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Many patients with hepatitis C chronic infection (HCV+ patients) experience symptoms (fatigue, dyspnea) not proportional to the liver involvement and resemble symptoms of heart failure (HF). To our knowledge, no study evaluated at the same time serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tumor necrosis factor α (TNF-α) in HCV+ patients. Circulating NT-proBNP and TNF-α were assayed in 60 HCV+ patients, and in 60 sex- and age-matched controls. HCV+ patients showed significantly higher mean NT-proBNP and TNF-α levels than controls (P< 0.003). By defining high NT-proBNP level as a value higher than 125 pg/mL (the single cutoff point for outpatients under 75 years of age), 28% of HCV+ and 7% controls had high NT-proBNP (chi-square; P< 0.002). With a cutoff point of 900 pg/mL (that should be used for ruling in HF in patients age 50–75; such as the patients in our study), 3% HCV+ and 0 controls had high NT-proBNP. In conclusion, the study demonstrates high levels of circulating NT-proBNP and TNF-α in HCV+ patients. The increase of NT-proBNP may indicate the presence of a subclinical cardiac dysfunction. Further prospective studies quantifying symptoms and correlating these with echocardiographic parameters are needed to confirm this association. [ABSTRACT FROM AUTHOR]

In papillary thyroid carcinomas (PTCs), oncogenes activate a transcriptional program including the upregulation of CXCL10 chemokine, which stimulates proliferation and invasion. Furthermore, peroxisome proliferator-activated receptor-γ (PPARγ) activators thiazolidinediones (TZDs) modulate CXCL10 secretion in normal thyroid follicular cells (TFC), and inhibit PTC growth. Until now, no study has evaluated the effect of cytokines on CXCL10 secretion in PTCs, nor the effect of PPARγ activation. The combined effects of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) stimulation on CXCL10 secretion in primary cells from PTCs and TFC were tested. Furthermore, the effect of PPARγ activation by TZDs, on CXCL10 secretion and proliferation in these cell types was studied. In primary cultures of TFC and PTCs CXCL10 production was absent under basal conditions; a similar dose-dependent secretion of CXCL10 was induced by IFNγ in both cell types. TNFα alone induced a slight but significant CXCL10 secretion only in PTCs. The stimulation with IFNγ+TNFα induced a synergistic CXCL10 release in both cell types; however, a secretion more than ten times higher was induced in PTCs. Treatment of TFC with TZDs dose-dependently suppressed IFNγ+TNFα-induced CXCL10 release, while TZDs stimulated CXCL10 secretion in PTCs. A significant antiproliferative effect by TZDs was observed only in PTCs. In conclusion, a dysregulation of CXCL10 secretion has been shown in PTCs. In fact, a CXCL10 secretion more than ten times higher has been induced by IFNγ+TNFα in PTCs with respect to TFC. Moreover, TZDs inhibited CXCL10 secretion in TFC and stimulated it in PTCs. The effect of TZDs on CXCL10 was unrelated to the significant antiproliferative effect in PTCs. [ABSTRACT FROM AUTHOR]

To evaluate CXCL10 and CCL2 in patients with hepatitis C virus chronic infection in presence/absence of autoimmune thyroiditis (AT). CXCL10 was significantly higher in: (1) patients with AT than controls without AT (control 1) (P218 pg/mL, 2% of control 1, 14% of patients with AT, 68% of patients with hepatitis C infection, 81% of HCVAT had high CXCL10 (P< 0.0001; chi-square). CCL2 was similar in control 1 and patients with AT. CCL2 was significantly higher in: (1) patients with hepatitis C infection than control 1 (P 0.04; ANOVA); (2) HCVAT than patients with AT (P 0.03) and control 1 (P 0.02); no difference was observed between HCV with or without AT. Our study demonstrates: (1) higher circulating CXCL10 and CCL2 in patients with hepatitis C virus chronic infection than in controls; (2) higher CXCL10 in HCVAT than in patients with hepatitis C infection, suggesting a stronger Th1 immune response in these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Anaplastic thyroid cancer (ATC) is often unoperable and chemotherapy and radiotherapy are the main treatments. Until now ‘primary ATC cell cultures’ (ANA) have been developed from surgical biopsies. The possibility to obtain ANA from fine-needle aspiration (FNA-ANA) and to test their sensitivity to different drugs could increase the effectiveness of treatments and avoid unnecessary surgical procedures. DESIGN: To obtain FNA-ANA from six ATC patients before undergoing surgery and to evaluate the chemosensitivity of FNA-ANA to chemotherapeutic agents and thiazolidinediones (TZD). METHODS AND RESULTS: FNA-ANA from the six ATC patients were cultured in RPMI 1640 and propagated in DMEM. Chemosensitivity was evaluated by inhibiting the proliferation with increasing concentrations of five different chemotherapeutic agents (bleomycin, cisplatin, gemcitabine, etoposide, and carboplatin) or TZD (rosiglitazone). Chemotherapeutic agents significantly inhibited (P<0.0001) FNA-ANA proliferation, such as TZD (P<0.001); etoposide was the most effective in reducing cell growth. Another ANA culture for each patient was obtained from a biopsy specimen; the results for the chemosensitivity tests were similar to those obtained with FNA-ANA. The V600EBRAF mutation was observed in two ATC patients; the inhibition of proliferation by drugs was similar in tumors with or without V600EBRAF mutation. CONCLUSIONS: Our study demonstrates 1) the possibility to obtain FNA-ANA, and opens the way to the use of FNA-ANA to test the chemosensitivity to different drugs (chemotherapeutic agents or TZD; and possibly the radiosensitivity) in each patient, avoiding unnecessary surgical procedures and the administration of inactive chemotherapeutics; and 2) that etoposide is highly effective in reducing ATC cell growth in vitro. [ABSTRACT FROM AUTHOR]

Objective:The present study prospectively investigated prevalence and features of thyroid cancer in patients with hepatitis C virus–related chronic hepatitis (HCV) in comparison to two samples from the general population with different iodine intake. Design:We studied the prevalence of thyroid cancer in 308 unselected HCV patients in comparison to two population-based, gender- and age-matched control groups: 1) 616 subjects from an iodine deficient area; 2) 616 subjects from an iodine-sufficient area. Thyroid status was assessed by measurement of circulating thyroid hormones and autoantibodies, thyroid ultrasonography, and when indicated, fine-needle aspiration cytology. Main outcome:Circulating thyrotropin, anti-thyroglobulin, and anti-thyroperoxidase antibodies levels, and the prevalence of hypothyroidism were significantly higher in HCV patients (p< 0.001 for all). Six patients with papillary thyroid cancer were detected among HCV patients, whereas no case was observed in control 1 (p 0.001), and only one case was observed in control 2 (p 0.003). In HCV patients 83 with thyroid cancer had evidence of thyroid autoimmunity vs31 of the other HCV patients (p 0.02). Conclusions: These data suggest a high prevalence of thyroid papillary cancer in HCV patients, overall in presence of thyroid autoimmunity; careful thyroid monitoring is indicated during the follow-up of these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Several studies have reported the association of systemic sclerosis (SSc) with thyroid autoimmune disorders, but most of them have neither an appropriate control group nor include a complete thyroid work-up. DESIGN: The aim of our study was to evaluate the prevalence of thyroid disorders in a large number of patients with SSc using a complete clinical evaluation. METHODS: Thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroglobulin and antithyroid-peroxidase (AbTPO) autoantibodies, thyroid ultrasonography and blood flow and fine needle aspiration were performed in 202 SSc patients versus 404 gender- and age-matched controls from the general population, with similar iodine intake, to evaluate the prevalence of clinical and subclinical thyroid disorders. RESULTS: Odds ratio (OR) for female SSc versus controls was: for subclinical hypothyroidism, 3.2 (95% CI) = 1.8–5.7); for clinical hypothyroidism, 14.5 (95% CI = 2.3–90.9); for AbTPO positivity, 2.7 (95% CI = 1.8–4.1); for hypoechoic pattern, 3.2 (95% CI = 2.2–4.7); for thyroid autoimmunity, 3.7 (95% CI = 2.6–5.4); for thyroid volume <6 ml, 1.8 (95% CI = 1.2–2.7). OR for thyroid autoimmunity in male SSc versus controls was 10.8 (95% CI = 2.2–52.4). Mean values of TSH in female SSc, and of AbTPO in female and male SSc were higher (P <0.01) than in controls. We observed three cases of Graves’ disease in female SSc versus zero in controls (P = 0.0140), and two cases of papillary thyroid cancer in SSc patients. CONCLUSIONS: Thyroid function, AbTPO and ultrasonography should be tested as part of the clinical profile in SSc patients. Females, subjects with positive AbTPO and hypoechoic and small thyroid should have thyroid function follow-up and appropriate treatment in due course. [ABSTRACT FROM AUTHOR]

Background. The ‘RISchio CArdiovascolare nei pazienti afferenti all’ Area Vasta In Dialisi (RISCAVID) study is an observational and prospective trial including the whole chronic haemodialysis (HD) population in the northwest part of Tuscany (1.235 million people). The aim of the study was to elucidate the relevance of traditional and non-traditional risk factors of mortality and morbidity in HD patients as well as the impact of different HD modalities. Methods. A total of 757 HD patients (mean age 66 ± 14 years, mean dialytic age 70 ± 76 months, diabetes 19%) were prospectively followed up for 30 months and all-cause mortality, cardiovascular (CV) mortality and non-fatal CV events (acute myocardial infarction and stroke) were registered. At the time of the enrolment, demographic, clinical and laboratory data of the whole population were entered into a centralized database. Serum albumin, high-sensitive C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-8 (IL-8) were centrally determined at the start of the study. Patients were stratified into three groups according to the HD modality: standard bicarbonate HD (BHD) (n = 424), haemodiafiltration (HDF) with sterile bags (n = 204) and online HDF (n = 129). The Cox proportional hazards regression assessed adjusted differences in CV morbidity and mortality risk; a multivariate analysis was also performed. Results. All-cause and CV mortality was 12.9%/year and 5.9%/year, respectively. Patients with combined high levels of CRP and pro-inflammatory cytokines showed an increased risk for CV (RR 1.9, P P P P Conclusions. Data at 30 months from this study showed the synergic effect of CRP and pro-inflammatory cytokines as the strong predictors of all-cause and CV mortality. HDF was associated with an improved cumulative survival independent of the dialysis dose. [ABSTRACT FROM AUTHOR]