Giulia Elisa Cambi

Response of Serum Proteome in Patients Undergoing Infrarenal Aortic Aneurysm Repair

Background:Postoperative organ dysfunction in conventional surgery for abdominal aortic aneurysm (AAA) is associated with a complex inflammatory reaction, with activation of coagulation and fibrinolysis. A prospective,observational study was performed to define the complex plasma proteomic changes after AAA repair and to identify factor(s) that may affect myocardial function in uncomplicated procedures. Methods:Ten patients undergoing infrarenal AAA repair were investigated. Eight subjects subjected to major abdominal surgery served as controls. Hemodynamic changes were continuously monitored by using the pressure recording analytical method technique. The time course of plasma proteins was investigated after induction of anesthesia and at different times after surgery (6 h, 12 h, 24 h, 36 h) by using two-dimensional difference gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and Western blot. The effects of plasma on the functional properties of isolated rat ventricular myocytes were also investigated. Results:In AAA patients alone, 18 spots were found to change more than two-fold in expression level, spot identification revealing an increased thrombin generation 6 h after surgery. At the same time cardiac cycle efficiency significantly reduced versus baseline (–0.5 ± 0.9 vs. 0.18 ± 0.3 in AAA patients, P < 0.01; 0.4 ± 0.1 vs. 0.2 ± 0.3 in control surgery, not significant; P < 0.01 group × time interaction at ANOVA). Plasma obtained 6 h after AAA surgery dose-dependently inhibited contractile function of control rat myocytes (percent shortening fell by 51% with 10% of AAA plasma and was abolished with 20% of AAA plasma, P < 0.001 for both). The inhibitory response was abolished by thrombin antagonism. Conclusions:These findings show for the first time the possible role of thrombin generation within the complex activation of inflammatory response in causing hemodynamic instability in the early postoperative period after AAA surgery.

Index Measured at an Intermediate Altitude to Predict Impending Acute Mountain Sickness

PURPOSE Acute mountain sickness (AMS) is a neurological disorder that may be unpredictably experienced by subjects ascending at a high altitude. The aim of the present study was to develop a predictive index, measured at an intermediate altitude, to predict the onset of AMS at a higher altitude. METHODS In the first part, 47 subjects were investigated and blood withdrawals were performed before ascent, at an intermediate altitude (3440 m), and after acute and chronic exposition to high altitude (Mount Everest Base Camp, 5400 m (MEBC1 and MEBC2)). Parameters independently associated to the Lake Louise scoring (LLS) system, including the self-reported and the clinical sections, and coefficients estimated from the model obtained through stepwise regression analysis were used to create a predictive index. The possibility of the index, measured after an overnight stay at intermediate altitude (Gnifetti hut, 3647 m), to predict AMS (defined as headache and LLS ≥ 4) at final altitude (Capanna Margherita, 4559 m), was then investigated in a prospective study performed on 44 subjects in the Italian Alps. RESULTS During the expedition to MEBC, oxygen saturation, hematocrit, day of expedition, and maximum velocity of clot formation were selected as independently associated with LLS and were included in the predictive index. In the Italian Alps, subjects with a predictive index value ≥ 5.92 at an intermediate altitude had an odds ratio of 8.1 (95% confidence limits = 1.7-38.6, sensitivity = 85%, specificity = 59%) for developing AMS within 48 h of reaching high altitude. CONCLUSION In conclusion, a predictive index combining clinical and hematological parameters measured at an intermediate step on the way to the top may provide information on impending AMS.

The impact of fine-tuning of optical recognition system on database reliability

Although optical reading systems are important tools to transfer data from a paper form to electronic databases, the impact of system fine-tuning on the final error rate is not usually considered. At the end of a multi-step process involving paper form design training of operators, and fine-tuning procedure, the final rate of error can be reduced from 0.65% to 0.05%. Fine-tuning should be introduced as a standard procedure while using optical reading systems.

SEASONAL CHANGES AND MORNING BLOOD PRESSURE SURGE. WHICH ROLE FOR OUTDOOR AND INDOOR AIR TEMPERATURE?: PP.29.147

Objective: Important climate related variations of clinic and ambulatory blood pressure (BP) have been repeatedly reported. However, notwithstanding the wide use of indoor climate control systems, specially in winter, no information is available regarding the role of air temperature values measured proximally to the patient, in particular when focussing on specific components of the 24 h BP profile, such as the morning BP surge (MBPS). Design and Methods: To investigate whether MBPS is affected by outdoor air temperature or by the air temperature measured proximally to the patient, 2120 hypertensives underwent 24 h ambulatory blood pressure (ABP) monitoring with a battery-powered “HOBO” temperature data logger fitted to the carrying pouch of the ABP monitor. Predictors of MBPS were investigated with a multivariate stepwise regression model including age, gender, body mass index, office systolic BP, 24 h average ABP, mean 24 h outdoor atmospheric pressure and mean 24 h air temperature measured both outdoor and by HOBO as independent variables. Results: Stepwise multiple regression analysis carried out in the 1728 subjects included in the final analysis selected outdoor air temperature(beta = -0.09;p < 0.0001), 24 h ABP(beta = -0.72;p < 0.0001), and age(beta = -0.06;p < 0.002) as negative independent predictors of MBPS, with systolic office BP selected as a positive independent predictor (beta = 1,04;p < 0.0001)(r = 0.610); no significant effect of HOBO air temperature was observed. When subjects were stratified according to age, the effect on MBPS of outdoor air temperature was detectable in subjects >65 yrs (beta = -0.086; p < 0.002), whereas the only determinants of MBPS in subjects < 50 yrs were office SBP (positive) and 24 h average SBP(negative). Conclusions: These results confirm and extend previous observation on the occurrence of seasonal changes in 24 h BP profiles, by providing new evidence that only air temperature measured outdoor affects BP morning surge in addition to office BP, 24 h ABP and age, whereas no role appears to be played by air temperature measured proximally to the patient. The clinical implications of these findings for BP control would need to be further tested by ad hoc studies.

Can mountain sickness symptoms be predicted on the basis of blood coagulation parameters

Objective: The present study was performed to investigate the possible occurrence of global changes of blood coagulation (thromboelastometry) during exposure to high altitude hypoxia, and their relation with the occurrence of mountain sickness symptoms (quantified by the Lake Louise Score, LLS), in the frame of the HIGH altitude Cardiovascular Research(HIGHCARE) project at Everest base camp (BC,5400 m). Design and Method: All participants (n = 47;40 ± 9 yrs)to HIGHCARE expedition underwent baseline clinical and instrumental evaluation at sea level(baseline), the day after reaching 3400 m by helicopter (Namche), after acute (BC1) and prolonged (2 weeks,BC2) exposure at 5400 m. Thromboelastometry (ROTEM Pentapharm, Munich, Germany), was performed on simple recalcified citrated plasma (spontaneous contact activation,NATEM) and upon addition of ellagic acid (intrinsic pathway,INTEM). All clinical and instrumental parameters were then entered in stepwise multivariate regression analysis to select independent predictors of LLS, which was determined in each study conditions. Results: At Namche 23 out of 47 subjects had no symptoms of high altitude sickness (LLS = 0) with LLS>3 in 2 subjects. At BC1 40 subjects had symptoms, 14 reporting a LLS >3 (0 in only 7 subjects). After chronic adaptation(BC2), only 17 had symptoms (LLS >3 in 1 subject). Oxygen saturation (beta = -0.859;p < 0.0001), haematocrit (beta-0.228;p < 0.004), expedition day (-0.263;p < 0.006) and maximum velocity of clot formation at INTEM assay (beta = 0.176;p < 0.013) were identified as independent predictor of LLS at stepwise regression analysis. A score index, calculated on the basis of the four predictors corrected for regression coefficients, was then retrospectively used to stratify subjects in three classes of mountain sickness risk, according to data measured at Namche (acute hypoxia exposure).One out of 12 subjects in the first tertile versus 12 out of the remaining 35 subjects had LLS>3 at BC1(p < 0.001). Conclusions: INTEM assay revealed a reduced activity of coagulation intrinsic pathway at altitude. However the maximum velocity of clot formation at INTEM assay was selected as a positive independent predictor of LLS, indicating a link between rheological changes and adaptation to altitude.