Plasma soluble suppression of tumorigenesis 2 measured in the emergency department for diagnosis and outcome prediction of sepsis: A single-center prospective study.

BACKGROUND AND AIMS: The diagnostic and prognostic performance of soluble Suppression of Tumorigenicity 2 (sST2) in suspected septic patients presenting to the Emergency Department (ED) is largely unknown. MATERIALS AND METHODS: Patients were included in this prospective study if there was high suspicion of sepsis. The plasma level of sST2 was measured during initial ED evaluation. Outcomes were the evaluation of (1) sST2 diagnostic performance (alone and in combination with procalcitonin [PCT]), and (2) sST2 ability to predict 30-day and 90-day all-cause mortality. RESULTS: Among 569 patients included, 481 (84.5 %) had sepsis or septic shock. Plasma sST2 levels were more elevated in septic patients (159 [71-331] vs 50 [31-103] ng/mL, P < 0.001). The AUC of sST2 for sepsis diagnosis was lower than the AUC of PCT (0.76 vs 0.85, P = 0.03). The best cut-off for sST2 was 61.7 ng/mL, with a sensitivity of 79.9 % and a specificity of 70.6 %. sST2 was able to correctly reclassify septic patients with PCT <0.5 (NRI 28.9 % [P = 0.02]). sST2 level was an independent predictor of 30-day mortality in a model including clinical variables (aHR 2.03 [1.24-3.33], C-index 0.69). CONCLUSION: sST2 could be a useful adjunct in diagnosing sepsis and in all-cause mortality prediction.

Prognostic Value of Mid-Regional Proadrenomedullin Sampled at Presentation and after 72 Hours in Septic Patients Presenting to the Emergency Department: An Observational Two-Center Study.

The prognostic value of mid-regional proADM (MR-proADM) in septic patients presenting to the emergency department (ED) is not well established. In this prospective observational study enrolling septic patients evaluated in two EDs, MR-proADM was measured at arrival (t0) and after 72 h (t72). MR-proADM%change was calculated as follows: (MR-proADMt72h - MR-proADMt0)/MR-proADMt0. In total, 147 patients were included in the study, including 109 with a final diagnosis of sepsis and 38 with septic shock, according to the Sepsis-3 criteria. The overall 28-day mortality (outcome) rate was 12.9%. The AUC for outcome prognostication was 0.66 (95% CI 0.51-0.80) for MR-proADMt0, 0.77 (95% CI 0.63-0.92) for MR-proADMt72 and 0.74 (95% CI 0.64-0.84) for MR-proADM%change. MR-proADMt0 ≥ 2.78 nmol/L, MR-proADMt72 ≥ 2.7 nmol/L and MR-proADM%change ≥ -15.2% showed statistically significant log-rank test results and sensitivity/specificity of 81/65%, 69/80% and 75/70% respectively. In regression analysis, MR-proADM%change was a significant outcome predictor both in univariate and multivariate analysis, after adjustment for age, SOFA and APACHEII scores, providing up to 80% of added prognostic value. In conclusion, time trends of MR-proADM may provide additional insights for patient risk stratification over single sampling. MR-proADM levels sampled both at presentation and after 72 h predicted 28-day survival in septic patients presenting to the ED.

Prospective diagnostic and prognostic study of copeptin in suspected acute aortic syndromes.

Acute aortic syndromes (AAS) are cardiovascular emergencies with unmet diagnostic needs. Copeptin is released upon stress conditions and is approved for rule-out of myocardial infarction (MI). As MI and AAS share presenting symptoms, stress mechanisms and necessity for rapid diagnosis, copeptin appears as an attractive biomarker also for AAS. We thus performed a diagnostic and observational study in Emergency Department (ED) outpatients. Inclusion criteria were chest/abdominal/back pain, syncope and/or perfusion deficit, plus AAS in differential diagnosis. Blood samples were obtained in the ED. 313 patients were analyzed and 105 (33.5%) were diagnosed with AAS. Median copeptin was 38.91 pmol/L (interquartile range, IQR, 16.33-173.4) in AAS and 7.51 pmol/L (IQR 3.58-15.08) in alternative diagnoses (P < 0.001). Copeptin (≥10 pmol/L) had a sensitivity of 80.8% (95% confidence interval, CI, 72.2-87.2) and a specificity of 63.6% (CI 56.9-69.9) for AAS. Within 6 hours, the sensitivity and specificity were 88.7% (CI 79.3-94.2) and 52.4% (CI 42.9-61.8) respectively. Combination with D-dimer did not increase the diagnostic yield. Furthermore, copeptin ≥25 pmol/L predicted mortality in patients with alternative diagnoses but not with AAS. In conclusion, copeptin increases in most patients with AAS within the first hours, but the accuracy of copeptin for diagnosis AAS is suboptimal.

Thrombopoietin as Early Biomarker of Disease Severity in Patients With Acute Pancreatitis.

OBJECTIVES: To study the concentrations of thrombopoietin (TPO), a growth factor recently involved in the pathogenesis of experimental acute pancreatitis (AP), and its potential role as an early diagnostic and prognostic biomarker in patients with AP. METHODS: Thrombopoietin was measured in 44 AP patients, 18 patients with nonpancreatic acute abdominal pain, and 18 healthy volunteers. Acute pancreatitis severity was classified on the basis of the 2012 International Atlanta Symposium on Acute Pancreatitis criteria. RESULTS: Thrombopoietin levels did not differ between AP patients and control subjects, whereas these were higher in patients with moderately severe or severe AP compared with those with mild AP. Receiver operating characteristic curve analysis of TPO for severe AP diagnosis showed an area under the curve of 0.80. A cutoff value of 31.48 pg/mL showed the highest sensitivity, allowing to rule out severe AP when TPO was lower, whereas TPO higher than 98.23 pg/mL was associated with severe AP with high specificity (93.5%). Furthermore, TPO levels were greater in AP patients developing organ dysfunction or sepsis and in nonsurvivors compared with survivors. CONCLUSIONS: Our data provide the first evidence for TPO as potential early prognostic biomarker in AP patients. High TPO levels at hospital admission may predict organ dysfunction, sepsis, and fatal outcome in AP patients.

Multicentre Italian analysis on cardiovascular diseases: impact of immigrants' referral to emergency department.

During the recent years, immigration in Italy has increased. There are few data on the health status of immigrants and there is a need to improve their healthcare. Cardiovascular disorders account for 7.6% of immigrants' diseases and cause 3.6% of the total deaths. Lack of healthcare services to general medicine support and prescriptions leads immigrants to contact the Emergency Department (ED) to receive medical assistance. Primary endpoints of this study were to assess the use of national healthcare system by immigrants and to determine the incidence of cardiovascular diseases, and the frequency and type of risk factors for cardiovascular diseases in these patients. A no-profit, observational, multicentre study was conducted from April to September 2012. We studied 642 foreign patients referring to the ED for various symptoms/signs. One hundred and fourteen patients referred for suspected cardiovascular disease and 105 had a confirmed final diagnosis of cardiovascular disease. The more represented ethnic origin was Caucasian (59%), whereas the most represented country was Romania (24%). The main symptom recorded at ED arrival was chest pain (37.1%). Final cardiovascular diagnoses were represented by: hypertensive crisis (28.5%), acute coronary syndrome (20%), acute heart failure (12.3%), atrial fibrillation (10.4%) and chest pain (10.4%). Past medical history of cardiovascular disease, hypertension, obesity and male sex showed independent significant predictive value for cardiovascular disease diagnosis.Our study provides support for the development of specific primary prevention of cardiovascular risk factors in immigrants with the important role of culturally competent education of individuals and families. Better outpatient management seems to be needed in order to limit the need for emergency room referral.

Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis.

The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

Plasma Lactate Dehydrogenase Levels Predict Mortality in Acute Aortic Syndromes: A Diagnostic Accuracy and Observational Outcome Study.

In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far.This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency Departments suspected of having AAS underwent LDH assay at presentation. A final diagnosis was obtained by aortic imaging. Patients diagnosed with AAS were followed-up for in-hospital mortality.One thousand five hundred seventy-eight consecutive patients were clinically eligible, and 999 patients were included in the study. The final diagnosis was AAS in 201 (20.1%) patients. Median LDH was 424 U/L (interquartile range [IQR] 367-557) in patients with AAS and 383 U/L (IQR 331-460) in patients with alternative diagnoses (P < 0.001). Using a cutoff of 450 U/L, the sensitivity of LDH for AAS was 44% (95% confidence interval [CI] 37-51) and the specificity was 73% (95% CI 69-76). Overall in-hospital mortality for AAS was 23.8%. Mortality was 32.6% in patients with LDH ≥ 450 U/L and 16.8% in patients with LDH < 450 U/L (P = 0.006). Following stratification according to LDH quartiles, in-hospital mortality was 12% in the first (lowest) quartile, 18.4% in the second quartile, 23.5% in the third quartile, and 38% in the fourth (highest) quartile (P = 0.01). LDH ≥ 450 U/L was further identified as an independent predictor of death in AAS both in univariate and in stepwise logistic regression analyses (odds ratio 2.28, 95% CI 1.11-4.66; P = 0.025), in addition to well-established risk markers such as advanced age and hypotension. Subgroup analysis showed excess mortality in association with LDH ≥ 450 U/L in elderly, hemodynamically stable and in nonsurgically treated patients.Plasma LDH constitutes a biomarker of poor outcome in patients with AAS. LDH is a rapid and universally available assay that could be used to improve risk stratification and to individualize treatment in patient groups where options are controversial.

Lung Ultrasound-Implemented Diagnosis of Acute Decompensated Heart Failure in the ED: A SIMEU Multicenter Study.

BACKGROUND: Lung ultrasonography (LUS) has emerged as a noninvasive tool for the differential diagnosis of pulmonary diseases. However, its use for the diagnosis of acute decompensated heart failure (ADHF) still raises some concerns. We tested the hypothesis that an integrated approach implementing LUS with clinical assessment would have higher diagnostic accuracy than a standard workup in differentiating ADHF from noncardiogenic dyspnea in the ED. METHODS: We conducted a multicenter, prospective cohort study in seven Italian EDs. For patients presenting with acute dyspnea, the emergency physician was asked to categorize the diagnosis as ADHF or noncardiogenic dyspnea after (1) the initial clinical assessment and (2) after performing LUS ("LUS-implemented" diagnosis). All patients also underwent chest radiography. After discharge, the cause of each patient's dyspnea was determined by independent review of the entire medical record. The diagnostic accuracy of the different approaches was then compared. RESULTS: The study enrolled 1,005 patients. The LUS-implemented approach had a significantly higher accuracy (sensitivity, 97% [95% CI, 95%-98.3%]; specificity, 97.4% [95% CI, 95.7%-98.6%]) in differentiating ADHF from noncardiac causes of acute dyspnea than the initial clinical workup (sensitivity, 85.3% [95% CI, 81.8%-88.4%]; specificity, 90% [95% CI, 87.2%-92.4%]), chest radiography alone (sensitivity, 69.5% [95% CI, 65.1%-73.7%]; specificity, 82.1% [95% CI, 78.6%-85.2%]), and natriuretic peptides (sensitivity, 85% [95% CI, 80.3%-89%]; specificity, 61.7% [95% CI, 54.6%-68.3%]; n = 486). Net reclassification index of the LUS-implemented approach compared with standard workup was 19.1%. CONCLUSIONS: The implementation of LUS with the clinical evaluation may improve accuracy of ADHF diagnosis in patients presenting to the ED. TRIAL REGISTRY: Clinicaltrials.gov; No.: NCT01287429; URL: www.clinicaltrials.gov.

May thrombopoietin be a useful marker of sepsis severity assessment in patients with SIRS entering the emergency department?

BACKGROUND: Thrombopoietin (TPO), a growth factor primarily involved in regulating thrombopoiesis, has been recently implicated in the pathogenesis of sepsis. TPO levels are, indeed, greatly increased in patients with sepsis compared to control subjects, and correlate with sepsis severity. The aim of this study was to evaluate TPO as predictive biomarker of sepsis and of sepsis severity in patients entering the emergency department (ED) with systemic inflammatory response syndrome (SIRS). METHODS: This was a prospective observational study. Ours is a sub-study of the 'Need-speed trial', a multi-center observational study involving six Italian centers affiliated to the GREAT Italian Network. TPO was measured by ELISA. RESULTS: We enrolled 13 patients with SIRS (6 with acute pancreatitis, 3 with acute heart failure, 1 with pulmonary embolism, and 3 with allergic reactions), and 40 patients with sepsis, eight of whom had severe sepsis and three septic shock. TPO was significantly higher in patients with sepsis than with SIRS. In addition, TPO was higher in patients with severe sepsis than with sepsis, and in patients with septic shock than with severe sepsis, although these differences did not reach the statistical significance. CONCLUSIONS: Our preliminary results suggest that TPO may have the potential to be considered a promising early biomarker for both the diagnosis of sepsis and the assessment of sepsis severity in patients with SIRS entering the ED.

Role of presepsin for the evaluation of sepsis in the emergency department.

Sepsis, severe sepsis and septic shock are among the most common conditions handled in the emergency department (ED). According to new Sepsis Guidelines, early diagnosis and treatment are the keys to improve survival. Plasma C-reactive protein (CRP) and procalcitonin (PCT) levels, when associated with documented or suspected infection, are now part of the definitions of sepsis. Blood culture is the gold standard method for detecting microorganisms but it requires too much time for results to be known. Sensitive biomarkers are required for early diagnosis and as indexes of prognosis sepsis. CRP is one of the acute phase proteins synthesized by the liver: it has a great sensitivity but a very poor specificity for bacterial infections. Moreover, the evolution of sepsis does not correlate with CRP plasma changes. In recent years PCT has been widely used for sepsis differential diagnosis, because of its close correlation with infections, but it still retains some limitations and false positivity (such as in multiple trauma and burns). Soluble CD14 subtype (sCD14-ST), also known as presepsin, is a novel and promising biomarker that has been shown to increase significantly in patients with sepsis, in comparison to the healthy population. Studies pointed out the capability of this biomarker for diagnosing sepsis, assessing the severity of the disease and providing a prognostic evaluation of patient outcome. In this mini review we mainly focused on presepsin: we evaluate its diagnostic and prognostic roles in patients presenting to the ED with systemic inflammatory response syndrome (SIRS), suspected sepsis or septic shock.

Bleeding prevalence and transfusion requirement in patients with thrombocytopenia in the emergency department.

BACKGROUND: Thrombocytopenia is the most common coagulation disorder in critically ill patients. No studies have investigated the epidemiology and clinical impact of this condition in emergency department (ED) patients. We aimed to investigate epidemiological features, incidence of bleeding, and diagnostic and therapeutic requirements of patients with thrombocytopenia admitted to the ED. METHODS: We performed a retrospective observational study enrolling all patients admitted to the medical-surgical ED of the "Città della Salute e della Scienza di Torino" Hospital with a platelet count <150×10(9) PLTs/L, during four non-consecutive months. There were no exclusion criteria. RESULTS: The study included 1218 patients. The percentage of patients with severe (<50×10(9) PLTs/L) or very severe (<20×10(9) PLTs/L) thrombocytopenia was about 12%. Thrombocytopenia associated with liver cirrhosis was the most represented etiology. On the contrary, the most frequent cause in patients with newly recognized low platelet count was disseminated intravascular coagulation/sepsis. The incidence of bleeding and hypovolemia, as well as the need of transfusional support and mechanical, surgical or endoscopic hemostasis progressively increased with the severity of thrombocytopenia. CONCLUSIONS: Our results suggest that the detection of a platelet count lower than 50×10(9) PLTs/L may help to identify patients with higher bleeding risk in the ED setting. Additional studies are required to evaluate whether, in this setting, thrombocytopenia may represent an independent risk factor for bleeding episodes and increased mortality.

Thirty and ninety days mortality predictive value of admission and in-hospital procalcitonin and mid-regional pro-adrenomedullin testing in patients with dyspnea. Results from the VERyfing DYspnea trial.

INTRODUCTION: Mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) demonstrated usefulness for management of emergency department patients with dyspnea. METHODS: To evaluate in patients with dyspnea, the prognostic value for 30 and 90 days mortality and readmission of PCT, MR-proADM, and MR-proANP, a multicenter prospective study was performed evaluating biomarkers at admission, 24 and 72 hours after admission. Based on final diagnosis, patients were divided into acute heart failure (AHF), primary lung diseases, or both (AHF + NO AHF). RESULTS: Five hundred one patients were enrolled. Procalcitonin and MR-proADM values at admission and at 72 hours were significantly (P < .001) predictive for 30-day mortality: baseline PCT with an area under the curve (AUC) of 0.70 and PCT at 72 hours with an AUC of 0.61; baseline MR-proADM with an AUC of 0.62 and MR-proADM at 72 hours with an AUC of 0.68. As for 90-day mortality, both PCT and MR-proADM baseline and 72 hours values showed a significant (P < .0001) predictive ability: baseline PCT with an AUC of 0.73 and 72 hours PCT with an AUC of 0.64; baseline MR-proADM with an AUC of 0.66 and 72 hours MR-proADM with an AUC of 0.71. In AHF, group biomarkers predicted rehospitalization and mortality at 90 days, whereas in AHF + NO AHF group, they predict mortality at 30 and 90 days. CONCLUSIONS: In patients admitted for dyspnea, assessment of PCT plus MR-proADM improves risk stratification and management. Combined use of biomarkers is able to predict in the total cohort both rehospitalization and death at 30 and 90 days.

Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: a multicenter prospective study.

INTRODUCTION: Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock. METHODS: This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records. RESULTS: Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival. CONCLUSIONS: In our experience, presepsin was useful in the early diagnosis of infection in a complex population of patients with SIRS, sepsis, severe sepsis and septic shock who presented to the ED. Presepsin showed a significant prognostic value, and initial values were significantly correlated with in-hospital mortality of patients affected by sepsis, severe sepsis or septic shock.

Berberine behind the thriller of marked symptomatic bradycardia.

Patients with chronic aortic dissections are at high risk of catheter-induced complications. We report a Berberine is used in traditional Chinese medicine for the treatment of congestive heart failure, hypertension, diabetes, and dyslipidaemia and has a good safety profile. We report a case of a 53-year-old sportsman referred to our hospital for the onset of fatigue and dyspnoea upon exertion after he started berberine to treat hypercholesterolaemia. An electrocardiogram showed sinus bradycardia (45 bpm), first-degree atrioventricular block, and competitive junctional rhythm. An ergometric stress test showed slightly reduced chronotropic competence and the presence of runs of competitive junctional rhythm, atrial tachycardia, and sinus pauses in the recovery. After 10 d of wash-out from berberine, the patient experienced a complete resolution of symptoms, and an ergometric stress test showed good chronotropic competence. An electrocardiogram Holter showed a latent hypervagotonic state. This is the first case report that shows that berberine could present certain side effects in hypervagotonic people, even in the absence of a situation that could cause drug accumulation. Therefore, berberine's use should be carefully weighed in hypervagotonic people due to the drug's bradycardic and antiarrhythmic properties, which could became proarrhythmic, exposing patients to potential health risks.

Rule out of acute aortic dissection with plasma matrix metalloproteinase 8 in the emergency department.

INTRODUCTION: Matrix metalloproteinases (MMPs) are involved in aortic pathophysiology. Preliminary studies have detected increased plasma levels of MMP8 and MMP9 in patients with acute aortic dissection (AAD). However, the performance of plasma MMP8 and MMP9 for the diagnosis of AAD in the emergency department is at present unknown. METHODS: The levels of MMP8 and MMP9 were measured by ELISA on plasma samples obtained from 126 consecutive patients evaluated in the emergency department for suspected AAD. All patients were subjected to urgent computed tomography (CT) scan for final diagnosis. RESULTS: In the study cohort (N = 126), AAD was diagnosed in 52 patients and ruled out in 74 patients. Median plasma MMP8 levels were 36.4 (interquartile range 24.8 to 69.3) ng/ml in patients with AAD and 13.2 (8.1 to 31.8) ng/ml in patients receiving an alternative final diagnosis (P <0.0001). Median plasma MMP9 levels were 169.2 (93.0 to 261.8) ng/ml in patients with AAD and 80.5 (41.8 to 140.6) ng/ml in patients receiving an alternative final diagnosis (P = 0.001). The area under the curve (AUC) on receiver-operating characteristic (ROC) analysis of MMP8 and MMP9 for the diagnosis of AAD was respectively 0.75 and 0.70, as compared to 0.87 of D-dimer. At the cutoff of 3.6 ng/ml, plasma MMP8 had a sensitivity of 100.0% (95% CI, 93.2% to 100.0%) and a specificity of 9.5% (95% CI, 3.9% to 18.5%) and ruled out AAD in 5.6% of patients. Combination of plasma MMP8 with D-dimer increased the AUC on ROC analysis to 0.89. Presence of MMP8 <11.0 ng/ml and D-dimer <1.0 or <2.0 µg/ml provided a negative predictive value of 100% and ruled out AAD in 13.6% and 21.4% of patients respectively. CONCLUSIONS: Low levels of plasma MMP8 can rule out AAD in a minority of patients. Combination of plasma MMP8 and D-dimer at individually suboptimal cutoffs could safely rule out AAD in a substantial proportion of patients evaluated in the emergency department.

[Identification and evaluation of liver damage in subjects exposed to occupational risk from general anesthetics]. / Identificazione e valutazione del danno epatico in soggetti esposti a rischio occupazionale da anestetici generali.

BACKGROUND: The program Hepascore was produced by an interdisciplinary group working in the Laboratory of Clinical Informatics of the San Giovanni Battista Hospital in Turin with the aim of supporting physicians in the early diagnosis of hepatic damage and in its qualitative and quantitative characterization. The methodology used by this program can be useful especially for investigations concerning Industrial Medicine, which intend to control the occupational risk due to environmental exposure, not only to perform an early diagnosis (secondary prevention), but also to control the temporal evolution of the disease, by comparing significant data in a reproducible way. OBJECTIVE: This study was conducted with the aim of monitoring, by using the screening protocol of Hepascore, a group of workers exposed to an occupational risk by general anaesthetics, assessing the reliability of the proposed model and comparing it to the conventional approach in a cost/effectiveness analysis. METHODS: We evaluated 280 subjects (nurses and physicians) professionally exposed to anaesthetic gas; the environmental presence of anaesthetic agents was tested in all operating room of the hospital by the measurement of halogenated anaesthetics and nitrogen protoxide in the air. All the 280 subjects were submitted to a complete clinical evaluation and laboratory analyses, as recommended by monitoring protocols; in parallel, but independently from the clinical evaluation, also the sequential way used in the program Hepascore (a first screening phase evaluating only a few laboratory parameters, followed by a confirmation phase based on a larger number of blood tests with more restricted limits) was performed. The protocol applied in this study foresaw that subjects in which clinical evaluation and/or Hepascore brought to suspect a 'likely' liver alteration, had to be investigated thoroughly and to be reevaluated after 6 months by clinical examination and by Hepascore. RESULTS: The environmental determinations did never demonstrate the presence of anaesthetics over the threshold value (50 ppm for the N2O and 2 ppm for halogenated anaesthetics). The conventional clinical evaluation recognized as pathological 22 subjects with one or more liver parameters altered, which were explained as mild cytolytic or cholestatic alterations. The screening protocol carried out by Hepascore in the preliminary phase evidenced as pathological 38 subjects on 280 and 22 of them (corresponding to the 22 subjects identified by the clinical evaluation) were confirmed in the following phase (disease likely). CONCLUSIONS: This fact confirms that the sequential approach used by Hepascore provides the same outcomes obtained by performing all tests in the entire population under study, allowing a saving of 57% of the total cost spent for the traditional evaluation. The sequential approach proposed by Hepascore could be employed in all the clinical settings in which an evaluation of liver functional state is required, both in presence of environmental risk factors and in the case of a programme for the optimization of the population's food habits.

Nitric oxide level profile in human liver transplantation.

The aim of this study was to monitor nitric oxide blood levels at various times intraoperatively and following liver transplantation in humans. Nitric oxide production was assessed directly as circulating nitrosyl-hemoglobin adducts by electron paramagnetic resonance spectroscopy in 22 patients undergoing orthotopic liver transplantation. Two significant peaks in nitrosylhemoglobin levels were detected at 5 and 60 min after reperfusion (5.02 +/- 3.33 arbitrary units and 5.75 +/- 4.19, respectively, vs 3.33 +/- 2.28 under basal state; P < 0.05 for both comparisons). Postoperative nitrosyl-hemoglobin levels remained elevated, up to 5.42 +/- 0.89 arbitrary units (P < 0.05 vs basal values). Neither soluble intercellular adhesion molecule-1 or soluble endothelial-leukocyte adhesion molecule concentrations were altered intraoperatively. Only the former was significantly raised after transplantation. Neutrophil elastase levels showed an early increase and remained high throughout surgery, returning to basal values after transplantation. No correlations were found among studied parameters. These data suggest that nitric oxide may play a role in ischemia-reperfusion phases in human liver transplantation. Mechanisms other than leukocyte-endothelial adhesion and neutrophil activation seem to affect nitric oxide production under these conditions.