Alessandra Barassi

The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis

In light-chain (AL) amyloidosis, prognosis is dictated by cardiac dysfunction. N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn) are used to assess the severity of cardiac damage. We evaluated the prognostic relevance of a high-sensitivity (hs) cTnT assay, NT-proBNP, and cardiac troponin I in 171 consecutive patients with AL amyloidosis at presentation and 6 months after treatment. Response and progression of NT-proBNP were defined as more than 30% and more than 300 ng/L changes. All 3 markers predicted survival, but the best multivariable model included hs-cTnT. The hs-cTnT prognostic cutoff was 77 ng/L (median survival 10.6 months for patients with hs-cTnT above the cutoff). After treatment, response and progression of NT-proBNP and a more than 75% increase of hs-cTnT were independent prognostic determinant. In AL amyloidosis, hs-cTnT is the best baseline prognostic marker. Therapy should be aimed at preventing progression of cardiac biomarkers, whereas NT-proBNP response confers an additional survival benefit.

T-cell phenotypes, apoptosis and inflammation in HIV+ patients on virologically effective cART with early atherosclerosis.

Objective We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia, and atherosclerosis evaluated by carotid intima-media thickness (IMT) in a cohort of HIV-positive patients undergoing long-term virologically suppressive combination antiretroviral therapy (cART). Design We studied 163 patients receiving virologically suppressive cART. Methods We measured IMT (carotid ultrasound); CD4+/CD8+ T-cell activation (CD38, CD45R0), differentiation (CD127), apoptosis (CD95), and senescence (CD28, CD57) (flow cytometry); plasma sCD14, IL-6, TNF- α, sVCAM-1, hs-CRP, anti-CMV IgG (ELISA); LPS (LAL). The results were compared by Mann-Whitney, Kruskal-Wallis or Chi-square tests, and factors associated with IMT were evaluated by multivariable logistic regression. Results Of 163 patients, 112 demonstrated normal IMT (nIMT), whereas 51 (31.3%) had pathological IMT (pIMT: ≥1 mm). Of the patients with pIMT, 22 demonstrated an increased IMT (iIMT), and 29 were shown to have plaques. These patient groups had comparable nadir and current CD4+, VLs and total length of time on cART. Despite similar proportions of CD38-expressing CD8+ cells (p = .95), pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p = .038) and apoptotic CD4+CD95+ (p = .01) and CD8+CD95+ cells (p = .003). In comparison to nIMT patients, iIMT patients tended to have lower numbers of early differentiated CD28+CD57− memory CD4+ (p = .048) and CD28–CD57−CD8+ cells (p = .006), both of which are associated with a higher proliferative potential. Despite no differences in plasma LPS levels, pIMT patients showed significantly higher circulating levels of sCD14 than did nIMT patients (p = .046). No differences in anti-CMV IgG was shown. Although circulating levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical cardiovascular predictors. Conclusions Despite the provision of full viral suppression by cART, a hyperactivated, pro-apoptotic T-cell profile characterizes HIV-infected patients with early vascular damage, for whom the potential contribution of subclinical endotoxemia and anti-CMV immunity should be investigated further.

Prognostic Role of Clinical and Laboratory Criteria To Identify Early Ventilator-Associated Pneumonia in Brain Injury*

BACKGROUND We investigated the role of the clinical pulmonary infection score (CPIS), serum levels of procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) in the detection of patients with early ventilator-associated pneumonia (VAP). METHODS Observational study in a university hospital. In 58 patients with severe brain injury receiving mechanical ventilation, CPIS, PCT, CRP and SAA were evaluated at ICU entry and at days 3 to 4 of hospital stay for VAP diagnosis (confirmed by endotracheal aspirate or BAL cultures). RESULTS We found the following: (1) PCT at entry was increased in patients who later had early VAP develop (25 patients) compared to no VAP (median, 1.4 ng/mL; 25-75 percentiles, 0.14-0.78; vs median, 0.2 ng/mL; 25-75 percentiles, 0.76-2.4, p<0.001; sensitivity, 76%; and specificity, 75%); (2) CPIS increased at the day of VAP diagnosis, compared to entry (median, 6.6+/-1.1 vs 1.5+/-1.1, p<0.001; sensitivity, 97%; specificity, 100%), while other serum inflammatory markers did not change; and (3) deterioration in oxygenation and changes in tracheal secretions were the main determinants of CPIS changes. CONCLUSIONS PCT may be a useful marker to predict which patients subsequently have early VAP. The CPIS could help as an early way to detect the patients with early VAP and who need further diagnostic testing.

Oxidative Stress and Antioxidant Status in Patients with Erectile Dysfunction

INTRODUCTION Erectile dysfunction (ED) is increasingly recognized as a public health problem. The interaction between nitric oxide and reactive oxygen species is one of the important mechanisms implicated in the pathophysiological process of ED. Plasma contains various antioxidant components to prevent free-radical injury. AIM The aim of this study was to determine and compare the oxidative and antioxidant status of peripheral venous blood in patients with ED of arteriogenic and non-arteriogenic origin. METHODS Oxidative stress and antioxidant status were assessed in 40 patients with ED and 20 healthy controls. MAIN OUTCOME MEASURES Plasma reactive oxygen metabolite (ROM) concentrations were measured as an indicator of oxidative stress, and plasma total antioxidant status (TAS) to indicate antioxidant defense. RESULTS Plasma ROM concentrations were higher (349.75 +/- 53.35 standard deviation [SD] U.Carr vs. 285.43 +/- 25.58 U.Carr, P < 0.001) and plasma TAS lower (0.54 +/- 0.16 SD mmol/L vs. 0.94 +/- 0.28 SD mmol/L, P < 0.0001) in patients with arteriogenic ED in comparison to those in patients with non-arteriogenic ED. Plasma ROM and TAS in controls were not significantly different from those in non-arteriogenic ED. Conclusions. This observation may be useful to better understand and distinguish arteriogenic from non-arteriogenic ED using laboratory tests. In addition, our findings provide important support for an antioxidant therapy to try to correct oxidative stress in arteriogenic ED patients.

Changes in lipid profile in response to three different protocols of whole-body cryostimulation treatments.

Systemic cryostimulation is useful treatment, both in sport and medicine, during which human body is exposed to very low, cryogenic temperature (below -100 degrees C). Although there exists some evidence of its beneficial effect in biological regeneration, so far it has not been unequivocally determined if the positive effect of repeated stimulations depends on their number in a series. The aim of this research was to estimate the influence of 5, 10 and 20 sessions of 3 min-long exposures to cryogenic temperature (-130 degrees C) on the lipid profile in physically active men. Sixty-nine healthy volunteers participated in the study. The blood samples were taken in the morning, after overnight fasting, before the first cryostimulation session, and the following morning after the last one (5th,10th, 20th). In serum specimens the concentration of total cholesterol (TCh), HDL cholesterol and triglicerydes were determined using enzymatic methods. LDL cholesterol level was calculated using Friedewald formula. The changes in lipid profile (LDL decrease with simultaneously HDL increase) occurred after at least 10 sessions of cryostimulation.

Serum leptin, but not adiponectin and receptor for advanced glycation end products, is able to distinguish autoimmune pancreatitis from both chronic pancreatitis and pancreatic neoplasms

Abstract Objective. Serum leptin and adiponectin determinations have been proposed as markers for distinguishing pancreatic cancer and chronic pancreatitis from autoimmune pancreatitis; however, no studies exist in patients with autoimmune pancreatitis and in those with intraductal papillary mucinous tumors of the pancreas. The aim of this paper was to evaluate the circulating concentrations of receptor for advanced glycation end products (RAGE), leptin and adiponectin in patients with chronic pancreatic diseases. Material and methods. Seventy-five consecutive patients with chronic pancreatic diseases (47 males, 28 females; mean age 67.0 ± 13.2 years; range 37–97 years) were studied: six (8.0%) had autoimmune pancreatitis, 23 (30.7%) had chronic pancreatitis, 34 (45.3%) had pancreatic cancer and the remaining 12 (16.0%) had intraductal papillary mutinous tumors of the pancreas. Leptin, adiponectin and RAGE were determined in serum using commercially available kits. The leptin concentrations were normalized to the lower and upper reference limits because of the different gender reference ranges. Results. Normalized leptin concentrations were significantly lower in chronic pancreatitis patients (0.53 ± 1.28; p = 0.008) and in those with pancreatic cancer (0.12 ± 0.33; p < 0.001) compared to the overall population (0.58 ± 1.23), whereas autoimmune pancreatitis patients had significantly higher concentrations of this protein (2.18 ± 2.56; p = 0.004) compared to the overall population. RAGE and adiponectin concentrations were similar among the four groups of patients studied. Among the clinical variables considered, only pain was significantly related to leptin concentrations (patients with pain 0.18 ± 0.54, patients without pain 1.07 ± 1.64; p = 0.001). Conclusion. Serum leptin seems to be a good serum marker for differentiating autoimmune pancreatitis patients from those with chronic pancreatitis and pancreatic cancer.

Vitamin D and Erectile Dysfunction

INTRODUCTION Endothelial dysfunction has been demonstrated to play an important role in pathogenesis of erectile dysfunction (ED) and vitamin D deficiency is deemed to promote endothelial dysfunctions. AIM To evaluate the status of serum vitamin D in a group of patients with ED. METHODS Diagnosis and severity of ED was based on the IIEF-5 and its aetiology was classified as arteriogenic (A-ED), borderline (BL-ED), and non-arteriogenic (NA-ED) with penile-echo-color-Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum vitamin D and intact PTH concentrations were measured. MAIN OUTCOME MEASURES Vitamin D levels of men with A-ED were compared with those of male with BL-ED and NA-ED. RESULTS Fifty patients were classified as A-ED, 28 as ED-BL and 65 as NA-ED, for a total of 143 cases. Mean vitamin D level was 21.3 ng/mL; vitamin D deficiency (<20 ng/mL) was present in 45.9% and only 20.2% had optimal vitamin D levels. Patients with severe/complete-ED had vitamin D level significantly lower (P = 0.02) than those with mild-ED. Vitamin level was negatively correlated with PTH and the correlation was more marked in subjects with vitamin D deficiency. Vitamin D deficiency in A-ED was significantly lower (P = 0.01) than in NA-ED patients. Penile-echo-color-Doppler revealed that A-ED (PSV ≤ 25 cm/second) was more frequent in those with vitamin D deficiency as compared with those with vitamin >20 ng/dL (45% vs. 24%; P < 0.05) and in the same population median PSV values were lower (26 vs. 38; P < 0.001) in vitamin D subjects. CONCLUSION Our study shows that a significant proportion of ED patients have a vitamin D deficiency and that this condition is more frequent in patients with the arteriogenic etiology. Low levels of vitamin D might increase the ED risk by promoting endothelial dysfunction. Men with ED should be analyzed for vitamin D levels and particularly to A-ED patients with a low level a vitamin D supplementation is suggested.

Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and L‐arginine in patients with arteriogenic and non‐arteriogenic erectile dysfunction

The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been linked to endothelial dysfunction. We investigated the relation between ADMA, symmetric dimethylarginine (SDMA) and L-arginine concentrations and erectile dysfunction. We compared plasma levels of ADMA, SDMA and L-arginine in 61 men in good health with erectile dysfunction of arteriogenic and non-arteriogenic origin. Diagnosis of erectile dysfunction was based on the International Index of Erectile Function Score and its aetiology was classified with penile echo-colour-Doppler in basal condition and after intracavernous injection of prostaglandin E1. The ADMA and SDMA concentrations were significantly higher in men with arteriogenic erectile dysfunction compared with those with erectile dysfunction of non-arteriogenic origin (p < 0.05) and the concentrations in both subgroups were significantly higher than in controls (p < 0.001). There was a negative correlation between ADMA and International Index of Erectile Function Score only in arteriogenic erectile dysfunction subgroup. L-arginine did not differ significantly neither between the two erectile dysfunction subgroups (p > 0.05) nor between each of the two erectile dysfunction subgroups and controls (p > 0.05). The L-arginine/ADMA and the L-arginine/SDMA ratios in arteriogenic erectile dysfunction subgroups were significantly lower than both in controls (p < 0.05) and in non-arteriogenic erectile dysfunction patients (p < 0.05); the two ratios in non-arteriogenic erectile dysfunction patients did not differ from those in the controls (p > 0.05). We conclude that ADMA and SDMA concentrations are significantly higher and L-arginine/ADMA ratio lower in patients who have arteriogenic erectile dysfunction compared with both patients with non-arteriogenic erectile dysfunction and controls. The negative correlation between ADMA and severity of erectile dysfunction is present only in patients with arteriogenic erectile dysfunction. This study supports the importance to always distinguish arteriogenic from non-arteriogenic erectile dysfunction patients to study the complicate erectogenic mechanisms that lead to erectile dysfunction and also to provide potential therapeutic agents for patients with arteriogenic erectile dysfunction.

Protein profiling of Guillain-Barrè syndrome cerebrospinal fluid by two-dimensional electrophoresis and mass spectrometry.

Protein profiling of cerebrospinal fluid in Guillain-Barrè syndrome (GBS), an acute and immune-mediated disease affecting the peripheral nervous system, was performed by two-dimensional electrophoresis. Significant modulated spots in GBS patients vs. control groups (a group of multiple sclerosis patients and one of healthy donors) underwent MALDI-TOF/TOF investigation. Inflammation-related proteins, such as vitamin D-binding protein, beta-2 glycoprotein I (ApoH), and a complement component C3 isoform were up-regulated in GBS, whereas transthyretin (the monomer and the dimer forms), apolipoprotein E, albumin and five of its fragments were down-regulated. Then, we used an isoelectric-focusing-dinitrophenylhydrazine-based technique to analyse the extent of carbonylation and, as a result, of oxidative damage of GBS CSF proteome. We observed a major sensitivity to carbonylation for albumin and alpha-glycoprotein in inflammation and a selective increase of reactivity for a glycosylated Fab from an IgM globulin in GBS CSF. Our results add new proteins to candidate CSF features of GBS, and suggest that oxidative stress could contribute to the immunopathological mechanisms in this syndrome.

Differential cerebro spinal fluid proteome investigation of Leber hereditary optic neuropathy (LHON) and multiple sclerosis

Lebers hereditary optic neuropathy (LHON) is a genetic disease leading to the loss of central vision and optic nerve atrophy. The existence of occasional cases of LHON patients developing a Multiple Sclerosis (MS)-like illness and the hypothesis that mtDNA variants may be involved in MS suggest the possibility of some common molecular mechanisms linking the two diseases. We have pursued a comparative proteomics approach on cerebrospinal fluid (CSF) samples from LHON and MS patients, as well as healthy donors by employing 2-DE gel separations coupled to MALDI-TOF-MS and nLC-MS/MS investigations. 7 protein spots showed significant differential distribution among the three groups. Both CSF of LHON or MS patients are characterized by lower level of transthyretin dimer adduct while a specific up regulation of Apo A-IV was detected in LHON CSF.