The Role of Non-Invasive Mechanical Ventilation in the Management of Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) represents a major health concern, that causes a significant morbidity, a high risk of death and important health-care costs. The real dimension of this chronic disease is probably understimated both in its early and advanced stages and its prevalence is progressively rising in the general populations, because of both increase of elderly subjects and raised rates of smoke. To date it was estimated that COPD-related deaths represent the sixth leading cause of mortality worldwide. Acute exacerbations (AE) represent major events in the clinical course of COPD and negatively affect its outcomes, leading to lung function decrease, quality life worsening, high risks of hospital readmission, disability and death. Severe exacerbations of COPD are associated with acute respiratory failure (ARF), impairment of hypoxemia, various degree of carbon dioxide retention and acidosis. The ARF in COPD may occur as acute, chronic or acute-on-chronic failure. This condition worsens significantly the prognosis of these patients and may require an intensive treatment with ventilatory assistance combined with routine medical management. This therapeutic approach may be performed by means of invasive (IMV) or noninvasive mechanical ventilation (NIMV). The latter form is defined as the delivery of mechanical ventilation that avoids airway invasion. Two types of NIMV have been studied and applied to clinical practice in the last decades, they are represented by both external negative pressure and positive pressure ventilation modalities. In the last years noninvasive mechanical ventilation with positive pressure (NPPV) has been increasingly used as adjunctive therapeutic approach in these subjects. In addition several controlled trials and meta-analysis showed that this form of assisted ventilation is effective in the treatment of different diseases, including: COPD exacerbations, acute cardiogenic pulmonary edema, weaning from ventilator in COPD patients. The use of noninvasive mechanical ventilation in patients with COPD exacerbated and hypercapnic ARF is associated, in some instances, with a decreased need of endotracheal intubation, with lower incidence of adverse outcomes, as well as with reduced in hospital-mortality, length of hospitalisation and overall costs. This therapeutic approach is generally feasible, well-tolerated and may be successfully performed in different healthcare settings including: Emergency Departments, Intensive Care Units (ICUs), but also in Intermediate Respiratory Care Units (IRCUs) and, in selected cases, in non intensive units, such as General Wards. This report is a comprehensive review of the available studies, concerning the use of NIMV in the management of COPD patients with AE and respiratory failure and it describes its indications, limitations, proper locations and cost

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

Tensegrity model hypothesis: may this paradigm be useful to explain hepatic and pancreatic carcinogenesis in patients with persistent hepatitis B or hepatitis C virus infection?

CONTEXT: Hepatitis B (HBV) and hepatitis C virus (HCV) possess well-known oncogenic properties and may promote carcinogenesis in liver. However antigens and replicative sequences of HBV/HCV have been also detected in different extra-hepatic tissues, including the pancreas. Although epidemiological studies and meta-analyses have recently suggested that HBV/HCV may be also risk factors for pancreatic cancer and several researches have investigated the possible mechanisms and intra-/extra-cellular paths involved in pancreatic and hepatic carcinogenesis, to date, these complex processes remain largely unexplained. OBJECTIVES: In our paper, we aimed to propose a comprehensive and qualitative hypothetical model, describing how HBV/HCV may exert their oncogenic role. METHODS: We performed a systematic research of scientific literature, by searching MEDLINE, the Cochrane Library and EMBASE databases. The used keywords were: "chronic HBV/HCV", "pancreatic cancer", "liver carcinoma", "carcinogenesis mechanisms", "tensional integrity", "cytoskeleton", and "extracellular matrix". RESULTS: Taking advantage from available studies, we suggest an unifying hypothesis based on results and data, obtained from different areas of research. In particular we considered the well-defined model of tensional integrity and correlated it to changes induced by HBV/HCV in viscoelastic properties/stiffness of cellular/extracellular microenvironments. These events perturb the tightly-regulated feedback loop, which usually couples the intracellular-generated forces to substrate rigidity of extracellular compartments. Therefore, such a change strongly affects intracellular functions and cellular fate, by promoting a substantial deregulation of critical intracellular biochemical activities and genome expression. CONCLUSIONS: Our hypothesis might provide for the first time a reliable system, which correlates tensional integrity model with intra-/extra-cellular modifications, occurring in liver and pancreas during HBV/HCV-induced carcinogenesis. This approach might improve our understanding of pathogenetic mechanisms involved in the development of pancreatic and hepatic carcinogenesis , enhancing the possibility of their treatment. Furthermore, should the usefulness of this model be definitively confirmed, it might be also helpful to extend its field of application to other viruses-related cancers