Paolo Groff

Increased risk of hepatocellular carcinoma development in patients with cirrhosis and with high hepatocellular proliferation

The immunohistochemical determination of the accessory protein of DNA-polymerase delta (PCNA), a marker of an early S-phase of the cell cycle, was used to evaluate cell proliferation retrospectively in formalin-fixed, paraffin-embedded liver biopsy sections in a group of patients with cirrhosis of similar age and duration of follow up, and with no evidence of hepatocellular carcinoma (41), including 17 patients with and 24 without hepatocellular carcinoma appearance during follow up. Proliferation was expressed as total (PCNA-TOT) and strongly (PCNA-STRO) positive nuclei per 1000 hepatocytes. The presence of dysplasia was also recorded. Histological findings and biochemical data, at the time of liver biopsy, were compared in the two groups. While total PCNA positivities were not significantly different in the two groups, strong reactivity was significantly higher in patients who eventually developed hepato-cellular carcinoma (median 0.7 vs 2.6). Univariate analysis of histological and biochemical data at the time of biopsy, followed by a stepwise regression study, showed that the significant parameters for a time-dependent disease-free state were, in decreasing order: cholesterol, PCNA-STRO, PCNA-TOT and alpha foeto-protein. Other clinical, biochemical and histological parameters, including dysplasia, provided no further information. From these data, hepatocellular proliferation can be evaluated in patients with cirrhosis with a currently available technique. Patients with high cell proliferation are at increased risk of developing hepatocellular carcinoma and may require differentiated follow up.

Quantitative liver parameters of HCV infection: relation to HCV genotypes, viremia and response to interferon treatment

BACKGROUND/AIMS This study aimed to evaluate the relation between the number of hepatocytes positive for HCV antigens and the amount of HCV RNA in the liver and to evaluate the relationship between the above parameters and viremia levels, HCV genotype and response to interferon treatment. METHODS This was a retrospective study on 31 consecutive patients with chronic HCV-related liver disease, selected on the basis of the availability of frozen liver tissue for both liver HCV antigens detection and liver HCV RNA quantitation. HCV antigens (immunohistochemistry), liver and plasma HCV RNA (competitive RT-PCR), and HCV genotype (commercial kit) were studied. RESULTS A significant correlation (p=0.0005) was found between the amount of liver HCV RNA (log 10 copy/microg of extracted RNA) and the number of HCV-infected hepatocytes (scored from 0 to 3). These parameters were not significantly correlated with viremia levels. The highest liver HCV RNA levels and HCV antigen scores were found in patients infected with genotype 1b. Liver HCV RNA (median 541 x 10(3) vs 118 x 10(3) copy number/microg, p=0.031) and liver HCV antigens (mean score 2.3 vs 1.3, p=0.018) but not plasma HCV RNA (median 14956 x 10(3) vs 2885 [correction of 2.885] x 10(3) copy number/ml, ns) were significantly higher in patients not responding to interferon treatment compared to responders. CONCLUSIONS The tissue parameters tested in this study were significantly correlated, shared the same clinical implications and predicted short-term response to interferon treatment better than viremia levels. We suggest that these tests should be included in the study protocol of patients under evaluation for interferon treatment, basing the choice on local facilities.

Continuous positive airway pressure vs. pressure support ventilation in acute cardiogenic pulmonary edema: a randomized trial.

BACKGROUND Both non-invasive continuous positive airway pressure (nCPAP) and non-invasive pressure support ventilation (nPSV) have been shown to be effective treatment for acute cardiogenic pulmonary edema (ACPE). In patients with severe ACPE who are treated with standard medical treatment, the baseline intubation rate is approximately 24%. STUDY OBJECTIVE This study was conducted to compare the endotracheal intubation (ETI) rate using two techniques, nCPAP vs. nPSV. In addition, mortality rate, improvement in gas exchange, duration of ventilation, and hospital length of stay were also assessed. METHODS This prospective, multi-center, randomized study enrolled 80 patients with ACPE who were randomized to receive nCPAP or nPSV (40 patients in each group) via an oronasal mask. Inclusion criteria were severe dyspnea, respiratory rate > 30 breaths/min, use of respiratory accessory muscles, or PaO(2)/FiO(2) < 200. RESULTS ETI was required in 0 (0%) and in 3 (7.5%) patients in the nCPAP group and in the nPSV group, respectively (p = 0.241). No significant difference was observed in in-hospital mortality: 2 (5%) vs. 7 (17.5%) in nCPAP and nPSV groups, respectively (p = 0.154). No difference in hospital length of stay was observed between the two groups, nor was there a difference observed in duration of ventilation, despite a trend for reduced time with nPSV vs. nCPAP (5.91 ± 4.01 vs. 8.46 ± 7.14 h, respectively, p = 0.052). Both nCPAP and nPSV were effective in improving gas exchange, including in the subgroup of hypercapnic patients. CONCLUSIONS Both methods are effective treatment for patients with ACPE. Non-invasive CPAP should be considered as the first line of treatment because it is easier to use and less expensive than non-invasive PSV.

[ANMCO/SIMEU Consensus document: In-hospital management of patients presenting with chest pain].

Chest pain is a common general practice presentation that requires careful diagnostic assessment because of its diverse and potentially serious causes. However, the evaluation of acute chest pain remains challenging, despite many new insights over the past two decades. The percentage of patients presenting to the emergency departments because of acute chest pain appears to be increasing. Nowadays, there are two essential chest pain-related issues: 1) the missed diagnoses of acute coronary syndromes with a poor short-term prognosis; 2) the increasing percentage of hospitalizations of low-risk cases.It is well known that hospitalization of a low-risk chest pain patient can lead to unnecessary tests and procedures, with an increasing trend of complications and burden of costs. Therefore, the significantly reduced financial resources of healthcare systems induce physicians and administrators to improve the efficiency of care protocols for patients with acute chest pain. Despite the efforts of the Scientific Societies in producing statements on this topic, in Italy there is still a significant difference between emergency physicians and cardiologists in managing patients with chest pain. For this reason, the aim of the present consensus document is double: first, to review the evidence-based efficacy and utility of various diagnostic tools, and, second, to delineate the critical pathways (describing key steps) that need to be implemented in order to standardize the management of chest pain patients, making a correct diagnosis and treatment as uniform as possible across the entire country.

COPD exacerbations in the emergency department: Epidemiology and related costs. A retrospective cohort multicentre study from the Italian Society of Emergency Medicine (SIMEU)

Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) frequently cause patients with COPD to access the emergency department and have a negative impact on the course of the disease. The objectives of our study were: 1) describing the socio-demographic and clinical characteristics, and the clinical management, of patients with AECOPD, when they present to the emergency department; and 2) estimating the costs related to the management of these patients. We conducted a retrospective cohort study in Italy, collecting data on 4396 patients, from 34 centres. Patients had a mean (SD) age of 76,6 (10.6) years, and 61.2% of them where males. >70% of the patients had a moderate to very high comorbidity burden, and heart failure was present in 26.4% of the cohort. The 64.6% of patients were admitted to hospital wards, with a mean (SD) length of stay of 10.8 (9.8) days. The estimated cost per patient was 2617 €. CONCLUSIONS Patients attending the ED for an AECOPD are old and present important comorbidities. The rate of admission is high, and costs are remarkable.

Noninvasive ventilation in the emergency department: are protocols the key?

Noninvasive ventilation (NIV) is one of the greatest advances more commonly used in emergency departments (EDs) in the last decade [1]. Global results are influenced by complex relationships between severity of acute respiratory failure, appropriate skills and team experience, and well-organized healthcare resources and hospital policies [1,2]. However, still, the lack of homogeneity in NIV protocols and training programs is a key determinant factor [3].

ANMCO-SIMEU Consensus Document: in-hospital management of patients presenting with chest pain

Abstract Chest pain is a common general practice presentation that requires careful diagnostic assessment because of its diverse and potentially serious causes. However, the evaluation of acute chest pain remains challenging, despite many new insights over the past two decades. The percentage of patients presenting to the emergency departments because of acute chest pain appears to be increasing. Nowadays, there are two essential chest pain-related issues: (i) the missed diagnoses of acute coronary syndromes with a poor short-term prognosis; and (ii) the increasing percentage of hospitalizations of low-risk cases. It is well known that hospitalization of a low-risk chest pain patient can lead to unnecessary tests and procedures, with an increasing trend of complications and burden of costs. Therefore, the significantly reduced financial resources of healthcare systems induce physicians and administrators to improve the efficiency of care protocols for patients with acute chest pain. Despite the efforts of the Scientific Societies in producing statements on this topic, in Italy there is still a significant difference between emergency physicians and cardiologists in managing patients with chest pain. For this reason, the aim of the present consensus document is double: first, to review the evidence-based efficacy and utility of various diagnostic tools, and, second, to delineate the critical pathways (describing key steps) that need to be implemented in order to standardize the management of chest pain patients, making a correct diagnosis and treatment as uniform as possible across the entire country.

Noninvasive Ventilation and Medical Emergency Team in Ward Departments: Will It Be a Safe and Practical Battlefield?

To the Editor: Noninvasive mechanical ventilation (NIV) requires a properly trained healthcare organization, a factor that influences short-term outcomes, especially for patients who are more severely ill or have comorbidities.[1][1] Epidemiological data show that the location where NIV is

Use of non-invasive mechanical ventilation in the Emergency Department, clinical outcomes and correlates of failure

Background: Despite several studies having been carried in this organizational context, there is an absence of information about the effectiveness of non-invasive mechanical ventilation (NIV) in Emergency Departments (ED), based on a number of suitable patients with acute respiratory failure (ARF) of different aetiology. In particular, it has not yet been defined as to whether the context of the ED suits the necessary requirement of quality for the correct application of the method and if the obtained results are different from those taken in other studies in general or respiratory intensive care unit. Finally there are few data related to the predictive factors to NIV failure (endotracheal intubation, in-hospital mortality) when applied in the emergency setting. Methods: To answer these questions we have retrospectively studied a population of 210 patients (95 with COPD exsacerbation ; 92 with acute cardiogenic pulmonary oedema; 23 with severe community acquired pneumonia) treated for ARF in the “critical area” of four Italian level II Emergency Departments. For all patients demographic data; some comorbidities (diabetes, dementia, sopraventricular arrhythmias, obesity); the physiological scores (Kelly, SAPS II, Apache II); the need for pharmacological sedation; vital and blood gas parameters (evaluated at entry, after one hour of treatment and before its suspension); the ventilatory modality applied (CPAP or PSV + PEEP) and some parameters of in-hospital stay (duration of the hospitalization in the critical area, duration of ventilation, compliance to the treatment, patients refusal to continue it, development of skin necrosis, need for endotracheal intubation, in-hospital mortality) were considered. Finally demographic, event of death with Cox regression or to the need for ETI through linear regression analysis. Results: Globally, in-hospital mortality reached 13,3%, the percentage of failure with consequent endotracheal intubation amounted to 10,4% . Considering the single aetiologic groups in the patients with COPD, exsacerbation mortality and ETI percentage were 12,6% and 13,7% respectively; in ACPO patients these data respectively amounted to 3,3% and 4,3%; while for patients with severe CAP they respectively reached 34,7% and 21,7%. The following factors were independently correlated with in-hospital mortality: SAPS II > 35, presence of dementia for COPD patients; SAPS II > 35; presence of dementia, presence of sopraventricular arrhythmias for ACPO patients; SAPS II > 35, presence of sopraventricular arrhythmias, presence of dementia for CAP patients. Considering the whole population of 210 patients, the predictive factors of in-hospital mortality were the following: SAPS II > 35; presence of dementia; presence of sopraventricular arrhythmias; maintenance of a respiratory rate above 24 bpm during tratment. The following were factors independently correlated with the need for endotracheal intubation: male gender, pH 24 bpm, mean arterial pressure > 96 mmHg, all measured at one hour of treatment, for COPD patients; male gender sex, pH 24 bpm, PaCO2 > 54,5 mm Hg all measured after one hour treatment for ACPO patients. Given the low number of patients, it was not possible to perform the logistic regression and to calculate the matrix of covariance of the parameter for the CAP group. Considering the whole series of patients, the factors independently correlated to ETI resulting in the following: male gender; diagnosis of COPD; pH 24 bpm, mean arterial pressure >96 mm Hg, PaCO2 >54,5 mm Hg, all measured after one hour treatment. Conclusions: In conclusion, our study shows that NIV is practicable in the ED with safety and clinical results

Abstract 309 Continuous positive airway pressure versus noninvasive positive pressure ventilation in acute cardiogenic pulmonary edema: a prospective, randomized, multicentric study

309 Continuous positive airway pressure versus noninvasive positive pressure ventilation in acute cardiogenic pulmonary edema: a prospective, randomized, multicentric study G. Ferrari, P. Groff, G. De Filippi, F. Giostra, M. Mazzone, G. Portale, N. Gentiloni Silveri, F. Aprà, E. Vitale and F.Olliveri Emergency Department, St Giovanni Bosco Hospital, Turin, Policlinico St Orsola Malpighi, Bologna, Policlinico A. Gemelli, Rome, Policlinico St Anna, Ferrara, Italy. Background Although noninvasive airway positive pressure has shown to be an effective treatment for acute cardiogenic pulmonary edema (ACPE), the literature still lacks large randomized prospective multicentric studies that compares continuous positive airway pressure (CPAP) and noninvasive positive pressure ventilation (NIV). Aim Assess the efficacy and the safety of CPAP and NIV in patients with ACPE. Study design Multicentric, prospective randomized. End points are intubation rate, resolution time with the two methods, length of stay (LOS) in the ED, improvement in gas exchange, improvement in respiratory rate (RR) and heart rate (HR) and mortality. Methods Inclusion criteria are severe dyspnea at rest, RR430, PaO2/FiO2o250 and muscle fatigue. PSV was started at 10 cmH2O and increased to reach a Vte of 6–8ml/kg and to reduce RR; PEEP/ CPAP was started at 5 cmH2O and increased to keep SpO2492%, with a maximum level of 10 cmH2O allowed. Inspiratory fraction of oxygen (FiO2) was included between 1.0 and 0.4. Results A total of 110 patients were enrolled. Four were excluded because they did not meet clinical/radiological inclusion criteria; 106 patients were randomly assigned to receive CPAP or NIV. Mean age was 76.8710 and 77.4710.1 years and SAPS II score was 40.479.1 and 41.1710.2 in CPAP and NIV, respectively (P1⁄4NS). Initial mean values at randomization were as follows: CPAP – pH 7.2270.11, PaCO2 58.8718.5, PaO2/FiO2 132.2766.4, RR 32.776.03, HR 110.3721.6, mean arterial pressure (MAP) 125.1728.8 and SpO2 80.7717.1; NIV – pH 7.2570.010, PaCO2 58.2719, PaO2/FiO2 159.6796.4, RR 36.575.7, HR 107.4725.7, MAP 115.6725.7 and SpO2 83.2712.4. The two groups were homogenous for all physiological variables except for RR (P1⁄40.033). CPAP and NIV were applied for 6.876.82 and 7.2975.11 h, respectively (P1⁄40.184). No difference was observed for LOS in the ED (CPAP: 63.9751.2, NIV 60.978.4 h; P1⁄40.881) and for hospital LOS (CPAP: 13.271.9, NIV: 7.3671.08 days; P1⁄40.375). After 1 h of treatment, in both groups, a significant improvement was observed in gas exchange and in clinical–physiological variables: pH, PaO2/FiO2, CO2, RR, HR, SpO2 and MAP. Time course analysis also showed a significant improvement over time for all these variables (Po0.001); no difference was shown between the two treatments (P1⁄4NS). Three patients were intubated in the NIV group and no one was intubated in the CPAP group: no statistical difference was observed (P1⁄40.243); all patients who underwent ETI were also those with chronic obstructive pulmonary disease (COPD). No difference was observed in mortality rate: 15 patients died – four in the CPAP group and 11 in the NIV group (P1⁄40.092). Both CPAP and NIV improved gas exchange in normocapnic and hypercapnic patients. Severe obesity did not affect the outcome of CPAP or NIV in patients with ACPE. Conclusions Both CPAP and NIV result in early improvement of gas-exchange and vital signs in patients with ACPE, with no difference in resolution time and hospital LOS. Patients with ACPE and COPD may have a higher percentage of intubation rate.