Angela Alibrandi

Pulse wave velocity and augmentation index, but not intima-media thickness, are early indicators of vascular damage in hypercholesterolemic children

Eur J Clin Invest 2010; 40 (3): 250–257

Efficacy, Safety and Outcomes of ‘Inject and Cut’ Endoscopic Mucosal Resection for Large Sessile and Flat Colorectal Polyps

Background and Study Aims: The study examines the outcomes of the ‘inject and cut’ endoscopic mucosal resection (EMR), for large sessile and flat colorectal polyps. Patients and Methods: Between January 2006 and December 2008 all patients referred to our institution for EMR of large polyps were prospectively evaluated. The accuracy of lifting sign and the rate of en bloc and piecemeal resection, complications and recurrence were analyzed. Results: A total of 157 patients with 182 lesions (median size 24.7 ± 10.2 mm) were included in the study. The most frequent location was the sigmoid colon in 30.2%. Because of non-lifting sign, 5/182 lesions were referred to surgical resection and 177 (43 flat and 134 sessile) were resected, 79 (44.6%) en bloc and 98 (55.4%) piecemeal. There were 20 procedural (11.3%) and 2 late (1.1%) bleeding, 4 post-polypectomy syndrome (2.2%) and 2 perforations (1.1%). Bleeding was related to malignancy (p = 0.01). Intramucosal cancer was observed in 5 cases (2.8%) while invasive cancer was seen in 8 (4.5%). Malignancy was related to polyp size ≧30 mm (p = 0.002). Follow-up colonoscopy was performed in 147 patients with 172 EMR for a mean of 19.8 months. Recurrence was observed in 12/172 (6.9%) polyps. Conclusion: Inject and cut EMR is practical and effective with a low risk of complication and local recurrence.

Impact of hepatitis B virus (HBV) preS/S genomic variability on HBV surface antigen and HBV DNA serum levels

To evaluate whether hepatitis B virus (HBV) preS/S gene variability has any impact on serum hepatitis B surface antigen (HBsAg) levels and to analyze the replication capacity of naturally occurring preS/S variants, sera from 40 untreated patients with HBV‐related chronic liver disease (hepatitis B e antigen [HBeAg]‐positive, n = 11; HBeAg‐negative, n = 29) were virologically characterized. Additionally, phenotypic analysis of three different preS/S variant isolates (carrying a 183‐nucleotide deletion within the preS1 region, the deletion of preS2 start codon, and a stop signal at codon 182 within the S gene, respectively) was performed. HBV infecting 14 (35%) patients had single or multiple preS/S genomic mutations (i.e., preS1 and/or preS2 deletions, preS2 start codon mutations, C‐terminally truncated and/or “a” determinant mutated S protein). Presence of preS/S variants negatively correlated with HBsAg titers (r = −0.431; P = 0.005) and its prevalence did not significantly differ between HBeAg‐positive and HBeAg‐negative patients. No correlation was found between HBsAg and HBV DNA levels in patients infected with preS/S mutants, whereas a significant correlation was found between HBsAg and viremia levels (r = 0.607; P = 0.001) in patients infected with wild‐type HBV strains. HepG2 cells replicating the above‐mentioned three preS/S variants showed significant reduction of HBsAg secretion, retention of envelope proteins in the endoplasmic reticulum, less efficient virion secretion and nuclear accumulation of significantly higher amounts of covalently closed circular DNA compared with wild‐type HBV replicating cells. Conclusion: In patients infected with preS/S variants, HBV DNA replication and HBsAg synthesis/secretion appear to be dissociated. Therefore, the use of HBsAg titer as diagnostic/prognostic tool has to take into account the frequent emergence of preS/S variants in chronic HBV infection. (HEPATOLOGY 2012;)

Endoscopic ultrasound-guided fine needle aspiration with 22- and 25-gauge needles in solid pancreatic masses: A prospective comparative study with randomisation of needle sequence

BACKGROUND The difference in the diagnostic accuracy of 22- versus 25-gauge needles in EUS-FNA is not clear. AIMS To compare the rates of technical success, diagnostic accuracy and complications of EUS-FNA performed with 22-gauge and 25-gauge needles on the same solid pancreatic mass. METHODS All patients with solid pancreatic masses evaluated from September 2007 to December 2008 were enrolled and underwent EUS-FNA with both 22- and 25-gauge needles with randomisation of needle sequence. The accuracy of the EUS-FNA was determined by comparing the cytological results with the final surgical pathological diagnoses or with the results of a clinical follow-up. A cytological score with different qualitative parameters was created, and a comparison between these parameters was carried out for each needle. RESULTS Fifty patients with 50 pancreatic masses were recruited. Technical success was 100% and no complications occurred. Diagnostic accuracy was 94% and 86% for the 25- and 22-gauge needles, respectively. Analysis of the cytological score showed a tendency towards the 25-gauge needle, although the difference was not statistically significant. CONCLUSIONS EUS-FNA performed with 22- or 25-gauge needles had the same diagnostic accuracy. Our study results confirm a significant trend towards a better cytological diagnosis for the 25-gauge needle.

Replicative and Transcriptional Activities of Hepatitis B Virus in Patients Coinfected with Hepatitis B and Hepatitis Delta Viruses

ABSTRACT Hepatitis B virus (HBV) and hepatitis delta virus (HDV) interplay was investigated by examining liver and serum samples from 21 coinfected and 22 HBV-monoinfected patients with chronic liver disease. Different real-time PCR assays were applied to evaluate intrahepatic amounts of HBV DNA, covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA), pre-S/S RNAs, and HDV RNA. Besides HBV DNA and HDV RNA levels, HBsAg concentrations in the sera were also determined. HDV-coinfected cases showed significantly lower median levels of serum HBV DNA (−5 log), intrahepatic relaxed-circular DNA (−2 log), and cccDNA (−2 log) than those of HBV-monoinfected cases. Interestingly, pgRNA and pre-S/S RNA amounts were significantly lower (both −1 log) in HDV-positive patients, whereas serum HBsAg concentrations were comparable between the two patient groups. Pre-S/S RNA and HBsAg amounts per cccDNA molecule were higher in HDV-positive patients (3-fold and 1 log, respectively), showing that HBV replication was reduced, whereas synthesis of envelope proteins was not specifically decreased. The ratios of cccDNA to intracellular total HBV DNA showed a larger proportion of cccDNA molecules in HDV-positive cases. For these patients, both intrahepatic and serum HDV RNA amounts were associated with cccDNA but not with HBsAg or HBV DNA levels. Finally, HBV genomes with large deletions in the basal core promoter/precore region were detected in 5/21 HDV-positive patients but in no HDV-negative patients and were associated with lower viremia levels. These findings provide significant information about the interference exerted by HDV on HBV replication and transcription activities in the human liver.

Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency: an observational study.

Objective  We examined the effect of different conditions of nutritional iodine intake on maternal thyroid function throughout gestation in a cohort of healthy, anti‐thyroid antibody‐negative women from a mild‐moderately iodine‐deficient (ID) area.

Impact of occult hepatitis B virus infection on the outcome of chronic hepatitis C.

BACKGROUND & AIMS Occult hepatitis B virus infection (OBI) frequently occurs in patients with hepatitis C virus (HCV) related chronic hepatitis (CHC), but the influence of OBI on the CHC outcome is still uncertain. This observational cohort study evaluated the clinical evolution of CHC patients according to their OBI status. METHODS From 1991 to 2000, 326 hepatitis B surface antigen negative CHC patients were tested for OBI by the analysis of liver biopsy DNA extracts. A total of 128/326 cases (39.2%) tested OBI positive and 198/326 (60.8%) OBI negative. Ninety-four of 326 patients (37 OBI positive, 57 OBI negative) were followed-up for a median time of 11 years (range 5-19 years). During the follow-up, 79/94 patients underwent anti-HCV treatments and 25 [corrected] achieved a sustained virological response that occurred independently of their OBI status RESULTS Eighteen patients (13/37 OBI positive, 5/57 OBI negative, p < 0.01) developed hepatocellular carcinoma (HCC). Among the 76 non-HCC individuals, 15 subjects (8/24 OBI positive, 7/52 OBI negative, p < 0.05) developed advanced forms of cirrhosis. Eighteen patients died during follow-up and 2 underwent liver transplantation. OBI positive individuals had a cumulative survival rate significantly shorter than OBI negative individuals (p = 0.003). Liver-related deaths were more frequently found in OBI positive than OBI negative patients (12/37 OBI positive vs. 6/57 OBI negative patients respectively, p < 0.01). Finally, non-response to anti-HCV therapy was significantly associated with lower survival (p = 0.02). CONCLUSIONS Among CHC patients, occult HBV co-infected individuals are a category at high risk of progression toward cirrhosis, HCC development, and lower survival.

Increased prevalence of acromegaly in a highly polluted area

OBJECTIVE Despite the contribution of national registries and population-based reports, data concerning the epidemiology of acromegaly is scanty. In addition, the role of the environmental context has not been investigated. DESIGN Epidemiology of acromegaly was studied in the province of Messina (Sicily, Italy), focusing on the influence of environmental factors. METHODS Four zones, characterized by different degrees of exposition to environmental toxins due to industrial pollution, were identified in the province: area A (76,338 inhabitants), area B (287,328 inhabitants), area C (243,381 inhabitants), and area D (47,554 inhabitants) at low, middle-low, middle, and high industrial density respectively. We identified all acromegalics who were born and resided in the province of Messina, among patients either referred to our endocrine unit or referred elsewhere but recorded in the archives of the provincial healthcare agency. RESULTS In the province of Messina, we found 64 patients (2 in area A, 24 in area B, 28 in area C, and 10 in area D). Macroadenomas were 60%, the male/female ratio was 1, and mean age at diagnosis (±s.e.m.) was 45.4±1.6 years. Overall, prevalence was 97 c.p.m. in the province (26 c.p.m. in area A, 84 c.p.m. in area B, 115 c.p.m. in area C, and 210 c.p.m. in area D). Risk ratio (RR), calculated in every area assuming area A as a reference, showed an increased risk of developing acromegaly in people residing in area D (RR=8.03; P<0.0014). CONCLUSION This study confirms the prevalence of acromegaly reported recently. The increased risk of developing this disease in area D suggests that the pathogenetic role of environmental context needs to be better evaluated.

Smoke exposure and circulating progenitor cells: Evidence for modulation of antioxidant enzymes and cell count

BACKGROUND Cigarette smoking is involved in vascular inflammation and impairment of circulating progenitor cells (CPCs), including endothelial progenitor cells (EPCs). The study aim was to evaluate the redox balance of these cells in relation to smoking exposure. METHODS Circulating cells from 36 healthy smokers and 26 controls were isolated and identified by flow cytometry. ROS generation, mRNA and protein cell expression, and enzymatic activity of MnSOD, catalase, and GPx-1 were evaluated. RESULTS Smokers showed higher levels of CRP and fibrinogen and lower levels of HDL-C. ROS and MnSOD were higher (p<0.001), while catalase and GPx-1 were lower (p<0.001) as was EPC number (p<0.001) in smokers. CPC and EPC correlated with HDL-C, CRP, ROS and enzyme expression and activity. CONCLUSIONS Our data suggest that smoking exposure involves antioxidant enzymes in CPCs and EPCs and that the inflammatory response in smokers plays an important role in impairing cells and their antioxidant functions.

Circulating progenitor cells are increased in newly diagnosed untreated hypertensive patients with arterial stiffening but normal carotid intima-media thickness

Circulating progenitor cells (CPCs), including endothelial progenitor cells (EPCs), have a key role in endothelium repair. Cellular NADPH oxidase (Nox) enzymes, including Nox-containing gp91phox, represent a source of reactive oxygen species (ROS); ROS trigger protective signals but may also have detrimental effects. Cellular defenses against ROS include the enzymes manganese superoxide dismutase (MnSOD), catalase (CAT) and glutathione peroxidase type-1 (GPx-1). We investigated the relationships of CPCs with cellular gp91phox, MnSOD, CAT, GPx-1 and ROS levels and with carotid intima-media thickness (cIMT) and stiffness in hypertensives without additional risk factors for cardiovascular disease. CPCs from 53 newly diagnosed, untreated hypertensives and from 29 controls were isolated and identified by flow cytometry. gp91phox, MnSOD, CAT, and GPx-1 mRNA and protein expression and ROS generation were evaluated in enriched samples of CD34+ cells; cIMT and stiffness were assessed. Hypertensives showed higher arterial stiffness (P<0.001) but no difference in cIMT with respect to controls. ROS generation was slightly increased (P=0.04), whereas gp91phox, MnSOD, CAT and GPx-1 were significantly higher (P<0.001) with respect to controls, as was CPC number (P<0.001), but EPCs were no different. CPC and EPC numbers correlated with gp91phox, ROS and fibrinogen (P<0.001); moreover, gp91phox, MnSOD, CAT and GPx-1 were correlated with CPC number. In early phases of arterial hypertension, before the development of wall thickening and even in the presence of arterial mechanical impairment, CPC number may be increased to maintain an adequate number of EPCs in peripheral blood.