Hypersensitivity reactions to anti-SARS-CoV-2 vaccines: Basophil reactivity to excipients.

Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional allergy diagnostics but its role in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related hypersensitivity is ill-defined. Therefore, 89 patients with possible hypersensitivity (56 % with delayed mucocutaneous manifestations) to anti-SARS-CoV-2 vaccines were tested with BAT for Macrogol 3350, DMG-PEG 2000, PEG 20000, polysorbate-80 and trometamol and compared to 156 subjects undergoing pre-vaccine BAT. A positive BAT was associated with delayed reaction onset (p = 0.010) and resolution (p = 0.011). BAT was more frequently positive to DMG-PEG 2000 than to other excipients in both groups (p < 0.001). DMG-PEG 2000 reactivity was less frequent in vaccine-naïve (6 %) than vaccinated subjects (35 %, p < 0.001) and associated with mRNA-1273 vaccination. DMG-PEG 2000 BAT might therefore have a diagnostic role in subjects with delayed hypersensitivity reactions. Natural immunity might be a key player in basophil activation.

Particulate Matter Exposure and Allergic Rhinitis: The Role of Plasmatic Extracellular Vesicles and Bacterial Nasal Microbiome.

Particulate matter (PM) exposure is linked to the worsening of respiratory conditions, including allergic rhinitis (AR), as it can trigger nasal and systemic inflammation. To unveil the underlying molecular mechanisms, we investigated the effects of PM exposure on the release of plasmatic extracellular vesicles (EV) and on the complex cross-talk between the host and the nasal microbiome. To this aim, we evaluated the effects of PM10 and PM2.5 exposures on both the bacteria-derived-EV portion (bEV) and the host-derived EVs (hEV), as well as on bacterial nasal microbiome (bNM) features in 26 AR patients and 24 matched healthy subjects (HS). In addition, we assessed the role exerted by the bNM as a modifier of PM effects on the complex EV signaling network in the paradigmatic context of AR. We observed that PM exposure differently affected EV release and bNM composition in HS compared to AR, thus potentially contributing to the molecular mechanisms underlying AR. The obtained results represent the first step towards the understanding of the complex signaling network linking external stimuli, bNM composition, and the immune risponse.

Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study.

BACKGROUND: High-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA. METHODS: A consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0-1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features. RESULTS: 528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, p = 0.004 and 2.02, p = 0.012 for LAP and RI > 1.1, respectively) with borderline association with LAP-Vol (OR 1.52, p = 0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, p = 0.003 and 1.04, p = 0.002 for LAP-Vol, respectively). CONCLUSIONS: Our results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.

Occupational asthma and rhinitis due to wheat flour: sublingual specific immunotherapy treatment.

BACKGROUND: There are several potential sensitizers in the bakery environment and wheat flour appears to be the dominant sensitizer in most bakeries. Apart from traditional drug therapy or a change in profession, there are no effective therapies for workers who develop serious respiratory symptoms in the workplace. OBJECTIVES: To describe clinical and laboratory findings in workers with asthma and/or rhinitis induced by wheat flour who underwent sublingual specific immunotherapy (SLIT). METHODS: Since drug therapy and prevention strategies were not effective, five bakers were elected to undergo SLIT. A three-year study was led by administering a sublingual wheat flour extract. Questionnaires, allergy and respiratory tests were performed before and after SLIT. RESULTS: After SLIT an improvement in symptoms is observed in every patient: Asthma Control Test and a quality-of-life questionnaire show higher scores and as a result, workers have reduced the use of drug therapy. We observed significantly reduced exhaled nitric oxide (FeNO) and eosinophil cationic protein (ECP) levels after SLIT, hypothesizing that these parameters may be used to monitor the effectiveness of immunotherapy. The improvement of FEV1 (forced expiratory volume in 1second) and responsiveness to bronchoprovocative tests with methacholine denotes a possible role of SLIT in treating patients with low-respiratory tract involvement, even though more data are needed. DISCUSSIONS: This is the first report in the literature on the use of SLIT for baker's asthma and rhinitis. SLIT for occupational wheat flour allergy should be possible and efficient, saving vocational training, professionalism, and avoiding job loss.

Pilot study on non-celiac gluten sensitivity: effects of Bifidobacterium longum ES1 co-administered with a gluten-free diet.

BACKGROUND: Bifidobacterium longum ES1 is a strain probiotic, colonizing the human gut and capable of a degradative action on gliadin. In an attempt to find new nutritional solutions aimed at improving the quality of life of patients with non-celiac gluten sensitivity (NCGS) we evaluated the effectiveness of this strain, in association with a gluten-free diet, comparing its efficacy versus diet therapy alone. METHODS: The experimental design included a non-randomized, open-label, 1:1 intervention study in parallel groups. Enrolled patients with symptoms attributable to NCGS, and with negative diagnoses of both wheat allergy and celiac disease, were included in this three-month trial divided into four outpatient visits (baseline, T1, T2 and T3). Fifteen patients for each group completed the experimental protocol. RESULTS: Our results showed that a combination of diet and probiotic determined a more significant reduction in the frequency and intensity of intestinal and extra-intestinal symptoms, and a clear improvement in stool consistency. CONCLUSIONS: Although the study was carried out on a small number of patients, the results of our pilot trial suggest that a combined strategy of naturally gluten-free diet therapy with administration of the probiotic strain ES1 appears to offer a greater advantage than the dietary regime alone in improving the clinical symptomatic picture and in stabilizing the intestinal microbiota.

Coronary Plaque Features on CTA Can Identify Patients at Increased Risk of Cardiovascular Events.

OBJECTIVES: This study sought to assess whether coronary atherosclerosis analysis by coronary computed tomography angiography (CTA) may improve prognostic stratification among patients with diffuse coronary artery disease (CAD) BACKGROUND: Coronary CTA has recently emerged as a promising noninvasive tool for advanced analysis of coronary atherosclerosis. METHODS: The multicenter CAPIRE (Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation) study is part of the GISSI Outlier Project. A prospective cohort of subjects who underwent coronary CTA for suspected CAD was enrolled. Based on risk factor (RF) burden, patients were defined as having a low clinical risk (0 to 1 RF with the exclusion of patients with diabetes mellitus as single RF) or at high clinical risk (3 or more RFs). Patients with 2 RFs were not enrolled in the study. Coronary CTA advanced plaque assessment was performed. Outcome measures were 3 combined endpoints: acute coronary syndrome (ACS), cardiac death + ACS, and cardiac death + ACS + late revascularization. RESULTS: Among the 544 patients enrolled in the CAPIRE study, in 522 patients, a mean follow-up of 37 ± 10 months was obtained (16 patients were excluded due to 1 < segment involvement score <5 at core lab coronary CTA analysis and 6 patients were lost at follow-up). Higher atherosclerotic burden was found in patients with higher clinical risk, but prevalence of elevated noncalcified plaque volume did not significantly differ between low- versus high-risk patients. Quantitative plaque parameters by coronary CTA were associated with composite endpoints at multivariable analysis when corrected for univariate predictors. Elevated noncalcified plaque volume, expressed as dichotomic variable, was associated with all combined endpoints. Even if the low absolute number of events represents a limitation to the present study, patients with low noncalcified plaque volume had similar risk of cardiac events independently from the presence of multivessel disease, while patients with high noncalcified plaque volume had higher rates of cardiac events. CONCLUSIONS: The CAPIRE study confirmed the prognostic value of atherosclerosis assessment by coronary CTA, demonstrating high noncalcified plaque volume as the most ACS-predictive parameter in patients with extensive CAD. (GISSE Outliers CAPIRE [CAPIRE]; NCT02157662).

The imprinted gene Delta like non-canonical notch ligand 1 (Dlk1) associates with obesity and triggers insulin resistance through inhibition of skeletal muscle glucose uptake.

BACKGROUND: The imprinted gene Delta like non-canonical Notch ligand 1 (Dlk1) is considered an inhibitor of adipogenesis, but its in vivo impact on fat mass indeed remains elusive and controversial. METHODS: Fat deposits were assessed by MRI and DXA scanning in two cohorts of non-diabetic men, whereas glucose disposal rate (GDR) was determined during euglycemic hyperinsulinemic clamp. Blood analyte measurements were used for correlation and mediation analysis to investigate how age, BMI, and fat percentage affect the relation between DLK1 and GDR. Confirmatory animal studies performed in normal (NC) and high fat diet (HFD) fed Dlk1+/+ and Dlk1-/- mice included DXA scanning, glucose tolerance tests (GTTs), blood measurements, and skeletal muscle glucose uptake studies by positron emission tomography (PET), histology, qRT-PCR, and in vitro cell studies. FINDINGS: Overall, DLK1 is positively correlated with fat amounts, which is consistent with a negative linear relationship between DLK1 and GDR. This relationship is not mediated by age, BMI, or fat percentage. In support, DLK1 also correlates positively with HOMA-IR and ADIPO-IR in these humans, but has no linear relationship with the early diabetic inflammation marker MCP-1. In Dlk1-/- mice, the increase in fat percentage and adipocyte size induced by HFD is attenuated, and these animals are protected against insulin resistance. These Dlk1 effects seem independent of gluconeogenesis, but at least partly relies on increased in vivo glucose uptake in skeletal muscles by Dlk1 regulating the major glucose transporter Glut4 in vivo as well as in two independent cell lines. INTERPRETATION: Thus, instead of an adipogenic inhibitor, Dlk1 should be regarded as a factor causally linked to obesity and insulin resistance, and may be used to predict development of type 2 diabetes. FUND: The Danish Diabetes Academy supported by the Novo Nordisk Foundation, The Danish National Research Council (#09-073648), The Lundbeck Foundation, University of Southern Denmark, and Dep. Of Clinical Biochemistry and Pharmacology/Odense University Hospital, the Swedish Research Council, the Swedish Diabetes Foundation, the Strategic Research Program in Diabetes at Karolinska Institute and an EFSD/Lilly grant.

Basophil Activation Test Application in Drug Hypersensitivity Diagnosis: An Empirical Approach.

BACKGROUND: The diagnosis of drug hypersensitivity reactions (DHRs) is based both on clinical history and in vivo tests, such as specific IgE and cutaneous tests, when available. OBJECTIVES: The aim of this work was to evaluate the basophil activation test (BAT) as a supplementary tool for drug challenges and drug allergy diagnosis. METHOD: We evaluated 204 outpatients reporting DHRs. Available serum-specific IgE drugs were determined and cutaneous tests were performed when appropriate. BAT was performed immediately after blood sampling. The expression of CD63 was evaluated with flow cytometry. The test was considered positive when CD63 expression was > 5% and the stimulation index (the ratio of the percentage of CD63-expressing cells with drug exposure/percentage of CD63-expressing cells with wash buffer) was > 2. Patients who reported mild to severe reactions and those with a discrepancy between clinical history and BAT underwent a challenge test. RESULTS: The drugs that caused adverse reactions were mainly antibiotics (49%). Non-steroid anti-inflammatory drugs (NSAID) were cited as responsible for DHRs in 37%, with the remaining 14% being due to other drugs. BAT revealed a high specificity (92%) and low sensitivity for antibiotics (40%). For the suspected reactions to penicillin, both the in vitro tests supported 94% of the diagnoses. We also observed a high specificity in the case of challenge with NSAIDs (100% specificity). CONCLUSIONS: BAT is effective in discriminating adverse drug reactions, whilst only more critical cases require integrated evaluations and more complex clinical examinations. It is relevant that the concordance of anamnesis and in vitro tests reduce the need for challenge testing, limiting them to selected cases.

Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease.

OBJECTIVES: We explored the role of oxidative stress and inflammatory molecules as potential Parkinson (PD) biomarkers and correlated biological with non-motor abnormalities (olfactory impairment and dysautonomia), in patients with idiopathic REM behavior disorder (iRBD) (prodromal PD) and established PD. METHODS: We recruited 11 iRBD and 15 patients with idiopathic PD (Hohen&Yahr 1-3, on L-DOPA and dopamine agonists combination therapy) and 12 age- and sex-matched controls (CTRL). We measured total olfactory score (TOS), autonomic function [deep breathing (DB), lying to standing (LS) and Valsalva manoeuvre (VM) ratios], blood reduced glutathione (Br-GSH), oxidative stress and inflammatory markers (neopterin). RESULTS: Anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but absent in CTRL. Orthostatic hypotension was more common among iRBD (73%) and PD (60%) than in CTRL (25%). By univariable ordinal logistic regression, TOS, Br-GSH, LS and VM ratio worsened from CTRL to iRBD and PD groups. Only reduced Br-GSH levels (p=0.037, OR=0.994; 95%CI 0.988-1.000) were independently associated to PD. TOS correlated with Br-GSH (R=0.34, p=0.037), VM ratio (R=0.43, p=0.015), and neopterin (rho=0.39, p=0.016). CONCLUSIONS: Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular dysautonomia, a useful biomarker for an integrative, early diagnosis of PD.

[Basopil Activation Test (BAT) as a novel method for monitoring occupational exposure to Beta-lactams and intermediates of production]. / Utilizzo del test di attivazione dei basofili (BAT) nella sorveglianza sanitaria di lavoratori esposti a Beta--lattamici e ad intermedi di produzione.

BACKGROUND: Cutaneous tests and specific IgE are used in the diagnosis of allergy due to beta-lactans, although drug administration at therapeutic dosage is considered gold standard in drug allergy. OBJECTIVES: The diagnostic approach in symptomatic workers is more critical when they are exposed because of work, unlike reactions to drug in case of therapy. There is not a general consensus about markers in workers occupationally exposed to drugs. Indeed, basophil activation test (BAT) is a new and promising laboratory tool, particularly useful to test intermediate molecules involved in the production. In this article we show our experience on the health surveillance of workers exposed to beta lactams and intermediate molecule (7-ZACA) in a pharmaceutical industry. METHODS: We studied 15 workers divided into 3 groups: 5 exposed and symptomatic (group A), 5 exposed and asymptomatic (group B), 5 non exposed and asymptomatic (group C). RESULTS: BAT was positive for 7-ZACA in three subjects of group A, and in one subject of group B and one of group C. There was e concordance between clinical history, respiratory symptoms, and results of texts. It was possible to determine allergic nature of symptoms and sensitization in a preclinical phase, correctly discriminating symptoms related to irritants from the allergic ones. CONCLUSIONS: BAT, a simple and quick diagnostic procedure if compared to challenge, can be used as a useful and practical tool by occupational doctors for prevention measures, evaluation of ability to a specific job and reallocation of workers.

Inflammatory Markers and Genetic Polymorphisms in Workers Exposed to Flour Dust.

OBJECTIVE: The aim of this study is to evaluate inflammatory markers and pro-inflammatory CD14 and Toll-like Receptor 4 (TLR4) polymorphisms in workers exposed to flour dust. METHODS: Polymorphisms in TLR4 and CD14 were identified in our study population of 167 workers that included 63 healthy subjects (HS), 45 atopic subjects (A), and 59 subjects diagnosed clinically with occupational asthma/rhinitis (OAR). Endpoint measures in this study included fractional exhaled nitric oxide and serum concentrations of interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). RESULTS: We identified a polymorphism in CD14 (rs2569190) that may be differentially expressed (P = 0.06). IL-6 concentrations in the serum were significantly higher in the A and OAR groups (P < 0.01) than in subjects in the HS group, while IL-8 concentrations were significantly elevated only in the OAR group (P < 0.01). Interestingly, TNF-α concentrations in the OAR group were significantly reduced when compared with subjects in the HS group (P < 0.01). CONCLUSION: Cytokines are likely a defensive response in atopic and healthy workers. A protective genotype is hypothesized for occupational asthma.

Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population.

AIMS: Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting. METHODS AND RESULTS: Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR≤0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively. CONCLUSION: In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects.

Usefulness of High-Sensitivity Cardiac Troponin T for the Identification of Outlier Patients With Diffuse Coronary Atherosclerosis and Low-Risk Factors.

Novel high-sensitivity assay can detect very low levels of circulating cardiac troponin (hs-cTnT) in apparently healthy subjects. Within normal range, higher levels are associated with coronary artery disease (CAD) and cardiac abnormalities commonly associated to traditional risk factors (RFs) for CAD. Therefore, we investigated the relation between circulating hs-cTnT and CAD in patients with a spectrum of RF burden aiming to assess the added value of hs-cTnT to identify "outlier" patients with CAD despite a low RF burden. Hs-cTnT was measured in 525 stable patients without previous diagnosis of ischemic heart disease with 0 to 1 RF, excluded diabetes, (low-RF group, n = 263) or ≥2 RFs (multiple-RF group, n = 262) and without CAD (segment involvement score = 0) or diffuse CAD (segment involvement score >5) at coronary computed tomography angiography. Outlier patients with diffuse CAD despite low-RF burden had similar extent, severity, and plaque composition than patients with multiple RFs. Overall, hs-cTnT was measurable in 81% of patients with median value of 6.0 ng/L. In both groups, hs-cTnT concentration was higher in patients with CAD than in patients with normal coronary arteries (p <0.0001). Hs-cTnT was more accurate to detect patients with CAD in the low-RF group than in the multiple-RF group (p = 0.04). In multivariate analysis, higher level of hs-cTnT (>6 ng/L) was independently associated with CAD in low-RF group only. Despite very low circulating concentrations, hs-cTnT may identify with a good accuracy the outlier patients with diffuse CAD despite low-RF burden.

Coronary atherosclerosis in outlier subjects at the opposite extremes of traditional risk factors: Rationale and preliminary results of the Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation (CAPIRE) study.

Although it is generally accepted that cardiac ischemic events develop when coronary atherosclerosis (coronary artery disease [CAD]) has reached a critical threshold, this is true only to a first approximation. Indeed, there are patients with severe CAD who do not develop ischemic events; conversely, at the other extreme, individuals with minimal CAD may do. Similar exceptions to this paradigm include patients with diffuse CAD with a low risk factor (RF) profile and others with multiple RFs who develop only mild or no CAD. Therefore, the CAPIRE project was designed to investigate whether the specific study of these extreme outlier populations could provide clues for identification of yet unknown risk or protective factors for CAD and ischemic events. In the CAPIRE study, 481 subjects without previous symptoms or history of ischemic heart disease and normal left ventricular systolic function undergoing coronary computed tomography angiography have been selected based on coronary computed tomography angiography findings and cardiovascular RF profile. Therefore, in the whole population, 2 extreme outlier populations have been identified: (1) subjects with no CAD despite multiple RFs, and (2) at the opposite extreme, subjects with diffuse CAD despite a low-risk profile. Each subject has been characterized by clinical, anatomical imaging variables of CAD and baseline circulating biomarkers. Blood samples were collected and stored in a biological bank for further advanced investigations. The project is designed as a prospective, observational, international multicenter study with an initial cross-sectional analysis of clinical, imaging, and biomolecular variables in the selected groups and a longitudinal 5-year follow-up.

Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p < 0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 µmol/min/gO2 equivalents, p < 0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217.

Myocardial interleukin-6 in the setting of left ventricular mechanical assistance: relation with outcome and C-reactive protein.

BACKGROUND: In left ventricular assist device (LVAD) recipients, plasma levels of interleukin (IL)-6 are associated with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles, reflecting post-operative risk. However, it is not clear how the cardiac level of IL-6, detectable on the tissue samples at the time of implantation, can contribute to predict the post-operative outcome. METHODS: In 40 LVAD recipients, blood and myocardial samples from LV-apex were collected at the time of implantation to assess plasma and cardiac IL-6 levels. Serum C-reactive protein (CRP) levels were considered as inflammatory variable routinely used in LVAD-based therapy. RESULTS: Cardiac IL-6 levels did not correlate with either plasma IL-6 levels (R=0.296, p=0.063) and tissue IL-6 mRNA expression (R=-0.013, p=0.954). Contrary to what happened for the plasma IL-6 and CRP, no differences were observed in cardiac IL-6 levels with respect to INTERMACS profiles (p=0.090). Furthermore, cardiac IL-6 concentrations, unlike IL-6 and CRP circulating levels, were not correlated with the length of intensive care unit stay and hospitalization. CONCLUSIONS: Cardiac IL-6 levels do not contribute to improve risk profile of LVAD recipients in relation to clinical inpatient post-implantation. Instead, plasma IL-6 and serum CRP concentrations are more effective in predicting the severity of the clinical course in the early phase of LVAD therapy.