HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial.

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 µg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV-RNA levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg-IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies.

Effects of physical exercise on the female reproductive system.

The excess in physical activity could be closely linked to considerable negative consequences on the whole body. These dysfunctions called as "female athlete triad"' by the American College of Sports Medicine (ACSM) include amenorrhea, osteoporosis and disorder eating. The female athlete triad poses serious health risks, both on the short and on the long term, to the overall well-being of affected individuals. Sustained low energy availability can impair health, causing many medical complications within skeletal, endocrine, cardiovascular, reproductive and central nervous system. On the contrary, several studies have shown, that physical activity improves cardiovascular risk factors, hormonal profile and reproductive function. These improvements include a decrease in abdominal fat, blood glucose, blood lipids and insulin resistance, as well as improvements in menstrual cyclicity, ovulation and fertility, decreases in testosterone levels and Free Androgen Index (FAI) and increases in sex hormone binding globulin (SHBG). Other studies reported that physical activity improved self-esteem, depression and anxiety. Thus, the aim of this review is to elucidate the effect of physical exercise on female reproductive system and viceversa the impact of hormonal status on physical activity and metabolism. In addition this review supports the idea that physical exercise is a helpful tool for the management of obesity, prevention of cardiovascular, metabolic diseases and female reproductive organs related diseases (e.g. breast cancer). When the excess in physical activity leads up to the female athlete triad, it is imperative to treat each component of the triad by employing both pharmacological and non pharmacological treatments.

Massive bone allograft engineered with autologous vessels: A new perspective for the future.

Reconstruction is very important to ensure good function and quality of life after bone tumor resection. For metacarpals and phalanges, amputation and toe transfer are the gold-standard indications; nevertheless, allograft reconstruction must also be taken into account. Unfortunately, because of its inert biological behavior, it undergoes progressive resorption, with frequent fracture. Several attempts have been made to induce new vascularization in massive bone allograft, with poor results. However, neo-angiogenesis was reported with vascular loops, and we therefore hypothesized that heterologous graft integration could be enhanced by creating a vascular loop through the graft. A 50-year-old male with chondrosarcoma of the ring finger of the left hand underwent wide resection. An allogenic middle phalanx of comparable size was then prepared to fill the defect. Two small windows were performed proximally and distally on the radial surface of the allogenic phalanx, and a 4 cm-long vein graft was inserted inside the medullary canal. Metacarpophalangeal joint stability was achieved by collateral ligament reconstruction with micro-anchors. The distal part of the allograft was then stabilized to the middle phalanx with a 1.5 mm-thick micro-plate and screws. The radial proper palmar digital artery was proximally and distally sutured end-to-end to the vein graft, under microscopy. At 12-month follow-up, the allograft was fused, and histology performed at plate removal at 18 months revealed viable spindle cells with osteoblastic differentiation, without evidence of atypia, in a dense fibrous stroma. At 22 months' follow-up, the patient was apparently disease-free, and satisfied with his manual function.

Italian SARS-CoV-2 patients in intensive care: towards an identikit for subjects at risk?

OBJECTIVE: To investigate patient characteristics and factors that increase the risk of being admitted to intensive care and that influence survival in cases of SARS-CoV-2 pneumonia. PATIENTS AND METHODS: One-hundred and ninety-one SARS-CoV-2 patients were admitted to the "Fondazione Poliambulanza di Brescia" Hospital (Brescia, Lombardy, Italy) in the period 1st March 2020 to 11th April 2020. Data on demographics, clinical presentation at admission, co-morbidities, pharmacological treatment, admission to intensive care and death was recorded. Logistic regression and survival analysis were carried out to investigate the risk of being admitted to intensive care and the risk of death. RESULTS: The mean age of the study cohort was 64.6±9.9 years (range 20-88). Median BMI was 28.5±5 kg/m2. Fever (81%) and dyspnea (65%) were the most common symptoms on admission. Most of patients (63%) had at least one co-existing disease. The 157 (82%) patients admitted to intensive care were more likely to be of intermediate age (60-69 years; OR 3.23, 95% CI 1.32-8.38), overweight (OR 2.66, 95% CI 1.02-7.07) or obese (OR 5.63, 95% CI 1.73-21.09) and with lymphocytopenia (OR 2.75, 95% CI 1.17-6.89) than the 34 patients admitted to the ordinary ward. During intensive care, 50% of patients died and their death was associated with older age (HR 2.06, 95% CI 1.07-3.97), obesity (HR 2.23, 95% CI 1.15-4.35) and male gender (HR 1.9, 95% CI 1.02-3.57). CONCLUSIONS: We found that admission to intensive care and poor survival were associated with advanced age and higher body mass index, albeit with differences in statistical significance. Pre-existing diseases and symptoms on admission were not associated with different clinical outcomes. Interestingly, male gender was more prevalent among SARS-CoV-2 patients and was related negatively to survival, but it was not associated with more frequent admission to intensive care.

Regulation of eukaryotic abasic endonucleases and their role in genetic stability.

Abasic (AP) sites in DNA arise from spontaneous reactions or the action of DNA glycosylases and represent a loss of genetic information. The AP sites can be mutagenic or cytotoxic, and their repair is initiated by class II AP endonucleases, which incise immediately 5' to AP sites. The main enzyme of S. cerevisiae. Apn1, provides cellular resistance to oxidants (e.g., H2O2) or alkylating agents, and limits the spontaneous mutation rate. AP endonucleases from other species can replace Apn1 function in yeast to different extents. We studied the main human enzyme, Ape, with respect to its incision specificity in vitro and the expression of the APE gene in vivo. The results suggest that Ape evolved to act preferentially on AP sites compared to deoxyribose fragments located at oxidative strand breaks and that the incision modes of Ape and Apn1 may be fundamentally different. We also defined the functional APE promoter, and showed that APE expression is transiently downregulated during the regeneration of epidermis after wounding. This latter effect may lead to a window of vulnerability for DNA damage and perhaps mutagenesis during the healing of epidermal and other wounds. Such unexpected effects on the expression of DNA repair enzymes need to be taken into account in analyzing the susceptibility of different tissues to carcinogens.

Liver transplantation in Italy: current status. Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (A.I.S.F.).

The first liver transplant in Italy was performed in 1982. With the improvement in results, the number of patients followed, in recent years, has substantially increased in all centres. In parallel, the indications for liver transplantation have expanded and have raised the need for more organized structures where patients can be referred for evaluation and transplantation. Indications and contraindications to liver transplantation in Italy, the role of retransplantation, paediatric liver transplantation, waiting list management, liver transplantation outside Italy and the new Italian laws on organ donation are discussed. The multidisciplinary Study Group on Liver Transplantation of the Italian Association for the Study of the Liver (AISF) has collected information from all the Italian centres to ascertain the degree of consistency in their methods.

Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemia) and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey.

BACKGROUND: Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. AIM: To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. PATIENTS AND METHODS: This retrospective, cross-sectional study involved 1,195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. RESULTS: Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. CONCLUSIONS: This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.

Comparison of the promoters of the mouse (APEX) and human (APE) apurinic endonuclease genes.

We investigated the minimal promoter of APEX, which encodes mouse apurinic DNA repair endonuclease. A 1.85-kb fragment with APEX upstream sequences and approximately 290 bp of the transcribed region linked to a chloramphenicol acetyltransferase (CAT) reporter gene was assayed by transient transfection in NIH-3T3 cells. The minimal APEX promoter was comprised of approximately 190 bp of upstream and approximately 170 bp of transcribed DNA (exon 1 and most of intron 1). This approximately 360-bp region contains two CCAAT boxes and other consensus protein binding sites, but no TATA box. Deletion of the 5'-most CCAAT box decreased activity approximately 5-fold. The second CCAAT box (situated in exon 1) may play an independent role in APEX expression. Transcription start sites have been identified downstream of the second CCAAT box, and DNase I footprinting demonstrated NIH-3T3 nuclear proteins binding this region, including an Spl site located between the CCAAT boxes. Electrophoretic mobility-shift assays indicated binding by purified Sp1. Mouse proteins did not bind three myc-like (USF) sites in the APEX promoter, in contrast to the APE promoter. The APEX and APE promoter had similar activity in Hela cells, but in mouse cells, the murine promoter had approximately 5-fold higher activity than did the human promoter. Both the APEX and APE promoters exhibited bidirectional activity in their cognate cells.

Antiviral therapy in HBsAg-positive chronic liver disease (HBsAg+ve CLD): how many patients really need it?

One hundred and seventy-one consecutive patients with HBsAg+ve CLD were investigated in order to assess whether they were actively replicating the hepatitis B virus, and therefore eligible for antiviral therapy. Our results show that only 5.8% of patients were actively replicating B virus and therefore antiviral therapy, when available, could be used only for a small subgroup of patients suffering from CLD due to hepatitis B virus chronic infection.

[Behavior of blood lipids and lipoproteins in myocardial infarct]. / Atteggiamento lipido-lipoprotidemico ed infarto del miocardio

Blood lipids and lipoproteins were evaluated in male and female subjects of various ages with acute myocardial infarct. Values were within the limits of normal in less than 50%, mostly in the aged. II B (24%), IV (18%) and II A (11%) lipoprotidaemic pictures were the most common. It is felt that abnormal values are not necessarily part of the infarct picture; if present, they are mainly of the II B type.

[Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with Billroth II gastrectomy]. / La ERCP diagnostica e terapeutica nei pazienti gastroresecati secondo Billroth II.

BACKGROUND: Diagnostic and therapeutic endoscopic cholangiopancreatography (ERCP) is more difficult in patients with Billroth II gastrectomy. METHODS: Personal experience in the last 28 months with 38 ERCP regarding 33 Billroth II patients representing the 5.4% of total number of ERCP performed in the same period is reported. RESULTS: Choledochal lithiasis could be treated in all cases observed also if two observed patients necessitated of two ERCP procedure. Only one patient with biliary stenosis could not be treated because of failed sphincterotomy and deep incannulation. The most difficult step in the procedure was duodenal intubation. A final ERCP success rate was 79%. EST could be performed in most cases (16 out of 17 patients=94%). No complications are reported. The use of the lateral viewing duodenoscope is emphasized. CONCLUSIONS: Today, ERCP and endoscopic sphincterotomy (EST) give similar results and no higher risk in patients with regular anatomy or in patients with Billroth II gastrectomy.

[Prevalence of antibody to hepatitis C virus in hospital personnel]. / Prevalenza dell'anticorpo contro il virus dell'epatite C nel personale ospedaliero.

UNLABELLED: Prevalence of antibody to hepatitis C virus (anti-HCV) has been widely investigated in many categories; however no data are available on hospital personnel. The aim of our study was to investigate whether hospital personnel are at risk for HCV infection. METHODS: sera collected during a prospective study on HBV infection in hospital workers done in our institution in 1985 were analyzed for the ELISA test for anti-HCV from Ortho Diagnostic System. Sera were stored at -20 degrees C and were never defrosted until tested. A population of a consecutive series of healthy volunteer blood donors was used as a control group. RESULTS: the anti-HCV prevalence was higher in hospital personnel, than in blood donors (4.5 versus 1.1, p less than 0.001, Odds Ratio 4.5, Confidence Limits 2.9-7.2). CONCLUSION: although anti-HCV is not an "ideal" test for epidemiological purposes, our study suggests that hospital personnel is at high risk for HCV infection.

[Ultrasonically guided percutaneous treatment of renal cysts using ethanol and human fibrin glue (tissucol)]. / Il trattamento percutaneo eco-guidato delle cisti renali con etanolo e colla di fibrina umana (tissucol).

The sclerosant agents to be employed in the percutaneous treatment of renal cysts, according to the world wide published reports, are still topic of debate. The authors report the satisfying results obtained, once the cyst has been emptied under ultrasonographic control, by the injection into the cyst of ethanol 95% immediately followed by human fibrin glue (tissucol). In all ten patients so treated the complete and rapid disappearance of the cyst occurred without relapse after 6 months. The proposed procedure is also particularly suitable due to the lack of local and/or general complications deriving from the synergic, yet unprecedented, use of the two substances.

Quantification of fecal neutrophils by MPO determination (myeloperoxidase) in patients with invasive diarrhea. Cuantificación de neutrofilos fecales mediante la determinación de MPO (Mieloperoxidasa) en pacientes con diarrea invasiva.

Myeloperoxidase (MPO), a specific polymorphonuclear leukocyte enzyme, has been used previously to quantify the number of neutrophils in tissue. MPO activity was found to be linearly related to the number of neutrophil cells. In an attempt to use this method in leukocytes measuring in stool, fecal MPO was solubilized with hexadecyltrimethylammonium bromide and the MPO activity was measured by a dianisidine-H2O2 assay. Stools from 10 normal subjects and 39 patients with diarrhea produced by enteropathogenic bacteria were examined for leukocytes by MPO activity as well as microscopically using methylene blue stain, MPO activity was positive in 36 patients (92%) and leukocytes were present by microscopic observation in 30 (77%). Fecal leukocytes were not found in healthy controls and the MPO activity was undectable. Stool MPO activity had a range of from 1.6 to 2,830.0 x 10(3) UMPO per gram of feces (median 460.0). The number of neutrophils obtained through MPO activity had a range of 6.0 to 13,216.0/ mm3 (median 1,261.0). Fecal MPO activity is a simple biochemical assay for the detection and quantification of fecal leukocytes.

Lifestyle changes in the management of adulthood and childhood obesity.

Adulthood and childhood obesity is rapidly becoming an epidemic problem and it has a short and long term impact on health. Short term consequences are mostly represented by psychological effects, in fact obese children have more chances to develop psychological or psychiatric problems than non--obese children. The main long term effect is represented by the fact that childhood obesity continues into adulthood obesity and this results in negative effects in young adult life, since obesity increases the risk to develop morbidity and premature mortality. The obesity--related diseases are mostly represented by hypertension, type 2 diabetes, dyslipidaemia, cardiovascular diseases. Medical treatment should be discouraged in childhood because of the side effects and it should be only reserved for obese children with related medical complications. Lifestyle changes should be encouraged in both adulthood and childhood obesity. This review focuses on the management of obesity both in adulthood and in childhood, paying particular attention to lifestyle changes that should be recommended.

Autonomic nervous system in the control of energy balance and body weight: personal contributions.

The prevalence of obesity is increasing in the industrialized world, so that the World Health Organization considers obesity as a "pandemia" in rich populations. The autonomic nervous system plays a crucial role in the control of energy balance and body weight. This review summarizes our own data and perspectives, emphasizing the influence exerted by autonomic nervous system on energy expenditure and food intake, which are able to determine the body weight. Activation of the sympathetic discharge causes an increase in energy expenditure and a decrease in food intake, while reduction of food intake and body weight loss determines a reduction of the sympathetic activity. On the other hand, pathophysiological mechanisms of the obesity involve alterations of the sympathetic nervous system in accordance with the "Mona Lisa Hypothesis," an acronym for "most obesities known are low in sympathetic activity." Furthermore, the parasympathetic influences on the energy expenditure are analyzed in this review, showing that an increase in parasympathetic activity can induce a paradoxical enhancement of energy consumption.

[Biological premisses and therapeutic effect of immunological treatment with antilymphocytic globulin via the coeliac artery in hepatitis of immunological origin]. / Premesse biologiche ed effetto terapeutico del trattamento immunitario con perfusione della globulina antilinfocitaria per via arteriosa celiaca nelle epatiti umane a carattere immunitario.

The morphology of organ transplant rejection indicates that the circulation biophysics of the immunocompetent cells in the transplant capillaries is one of the most aspects of immune reaction haemodynamics. In the same way, the compromise of the liver-spleen arterial circulation observed in hepatitis of immunological origin may be interpreted on the basis of the spread of cellular aggregates, primarily lymphocytes whose reduced electrophoretic mobility is due to their being immunised with respect to the hepatic antigen. An immunological treatment, consisting of the perfusion of the liver with antilymphocyte globulins and other additives via the coeliac artery with the object of modifying the complex physico-chemical changes in the disturbed immunological dynamics, was carried out in 3 cases of hepatitis. The therapeutic results and their evaluation via a number of functional parameters are discussed.