Virological pattern of hepatitis B infection in an HIV-positive man with fatal fulminant hepatitis B: a case report

<p>Abstract</p> <p>Introduction</p> <p>There seem to be no published data concerning the clinical impact of populations of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of HIV-infected people with severe acute hepatitis.</p> <p>Case presentation</p> <p>A 26-year-old Caucasian man presenting to our hospital with clinical symptoms suggesting acute hepatitis was found to have an acute hepatitis B profile upon admission. He developed fatal fulminant hepatitis and was found to be heavily immunocompromised due to HIV-1 infection. He had a high plasma HBV and HIV load, and analysis of the partial pre-S1/pre-S2 domain showed the presence of mixed infection with D and F genotypes. Analysis of the point mutations within this region revealed the presence of HBV strains with amino acid substitutions at the immunodominant epitopes involved in B or T cell recognition. A homogeneous population of a pre-core mutant strain harbouring the A1896G and A1899G affecting HBeAg expression was invariably found in the liver tissue, plasma and peripheral blood mononuclear cells despite active HBeAg secretion; it was the dominant strain in the liver only, and was characterised by the presence of two point mutations in the direct repeat 1 domain involved in HBV replication activity. Taken together, these mutations are indicative of a highly replicative virus capable of evading immune responses.</p> <p>Conclusion</p> <p>This case report provides clinical evidence of a possible association between the rapid spread of highly replicative escape mutants and the development of fulminant hepatitis in a heavily immunocompromised patient. Virological surveillance of severe acute hepatitis B may be important in establishing an early treatment strategy involving antiviral drugs capable of preventing liver failure, especially in individuals for whom liver transplantation is not accepted as a standard indication.</p

IgA anti-Actin antibodies in children with celiac disease: comparison of immunofluorescence with Elisa assay in predicting severe intestinal damage

<p>Abstract</p> <p>Background</p> <p>Previous studies have demonstrated that the presence of serum IgA antibodies against actin filaments (AAA) in patients with celiac disease (CD) is strongly associated with mucosal damage and severe degrees of villous atrophy.</p> <p>The aims of the present study were (1) to verify the effectiveness of IgA-AAA in newly diagnosed CD patients in a clinical setting (2) to compare the immunofluorescence assay with ELISA assay; (3) to compare the correlation of our IgA anti-tissue transglutaminase antibodies (tTG-Ab) class with mucosal intestinal lesions.</p> <p>Methods</p> <p>90 patients underwent endoscopy and multiple biopsies for suspected CD on the basis of symptoms, in presence of positive tTG-Ab tests. Twenty biopsied and 25 not-biopsied subjects with negative tTG-Ab were tested as control groups.</p> <p>IgA-AAA assays were performed by indirect immunofluorescence using rat epithelial intestinal cells, and by ELISA with a commercial kit. tTG-Ab assay was a radio-binding assay.</p> <p>Intestinal specimens were collected by upper endoscopy and the histological study was done according to the Marsh's classification modified by Oberhuber (M/O). Auto-antibodies assays and histological evaluation have been performed blindly by skilled operators.</p> <p>Results</p> <p>CD diagnosis was confirmed in 82 patients (type I M/O in 2 patients, IIIA in 18 patients, IIIB in 29 patients and IIIC in 33 patients). Two patients with type 1 lesion in presence of positive tTG-Ab and abdominal complaints, started a gluten free diet.</p> <p>The rate of IgA-AAA positivity (sensitivity) by IFI and ELISA in histologically proven celiac disease patients, were 5.5% and 25% patients in IIIA, 27.5% and 34.4% patients in IIIB, 78.8% and 75% in IIIC patients, respectively.</p> <p>Patients with normal or nearly normal mucosa, regardless of tTG-Ab status, presented negative IgA-AAA IFI assay. On the other hand, 1 patient with normal mucosa but positive tTG-Ab, also presented positive IgA-AAA ELISA. All healthy non biopsied controls had negative IgA-AAA. tTG-Ab serum concentration was significantly correlated with more severe intestinal lesion (IIIB, IIIC M/O).</p> <p>Conclusions</p> <p>IgA-AAA may be undetectable in presence of severe mucosal damage. Histology is still necessary to diagnose celiac disease and IgA-AAA cannot be included in usual screening tests, because it has little to offer if compared to the well-established tTG-Ab.</p> <p>IgA-AAA could be an adjunctive, very useful tool to support the diagnosis of CD in case of suboptimal histology, when the biopsy is to be avoided for clinical reasons, or in case of negative parents' consensus.</p

c-MYC amplification and c-myc protein expression in pancreatic acinar cell carcinomas. New insights into the molecular signature of these rare cancers.

The molecular alterations of pancreatic acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MANECs) are not completely understood, and the possible role of c-MYC amplification in tumor development, progression, and prognosis is not known. We have investigated c-MYC gene amplification in a series of 35 ACCs and 4 MANECs to evaluate its frequency and a possible prognostic role. Gene amplification was investigated using interphasic fluorescence in situ hybridization analysis simultaneously hybridizing c-MYC and the centromere of chromosome 8 probes. Protein expression was immunohistochemically investigated using a specific monoclonal anti-c-myc antibody. Twenty cases had clones with different polysomies of chromosome 8 in absence of c-MYC amplification, and 5 cases had one amplified clone and other clones with chromosome 8 polysomy, while the remaining 14 cases were diploid for chromosome 8 and lacked c-MYC amplification. All MANECs showed c-MYC amplification and/or polysomy which were observed in 54% pure ACCs. Six cases (15.3%) showed nuclear immunoreactivity for c-myc, but only 4/39 cases showed simultaneous c-MYC amplification/polysomy and nuclear protein expression. c-myc immunoreactivity as well as c-MYC amplification and/or chromosome 8 polysomy was not statistically associated with prognosis. Our study demonstrates that a subset of ACCs shows c-MYC alterations including gene amplification and chromosome 8 polysomy. Although they are not associated with a different prognostic signature, the fact that these alterations are present in all MANECs suggests a role in the acinar-neuroendocrine differentiation possibly involved in the pathogenesis of MANECs

Correlations between Molecular Alterations, Histopathological Characteristics, and Poor Prognosis in Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. We sequenced 164 EAC samples of naïve patients (without chemo-radiotherapy) with high coverage using next-generation sequencing technologies. A total of 337 variants were identified across the whole cohort, with TP53 as the most frequently altered gene (67.27%). Missense mutations in TP53 correlated with worse cancer-specific survival (log-rank p = 0.001). In seven cases, we found disruptive mutations in HNF1alpha associated with other gene alterations. Moreover, we detected gene fusions through massive parallel sequencing of RNA, indicating that it is not a rare event in EAC. In conclusion, we report that a specific type of TP53 mutation (missense changes) negatively affected cancer-specific survival in EAC. HNF1alpha was identified as a new EAC-mutated gen

Adolescents’ Characteristics and Peer Relationships in Class: A Population Study

Abstract: Background: This study aimed to investigate differences in adolescents’ social relationships with classmates of diverse gender, socioeconomic status, immigrant background, and academic achievement. Methods: A population of 10th-grade students (N = 406,783; males = 50.3%; Mage = 15.57 years, SDage = 0.75) completed the Classmates Social Isolation Questionnaire (CSIQ), an instrument specifically designed to measure two distinct but correlated types of peer relationships in class: peer acceptance and peer friendship. To obtain reliable comparisons across diverse adolescent characteristics, the measurement invariance of the CSIQ was established by means of CFAs and then latent mean differences tests were performed. Results: Immigrant background, academic achievement, and socioeconomic status all proved to be important factors influencing relationships with classmates, while being a male or a female was less relevant. Being a first-generation immigrant adolescent appears to be the foremost risk factor for being less accepted by classmates, while having a low academic achievement is the greatest hindrance for having friends in the group of classmates, a finding that diverges from previous studies. Conclusions: This population study suggests that adolescent characteristics (especially immigrant background, socioeconomic status, and academic achievement) seem to affect social relationships with classmates

Misure di sismica passiva per la caratterizzazione dinamica dell’argine destro del fiume Po

Misure di sismica passiva per la caratterizzazione dinamica dell’argine destro del fiume P

Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease-free survival and overall survival in patients with gastric carcinoma

ntroduction: Cyclooxygenases regulate the production of prostaglandins and play a role in tumor development and progression. The authors investigated the prognostic impact of expression COX-2 in gastric cancer resected patients. Methods: A cohort of 194 patients with gastric cancer without distant metastasis who underwent R0 gastric resection were enrolled in this study. Association between factors including clinico-pathological variables and COX-2 scores, were assessed. Results: A correlation between COX-2 expression, grading and advanced penetration dept (mean COX-2 expression 74% in early gastric cancer (EGC) versus 52% in non-EGC, p=0.0017). There was an association between COX-2 expression and the presence of lymph-nodes metastasis (p<0,0001, 2) We also observed a significant association between COX-2 expression and relapse of disease (p=0.05 KM) but not with poor survival. Conclusions: High COX-2 protein expression, serosal invasion (pT3-pT4), and presence of lymph-node metastasis are poor prognostic factors in patients with gastric carcinoma without distant metastasis