148 research outputs found

    Hepatitis C Virus (HCV) genotypes distribution among hepatocellular carcinoma patients in Southern Italy: a three year retrospective study

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    Abstract Background Hepatocellular carcinoma (HCC) is one of the major cause for cancer in the world. Aim of this case-control study was to investigate the distribution pattern of HCV genotypes among HCC patients and suggest whether infection with specific subtypes may be associated with an increased risk of progression to cancer. Methods 152 HCC anti-HCV positive patients, fulfilling the criteria from the Barcelona 2000 EASL conference, and 568 patients HCV chronically infected but without HCC as control group were included in the study. Serum of each patient was evaluated for viral load estimation and genotyping. Results Males with HCC significantly showed to have quite 2 times higher risk of exposure to HCV infection (OR = 1.72; 95% CI = 1.15–2.58). Moreover, HCC was significantly associated with older age. In fact, > 50 years older patients showed to have a higher risk of developing HCC (OR = 17.4; 95% CI = 4.24 to 71.36) compared to younger patients. HCV RNA rate was significantly higher (83.7%) among HCC patients than in the control group (61.4%, p < 0.001) and the most prevalent genotype was 1b (68.0% in HCC vs 54.4% in the control group, p < 0.005). HCC patients significantly have a risk of exposure to HCV 1b infection almost 2 times greater than the control group (OR = 1.8; 95% CI = 1.11–2.82). The multivariate-adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non-1b was 1.65 (1.16–2.33). Conclusions Our study detected a significantly higher rate of HCV RNA positivity and a higher rate of HCV 1b infection in HCC patients, suggesting the strict association between subtype 1b infection and HCC. A prospective study with larger number of samples would be needed to confirm our results

    Impact of endobiliary radiofrequency ablation on survival of patients with unresectable cholangiocarcinoma: a narrative review

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    Cholangiocarcinoma (CCA) is a rare cancer originating from the biliary epithelium and accounts for about 3% of all gastrointestinal malignancies. Unfortunately, the majority of patients are not eligible for surgical resection at the time of diagnosis, because of the locally advanced stage or metastatic disease. The overall survival time of unresectable CCA is generally less than 1 year, despite current chemotherapy regimens. Biliary drainage is often required as a palliative treatment for patients with unresectable CCA. Recurrent jaundice and cholangitis tend to occur because of reobstruction of the biliary stents. This not only jeopardizes the efficacy of chemotherapy, but also causes significant morbidity and mortality. Effective control of tumor growth is crucial for prolonging stent patency and consequently patient survival. Recently, endobiliary radiofrequency ablation (ERFA) has been experimented as a treatment modality to reduce tumor mass, and delay tumor growth, extending stent patency. Ablation is accomplished by means of high-frequency alternating current which is released from the active electrode of an endobiliary probe placed in a biliary stricture. It has been shown that tumor necrosis releases intracellular particles which are highly immunogenic and activate antigen-presenting cells, enhancing local immunity directed against the tumor. This immunogenic response could potentially enhance tumor suppression and be responsible for improved survival of patients with unresectable CCA who undergo ERFA. Several studies have demonstrated that ERFA is associated with an increased median survival of approximately 6 months in patients with unresectable CCA. Furthermore, recent data support the hypothesis that ERFA could ameliorate the efficacy of chemotherapy administered to patients with unresectable CCA, without increasing the risk of complications. This narrative review discusses the results of the studies published in recent years and focuses on the impact that ERFA could have on overall survival of patients with unresectable cholangiocarcinoma

    Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

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    To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

    Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization.

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    Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications

    LA FREQUENZA CARDIACA COME FATTORE DI RISCHIO NELL'ANZIANO

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    ASPETI CLINICI DELLA CARDIOPATIA ISCHEMICA DELL'ANZIANO

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    Heart rate and blood pressure variability in subjects with vasovagal syncope

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    Autonomic nervous system control in subjects with vasovagal syncope is controversial. In the present study, we used short-term spectral analysis to evaluate autonomic control in subjects with recurrent vasovagal syncope. We assessed the ability of spectral indices of HR (heart rate) variability to predict tilt-test responses. A series of 47 outpatients with recurrent vasovagal syncope and with positive responses to head-up tilt testing underwent a further study of RR variability during controlled breathing at rest and during tilt testing. During controlled breathing, RR interval variability of total power (TPRR; P < 0.001), low-frequency power (LFRR; P < 0.05), high-frequency power (HFRR; P < 0.001) and HF expressed in normalized units (HFnu(RR); P < 0.001) were all higher, and LF expressed in normalized units (LFnu(RR)) and LF/HF ratio were lower in subjects with vasovagal syncope than in controls (P < 0.001). To assess the ability of spectral components of RR variability to predict tilt-test responses, we prospectively studied 109 subjects with recurrent vasovagal syncope. The two normalized measures, HFn(RR) and LFnu(RR), determined during controlled breathing alone predicted a positive tilt-test response (sensitivity, 76%; specificity, 99%; positive predictive value, 96%; and negative predictive value, 90%). During tilting, subjects with vasovagal syncope had lower SBP (systolic blood pressure; P < 0.05), LF component of peak SBP variability (LFSBP) and Unu(RR) than controls, and higher TPRR, HFRR, HFnu(RR) and alpha HF (P < 0.001). These spectral data indicate that vagal sinus modulation is increased at rest in subjects with vasovagal syncope. Spectral analysis of RR variability during controlled breathing, a procedure that predicts tilt-test responses, could be a useful guide in choosing the method of tilt testing
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