Volume 26 (2018): Issue 3 (July 2018)

Introduction: Several landmark studies, which enrolled heart failure (HF) patients who were ambulatory at the time of inclusion, identified iron deficiency (ID) as an important therapeutic target: intravenous iron administration with ferric carboxymaltose (FCM) improves morbidity, exercise capacity, and quality of life in patients with HF and reduced EF (HFrEF). However, there is still limited knowledge about ID prevalence during hospitalization for Worsening Chronic HF (WCHF) and about the relationship between ID during hospitalization and post-discharge outcomes. Although previous studies documented ID as an independent risk factor for poor outcomes in HFrEF, its prognostic significance in HF patients with EF>40% remains unclear.

Method and Results: The FERIC-RO study is a prospective, multicenter, observational study with longitudinal follow up, conducted in 9 Romanian hospitals that will include 200 consecutive patients admitted for worsening HF. A comprehensive description of the Iron metabolism biomarkers will be performed on discharge and 1-month follow up. The primary endpoint is defined as the prevalence of ID on discharge and 1-month post-discharge, and the secondary endpoints include: all-cause re-hospitalization and all-cause-mortality at 1 and 3 months follow up, and quality of life on discharge and 1-month.

Conclusions: FERIC-RO will provide new evidence about the prevalence and the predictors of ID in patients hospitalized for WCHF regardless of LVEF. Furthermore, the study will explore the relationship between in-hospital ID and post-discharge outcomes. The results of FERIC-RO will thus be highly relevant to the management of patients hospitalized for AHF.

Introduction: Reduced serum levels of paraoxonase 1 (PON1) activities are associated with diseases involving increased oxidative stress, such as acute coronary syndrome. We aimed to determine whether serum PON1 activities are a prognostic factor for one-year survival following ST-elevation myocardial infarction (STEMI).

Material and methods: We prospectively followed for one-year 75 patients diagnosed and treated for STEMI. Clinical, laboratory and imagistic data were gathered after coronary angiography. PON1 activities (paraoxonase, arylesterase, and lactonase) were assayed spectophotometrically on samples of heparinized plasma taken from the patients in a timeframe of maximum 20 minutes after coronary angiography.

Results: Increased mortality was linked to age (patients over 68 years), permanent atrial fibrillation or left ventricular ejection fraction (LVEF) <40% (associated with global hypokinesia, apical or septal akinesia), trivascular disease atherosclerosis, reduced PON1 activities (paraoxonase <18.4 IU/mL, arylesterase <12.6 IU/mL, lactonase <27.6 IU/mL), and glomerular filtration rate levels <54 mL/min/1.73m2. Multivariate survival analysis showed the independent prognostic role of age (HR 3.92; 95%CI 1.08-14.16; p=0.03), LVEF (HR 9.93; 95%CI 2.20-44.86; p=0.003) and arylesterase (HR 4.25; 95%CI 0.94-19.18; p=0.05) for one-year mortality.

Conclusion: Reduced arylesterase activity of PON1 is an independent predictor of one-year survival after acute myocardial infarction.

Introduction: The magnitude of the very early coronary artery bypass grafting (CABG)-related inflammatory response has been shown to influence post-CABG outcomes. However, the dynamics of the systemic inflammatory response to CABG beyond the very early postoperative phase and its relevance to clinical outcomes are not fully understood.

Methods: Circulating levels of several inflammatory markers were determined in 30 consecutive patients undergoing elective isolated on-pump CABG one day prior (D0-1), and 2 (D2) and 5 days post-CABG.

Results: CABG was associated with a significant increase in all studied inflammatory marker levels (all p<0.05 for D2 versus D0-1). D2 post-CABG IL-6 and IL-8 levels were both significantly positively correlated with extracorporeal circulation (ECC) and aortic clamping (AC) times (all p<0.05), whereas a weaker correlation was observed between D2 post-CABG IL-8 levels and total surgery time (r=0.42, p=0.02). In multiple regression analysis, D2 IL-8 levels independently predicted post-CABG kidney (p= 0.02) and liver (p = 0.04) dysfunction, as well as a sum of post-CABG major complications ≥2 (p = 0.04).

Conclusions: In this prospective study, longer duration of cardiopulmonary bypass caused a larger post-CABG inflammatory surge, whereas the duration of total CABG surgery had a less significant effect. IL-8 hyperresponders had greater risk of developing kidney and liver dysfunction and presented more major post-CABG complications. These data suggest that targeting the IL-8 pathway using antiinflammatory agents, or simply by shortening the duration of cardiopulmonary bypass could improve the in-hospital post-CABG outcomes in this population.

Pulmonary arterial hypertension (PAH) is a progressive disease with a complex pathogenesis. The polymorphism of the gene of multidrug resistance-1 (MDR1) has been associated with many diseases including PAH.

Objective. In this study we aimed to investigate the relevance of the MDR1 polymorphism to pediatric PAH clinical course.

Methods. A total of 40 pediatric patients with PAH (secondary to congenital heart defects or idiopathic) and 40 control subjects were enrolled. Patients with PAH were divided into 2 groups, according to their evolution: 28 patients who remained clinically stable at 12-months (non-worsening group) and 12 patients who presented clinical worsening at 12-months (worsening group). Genomic DNA was genotyped for MDR1 gene polymorphisms as follows: C1236T, G2677T and C3435T.

Results. There were no significant differences between PAH children groups (clinical worsening and non-worsening) nor between PAH children and controls in terms of frequency distribution of the three studied genotypes or alleles.

Conclusions. The MDR1 polymorphism could not be correlated with the clinical evolution of pediatric PAH patients in our study.

Background: Twenty-four hours dynamic blood pressure (BP) behaviour displays dipper profile defined as nocturnal systolic BP (SBP) reduction>10% compared to daytime. Non-dipper profile, nocturnal absence of SBP fall, associates an increased cardiovascular risk. We investigated the concomitant association of inflammatory bio-markers - high-sensitivity- C-reactive protein (hs-CRP), Human Chitinase3-like1 (YKL-40) and autonomic nervous system (total brain-derived neurotrophic factor, BDNF) with respect to non-dipping blood pressure status.

Material and method: Using 24h automatic BP measurements, 80 known hypertensive patients were divided into two groups: dipper group included fifty-one dipper patients (age 55.6 ±13.5 years) and non-dipper group consisted of 29 non-dipper subjects (62.07±12.03 years). Serum levels of hs-CRP were evaluated with enhanced immunoturbidimetric assay. Plasma levels of YKL-40 were measured by commercial sandwich ELISA using microplate coated with a monoclonal antibody for CHI3L1. Plasma levels of total BDNF were determined using quantitative sandwich enzyme-linked immunoassay. Statistical analysis of obtained data was performed.

Results: In the non-dipper group, a significant positive association with age over 60 years, hs-CRP values above 1.90 mg/dl was observed along with increased mean values of YKL-40. Non-dipper status is independently and statistically significantly associated with elevated levels of hs-CRP (OR: 3.248, 95% CI: 1.022-10.317, p=0.046) in multivariate odds ratio analysis. No statistically significant positive association between a median total BDNF plasma level of 1430 pg/ml and the non-dipper hypertension profile was identified.

Conclusion: Our study demonstrated that patients over 60 years, in particular, have a higher probability to present a non-dipping pattern of hypertension. hs-CRP and YKL-40 values are more likely to increase in the non-dipping hypertensive patients, and hs-CRP values above 1.9 mg/dl can identify the presence of a non-dipper blood pressure profile.

Background: Psoriasis is a multifactorial and inflammatory chronic skin disease indicated with T-cell-mediated keratinocyte hyper-proliferation. Demographic, epidemiological (family, twin), serological, and genetic studies have clearly demonstrated that psoriasis is a polygenic and multifactorial disease.

Aim: The objectives of the study are; to determine the prevalence of the polymorphisms of FAS (Fas cell surface receptor gene) -671 A>G (rs:1800682) and FASLG (Fas ligand gene) -844 T>C (rs:763110), to investigate the serum levels of sFas and sFasL, and also to discover any relationship between gene polymorphisms and serum levels in psoriatic patients.

Material and Methods: 50 treated and 69 untreated patients, and 140 healthy controls were included in the study. Polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The serum levels were measured in randomly selected treated (39) and untreated (40) patients, also in 84 healthy controls using micro-ELISA technique.

Results: There was no statistical difference between polymorphisms in the patient and control groups. However, sFas and sFasL levels in both treated and untreated patients were higher than that of the controls.

Conclusion: The investigated FAS and FASLG polymorphisms were not found to be directly associated with the psoriasis. Elevated sFas and sFasL levels in psoriatic patients showed that these factors may possess a significant role in the pathogenesis of psoriasis.

Background: The clinical utility of non-invasive markers in the diagnosis and monitoring of ulcerative colitis (UC) has been intensively studied. The aim of our study was to evaluate the value of fecal calprotectin (FC) in differentiating between UC and irritable bowel syndrome (IBS), and in estimating inflammatory activity in UC.

Method: A total number of 140 patients were included in the study. All patients underwent ileocolonoscopy with biopsies, quantitative determination of FC, and blood tests (white blood cell count, CRP, ESR). The severity of UC was assessed by using the Ulcerative Colitis Disease Activity Index (UCDAI) and Mayo endoscopic score.

Results: In patients with active UC the mean values of FC were 373.8 +/- 146.3 μg/g, significantly higher than those in the inactive UC (mean values 36.04 +/- 13.25 μg/g), and in IBS (42.9 +/- 16.00 μg/g). In univariate regression analysis, elevated FC levels strongly correlated with pancolitis (p=0.0001), UCDAI and Mayo scores (p=0.0001), and elevated CRP levels. In multivariate regression model, FC was positively associated with severe pancolitis, and elevated CRP. The optimal cutoff value of FC for the prediction of severe pancolitis (Mayo score˃ 3) was 540 μg/g. We obtained 71.4% sensitivity (CI95%: 41.95-91.6) and 96.1% specificity (CI95%: 89.2 -99.2) of FC in assessing the severity of inflammation in UC patients.

Conclusion: FC is a promising marker that can be used in clinical practice to select patients with organic intestinal disorders, compared with those with functional disorders. It also correlates very well with the extent of lesions and the severity of clinical symptoms in UC, with increased sensitivity and specificity.

Chronic hyperglycemia is an important cause for the development of chronic complications of diabetes, but glycemic variability has emerged in recent years as an independent contributor to diabetes-related complications. Our objective was to evaluate glycemic variability in patients with T2DM treated with insulin compared with other antidiabetic drugs. In this retrospective study, we collected 24-hour continuous glucose monitoring (CGM) recording data from 95 patients with T2DM, of which 27 treated with insulin and 68 with non-insulin treatment. We calculated and compared 16 glucose variability parameters in the insulin-treated and non-insulin treated groups. Insulin treated patients had significantly higher values of parameters describing the amplitude of glucose value fluctuations (standard deviation of glucose values, percentage coefficient of variation [%CV], and mean amplitude of glycemic excursion [MAGE], p <0.05) and time-dependent glucose variability (percentage of time with glycemic values below 70 mg/dl and continuous overall net glycemic action [CONGA] at 2, 4 and 6 hours, p <0.05). In conclusion, insulin therapy in T2DM is correlated with significantly higher glycemic variability.