Efficacy of non-invasive mechanical ventilation in the general ward in patients with chronic obstructive pulmonary disease admitted for hypercapnic acute respiratory failure and pH < 7.35: a feasibility pilot study.

AIM: To date non-invasive (NIV) mechanical ventilation use is not recommended in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) and pH < 7.30 outside a 'protected environment'. We assessed NIV efficacy and feasibility in improving arterial blood gases (ABG) and in-hospital outcome in patients with ARF and severe respiratory acidosis (RA) admitted to an experienced rural medical ward. METHODS: This paper is a prospective pilot cohort study conducted in the General Medicine Ward of Budrio's District Hospital. Two hundred and seventy-two patients with ARF were admitted to our Department, 112, meeting predefined inclusion criteria (pH < 7.35, PaCO2 > 45 mmHg). Patients were divided according to the severity of acidosis into: group A (pH < 7.26), group B (7.26 ≤ pH < 7.30) and group C (7.30 ≤ pH < 7.35). ABG were assessed at admission, at 2-6 h, 24 h, 48 h and at discharge. RESULTS: Group A included 55 patients (24 men, mean age: 80.8 ± 8.3 years), group B 31 (12 men, mean age: 80.3 ± 9.4 years) and group C 26 (15 men, mean age: 78.6 ± 9.9 years). ABG improved within the first hours in 92/112 (82%) patients, who were all successfully discharged. Eighteen percent (20/112) of the patients died during the hospital stay, no significant difference emerged in mortality rate (MR) within the groups (23%, 16% and 8%, for groups A, B and C, respectively) and between patients with or without pneumonia: 8/29 (27%) versus 12/83 (14%). On multivariable analysis, only age and Glasgow Coma Scale had an impact on the clinical outcome. CONCLUSION: In a non-'highly protected' environment such as an experienced medical ward of a rural hospital, NIV is effective not only in patients with mild, but also with severe forms of RA. MR did not vary according to the level of initial pH.

Possible role of tocopherols in the modulation of host microRNA with potential antiviral activity in patients with hepatitis B virus-related persistent infection: a systematic review.

Hepatitis B virus (HBV) infection represents a serious global health problem and persistent HBV infection is associated with an increased risk of cirrhosis, hepatocellular carcinoma and liver failure. Recently, the study of the role of microRNA (miRNA) in the pathogenesis of HBV has gained considerable interest as well as new treatments against this pathogen have been approved. A few studies have investigated the antiviral activity of vitamin E (VE) in chronic HBV carriers. Herein, we review the possible role of tocopherols in the modulation of host miRNA with potential anti-HBV activity. A systematic research of the scientific literature was performed by searching the MEDLINE, Cochrane Library and EMBASE databases. The keywords used were 'HBV therapy', 'HBV treatment', 'VE antiviral effects', 'tocopherol antiviral activity', 'miRNA antiviral activity' and 'VE microRNA'. Reports describing the role of miRNA in the regulation of HBV life cycle, in vitro and in vivo available studies reporting the effects of VE on miRNA expression profiles and epigenetic networks, and clinical trials reporting the use of VE in patients with HBV-related chronic hepatitis were identified and examined. Based on the clinical results obtained in VE-treated chronic HBV carriers, we provide a reliable hypothesis for the possible role of this vitamin in the modulation of host miRNA profiles perturbed by this viral pathogen and in the regulation of some cellular miRNA with a suggested potential anti-HBV activity. This approach may contribute to the improvement of our understanding of pathogenetic mechanisms involved in HBV infection and increase the possibility of its management and treatment.

Association between hepatitis B or hepatitis C virus infection and risk of pancreatic adenocarcinoma development: a systematic review and meta-analysis.

BACKGROUND: Pancreatic adenocarcinoma (PAC) is an aggressive cancer with a poor prognosis. To date, PAC causes are still largely unknown. Antigens and replicative sequences of oncogenic hepatitis B (HBV) and hepatitis C (HCV) virus were detected in different extra-hepatic tissues, including pancreas. OBJECTIVE: a systematic review and meta-analysis of epidemiological studies assessing PAC risk in patients with HBV/HCV chronic infections. METHODS: In September 2012, we extracted the articles published in Medline, Embase and the Cochrane Library, using the following search terms: "chronic HBV" and "HCV", "hepatitis", "PAC", "risk factors", "epidemiology". Only case/control (C/C), prospective/retrospective cohort studies (PCS/RCS) written in English were collected. RESULTS: four hospital-based C/C studies and one PCS, in HBV-infected patients and two hospital-based C/C studies and one RCS in HCV-infected subjects met inclusion criteria. In these studies HBsAg positivity enhanced significantly PAC risk (RR = 1.18, 95% CI:1.04-1.33), whereas HBeAg positivity (RR = 1.31, 95% CI:0.85-2.02) as well as HBsAg negative/HBcAb positive/HBsAb positive pattern (RR = 1.12, 95% CI:0.78-1.59) and HBsAg negative/HBcAb positive/HBsAb negative pattern (RR = 1.30, 95% CI:0.93-1.84) did not. Relationship between PAC risk and anti-HCV positivity was not significant, although it reached a borderline value (RR = 1.160, 95% CI:0.99-1.3). CONCLUSIONS: HBV/HCV infection may represent a risk factor for PAC, but the small number of available researches, involving mainly populations of Asian ethnicity and the substantial variation between different geographical areas in seroprevalence of HBV/HCV-antigens/antibodies and genotypes are limiting factors to present meta-analysis.

Serum hepatitis B surface antigen monitoring in long-term lamivudine-treated hepatitis B virus patients.

Serum hepatitis B virus surface antigen (HBsAg) levels have been suggested to predict interferon response in chronic hepatitis B. A few data are available on the role of HBsAg measurement in nucleos(t)ide analogues (NA) treatment. We retrospectively investigated the relation between HBsAg changes and main treatment outcomes during long-term lamivudine treatment in hepatitis e antigen (HBeAg)-negative chronic hepatitis B. A total of 42 HBeAg-negative patients were consecutively enrolled in an open-label study on long-term lamivudine monotherapy (150 mg/die). Serum HBsAg levels were quantified every 6 months by Architect assay (Abbott Diagnostics). HBV-DNA was quantified quarterly by real-time PCR (Roche Diagnostics). The median duration of lamivudine treatment was 66 months (20-153). One patient (2%) was a primary nonresponder, 35 (83%) developed virological breakthrough (VB) and the remaining six patients (14%) were classified as long-term on-treatment responders. During treatment, HBsAg levels decreased only in long-term on-treatment responders, while no changes were observed in resistant patients. Failure to achieve a decrease of 0.7 log(10) IU/mL in serum HBsAg at month six of lamivudine had a positive predictive value of developing VB of 90% and a negative predictive value of 100%. These high predictive values were also maintained in the subgroup of patients negative for HBV-DNA at month six. The results of this study with a small sample size suggest a role of on-treatment HBsAg quantification in the management of lamivudine-treated patients. If validated prospectively in a larger patient cohort, HBsAg measurements would be a useful adjunct to optimize antiviral therapy.

[The Antonine Plague and the decline of the Roman Empire]. / La peste antonina e il declino dell'Impero Romano. Ruolo della guerra partica e della guerra marcomannica tra il 164 e il 182 d.c. nella diffusione del contagio.

The Antonine Plague, which flared up during the reign of Marcus Aurelius from 165 AD and continued under the rule of his son Commodus, played such a major role that the pathocenosis in the Ancient World was changed. The spread of the epidemic was favoured by the occurrence of two military episodes in which Marcus Aurelius himself took part: the Parthian War in Mesopotamia and the wars against the Marcomanni in northeastern Italy, in Noricum and in Pannonia. Accounts of the clinical features of the epidemic are scant and disjointed, with the main source being Galen, who witnessed the plague. Unfortunately, the great physician provides us with only a brief presentation of the disease, his aim being to supply therapeutic approaches, thus passing over the accurate description of the disease symptoms. Although the reports of some clinical cases treated by Galen lead us to think that the Antonine plague was caused by smallpox, palaeopathological confirmation is lacking. Some archaeological evidence (such as terracotta finds) from Italy might reinforce this opinion. In these finds, some details can be observed, suggesting the artist's purpose to represent the classic smallpox pustules, typical signs of the disease. The extent of the epidemic has been extensively debated: the majority of authors agree that the impact of the plague was severe, influencing military conscription, the agricultural and urban economy, and depleting the coffers of the State. The Antonine plague affected ancient Roman traditions, also leaving a mark on artistic expression; a renewal of spirituality and religiousness was recorded. These events created the conditions for the spread of monotheistic religions, such as Mithraism and Christianity. This period, characterized by health, social and economic crises, paved the way for the entry into the Empire of neighbouring barbarian tribes and the recruitment of barbarian troops into the Roman army; these events particularly favoured the cultural and political growth of these populations. The Antonine Plague may well have created the conditions for the decline of the Roman Empire and, afterwards, for its fall in the West in the fifth century AD.

[Contribution of palaeopathology to defining the pathocoenosis of infectious diseases (Part two)]. / Apporti della paleopatologia alla definizione della patocenosi delle malattieinfettive (II parte).

In the second part of their review the authors focus on palaeopathological studies, performed in mummified tissues, with reference to infectious diseases. The analysis of samples obtained from both natural and artificial mummies may provide, in some favourable events, a more complete knowledge of these findings in comparison to information obtained from only comprehensive examination of the skeleton. The acquired data enable us to understand not only the diseases which afflicted mankind, but also dietary and hygiene conditions of ancient populations. We report knowledge acquired regarding some palaeopathological conditions, including schistosomiasis, smallpox, cisticercosis, trichinosis, ascaridiasis, echinococcosis, filariasis, hepatitis E virus, condylomatosis, pulmonary tubercolosis, pediculosis, visceral leishmaniasis as well as Diphyllobotrium sp., Dicrocoelium dendriticum and Fasciola hepatica infestations. In addition some interesting findings concerning the relationship between dietary and food intake colonized by streptomyces are described. This review reports the discovery of human remains from different geographic areas: while most of these studies describe findings in two Mediterranean countries (Italy and Egypt), some refer to Britain and German-speaking countries (Austria and Germany) as well as the area in Africa known as Nubia, along the Nile. Both histological and biomolecular diagnosis are useful not only to identify a specific disease in a subject from the remote past, but also to achieve information concerning its frequency and evolution. Such knowledge may thus allow us to understand the intensity of cultural exchanges and links among different populations and the role of these relationships in transmitting and spreading infectious diseases in a certain geographic area.

[Contribution of paleopathology to defining the pathocoenosis of infectious diseases (Part one)]. / Apporti della paleopatologia alla definizione della patocenosi delle malattie infettive (prima parte).

Studying the remains of mummies obtained by archaeological research may provide key information concerning historical pathocoenosis. Paleopathology makes it possible to recognise, characterise and connect different features involved in human pathocoenosis, such as epidemiology, in a historical perspective, and cultural development, via the introduction of new livestock farming techniques and agriculture in general. Several distinct pathologies may produce direct and indirect changes in the skeleton of affected individuals. Therefore bone remains represent very important sources of information to study such diseases. Changes related to trauma and nutrition deficiency as well as secondary signs, induced by tuberculosis, brucellosis, leprosy, syphilis, malaria, periostitis and aspecific osteomyelitis, persist in bones. In addition, other diseases may cause indirect alterations and subsequent secondary bone in the skeleton via different mechanisms. A secondary bone dimorphism may be induced by poliomyelitis. Aspecific lesions may arise in a skeletal bone and then cause secondary alterations in near-bone segments. Reviewing studies of paleopathologic research found in the literature, we emphasize the relationship between the appearance of major infectious diseases and the development of human activities; whereas it is clear that the introduction of livestock farming had a key role in the pathocoenosis of distinct infections such as tuberculosis, brucellosis and leprosy, some doubts and uncertainty remain in relation to the origin of others with epidemiologically important pathologies, such as syphilis.

Comprehensive complexity assessment as a key tool for the prediction of in-hospital mortality in heart failure of aged patients admitted to internal medicine wards.

Congestive heart failure (CHF) and cognitive impairment are both common problems in old age, associated with significant mortality, impaired quality of life and disability. This study evaluated patients with CHF, admitted to internal medicine and geriatric wards. We identified factors associated with a high risk of in-hospital mortality. Hospitalized CHF subjects with increased risk of in-hospital death present a clinical profile including: very old age, overt cognitive dysfunction, predisposition to falls, dependency, social-family problems, impairment in sphincter control and feeding ability, presence of bedsores, digoxin but not warfarin treatment, hypo-dysproteinemia and hypernatremia and mild renal impairment. We observed that patients admitted to our Internal Medicine Departments, in addition to CHF, present a high grade of complex therapeutic needs and that comorbidity, by itself, does not reflect complexity. Our data support the hypothesis that CHF has different patterns of severity and prognosis in young and in old or very old age groups.

[The Spanish influenza pandemic]. / La pandemia influenzale "spagnola".

The influenza pandemic of 1918-1919, so-called Spanish influenza, spread to almost all nations worldwide. This outbreak is thought to have killed 25 million people, although some have claimed that the epidemic resulted in as many as 40 million deaths. This pandemic was a particularly dramatic event, because it occurred at the end of World War I, when both armies and the civilian population, in nations involved in the war, were exhausted. In Italy 600,000 people are estimated to have died of Spanish influenza. Together with the death of 650,000 soldiers during the war, this had a major demographic impact. We describe the course of the epidemic in Italy as a whole and in Bologna in particular. In Bologna and in its province we analysed the lists drawn up at the end of the World War I by the Central Records Office in Bologna, which coordinated research into causes of death of soldiers engaged in the conflict. We also examined the trend of burials at Certosa in Bologna in the first decades of the last century in order to establish, during the two-year period 1918-1919, the impact of the epidemic upon annual mortality. In Bologna the impact of the epidemic, albeit important in comparison to other situations, was not particularly dramatic. No special preventive measures were adopted, with the exception of isolating seriously ill patients in a former school converted by the military authorities into a hospital. Family doctors worked together actively with the city's medical authorities when the epidemiological survey was carried out.

Vitamin E as treatment for chronic hepatitis B: results of a randomized controlled pilot trial.

BACKGROUND AND AIMS: Interferon-alpha treatment has been the treatment of choice for chronic hepatitis with unpredictable results. Recently, Lamivudine has been licensed for use against HBV infection with good results. Unfortunately, recurrence of viremia after lamivudine withdrawal is common and prolonged treatment can induce the emergence of resistant mutant strains. It has been shown that vitamin E can increase the host immune response, and this may provide protection against infectious diseases. METHODS: We evaluated vitamin E supplementation as therapy for chronic hepatitis B in a pilot study including 32 patients. Patients were randomly allocated to receive vitamin E at the dose of 300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They were seen monthly during the first 3 months and thereafter quarterly for additional 12 months. RESULTS: The two groups were comparable at enrollment. At the end of the study period, alanine aminotransferase (ALT) normalization was observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the controls (P=0.011); HBV-DNA negativization was observed in 8 (53%) patients in the vitamin E group as compared to 3 (18%) in the control group, respectively (P=0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in 7 (47%) patients taking vitamin E and in none of the controls (P=0.0019). CONCLUSION: Vitamin E supplementation might be effective in the treatment of chronic hepatitis B.

Hepatitis B and C virus infections as possible risk factor for pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAC) is a very aggressive and lethal cancer, with a very poor prognosis, because of absence of early symptoms, advanced stage at presentation, early metastatic dissemination and lack of both specific tests to detect its growth in the initial phases and effective systemic therapies. To date, the causes of PAC still remain largely unknown, but multiple lines of evidence from epidemiological and laboratory researches suggest that about 15-20% of all cancers are linked in some way to chronic infection, in particular it has been shown that several viruses have a role in human carcinogenesis. The purpose of this report is to discuss the hypothesis that two well-known oncogenic viruses, Human B hepatitis (HBV) and Human C hepatitis (HCV) are a possible risk factor for this cancer. Therefore, with the aim to examine the potential link between these viruses and PAC, we performed a selection of observational studies evaluating this association and we hypothesized that some pathogenetic mechanisms involved in liver carcinogenesis might be in common with pancreatic cancer development in patients with serum markers of present or past HBV and HCV infections. To date the available observational studies performed are few, heterogeneous in design as well as in end-points and with not univocal results, nevertheless they might represent the starting-point for future larger and better designed clinical trials to define this hypothesized relationship. Should these further studies confirm an association between HBV/HCV infection and PAC, screening programs might be justified in patients with active or previous hepatitis B and C viral infection.

Value of endoscopic ultrasonography in the management of portal hypertension.

Using endoscopic ultrasonography (EUS) a large part of the portal venous system can be visualized. In 40 patients with portal hypertension (PH) and in 48 control subjects EUS displayed the azygos, splenic, mesenteric and portal veins in both groups. However, esophageal and gastric varices, peri- esophageal and peri-gastric collateral veins and submucosal gastric venules were displayed only in patients with PH. EUS was inferior to endoscopy for detecting and grading esophageal varices (p less than 0.0005), but superior in the detection of varices in the fundus of the stomach (p less than 0.0005). EUS cannot be considered a reliable method for the study of esophageal varices: it has an overall sensitivity of 50%, does not permit flow measurements, and does not provide information that could be used to estimate the risk of bleeding. EUS has been demonstrated to be superior to endoscopy in the diagnosis of gastric varices. This finding is extremely important for the optimal selection of treatment of patients with portal hypertension. EUS can detect portal hypertensive gastropathy; thus inflammatory gastritis can be more easily distinguished from congestive gastropathy and therapeutic decisions are strongly influenced.

Evaluation of an automated instrument for viability and concentration measurements of cryopreserved hematopoietic cells.

Two important parameters for determination of deleterious effects of cellular processing on hematopoietic progenitor cells are cell viability and concentration. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital evaluated the Beckman Coulter Vi-Cell automated instrument for the measurement of these two parameters. Using 33 thawed hematopoietic progenitor cell samples, automated Vi-Cell viability results were compared to those obtained using the standard trypan blue manual method. In addition, cell concentrations from these samples were compared with results from the Model Z2 Coulter Counter. Chinese Hamster Ovary cells were used for the evaluation of Vi-Cell linearity at the Beckman Coulter Cellular Analysis Development Center. Significant correlation was obtained when the two methods were compared for both cell concentration and percentage viability (P < .0001). The results of the linearity study indicated that the Vi-Cell is linear from approximately 5 x 10(4) to greater than 1 x 10(7) cells/mL. The Vi-Cell uses sample volumes as low as 0.5 mL; cell diameters may be 2 to 70 microns. The Vi-Cell automated instrument offers many significant advantages for cell analyses in today's busy laboratory environment.

Serum alpha-fetoprotein assay in normal pregnant women. Perspectives of clinical use for purposes of diagnosis and prognosis.

Radioimmunological assay of alpha-fetoprotein (AFP) has been performed in the serum of normal women at various stages of pregnancy and at the time of parturition; a total of 208 assay was carried out, AFP values rose until the 33rd week and at the time of childbirth dropped to levels about half of the maximum reached. No correlations were found between AFP values, neonatal weight and parity while the sex of the fetus appearech to have some influence. It is to be hoped that the application of these potential uses can be envisaged in the near future.

Interferon-alpha plus ribavirin in chronic hepatitis C resistant to previous interferon-alpha course: results of a randomized multicenter trial.

BACKGROUND/AIMS: Interferon-alpha plus ribavirin seem to be more efficacious than interferon monotherapy in chronic hepatitis C. In a multicenter randomized trial, we evaluated the efficacy of this association for interferon-alpha resistant chronic hepatitis C. METHODS: Fifty patients who were non-responders to recombinant or lymphoblastoid interferon-alpha were randomized to receive either ribavirin (800 mg/day) plus leucocytic interferon-alpha (3 mega units thrice weekly) or the same dose of interferon-alpha alone, for 6 months. Effects of therapy were evaluated by serum aminotransferase and hepatitis C virus RNA levels and control liver biopsies. RESULTS: At the end of treatment, aminotransferase levels become normal in 9/26 patients receiving combination therapy (35% [confidence interval, 16% to 53%]) and in 2/24 receiving interferon-alpha alone (8% [confidence interval, -3% to 19%]) (p = 0.03). Aminotransferase normalization was never associated with hepatitis C virus RNA clearance. All patients with normal aminotransferase relapsed after discontinuation of therapy. At the end of treatment, mean hepatitis C virus RNA levels significantly decreased only in the group receiving combination therapy, but returned to pretreatment values 6 months thereafter. No histological improvement was observed in either group. CONCLUSIONS: There is no indication for treatment with interferon-alpha at the dose of 3 mega units thrice weekly plus 800 mg/day of ribavirin for 6 months in chronic hepatitis C resistant to interferon-alpha.

Prevalence of monoclonal gammopathies in patients with hepatitis C virus infection.

BACKGROUND: An association between monoclonal gammopathies and chronic liver diseases has been reported. OBJECTIVE: To determine the prevalence of monoclonal gammopathies in patients with chronic hepatitis C virus (HCV) infection and the possible association of monoclonal gammopathies with HCV genotypes. DESIGN: Prospective study. SETTING: Departments of internal medicine and hematology at two university hospitals in Italy. PATIENTS: 239 HCV-positive and 98 HCV-negative patients with chronic liver diseases were recruited consecutively. MEASUREMENTS: Clinical data were gathered, liver histologic examination was done, serum immunoglobulin and cryoglobulin levels were measured, and immunoelectrophoresis was done for monoclonal component detection. Patients with monoclonal gammopathy had serum HCV RNA measured and HCV genotype determined by polymerase chain reaction and had histologic examination of bone marrow. RESULTS: Monoclonal band was detected in 11% of HCV-positive patients and in 1% of HCV-negative patients (P = 0.004). The prevalence of HCV genotype 2a/c was higher in patients with monoclonal gammopathies than in those without (50% compared with 18%; P = 0.009). CONCLUSION: The prevalence of monoclonal gammopathies in patients with HCV-related chronic liver disease is striking and is often associated with genotype 2a/c infection.