Oncology and Cardiac Rehabilitation: An Underrated Relationship.

Cancer and cardiovascular diseases are globally the leading causes of mortality and morbidity. These conditions are closely related, beyond that of sharing many risk factors. The term bidirectional relationship indicates that cardiovascular diseases increase the likelihood of getting cancer and vice versa. The biological and biochemical pathways underlying this close relationship will be analyzed. In this new overlapping scenario, physical activity and exercise are proven protective behaviors against both cardiovascular diseases and cancer. Many observational studies link an increase in physical activity to a reduction in either the development or progression of cancer, as well as to a reduction in risk in cardiovascular diseases, a non-negligible cause of death for long-term cancer survivors. Exercise is an effective tool for improving cardio-respiratory fitness, quality of life, psychological wellbeing, reducing fatigue, anxiety and depression. Finally, it can counteract the toxic effects of cancer therapy. The protection obtained from physical activity and exercise will be discussed in the various stages of the cancer continuum, from diagnosis, to adjuvant therapy, and from the metastatic phase to long-term effects. Particular attention will be paid to the shelter against chemotherapy, radiotherapy, cardiovascular risk factors or new onset cardiovascular diseases. Cardio-Oncology Rehabilitation is an exercise-based multi-component intervention, starting from the model of Cardiac Rehabilitation, with few modifications, to improve care and the prognosis of a patient's cancer. The network of professionals dedicated to Cardiac Rehabilitation is a ready-to-use resource, for implementing Cardio-Oncology Rehabilitation.

Indications and limitations of the fixator TGF "Gex-Fix" in proximal end humeral fractures.

The incidence of fractures of the humerus has increased exponentially in recent years. The most used classifications for humerus fracture are morphological (Neer), biological (AO/ASIF) and descriptive (Hertel). The types of surgical treatment for humerus fracture include prosthetic replacement and synthesis using different devices, including the Tension Guide Fixator (TGF), Gex-Fix. External fixation for displaced proximal humeral fractures avoids dissection and soft tissue stripping and has been reported by some authors to be associated with higher union rates, a lower incidence of avascular necrosis, less scarring of the scapulohumeral interface, and faster rehabilitation compared with open reduction and internal fixation. Other authors have reported that external fixation does not ensure acceptable reduction and fracture stability, particularly in patients with osteoporosis. The external fixation technique involves the introduction of Steinmann's pin to keep manual reduction, the introduction of two K-wires in the humeral head, the removal of the Steinmann's pin, and the introduction of two fiches on the humeral shaft. Hub connectors are mounted on the wires and on the chips to connect the outer bar and tensioning system. A total of 84 patients aged 42-84 years with proximal end humeral fractures (66% had two-part fractures) were treated with Fixator TGF in this study from December 2007 to June 2012. The postoperative recovery was earlier and the active-assisted motion was less painful than has been reported with other surgical techniques. The TGF was removed without anaesthesia at the outpatient clinic at a mean of 7 weeks (range 5-8 weeks) after surgery, and there was no loss of reduction or secondary displacement after removal. These results, after five years of experience, confirm that the best indication for this fixator is two- or three-part fractures because the device enables early active mobilisation. The limitations of this fixator are evident in fractures in which closed reduction is not possible and in three-part fractures with varus displacement because the TGF has less stability than other systems, such as the plate or cage. The short learning curve, reduced surgical time and risk, and low cost encourage the use of this technique.

Neutron ESR dosimetry through ammonium tartrate with low Gd content.

This paper continues analyses on organic compounds for application in neutron dosimetry performed through electron spin resonance (ESR). Here, the authors present the results obtained by ESR measurements of a blend of ammonium tartrate dosemeters and gadolinium oxide (5 % by weight). The choice of low amount of Gd is due to the need of improving neutron sensitivity while not significantly influencing tissue equivalence. A study of the effect of gadolinium presence on tissue equivalence was carried out. The experiments show that the neutron sensitivity is enhanced by more than an order of magnitude even with this small additive content. Monte Carlo simulations on the increment of energy release due to gadolinium presence were carried, and the results were in good agreement with the experimental data.

Hepatitis B immunity in teenagers vaccinated as infants: an Italian 17-year follow-up study.

We assessed the persistence of hepatitis B surface antigen antibody (anti-HBs) and immune memory in a cohort of 571 teenagers vaccinated against hepatitis B as infants, 17 years earlier. Vaccinees were followed-up in 2003 and in 2010 (i.e. 10 years and 17 years after primary vaccination, respectively). When tested in 2003, 199 vaccinees (group A) had anti-HBs <10 mIU/mL and were boosted, 372 (group B) were not boosted because they had anti-HBs ≥10 mIU/mL (n = 344) or refused booster (n = 28) despite anti-HBs <10 mIU/mL. In 2010, 72.9% (416/571) of participants had anti-HBs ≥10 mIU/mL (67.3% in group A vs. 75.8% in group B; p 0.03). The geometric mean concentrations (GMCs) were similar in both groups. Between 2003 and 2010, anti-HBs concentrations in previously boosted individuals markedly declined with GMC dropping from 486 to 27.7 mIU/mL (p <0.001). Fifteen vaccinees showed a marked increase of antibody, possibly due to natural booster. In 2010, 96 individuals (37 of group A and 59 of group B) with anti-HBs <10 mIU/mL were boosted; all vaccinees of the former group and all but two of the latter had an anamnestic response. Post-booster GMC was higher in group B (895.6 vs. 492.2 mIU/mL; p 0.039). This finding shows that the immune memory for HBsAg persists beyond the time at which anti-HBs disappears, conferring long-term protection.

EPR/alanine pellets with low Gd content for neutron dosimetry.

This paper reports on results obtained by electron paramagnetic resonance (EPR) measurements and Monte Carlo (MC) simulation on a blend of alanine added with low content of gadolinium oxide (5 % by weight) to improve the sensitivity to thermal neutron without excessively affecting tissue equivalence. The sensitivity is enhanced by this doping procedure of more an order of magnitude. The results are compared with those obtained with the addition of boric acid (50 % by weight) where boron is in its natural isotopic composition in order to produce low-cost EPR dosemeters. The gadolinium addition influences neutron sensitivity more than the boron addition. The presence of additives does not substantially change the fading of the EPR signal induced by neutrons. The MC simulations agree the experimental results in case of gadolinium addition.

Wound drainages in total hip arthroplasty: to use or not to use? Review of the literature on current practice.

Aim of this study is to analyze data reported in literature concerning the efficacy of using wound low-vacuum suction drainages in orthopedic surgery after total hip arthroplasty. We analyzed studies concerning the use of drainages in prosthetic hip replacement surgery, performing our research through Pubmed, Cochrane database and Google Scholar, and selecting the ones evaluating the following parameters: bleeding, the need for blood transfusions, number or reinforcement of post-operative medications, length of hospitalization, functional results, periprosthetic and surgical wound infection, post-operative hematoma. Our review did not show any demonstrated advantage from the use of wound drainages in total hip arthroplasty. Moreover, some studies enlighted a possible complication related to their employment, represented by the greater need for blood transfusions. Despite the absence of a statistically demonstrated positive influence on wound outcome using suction drains after total hip replacement, many orthopedic surgeons still recommend using drainages, just because there is no certified proof of a negative effect.

A chamber to test the response of radon detectors to changing environmental conditions.

Radon risk assessment is carried out by means of accurate measurements with active or passive instrumentation. All radon detectors must be calibrated and tested using a radon chamber containing a known concentration of radon produced by specific sources of (226)Ra. Some chambers can also be used to test the response of detectors as a function of environmental conditions. In this case, a calibration curve can be inferred with respect to change in one of the considered parameters. For this aim, a new radon chamber was designed and realised to perform calibration and to study the detector response in a large range of variation of the environmental parameters (pressure, 700-1100 mbar; temperature, 5-50°C; humidity, 10-90 %). The first experiments conducted to study the influence of environmental parameters on the detector response have shown flexibility and ease of use of the chamber.

[Past and present of pneumonia]. / A proposito di polmoniti: raffronto tra passato e presente.

A comparison is made between the most common types of pneumonias usually observed when Vincenzo Cuomo was active and those of the present day. Socially-transmitted pneumonias are contrasted with hospital-acquired pneumonias, mostly due to Gram negative bacteria, often multiresistant to antibiotics. Additional pneumonias are due to mycoplasmas, rickettsiae and Legionella and also to viruses, such as Cytomegalovirus, for example.

A practical and transferable methodology for dose estimation in irradiated spices, based on thermoluminescence dosimetry.

The thermoluminescence technique is recommended by the European Committee for Standardization for the detection of irradiated food containing silicates as contaminants. In this work, the applicability of the thermoluminescence technique as a quantitative method to assess the original dose in irradiated oregano was studied; the additive-dose method was used, with reirradiation doses up to 600 Gy. The proposed new procedure allows to clearly discriminate irradiated from unirradiated samples, even after one year storage, and it gives an acceptable estimation of the original dose; the overall modified procedure requires only one day to be completed.

Chronic hepatitis C in the advanced adult and elderly subjects.

Aging is associated with a complex remodeling of the immune system. While adaptive immune responses show impairment with aging, innate immune responses tend to improve it. Low numbers of CD3+, CD4+ and CD8 T cells have been observed in aged individuals. B lymphocytes tend to diminish as well. However, an increase in NK cells and effector T lymphocytes (CD28- CD8) can be shown. Effector T lymphocytes are characterized by: 1) expression of markers of cytotoxicity; 2) high levels of NK activity; 3) expression of the same inhibitory receptors as NK cells; 4) no cytokine production. For effector T lymphocyte-mediated cytotoxicity of virus-infected cells to occur, viral epitopes need to be exposed on the cell surface in the absence of MCH class I molecule expression, just as it has been shown with NK cells. Indeed, chronic infection with intracellular parasites is known to hinder MHC class I expression on cell surface. In elderly patients with chronic hepatitis C, infected hepatocytes can be shown to express a wide variety of HCV antigens, reflecting latency or active replication, as opposed to low or absent MHC class I expression. This favors elimination of infected hepatocytes by NK cells and effector T lymphocytes. A negative correlation has been observed between outcome of hepatitis and patients' age. Liver biopsies from elderly patients generally show chronic active hepatitis or cirrhosis, which are far less commonly observed in young patients or young adults. Overproduction of proinflammatory cytokines, namely TNF-alpha, IL-1 and IL-6, is responsible for enhanced immuno-phlogosis and underlies a more extensive damage to liver parenchyma. Since interferon-alpha has been shown to upregulate MHC class I molecule expression on infected hepatocytes, it may turn useful as a tool to inhibit NK cell- and effector T lymphocyte-mediated cytotoxicity. Thus, a rationale exists to recommend interferon-a administration in hepatitis C patients, especially in elderly patients. If the data presented here can contribute to foster research into interferon-a treatment of elderly patients with hepatitis C, our goal will be reached.

Room temperature instability of E'gamma centers induced by gamma irradiation in amorphous SiO2.

We study by optical absorption measurements the stability of E'(gamma) centers induced in amorphous silica at room temperature by gamma irradiation up to 79 kGy. A significant portion of the defects spontaneously decay after the end of irradiation, thus allowing the partial recovery of the transparency loss initially induced by irradiation. The decay kinetics observed after gamma irradiation with a 0.6 kGy dose closely resembles that measured after exposure to 2000 pulses of pulsed ultraviolet (4.7 eV) laser light of 40 mJ/cm(2) energy density per pulse. In this regime, annealing is ascribed to the reaction of the induced E'(gamma) centers with diffusing H(2) of radiolytic origin. At higher gamma doses, the decay kinetics becomes unexpectedly slower notwithstanding the progressive growth of the concentration of induced defects. In particular, the annealing kinetics of E'(gamma) centers after 79 kGy irradiation is inconsistent with the reaction parameters between the defect and H(2). To explain this result, on the basis of the quantitative analysis of the kinetics, we propose water-related species to be responsible for the slow room temperature annealing of E'(gamma) after irradiation with such a dose. This model is qualitatively supported by results obtained by IR absorption measurements, which show an increase of the absorption in the spectral region of Si-OH groups.

[Health promotion through physical activity: territorial models and experiences]. / Promuovere la salute attraverso l'attività motoria: modelli ed esperienze territoriali.

Scientific evidences support the preventive role of physical activity in relation to different multifactorial pathologies. Health's promotion through the spreading of lifestyles that encourage movement, does not represent just an action in contrast with "sedentary life" risk-factor, but also a priority for "quality" of life, with relevant economical and social benefits. WHO indicates physical activity as one of the priorities for an effective prevention. Besides, the EU supports the realization and the diffusion of some prevention-programs. Main pilot experiences developed in Italy and other countries are summarized. Attention is focused on the role of the competences and structures involved in an integrated approach based on availability of medical support, social services and local structures, considering recent developments in health prevention and promotion. In Italy and Europe, new opportunities to implement health promotion through physical activity are offered by the development of higher education in movement and sport sciences.

[Secondary pulmonary hypertension in the elderly: pathophysiological and clinical aspects from an observed case]. / Ipertensione polmonare secondaria negli anziani: aspetti fisio- patologici e clinici da un caso venuto alla nostra osservazione.

The authors report the case of a 76-year-old woman with severe pulmonary hypertension (80 mmHg). She had been suffering for years from chronic bronchitis and presented tricuspid insufficiency. The case report refers to the association between valvular insufficiency and/or chronic bronchitis and pulmonary hypertension. This condition--if severe--results in progressive disability and death. The treatment of severe pulmonary hypertension has not been taken into account, since it has proven to be ineffective and has side effects. The early detection and the prevention of the underlying causes represent the only available therapy. Sclerotic valvulopathy occurs more frequently in the elderly; it represents the major cause of valvular insufficiency/stenosis, especially if compared to the significant decrease in rheumatic disease in Western countries. Chronic bronchitis is characterized by a slow progression, in patients younger than fifty, by a decay worsened by aging. These data show that symptomatic pulmonary hypertension may often occur in the elderly (age > or =65 years). This paper results from our clinical experience on preventive measures in elderly patients with symptomatic pulmonary hypertension. If the material presented in this work succeeds in promoting new research or possible preventive measures to arrest or to slow down the course of this condition in the elderly, it will hit its target.

Interferon-gamma: biologic functions and HCV terapy (type I/II) (2 of 2 parts).

PURPOSE: To discuss exhaustively: 1) the interferon-gamma in inducing and modulating of immune responses; 2) impairment of IFN-gamma production that plays an important role in the persistence of infection, chronicity of inflammation, evolution in fibrosis; 3) in "vivo" effects of combination treatment with recombinant interferon-gamma and alpha in chronic HCV-infection. DESIGN: We reviewed the most important recent studios on relationship between IFN-gamma and chronic course of hepatitis C. OVERVIEW: IFN-gamma is also a potent activator of macrophages. Exposure to IFN-gamma greatly enhances the microbicidal (and, to a lesser degree, citotoxic) activity of macrophages and induces them to secrete nitric oxide and monokines such as IL-1, IL-6, IL-8, and TFNalpha. It also activates neutrophils, NK cells, and vascular endothelial cells. Although IFN-gamma tends to promote the differentiation of B cells and CD8 T cells into immunologically active effectors, it does not promote lymphocyte proliferation. It enhances the activity of Thl cells, but inhibits the production of Th2 cells. IFN-gamma not only decreases the production of IL-4 by Th2 cells but also potently blocks the effects of IL-4 on B cells, promoting IgG1 production at the expense of IgE production. The inadequate Thl immunity as well as the weak HCV-specific T-cell response at the site of inflammation is associated with failure to clear the virus and a chronic course of disease. The production of IL-12 is critical for induction of Thl immunity, directed towards elimination of intracellular pathogenes and viruses. The core protein of HCV seems to have a suppressive action on IL-12 production at the transcriptional level. The specific Thl cell defect is correlated with insufficient Th and CTL responses, and lower production of type 1 cytokine (IL-2, IFN-gamma, lymphokine-activated killer cells). Taken together, these results are probably responsible for non-eradication of HCV infection. Particularly the effects of interferon-gamma may include inhibition of HCV virion production by an effect on viral RNA and protein synthesis, enhancement of immune lysis of HCV infected cells, inhibition of hepatic fibrosis by an effect on TGF-beta, and an effect on HCV induced carcinogenesis. These data suggest an HCV-related cellular immune defect in patients with hepatitis C that can be restored in most patients by IL-12. CONCLUSIONS: The efficacy of IFN monotherapy in the HCV replicon system has been reported using IFN-alpha, IFN-gamma and IFN-beta. A recent clinical study to treatment chronic HCV involving sequential administration of IFN-alpha followed by IFN-gamma (IFN-alpha2b + IFN-gamma) showed a greater improvement over IFN monotherapy. This type of approach may lead to significant improvements in the therapeutic arsenal against chronic HCV infection.

Interferon-gamma: biologic functions and HCV therapy (type I/II) (1 of 2 parts).

PURPOSE: This review is aimed at exhaustively presenting and discussing the interferon-gamma (IFN-gamma), a cytokine that plays an important role in inducing and modulating an array of immune responses. DESIGN: A review of the most significant and recent clinical trials was performed. OVERVIEW: Although IFN-gamma has some antiviral activity, it is much less active in this regard than type I IFNs. IFN-gamma is involved in the regulation of nearly all phases of the immune and inflammatory responses, including the activation and differentiation of T cells, B cells, NK cells, macrophages, and others. It is therefore best regarded as a distint immunoregulatory cytokine. IFN-gamma secretion is a hallmark of Th1 lymphocytes. It is also secreted by nearly all CD8 T cells, by some Th0 cells, and by NK cells. Each of these cell types secretes IFN-gamma only when activated, usually as part of immune response and especially in response to IL-2 and IL-12. IFN-gamma production is inhibited by IL-4, IL-10, TGFbeta, glucocorticoids, cyclosporin A and FK506. Nearly all cell types express the heterodimeric receptor for IFN-beta and respond to this cytokine by increasing the surface expression of class I MHC proteins. As a result, virtually any cell in the vicinity of an IFN-beta-secreting cell becomes more efficient at presenting endogenous antigens and hence a better target for cytotoxic killing if it harbors an intracellular pathogen. Unlike the type I IFNs, IFN-gamma also increases the expression of class II MHC proteins on professional APCs, and so promotes antigen presentation to helper T cells as well. It also induces de novo expression of class II MHC proteins on venular endothelial cells and on some other epithelial and connective tissue cells that do not otherwise express them, thus enabling these cell types to function as temporary APCs at sites of intense immune reactions. The effector functions of NK cells are to lyse virus-infected cells and to secrete IFN-gamma, which activates macrofages to destroy phagocytosed microbes. The mechanism of NK cell-mediates cytolysis is essentially the same as that of cytolysis by CTLS. NK cells lyse virally infected cells before antigen specific CTLS came become fully active, that is, during the first few days after viral infection. NK cells are expanded and activated by cytokines of innate immunity, such as IL-12 and IL-15, and they kill infected cells, especially those that display reduced levels of class I molecoles. Some tumors, especially those of hematopoietic origin, are targets of NK cells, perlevels or types of class I MHC molecules. Therefore, IFN-gamma serves critical functions in innate immunity and in specific cell-mediated immunity (in addition, IFN activates neutrophilis and stimulates the cytolitic activity of NK cells). Many IFNs-gamma induced effects result in heigtened immune surveillance. CONCLUSIONS: IFN-gamma is a remarkable cytokine that orchestrates many distinct cellular programs through transcriptional control over large numbers of genes. Many IFNs-gamma-induced effects resulting in heightend immune surveillance and immune system function during infection have been discussed in this review. As the pathogens (microorganism with the potential to cause tissue injury or disease) augment local IFN-gamma production, and IFN-gamma augments the immune system response, an important function of IFN-gamma during in vivo infection is suggested. IFN-gamma is primarily secreted by activated T cells and natural killer cells, and can promote macrophage activation, mediate antiviral e antibacterial immunity, enhance antigen presentation, orchestrate activation of the innate immune system, coordinate lymphocyte-endothelium interaction, regulate Th1/Th2 balance, and control cellular proliferation and apoptosis.

Role of hemochromatosis genes in chronic hepatitis C.

PURPOSE: Hereditary hemochromatosis is commonly associated with iron overload and hepatitis C virus (HCV). Association between hemochromatosis C282Y or H63D mutation has been observed, although not uniformly, and iron overload is also commonly found in chronic HCV hepatitis. This study explored the contribution of genetic hemochromatosis to iron accumulation in hepatitis C. DESIGN: Review of current literature. RESULTS: The prevalence of increased serum iron stores in patients with HCV infection is 28% (patients having an elevated ferritin or transferrin saturation). Patients with elevated serum iron markers have more active chronic hepatitis with more liver fibrosis. In the opinion of the experts HFE mutations are not associated with a high hepatic iron content. No relation was detected between hepatic iron stores and HFE gene mutation. Significant iron deposition in the liver was uncommon and overall the quantity of iron that was detectable histologically and biochemically was unrelated to the grade and stage of HCV related liver injury. The mechanism by which liver iron accumulates in patients is unclear. CONCLUSIONS: Carriage of HFE mutations does not have a role in the accumulation of iron or the liver disease in HCV. These findings do not support a role for iron depletion in patients with chronic HCV infection, including these with elevated serum studies.

[The Epidemiologic Observatory and the Epidemiology Service: the Campania Region experience]. / Osservatorio Epidemiologico e Servizi di Epidemiologia: l'esperienza della Regione Campania.

As an effect of recent Laws, epidemiology will be more and more involved in the assessment of goals in Public Health and policy making, so that the debate about structure and placing of epidemiological function is more than ever actual. In this view, the route of epidemiology in Campania Region is explained, with a detailed description of the history and laws as well as of the structure and functions of both central and local units in charge of epidemiological function; weaknesses and strengths of the current system are fully examined and an hypothesis for an organizational model in the next future is formulated.

Case fatality rate of acute viral hepatitis in Italy: 1995-2000. An update.

BACKGROUND: Fulminant hepatic failure is the most serious complication of viral hepatitis. Although this event occurs rarely, it may be fatal. AIMS: To evaluate the case fatality rate (several deaths divided by number of cases x 100) for each viral hepatitis type in Italy from 1995 to 2000. PATIENTS: Acute hepatitis cases identified by the surveillance system for acute viral hepatitis, which covers approximately 58% of the Italian population. RESULTS: Twenty-five deaths (0.1%) occurred among the 18 460 acute viral hepatitis cases observed from 1995 to 2000, a rate threefold lower than the 0.3% reported during the period 1985-1994. The highest case fatality rate (0.4%) was seen for acute hepatitis B (18 deaths among 4257 cases). Only one death (0.01%) occurred among the 11 063 acute hepatitis A cases and two deaths (0.1%) among the 1536 acute hepatitis C cases. No deaths were observed among the 309 acute hepatitis A cases superimposed on chronic HBsAg carriers and the 166 superimposed on chronic HCV carriers. Intravenous drug use (22.2% of cases) and other parenteral exposures (22.2% of cases) were the most frequent non-mutually exclusive sources of infection reported by subjects who died of acute hepatitis B. CONCLUSIONS: Analysis of surveillance system data from 1995 to 2000 indicates that, in Italy, deaths due to acute viral hepatitis are rare, but most commonly observed with acute hepatitis B. There is no evidence that acute hepatitis A may be fatal in chronic HBsAg or HCV carriers. The overall better survival rate may probably reflect improvements in the treatment of fulminant hepatitis in the last few years in Italy.

Case fatality rate of acute viral hepatitis in Italy: 1995–2000. An update

Background. Fulminant hepatic failure is the most serious complication of viral hepatitis. Although this event occurs rarely, it may be fatal. Aims. To evaluate the case fatality rate (several deaths divided by number of cases ×100) for each viral hepatitis type in Italy from 1995 to 2000. Patients. Acute hepatitis cases identified by the surveillance system for acute viral hepatitis, which covers approximately 58% of the Italian population. Results. Twenty-five deaths (0.1%) occurred among the 18 460 acute viral hepatitis cases observed from 1995 to 2000, a rate threefold lower than the 0.3% reported during the period 1985–1994. The highest case fatality rate (0.4%) was seen for acute hepatitis B (18 deaths among 4257 cases). Only one death (0.01%) occurred among the 11 063 acute hepatitis A cases and two deaths (0.1%) among the 1536 acute hepatitis C cases. No deaths were observed among the 309 acute hepatitis A cases superimposed on chronic HBsAg carriers and the 166 superimposed on chronic HCV carriers. Intravenous drug use (22.2% of cases) and other parenteral exposures (22.2% of cases) were the most frequent non-mutually exclusive sources of infection reported by subjects who died of acute hepatitis B. Conclusions. Analysis of surveillance system data from 1995 to 2000 indicates that, in Italy, deaths due to acute viral hepatitis are rare, but most commonly observed with acute hepatitis B. There is no evidence that acute hepatitis A may be fatal in chronic HBsAg or HCV carriers. The overall better survival rate may probably reflect improvements in the treatment of fulminant hepatitis in the last few years in Italy