Acute hyperbilirubinemia determines an early subclinical renal damage: Evaluation of tubular biomarkers in cholemic nephropathy.

BACKGROUND AND AIMS: Cholemic nephropathy is a cause of acute kidney injury occurring in patients with jaundice. The aim of this study was to evaluate early renal function impairment in patients with mild acute hyperbilirubinemia in the absence of alterations of the common parameters used in clinical practice (serum creatinine or urea) and with normal renal morphology. We studied urinary biomarkers of tubular damage urinary neutrophil gelatinase-associated lipocalin (u-NGAL), urinary beta-2-microglobulin (u-B2M), urinary osteopontin (u-OPN), urinary trefoil factor 3 (u-TFF3) and urinary Cystatin C (u-Cys). METHODS: This is a case-control study investigating the following urinary biomarkers of tubular damage: u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys, in patients with mild acute hyperbilirubinemia. Seventy-four patients were included in this study: 36 patients with jaundice and 38 patients without jaundice. RESULTS: Subjects with jaundice (total bilirubin 12.4 ± 7.3 mg/dL) showed higher u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys compared with controls. After logistic regression analyses, including the following independent variables: age, estimated Glomerular Filtration Rate (eGFR), haemoglobin, diabetes, hypertension and jaundice, we observed a higher risk of elevated u-NGAL values (OR = 3.8, 95% CI 1.07-13.5, p = .03) and u-B2M (OR = 9.4, 95% CI 2.3-38.9, p = .0018) in jaundiced subjects. Moreover, urinary biomarkers had a direct correlation with serum cholestasis indexes. CONCLUSIONS: This study demonstrated increased urinary biomarkers of tubular damage (u-NGAL, u-B2M, u-OPN, u-TFF3, and u-Cys) in patients with mild hyperbilirubinemia in comparison with a control group. These findings suggest early renal tubular damage in the absence of alterations of the normal parameters used in clinical practice (eGFR, serum urea and renal morphology).

Myocardial deformational adaptations to different forms of training: a real-time three-dimensional speckle tracking echocardiographic study.

The hemodynamic load due to physical activity leads to structural and functional cardiac adaptations known as "Athlete's heart". We aimed to compare myocardial performance in different groups of trained athletes by means of 3D echocardiography and 3D speckle tracking echocardiography (3D-STE). 66 athletes [26 strength-trained athletes (STA) and 40 endurance athletes (ETA)] were prospectively enrolled. A control group of 40 sedentary subjects (sedentary group) was also included. All subjects underwent both standard and 3D evaluation of left ventricular (LV) function including 3D-STE. Left ventricular mass indexed for body surface area, LV end-diastolic (LV Dd) thickness of interventricular septum and posterior wall thickness mean values were significantly increased in athletes (p < 0.001, p < 0.01 and p < 0.001, respectively). LV diastolic diameter index had a significantly higher mean value in ETA in respect to sedentary group (p = 0.001). Despite a preserved mean value of LV ejection fraction (LV EF) in all the groups, subjects in STA group showed a significant reduction of strain in the longitudinal, radial and circumferential directions (p < 0.05 for all). Area strain mean value was also reduced in STA group (p < 0.01). In the overall population, an inverse relationship between longitudinal strain and LV Dd index (r = -0.260, p = 0.008), the E/A ratio (r = -0.249, p = 0.010) and the E' velocity (r = -0.259, p = 0.009) has been identified. Sport-specific patterns of ventricular morphological and functional remodeling are present in athletes performing different kinds of training. 3D-STE is a useful and feasible echocardiographic technique for the assessment of sport-specific pattern of deformational adaptations.

Early cardiovascular remodelling in Fabry disease.

AIMS: Fabry disease (FD) is a rare X-linked genetic disorder caused by the deficiency or absent activity of lysosomal α-galactosidase A. Cardiovascular remodelling is a hallmark of FD. The present study aimed to comprehensively evaluate the cardiac, vascular and microvascular status in a population of patients with genetic mutations for FD without left ventricular hypertrophy (LVH). METHODS AND RESULTS: This study includes subjects carrying genetic mutations for FD (Fabry disease mutation-carrier, FDMC) without LVH (n = 19). A group of control subjects (n = 19) matched for age, sex, body mass index and cardiovascular risk factors were also included. All subjects underwent echocardiography, carotid ultrasound scan, endothelial flow-mediated dilatation (FMD) and nailfold capillaroscopy (NFC) assessment. When compared to the subjects in the control group, FDMC patients showed significantly lower mean values of systolic myocardial velocity (7.33 ± 1.28 vs. 10.08 ± 1.63 cm/s, p < 0.0001), longitudinal systolic strain (-18.07 ± 1.72 vs. -21.15 ± 2.22%, p < 0.0001), significantly higher E/E' mean values (7.15 ± 1.54 vs. 5.98 ± 1.27, p = 0.016) and intima-media thickness mean values (0.80 ± 0.20 vs. 0.61 ± 0.19 mm, p = 0.005), significantly lower FMD (8.3 ± 4.6 vs. 12.2 ± 5.0%, p = 0.02), more atypical capillaries and irregular NFC architecture in FDMC than control subjects (52.6 vs. 0%, p < 0.0001; 78.9 vs. 36.8%, p = 0.02 respectively). CONCLUSIONS: FD progressively involves cardiac, macrovascular and microvascular systems in an early stage. These features are present even in asymptomatic mutation carriers without LVH.

Controlling Nutritional Status (CONUT) Score as a Potential Prognostic Indicator of In-Hospital Mortality, Sepsis and Length of Stay in an Internal Medicine Department.

The controlling nutritional status (CONUT) score represents poor nutritional status and has been identified as an indicator of adverse outcomes. Our aim was to evaluate the prognostic role of the CONUT score on in-hospital outcomes in an Internal Medicine Department. This is a retrospective study analyzing data from 369 patients, divided into four groups based on the CONUT score: normal (0-1), mild-high (2-4), moderate-high (5-8), and marked high (9-12). In-hospital all-cause mortality increased from normal to marked high CONUT score group (2.2% vs. 3.6% vs. 13.4% vs. 15.3%, p < 0.009). Furthermore, a higher CONUT score was linked to a longer length of hospital stay (LOS) (9.48 ± 6.22 vs. 11.09 ± 7.11 vs. 12.45 ± 7.88 vs. 13.10 ± 8.12, p < 0.013) and an increased prevalence of sepsis. The excess risk of a high CONUT score relative to a low CONUT score remained significant after adjusting for confounders (all-cause mortality: OR: 3.3, 95% CI: 1.1-9.7, p < 0.02; sepsis: OR: 2.7, 95% CI: 1.5-4.9, p < 0.01; LOS: OR: 2.1, 95% CI: 1.2-3.9, p < 0.007). The present study demonstrated that an increased CONUT score is related to a higher risk of short-term in-hospital death and complications.

Increased Platelet Reactivity and Proinflammatory Profile Are Associated with Intima-Media Thickness and Arterial Stiffness in Prediabetes.

Alterations of glucose homeostasis are associated with subclinical vascular damage; however, the role of platelet reactivity in this process has not been fully investigated. In this cross-sectional study, we evaluated the correlation between markers of platelet reactivity and inflammation and markers of vascular disease in subjects with prediabetes. Markers of platelet reactivity such as 11-dehydro-thromboxane B2 urinary levels (11-dh-TXB2) and mean platelet volume (MPV) and inflammatory indexes such as platelet-to-lymphocyte ratio (PLR) were evaluated in subjects with prediabetes (n = 48), new-onset type 2 diabetes (NODM, n = 60) and controls (n = 62). Furthermore, we assessed the cardiovascular risk profile of the study population with arterial stiffness and quality intima-media thickness (qIMT). Subjects with prediabetes and NODM exhibited higher 11-dh-TXB2 urinary levels and MPV and a proinflammatory profile with an increased PLR, high-sensitivity C-reactive protein, ferritin and fibrinogen. Furthermore, after multiple regression analyses, we found that urinary 11-dh-TXB2 was one of the major determinants of IMT and arterial stiffness parameters. In conclusion, subjects with prediabetes exhibit increased platelet reactivity as well as a proinflammatory profile. Furthermore, this condition is associated with early markers of cardiovascular disease.

Early changes of left ventricular geometry and deformational analysis in obese subjects without cardiovascular risk factors: a three-dimensional and speckle tracking echocardiographic study.

Subclinical myocardial dysfunction has been identified in obese subjects without cardiovascular risks factors and has been defined as "obesity cardiomyopathy". We evaluated left ventricular (LV) function and geometry in obese patients by using a 3 dimensional echocardiography (3DE). We also aimed to look at the influence of ventricular geometry upon functional parameters of the LV by using 3D speckle tracking imaging (3D-STI). 30 consecutive and asymptomatic obese cases (OB group) with no comorbidities were prospectively enrolled. The control group included 30 healthy volunteers (HS group), matched for age and sex. All subjects underwent 3DE and 3D-STI. Ventricular geometry was evaluated with the LV sphericity index (LV SpI) and the LV diastolic volume to mass ratio (LV EDV/Mass ratio). LV Mass was significantly increased in OB group and the LV EDV/Mass ratio had a significantly lower mean value in this group (p < 0.001 and p = 0.002, respectively). LV SpI was significantly reduced in obese subjects (p < 0.001). A significant reduction in longitudinal (GLS), radial (GRS) and area strain (GAS) was observed in OB group (p = 0.001 for all) while circumferential mechanic (GCS) was not different between the two groups (p = 0.052). LV EDV to mass ratio was significantly related to GLS (r = -0.298, p = 0.022) and GAS (r = -0.289, p = 0.026). On multivariate analysis, GRS and GAS were independently related to LV SpI (ß = 0.222, p = 0.031 and ß = -0.222, p = 0.034, respectively). Geometrical and structural ventricular remodeling negatively influences functional properties of the LV in obese subjects without cardiovascular risks factors. Further studies are needed to assess the prognostic value of our findings.

Chemotherapy-Induced Cardiotoxicity: Subclinical Cardiac Dysfunction Evidence Using Speckle Tracking Echocardiography.

OBJECTIVES: In our study, we aimed to identify early markers of cardiac dysfunction in patients treated with mitoxantrone. We also looked at cardiac functional changes during therapy by analyzing longitudinal deformation and by measuring left ventricular (LV) and left atrial (LA) global strain. MATERIALS AND METHODS: LA and LV global longitudinal strain were analyzed in 20 patients affected by multiple sclerosis and treated with mitoxantrone. Patients underwent echocardiography before treatment, after every drug administration during the 12-months treatment period, and finally after 6 and 12 months of drug discontinuation. RESULTS: Compared with baseline values, patients showed a significant reduction of both LA and LV longitudinal global strain at the end of treatment with mitoxantrone (LA_GS% T10 vs. T0 values: 15,2 ± 12,5 vs. 20,2 ± 11,1; LV_GS%: ─16,4 ± 2,5 vs. ─17,4 ± 3,8). Strain reduction reverted after treatment discontinuation (LA_GS% FU vs. T0 values: 20,4 ± 15,7 vs. 20,2 ± 11,1; LV_GS%: ─17,3 ± 3,3 vs. ─17,4 ± 3,8). CONCLUSIONS: Impairment of longitudinal deformation during mitoxantrone therapy may indicate a dysfunction related to early myocardial damage. These findings appear to be reversible after treatment discontinuation.

Feasibility, reproducibility, and agreement between different speckle tracking echocardiographic techniques for the assessment of longitudinal deformation.

BACKGROUND: Left ventricular (LV) longitudinal deformation can be assessed with new echocardiographic techniques like triplane echocardiography (3PE) and four-dimensional echocardiography (4DE). We aimed to assess the feasibility, reproducibility, and agreement between these different speckle-tracking techniques for the assessment of longitudinal deformation. METHODS: 101 consecutive subjects underwent echocardiographic examination. 2D cine loops from the apical views, a triplane view, and an LV 4D full volume were acquired in all subjects. LV longitudinal strain was obtained for each imaging modality. RESULTS: 2DE analysis of LV strain was feasible in 90/101 subjects, 3PE strain in 89/101, and 4DE strain in 90/101. The mean value of 2DE and 3PE longitudinal strains was significantly higher with respect to 4DE. The relationship between 2DE and 3PE derived strains (r = 0.782) was significantly higher (z = 3.72, P < 0.001) than that between 2DE and 4DE (r = 0.429) and that between 3PE and 4DE (r = 0.510; z = 3.09, P = 0.001). The mean bias between 2DE and 4DE strains was -6.61 ± 7.31% while -6.42 ± 6.81% between 3PE and 4DE strains; the bias between 2DE and 3PE strain was of 0.21 ± 4.16%. Intraobserver and interobserver variabilities were acceptable among the techniques. CONCLUSIONS: Echocardiographic techniques for the assessment of longitudinal deformation are not interchangeable, and further studies are needed to assess specific reference values.