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Johansen M.E.,Copenhagen University | Jensen J.-U.,Copenhagen University | Jensen J.-U.,Hvidovre University Hospital | Bestle M.H.,North Zealand University Hospital | And 12 more authors.
PLoS ONE | Year: 2013

Background: Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to induce thrombocytopenia. Methods: Randomized trial allocated patients to antimicrobial treatment according to standard- of-care (SOC group) or drug-escalation in case of procalcitonin increases (high-exposure group). Patients were followed until death or day 28. Thrombocytopenia defined as absolute (platelet count ≤100x109/L) or relative (≥20% decrease in platelet count). Analyses were performed in the two randomized groups and as a merged cohort. Results: Of the 1147 patients with platelet data available, 18% had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17% developed this complication during follow-up; 57% developed relative thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4 was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71 [95% CI: 1.30 to 2.30], P<0.0001, respectively). Patients in the high-exposure group received more antimicrobials including piperacillin/tazobactam, meropenem and ciprofloxacin compared with the SOC group, whereas cefuroxime was used more frequently in the SOC group (p<0.05). Risk of absolute and relative thrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06; respectively), as well as absolute platelet count (daily difference, high-exposure vs. SOC -1.7 [-3.8-0.5], p=0.14) was comparable between groups. In observational analyses, use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48-2.92]; 1.44 [1.10-1.89], respectively), however only ciprofloxacin were associated with a reduction in absolute platelet count (p=0.0005). Conclusion: High exposure to broad-spectrum antimicrobials does not result in a reduction in thrombocytopenia in critically ill patients. However, single use of ciprofloxacin, and less so piperacillin/tazobactam, may contribute to a lower platelet count. Trial Registration: ClinicalTrials.gov NCT00271752 http://clinicaltrials.gov/ct2/show/NCT00271752 Copyright: © 2013 Johansen et al. Source

Gaborit F.,Herlev University Hospital | Bosselmann H.,North Zealand University Hospital | Tonder N.,North Zealand University Hospital | Iversen K.,Herlev University Hospital | And 5 more authors.
BMC Cardiovascular Disorders | Year: 2015

Background: Both impaired left ventricular (LV) global longitudinal strain (GLS) and increased plasma concentrations of natriuretic peptides(NP) are associated with a poor outcome in heart failure (HF). Increased levels of NP reflect increased wall stress of the LV. However, little is known about the relationship between LV GLS and NP. This aim of this study was to evaluate the relationship between the echocardiographic measure LV GLS and plasma levels of NP. Methods: We prospectively included 149 patients with verified systolic HF at the baseline visit in an outpatient HF clinic. LV GLS was assessed by two dimension speckle tracking and plasma concentrations of N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) and pro-atrial-natriuretic-peptide (proANP) were analysed. Results: The patients had a median age of 70 years, 28.2 % were females, 26.5 % were in functional class III-IV, median left ventricular ejection fraction (LVEF) was 33 % and median LV GLS was -11 %. LV GLS was associated with increased plasma concentrations of NT-proBNP and proANP in multivariate logistic regression (NT-proBNP: Odds RatioGLS: 7.25, 95 %-CI: 2.48-21.1, P < 0.001 and proANP: Odds RatioGLS: 3.26, 95-%-CI: 1.28-8.30, P = 0.013) and linear regression (NT-proBNP: βGLS: 1.19, 95 %-CI: 0.62-1.76, P < 0.001 and proANP: βGLS: 0.42, 95-%-CI: 0.11-0.72, P = 0.007) models after adjustment for traditional confounders (age, gender, body-mass-index, atrial fibrillation, renal function) and left atrial volume index. Conclusion: Impaired LV GLS is associated with increased plasma concentrations of NP and our data suggest that left ventricular myocardial mechanics estimated by LV GLS reflects myocardial wall stress in chronic systolic HF. © 2015 Gaborit et al. Source

Bosselmann H.,North Zealand University Hospital | Egstrup M.,Frederiksberg University Hospital | Rossing K.,Rigshospitalet | Gustafsson I.,Hvidovre University Hospital | And 5 more authors.
International Journal of Cardiology | Year: 2013

Objective To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF). Background It is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF. Methods Clinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5 years (interquartile range: 2-7.7 years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed. Results Median age was 73 years (51-83), 29% were female, LVEF was 30% (13-45), 74% were NYHA classes I-II and estimated glomerular filtration rate (eGFR) was 68 ml/min/1.73 m2 (18-157). A total of 252 patients died. All five biomarkers - log(NT-proBNP) (HR: 2.13, 95% CI: 1.57-2.87:, P < 0.001), hsTNT (HR: 3.07, 95% CI: 1.90-4.96 P < 0.001), proANP (HR: 1.02, 95% CI: 1.01-1.03, P < 0.001), copeptin (HR: 1.02, 95% CI: 1.01-1.03, P = 0.008) and proADM (HR: 2.37, 95% CI: 1.66-3.38, P < 0.001) - were associated with mortality risk, but not affected by RD (P > 0.05 for all interactions). Conclusion Established and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function. © 2013 Elsevier Ireland Ltd. Source

Maagaard L.,North Zealand University Hospital | Ankersen D.V.,North Zealand University Hospital | Vegh Z.,Semmelweis University | Burisch J.,Hvidovre University Hospital | And 3 more authors.
World Journal of Gastroenterology | Year: 2016

AIM: To investigate patient-reported outcomes from, and adherence to, a low FODMAP diet among patients suffering from irritable bowel syndrome and inflammatory bowel disease. METHODS: Consecutive patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) and co-existing IBS fulfilling the Rome III criteria, who previously attended an outpatient clinic for low FODMAP diet (LFD) dietary management and assessment by a gastroenterologist, were invited to participate in a retrospective questionnaire analysis. The questionnaires were sent and returned by regular mail and gathered information on recall of dietary treatment, efficacy, symptoms, adherence, satisfaction, change in disease course and stool type, and quality of life. Before study enrolment all patients had to sign an informed written consent. RESULTS: One hundred and eighty patients were included, 131 (73%) IBS and 49 (27%) IBD patients. Median age was 43 years (range: 18-85) and 147 (82%) were females. Median follow-up time was 16 mo (range: 2-80). Eighty-six percent reported either partial (54%) or full (32%) efficacy with greatest improvement of bloating (82%) and abdominal pain (71%). The proportion of patients with full efficacy tended to be greater in the IBD group than in the IBS group (42% vs 29%, P = 0.08). There was a significant reduction in patients with a chronic continuous disease course in both the IBS group (25%, P < 0.001) and IBD group (23%, P = 0.002) along with a significant increase in patients with a mild indolent disease course of 37% (P < 0.001) and 23% (P = 0.002), respectively. The proportion of patients having normal stools increased with 41% in the IBS group (P < 0.001) and 66% in the IBD group (P < 0.001). One-third of patients adhered to the diet and high adherence was associated with longer duration of dietary course (P < 0.001). Satisfaction with dietary management was seen in 83 (70%) IBS patients and 24 (55%) IBD patients. Eightyfour percent of patients lived on a modified LFD, where some foods rich in FODMAPs were reintroduced, and 16% followed the LFD by the book without deviations. Wheat, dairy products, and onions were the foods most often not reintroduced by patients. CONCLUSION: These data suggest that a diet low in FODMAPs is an efficacious treatment solution in the management of functional bowel symptoms for IBS and IBD patients. © 2016 Baishideng Publishing Group Inc. All rights reserved. Source

Gaborit F.S.,Herlev University Hospital | Gaborit F.S.,Copenhagen University | Bosselmann H.,North Zealand University Hospital | Kistorp C.,Herlev University Hospital | And 10 more authors.
BMC Cardiovascular Disorders | Year: 2016

Background: Galectin 3 (Gal-3) reflects cardiac fibrosis in heart failure HF, but has also been associated to renal fibrosis and impaired renal function. Previous research has suggested that Gal-3 could be a cardio-renal biomarker, but it has never been tested simultaneous in a single study whether Gal-3 reflects echocardiographic measures, neurohumoral activity and renal function. The aim of this study was to evaluate the relationship between plasma concentrations of Gal-3 and neurohumoral activity, myocardial and renal function in patients with HF, including advanced echocardiographic measures and 24-h urinary albumin excretion (albuminuria). Methods: We prospectively enrolled 132 patients with reduced left ventricular ejection fraction (LVEF) referred to an outpatient HF clinic. The patients had a median age of 70 years (interquartile rage: 64-75), 26.5 % were female, median LVEF was 33 % (27-39 %) and 30 % were in NYHA class III-IV. Results: Patients with plasma concentrations of Gal-3 above the median had significantly lower estimated glomerular filtration rate (eGFR) and this association remained significant in multivariate regression analysis (β: -0.010; 95 % CI -0.012--0.008; P < 0.001), adjusted for age, gender, medical treatment. Plasma concentrations of Gal-3 were not associated with albuminuria (Beta: 0.008; 95 % CI:-0.028-0.045; P = 0.652). There were no association between plasma concentrations of Gal-3 and myocardial function or structure estimated by LVEF, LVmassIndex, LVIDd, E/é or LV global longitudinal strain (P > 0.05 for all). In multivariate analyses plasma concentrations of Gal-3 were significantly associated with the cardiac biomarkers: NT-proBNP (β: 0.047; 95 % CI: 0.008-0.086; P = 0.020), proANP (β: 0.137; 95 % CI: 0.067-0.207; P < 0.001), chromogranin A (β: 0.123; 95 % CI: 0.052-0.194; P < 0.001) and Copeptin (β: 0.080; 95 % CI: 0.000-0.160; P = 0.049). Multivariate analysis was adjusted for eGFR, age, gender and medical treatment. Conclusions: Increased plasma concentrations of Gal-3 are associated with reduced eGFR and increased plasma concentrations of NT-proBNP, proANP, chromogranin A and Copeptin, but not with echocardiographic parameters reflecting myocardial function. These results suggest that Gal-3 reflects both increased neurohumoral activity and reduced eGFR, but not myocardial function in patients with systolic HF. © 2016 The Author(s). Source

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