svr 24 achievement two weeks after a tripled dose of daclatasvir in an hcv genotype 3 patient

Abstract Directly-acting antivirals (DAA) have changed the chronic hepatitis C virus (HCV) infection therapeutic scenario allowing virus eradication in more than 95% of patients, independently from the genotype, with 12 to 24-week treatment regimens. We describe a 51-year-old Pakistani man with a chronic HCV-genotype 3 (GT3a) infection with moderate liver fibrosis, who achieved sustained virological response (SVR) 24 after a tripled dose of Daclatasvir (DCV) taken erroneously associated to Sofosbuvir (SOF). The patient had a concomitant intestinal TB infection whose treatment had been delayed in order to firstly eradicate HCV to reduce the liver toxicity of anti-mycobacterial drugs. Thanks to the cultural mediator support, we explained to the patient the correct posology of each drug to take during the day consisting of 12 week SOF (400 mg daily) plus DCV (60 mg daily) regimen. He returned 13 days after for a programmed visit and we were surprised to learn that he had taken 3 pills of DCV (180 mg/daily) instead of one, thus ending DCV assumption after only 9 days while SOF was taken correctly. He complained no symptoms. We immediately performed blood test that showed alteration of lactate dehydrogenase, creatine phosphokinase, and creatin kinase MB activity. At day 15 we stopped SOF closely monitoring the patient. Blood test alterations returned normal after one week of treatment suspension, HCV viremia remained suppressed after 4, 12 and 24 weeks proving HCV eradication. If confirmed, these data could suggest that higher doses of DCV, if tolerated, might be employed in short-time HCV-GT3 treatment

Splenic rupture after colonoscopy: Report of a case and review of literature

Splenic rupture is a rare complication of colonoscopy. For this reason the diagnosis could be delayed and the outcome dismal. Fifty-four cases of splenic rupture after colonoscopy have been described in the literature. The majority of the cases required emergent or delayed splenectomy, 13 of these cases were treated conservatively. The main feature that stands out from the review of the literature is the "surprise" of this unexpected complication. This factor explains the elevated mortality (2 out of 54 cases), likely due to the delay in diagnosis. The case here described is probably among the most complex published in the literature; in fact the presence of dense intra-abdominal adhesions not only contributed to the complication itself, but also explain the confinement of the hemoperitoneum to the left supra-mesocolic space and the delayed presentation (13 days from the time of the trauma)

Abscess and cecum carcinoma in inguinal hernia: case report

Cecal adenocarcinoma within an inguinal hernial sac is an uncommon clinical condition. A primary adenocarcinoma of the cecum in a right sided inguinal hernia is presented and discussed. This case represents one of the unexpected findings in a hernia sac and also very rare septic evolution. This particular condition is a main dignostic and therapeutic challenge

Molecular diagnosis of pancreatic cancer: where do we stand?

Pancreatic cancer remains a disease with a dismal prognosis due mostly to its late diagnosis. An early diagnosis would have a significant impact on the prognosis and, eventually, on the incidence of the disease itself. Many progresses have been made in the molecular diagnosis of pancreatic cancer. High risk patients would likely benefits from biologic screening, before the general population. Most of the markers remain limited to phase I and II studies. The challenges include the lack of specificity of some of the markers, as well as the lack of standardization within the laboratories. Further research is necessary prior to the application of the currently known biomarkers for the diagnosis of pancreatic cancer

Clinical and biological markers in gastric cancer: update and perspectives.

Gastric cancer is the second cause of death from cancer worldwide and the only chance to reach better outcomes lays on an early diagnosis. The need for non-invasive, low-cost tests is invoked also in countries in which imaging and endoscopic screening have already showed the ability to improve early diagnosis and overall survival. Genomic medicine could allow a better understanding of regulatory pathways driving the development and growth of gastric cancer and the characterization of specific molecular targets actually stimulate new drug developments. The knowledge of the role of Helicobacter pylori (HP) in gastric tumor pathogenesis has put new insides in the understanding of this peculiar disease and enriched the field of gastric biomarkers

Strong correlation between diet and development of colorectal cancer.

Multiple factors have been described among the causes of non-hereditary colorectal cancer. In Western countries, the most common risk factors include upper-middle socioeconomic status and dietary regimens rich in proteins and animal fats. High consumption of red meats, smoked foods, cold cuts, or canned foods is believed to contribute to carcinogenesis as they directly affect epithlial turnover and cause metabolism of biliary acids. Dietary fibers have protective effects in that they capture the fats and biliary acids, thereby inhibiting their activity. Tobacco smoking acts both locally and systemically on the colorectal mucosa through the production of carcinogenic agents. Finally, the action of alcohol, in association with nicotine addiction, also increases the risk of developing colorectal tumors. Knowledge of dietary and environmental factors is of paramount importance in implementing preventive strategies for colorectal cancer

Biological and clinical markers in colorectal cancer: state of the art.

Colorectal cancer (CRC) is the World's third most common cancer. Its prognosis is closely related to the disease stage at the time of diagnosis. Here we review the role of clinical biomarkers (tissue, serum, and faecal) in the management of CRC. Molecular studies have recently widened the opportunity for testing new possible markers, but actually, only few markers can be recommended for practical use in clinic. In the next future the hope is to have a complete panel of clinical biomarkers to use in every setting of CRC disease, and at the same time: 1) to receive information about prognostic significance by their expression and 2) to be oriented in the choice of the adequate treatment

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects