9] (p = 0.049) for diabetics vs non-diabetics respectively). Moreover, a diabetes diagnosis was significantly associated with a high increase in EiA over time (top 10th percentile) even after adjusting for age, BMI, eGFR, METs, self-reported history of heart disease, systolic and diastolic blood pressure; OR = 4.4 (1.01–19.3 95% CI) (p = 0.049). Finally, elevated fasting blood glucose (≥ 100 mg/dl) was the strongest and only significant predictor for a greater increase in EiA over time after adjusting for all five metabolic syndrome components; blood glucose, waist circumference, blood triglycerides, HDL cholesterol, and BP criteria; OR = 4.0 (1.6–9.8 95% CI) (p Conclusions Patients with diabetes and/or elevated fasting blood glucose increase their exercise-induced urinary albumin excretion over time. The ability of EiA to predict major clinical outcomes in patients with and without diabetes needs to be determined in future studies. more...

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. more...

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 (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. more...

Background Imbalanced autonomic nervous system (ANS) activity is associated with poor cardiovascular outcome. However, clinically validated biomarkers to assess parasympathetic function are not yet available. We sought to evaluate parasympathetic dysfunction by measuring serum cholinesterase activity and to determine its relationship to high sensitive cardiac troponin T (hs-cTnT) as well as traditional non-invasive parameters of ANS function during exercise in apparently healthy individuals. Methods We enrolled 1526 individuals (mean age 49 ± 11 yr., 75% men) from the Tel Aviv Medical Center Inflammation Survey (TAMCIS). We used the acetylcholine (ACh) analog acetylthiocholine (ATCh) as a substrate that is hydrolyzed by both ACh degrading enzymes and reflects the total serum capacity for acetylcholine hydrolysis, referred to as cholinergic status (CS). All subjects performed a cardiac stress test reviewed on the spot by a cardiologist and multiple physiological and metabolic parameters including hs-cTnT were measured. Results CS values at rest predicted multiple exercise-hemodynamic changes. Heart rate recovery after exercise was inversely correlated to CS values (p 5 ng/L) presented with elevated CS levels compared to women with undetectable levels; 1423 ± 272.5 vs 1347 ± 297.9 (p = 0.02). An opposite trend was observed in men. Metabolic dysfunction parameters were also associated with CS elevation in both men and women. Conclusions Parasympathetic dysfunction assessed by total serum cholinesterase activity predicts hemodynamic changes during exercise. CS is also associated with hs-cTnT detection in women and inversely so in men. Future studies to assess the potential clinical use of this new sex-specific biomarker in cardiovascular disease risk stratification are warranted. Graphical Abstract Electronic supplementary material The online version of this article (10.1186/s10020-018-0063-0) contains supplementary material, which is available to authorized users. more...

Metabolic syndrome (MetS) and high-sensitivity cardiac troponin T (hs-TnT) are associated with higher risk for cardiovascular diseases (CVD). Our aim was to assess the relation between hs-TnT elevation and MetS in a general population sample.Individuals participating in an annual health survey program between 2010 and 2016 were included in the study. Blood samples including hs-TnT levels were collected. The study population was divided into three groups based on hs-TnT levels - undetectable (5 ng/L), intermediate (5-14 ng/L) and elevated (14 ng/L).A total of 5994 subjects were included in the study, the mean age was 48.5 and 4336 (72%) were males. Compared with subjects with undetectable hs-TnT the prevalence of MetS was higher in those with detectable and elevated levels - 392 (10%) vs. 270 (15%) and 51 (33%), respectively (p 0.001). In a multivariate model adjusted for age, gender and multiple co-morbidities, the number of MetS components and presence of MetS were significantly associated with an increased risk for detectable hs-TnT levels (OR = 1.02 {for each component}; 95% CI [1.00-1.05], p = 0.04) and (OR = 1.13; 95% CI [1.07-1.2], p 0.001) respectively. Only the waist, glucose and hypertension components of the MetS were significantly associated with elevated troponin.The MetS and its distinct components have a cumulative impact on hs-TnT levels in apparently healthy subjects. more...

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 90 mL/min/1.73 m2. 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 . more...

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. more...

Introduction: Patients with diabetes are prone to infections. An elevated C-reactive protein (CRP) level indicates an underlying infection/inflammation; hence, a reliable point-of-care (POC) CRP measurement, independent of glucose level, would be advantageous in rapid detection of an inflammatory process and allowing for appropriate therapy in a timely manner. Methods: A validation study of patients with type 2 diabetes mellitus diagnosed with an inflammatory condition either infectious or non-infectious underwent a capillary CRP measurement on the same blood drop used for the measurement of capillary glucose level. Results: 154 samples from patients with diabetes across a broad range of CRP levels that underwent capillary CRP measurement, demonstrating a linear profile of the dynamic range compared with the wide range CRP assay, with significant correlation of R2 = 0.9 and a slope of 0.98 (95% C.I: 0.91–1). Bland Altman analysis, presents a positive bias profile; the total difference between assays is 6.6 mg/L. The mean bias between methods is 13.34% (C.I 95% 9.8–17.5%). The total agreement between the methods is 89%, the observed Kappa index is: 0.71 with confidence interval of 0.57–0.84 indicating substantial agreement between the methods. C-reactive protein level is independent of glucose concentration. Conclusion: Point-of-care capillary CRP testing is a useful mean of early detection of infection/inflammation in patients with diabetes and enables the treating physician to rapidly assess and treat the patients underlying inflammatory process. more...

Impaired sympathetic/parasympathetic response, expressed by elevated Acetylcholinesterase (AChE) is associated with obesity, metabolic syndrome and inflammation. However, the association between morbid obesity and AChE and the changes in cholinergic tone following bariatric laparoscopic sleeve gastrectomy (LSG) surgery-induced weight reduction were never analyzed. Two studies are presented; the first (the “apparently healthy cohort”) was a cross-sectional study and the second (the “LSG cohort”) was a prospective-cohort study with 12 months of follow-up. The “apparently healthy cohort” included 1450 apparently healthy participants who volunteered to the Tel-Aviv Medical Center Inflammation Survey (TAMCIS) during a routine annual checkup visit. The “LSG cohort” included 77 morbid obese patients before and at 3, 6, and 12 months following LSG surgery. Main outcomes included anthropometric measurements, Hemoglobin A1c (HbA1C), serum AChE, insulin test and Homeostasis Model Assessment (HOMA). Among the TAMCIS participants, serum AChE activity increased with BMI in a dose-dependent manner until it reached a peak level at BMI of 30–35 kg/m², followed by a plateau. Following LSG, a significant decrease in AChE activity between baseline and 12 months post-surgery was found for men, but not for women (−122.2 ± 135.3, P more...

Objective This study sheds light on the importance of long-term follow-up of trauma survivors, posttraumatic stress disorder (PTSD) trajectories, and early detection of health risk factors in trauma survivors. The present study prospectively assessed the following over 23 years: (1) the association of psychological and physiologic stress during captivity with elevated C-reactive protein (CRP) levels and metabolic syndrome (MetS), which includes hypertension; elevated levels of insulin, triglycerides, and fasting glucose; decreased levels of high-density lipoprotein cholesterol; and obesity and (2) the implication of PTSD trajectories in elevated CRP levels and MetS. Methods Measurements were taken in 1991, 2003, 2008, and 2015. Participants were 116 Israeli combat veterans of the 1973 Yom Kippur War (of these, 101 were former prisoners of war [ex-POWs] and 15 were comparable controls). The medical assessments relevant for this study were body mass index, fasting blood glucose levels, and diabetes, blood pressure or a diagnosis of hypertension, high-density lipoprotein cholesterol and triglyceride levels, and medication intake. In addition, the PTSD Inventory was used to assess PTSD symptoms and trajectories over time according to DSM-IV-TR PTSD criteria. Results Captivity-in particular, the captivity stressors of weight loss, physical suffering, psychological suffering, and humiliation-was implicated in both elevated CRP levels and MetS, significantly so with elevated CRP levels (P = .01, R² = 0.33). Captivity-induced PTSD, in particular chronic and delayed PTSD trajectories, was associated with elevated CRP levels and MetS, significantly so for MetS (P = .05). Conclusions Monitoring inflammation using markers like CRP level in trauma survivors can be beneficial, particularly if PTSD is chronic or delayed. Clinicians treating trauma survivors should raise awareness of the importance of such measures in light of long-term health vulnerabilities. more...

Objectives: To evaluate the association between very small left atria (VSLA) on nongated computed tomography pulmonary angiography (CTPA) and mortality in patients without pulmonary embolism (PE). Methods: Patients who underwent nongated CTPA between 2011 and 2015 in order to rule out PE, and had an echocardiogram within 24 h of the CTPA, were retrospectively identified. The left atrial volume of nongated CTPA was calculated using automatic 4-chamber volumetric analysis software. The association between the lowest 5th percentile of the left atrial volume index, referred to as the VSLA group, and mortality was investigated after adjustment for age, gender, background diseases, and laboratory values. Results: The study cohort included 241 patients. Patients with VSLA had a left atrial volume index 2 (n = 11). Demographics and background diseases did not differ between the study groups. The median follow-up was 22.7 months (IQR 0.03-54.3). VSLA was an independent predictor of mortality (HRadj = 3.6; 95% CI 1.46-8.87; p = 0.005), along with malignancy (HRadj = 2.28; 95% CI 1.32-3.93; p = 0.003) and lower hemoglobin (HRadj = 0.86; 95% CI 0.76-0.99; p = 0.032). Conclusions: Our findings suggest that VSLA on nongated CTPA may serve as a marker for mortality. The use of CTPA volumetric analysis can help risk stratification in patients with dyspnea and no PE. more...

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.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.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).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. more...