Effects of Fibrinogen Concentrate Supplementation on Postoperative Bleeding in Infants Undergoing Complex Cardiac Surgery.

The use of allogeneic blood products to restore hemostasis during pediatric cardiac surgery is associated with major risks. Consequently, there has been a growing interest in new patient blood management strategies, such as those based on the use of fibrinogen concentrate (FC). Accumulating evidence has shown FC supplementation to be safe and effective. Nevertheless, no guidelines are available on using FC in the pediatric setting, and few objective evaluations have been provided in clinical practice. The endpoint of this monocenter retrospective study was the hemostatic effect of additional FC in infants undergoing complex cardiac surgery with cardiopulmonary bypass to manage persistent clinically relevant bleeding. After weaning from cardiopulmonary bypass and after protamine administration, patients were transfused with conventional allogeneic products such as packed red blood cells, fresh frozen plasma (FFP), and platelets. In the case of redo surgery, according to the institutional protocol, patients also received tranexamic acid. In case of clinically persistent relevant bleeding, according to the anesthesiologist's judgment and thromboelastography, patients received FC supplementation (group with FC) or further FFP transfusions without receiving FC supplementation (group without FC). The primary endpoint was the hemostatic effects of FC. Secondary endpoints were the functional hypofibrinogenemia threshold value (expressed as maximum amplitude fibrinogen, MA-Fib) and postoperative MA-Fib, fibrinogenemia, intraoperative transfusions, and adverse events (AEs). In total, 139 patients who underwent cardiac surgery with CPB and aged less than 2 years were enrolled: 70 patients received allogeneic blood products and FC supplementation (group FC); 69 patients received allogeneic products without FC supplementation (group without FC). Patients that received FC supplementation were characterized by a significantly longer time of extracorporeal circulation (p < 0.001) and aortic cross-clamping (p < 0.001), a significantly lower minimum temperature (p = 0.011), increased use of concentrated prothrombin complex (p = 0.016) and tranexamic acid (p = 0.010), and a significantly higher amount of packed red blood cells, platelets (p < 0.001) and fresh frozen plasma (p = 0.03). Postoperative bleeding and severe bleeding were not statistically different between patients treated with FC and those not treated with FC supplementation (p = 0.786 and p = 0.695, respectively); after adjustment, a trend toward reduced bleeding can be observed with FC (p = 0.064). Overall, 88% of patients with severe bleeding had MA-Fib < 10 mm; a moderate association between severe bleeding and MA-Fib (odds ratio 1.7, 95% CI 0.5-6.5, p = 0.425) was found. Increased MA-Fib and postoperative fibrinogen were higher in the FC group (p = 0.003 and p < 0.001, respectively) than in FFP. AEs in the FC group were comparable to those observed in less complicated surgeries. Our results suggest a potential role of FC in complex surgery in maintaining postoperative bleeding at a level comparable to less complicated surgical procedures and favoring the increase in postoperative MA-Fib and fibrinogen.

Veno-arterial CO2 difference and cardiac index in children after cardiac surgery.

Veno-arterial CO2 difference has been considered as a marker of low cardiac output. This study aimed to evaluate the correlation between veno-arterial CO2 difference and cardiac index estimated by MostCareTM in children after cardiac surgery and its association with other indirect perfusion parameters and the complex clinical course (vasoactive inotropic score above 15 or length of stay above 5 days).Data from 40 patients and 127 arterial and venous CO2 measurements for gap calculation taken 0-5 days postoperatively were available. The median (range) veno-arterial CO2 difference value was 9 (1-25 mmHg). The correlation between veno-arterial CO2 difference and cardiac index was not significant (r: -0.16, p = 0.08). However, there was a significant correlation between veno-arterial CO2 difference and vasoactive inotropic score (r: 0.21, p = 0.02), systolic arterial pressure (r: -0.43, p = 0.0001), dP/dtMAX (r: 0.26, p = 0.004), and arterio-venous O2 difference (r: 0.63, p = 0.0001). Systolic arterial pressure (OR 0.95, 95% CI 0.90-0.99), dP/dtMAX (OR 0.00, 95% CI 0.00-0.06), lactates (OR 1.87, 95% CI 1.21-3.31), and veno-arterial CO2 difference (OR 1.13, 95% CI 1.01-1.35) showed a significant univariate association with the complex clinical course. In conclusion, veno-arterial CO2 difference did not correlate with cardiac index estimated by MostCareTM in our cohort of post-cardiosurgical children, but it identified patients with the complex clinical course, especially when combined with other direct and indirect variables of perfusion.

Development of a binary classifier model from extended facial codes toward video-based pain recognition in cancer patients.

OBJECTIVES: The Automatic Pain Assessment (APA) relies on the exploitation of objective methods to evaluate the severity of pain and other pain-related characteristics. Facial expressions are the most investigated pain behavior features for APA. We constructed a binary classifier model for discriminating between the absence and presence of pain through video analysis. METHODS: A brief interview lasting approximately two-minute was conducted with cancer patients, and video recordings were taken during the session. The Delaware Pain Database and UNBC-McMaster Shoulder Pain dataset were used for training. A set of 17 Action Units (AUs) was adopted. For each image, the OpenFace toolkit was used to extract the considered AUs. The collected data were grouped and split into train and test sets: 80 % of the data was used as a training set and the remaining 20 % as the validation set. For continuous estimation, the entire patient video with frame prediction values of 0 (no pain) or 1 (pain), was imported into an annotator (ELAN 6.4). The developed Neural Network classifier consists of two dense layers. The first layer contains 17 nodes associated with the facial AUs extracted by OpenFace for each image. The output layer is a classification label of "pain" (1) or "no pain" (0). RESULTS: The classifier obtained an accuracy of ∼94 % after about 400 training epochs. The Area Under the ROC curve (AUROC) value was approximately 0.98. CONCLUSIONS: This study demonstrated that the use of a binary classifier model developed from selected AUs can be an effective tool for evaluating cancer pain. The implementation of an APA classifier can be useful for detecting potential pain fluctuations. In the context of APA research, further investigations are necessary to refine the process and particularly to combine this data with multi-parameter analyses such as speech analysis, text analysis, and data obtained from physiological parameters.

Pagan Gods as Figures of Speech: Dante's Use of Servius in the Vita Nova.

The article sets out to show the ideological significance of the quotations from Vergil, Lucan, Horace, Homer, and Ovid found in Vita Nova 16 [XXV], the celebrated passage where Dante cites these poets as examples of personification in classical literature. In the quotations from Vergil's Aeneid, Aeolus and Juno speak to each other, and Apollo speaks to the Trojans. In his framing of the quotations, Dante appears implicitly to regard pagan deities like Aeolus, Juno, and Apollo as inanimate things, raising the question as to why the author of the Vita Nova understood pagan gods in terms of poetic tropes. Focusing on the Vergilian quotations, this essay argues that Servius's commentary to the Aeneid represents one of the major sources that might have led Dante to construe pagan deities as rhetorical personifications.

Neurally adjusted ventilatory assist and lung transplant in a child: A case report.

OBJECTIVE: To report the successful application of neurally adjusted ventilatory assist to a child with cystic fibrosis who underwent single-lung transplantation. DESIGN: Case report. SETTING: Pediatric cardiac intensive care unit. PATIENT: A 15-yr-old male with cystic fibrosis was admitted to our pediatric cardiac intensive care unit after single-lung transplantation. The child had previously received two bowel resections at the age of 1 yr, right pneumonectomy at the age of 3 yrs, and endoscopic percutaneus gastrostomy at the age of 10 yrs. After transplant, the child failed several attempts of weaning off mechanical ventilation with pressure-support ventilation, due to infection, pneumothorax, and ventilator asynchrony that caused gastric distension and numerous episodes of nausea and vomiting. INTERVENTION: Use of neurally adjusted ventilatory assist to avoid patient-ventilator dyssynchrony and consequent gastric distension. CONCLUSIONS: The utilization of neurally adjusted ventilatory assist allowed to limit the risk of overassistance and prevent patient-ventilator asynchrony and to successfully wean the child off mechanical ventilation after single-lung transplant.

Establishment and Preliminary Characterization of Three Astrocytic Cells Lines Obtained from Primary Rat Astrocytes by Sub-Cloning.

Gliomas are complex and heterogeneous tumors that originate from the glial cells of the brain. The malignant cells undergo deep modifications of their metabolism, and acquire the capacity to invade the brain parenchyma and to induce epigenetic modifications in the other brain cell types. In spite of the efforts made to define the pathology at the molecular level, and to set novel approaches to reach the infiltrating cells, gliomas are still fatal. In order to gain a better knowledge of the cellular events that accompany astrocyte transformation, we developed three increasingly transformed astrocyte cell lines, starting from primary rat cortical astrocytes, and analyzed them at the cytogenetic and epigenetic level. In parallel, we also studied the expression of the differentiation-related H1.0 linker histone variant to evaluate its possible modification in relation with transformation. We found that the most modified astrocytes (A-FC6) have epigenetic and chromosomal alterations typical of cancer, and that the other two clones (A-GS1 and A-VV5) have intermediate properties. Surprisingly, the differentiation-specific somatic histone H1.0 steadily increases from the normal astrocytes to the most transformed ones. As a whole, our results suggest that these three cell lines, together with the starting primary cells, constitute a potential model for studying glioma development.

Metal-carbon nanotube contacts: the link between Schottky barrier and chemical bonding.

The field effect transistor based on carbon nanotubes (CNT) is a very promising candidate for post-CMOS microelectronics. Transport in the CNT channel is dominated by the Schottky barriers existing at the metal source contacts. The nature of the metal and the geometry of the contact appear to influence strongly the electrical behavior, but the mechanism is still rather obscure. Extensive calculations based on density functional theory performed for both end and side contacts and for two metals of very different nature, namely, Al and Pd, allow us to identify a clear connection between the character of the chemical bonding and the height of the Schottky barrier (SBH). Our results emphasize that a low SBH for hole conduction in a CNT implies that the pi-electron system of the latter is almost exclusively involved in the chemical bonding with the metal atoms at the interface and that the bonding is not too strong so that both orbital hybridization and topology are preserved. This is the case for Pd in both end and side configurations and to a large extent for Al but in the side geometry only. On the other hand, the coupling of the metal states with the sigma-like system or, in other words, the perturbation of the conjugation of the pi-system via sp3 C-hybridization is the mechanism that enhances the SBH. This is especially evident in the end contact with Al. By showing how the chemistry at the interfaces determines the SBH, our findings open the possibility of better controlling and designing "good contacts".

Lung ultrasound profile after cardiopulmonary bypass in paediatric cardiac surgery: first experience in a simple cohort.

Objectives: To explore the association between lung ultrasound (LUS) and clinical variables in children undergoing cardiopulmonary bypass (CPB). Methods: A retrospective analysis was conducted in patients weighing <20 kg and with an Aristotle score <9, scanned with LUS on postoperative day (POD) 0, 1 and 2. We defined three LUS profiles: profile A: the prevalence of confluent B lines ("white lung"); profile B: the prevalence of B lines and profile C: the prevalence of A lines (normal lung). Results: Median (interquartile range [IRQ]) weight, age and Aristotle score were 5.6 kg [IQR 4.0-6.0], 3.2 months [IQR 3.0-7.0] and 6.75 [IQR 6.0-8.0], respectively. No profile A patients were found. At POD1, we identified statistically significant differences between profile B and C patients: CPB time was 157 [IQR138-235] vs 95 [IQR 85-183] minutes ( P < 0.005); aortic clamp duration was 104 [IQR 87-142] vs 54 [IQR 49-72] minutes ( P = 0.007); time of mechanical ventilation was 41.5 [IQR 31.0-56.0] vs 15 [IQR 15-24] hours ( P < 0.001); and ICU length of stay was 2 [IQR 2-3] vs 4 [IQR 3-4] days ( P = 0.001), respectively. No differences were found between profile B and C patients at all the other time points. No statistically significant differences were found for blood gas values, urine output and fluid balance at all time points. Conclusions: In a small cohort of children undergoing CPB, the LUS profile on POD1 was associated with CPB time, aortic cross-clamp time and mechanical ventilation duration.

Lung ultrasonography and pediatric cardiac surgery: first experience with a new tool for postoperative lung complications.

Lung ultrasonography is a diagnostic tool increasingly used in critical care. Few data are available for the pediatric population. We describe our experience with lung ultrasonography for 5 pediatric patients with common post-cardiac surgery lung complications (pleural effusion, pneumothorax, atelectasis, pneumonia). Ultrasonography was useful also for lung recruitment. Such data were confirmed by chest radiographs or by computed tomography, or both. Lung ultrasonography can be considered as a useful, real-time, bedside tool to detect specific lung diseases, reliably implementing radiographic images and potentially decreasing the total number of radiographs in critically ill children with congenital heart diseases.

Comparative evaluation of high-flow nasal cannula and conventional oxygen therapy in paediatric cardiac surgical patients: a randomized controlled trial.

OBJECTIVES: The aim of this study was to compare high-flow nasal cannula (HFNC) and conventional O2 therapy (OT) in paediatric cardiac surgical patients; the primary objective of the study was to evaluate whether HFNC was able to improve PaCO2 elimination in the first 48 h after extubation postoperatively. METHODS: We conducted a randomized, controlled trial in pediatric cardiac surgical patients under 18 months of age. At the beginning of the weaning of ventilation, patients were randomly assigned to either of the following groups: OT or HFNC. Arterial blood samples were collected before and after extubation at the following time points: 1, 6, 12, 24 and 48 h. The primary outcome was comparison of arterial PaCO2 postextubation; secondary outcomes were PaO2 and PaO2/fractional inspired oxygen (FiO2) ratio, rate of treatment failure and need of respiratory support, rate of extubation failure, rate of atelectasis, simply to complications and the length of paediatric cardiac intensive care unit stay. RESULTS: Demographic and clinical variables were comparable in the two groups. Analysis of variance for repeated measures showed that PaCO2 was not significantly different between the HFNC and OT groups (P = 0.5), whereas PaO2 and PaO2/FiO2 were significantly improved in the HFNC group (P = 0.01 and P = 0.001). The rate of reintubation was not different in the two groups (P = 1.0), whereas the need for noninvasive respiratory support was 15% in the OT group and none in the HFNC group (P = 0.008). CONCLUSIONS: HFNC had no impact on PaCO2 values. The use of HFNC appeared to be safe and improved PaO2 in paediatric cardiac surgical patients.

Levosimendan infusion in newborns after corrective surgery for congenital heart disease: randomized controlled trial.

PURPOSE: To evaluate the safety and efficacy of levosimendan in neonates with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Neonates undergoing risk-adjusted classification for congenital heart surgery (RACHS) 3 and 4 procedures were randomized to receive either a 72 h continuous infusion of 0.1 µg/kg/min levosimendan or standard post-CPB inotrope infusion. RESULTS: Sixty-three patients (32 cases and 31 controls) were recruited. There were no differences between groups regarding demographic and baseline clinical data. No side effects were observed. There were no significant differences in mortality (1 vs. 3 patients, p = 0.35), length of mechanical ventilation (5.9 ± 5 vs. 6.9 ± 8 days, p = 0.54), and pediatric cardiac intensive care unit (PCICU) stay (11 ± 8 vs. 14 ± 14 days, p = 0.26). Low cardiac output syndrome occurred in 37 % of levosimendan patients and in 61 % of controls (p = 0.059, OR 0.38, 95 % CI 0.14-1.0). Postoperative heart rate, with a significant difference at 6 (p = 0.008), 12 (p = 0.037), and 24 h (p = 0.046), and lactate levels, with a significant difference at PCICU admission (p = 0.015) and after 6 h (p = 0.048), were lower in the levosimendan group. Inotropic score was significantly lower in the levosimendan group at PCICU admission, after 6 h and after 12 h, (p < 0.0001). According to multivariate analysis, a lower lactate level 6 h after PCICU admission was independently associated with levosimendan administration after correction for CPB time and the need for deep hypothermic circulatory arrest. CONCLUSIONS: Levosimendan infused in neonates undergoing cardiac surgery was well tolerated with a potential benefit of levosimendan on postoperative hemodynamic and metabolic parameters of RACHS 3-4 neonates.

Initial single-center experience with levosimendan infusion for perioperative management of univentricular heart with ductal-dependent systemic circulation.

The aim of this study was to evaluate the safety and the efficacy of levosimendan, a novel calcium sensitizer agent, on postoperative hemodynamic and metabolic parameters of neonates affected by single ventricle anatomy. Twenty consecutive neonates scheduled for the Norwood procedure with Blalock Taussig shunt were prospectively enrolled. All patients received an infusion of levosimendan at 0.1 µg/kg/min commencing 24 hours before surgery, and the infusion was continued for 48 hours after surgery. No side effects (intolerance to the drug, hypotension, arrhythmias) were shown. A median inotropic score (IS) of 37 was necessary to maintain a mean arterial pressure between 45 and 50 mm Hg at intensive care unit (ICU) admission: IS was significantly reduced after 72 hours (P < .05). Brain natriuretic peptide values decreased significantly from 1210 to 459 pg/mL in 72 hours (P < .05). Median SvO2 increased significantly from 38% to 59% during the evaluated period (P < .05). Cerebral near-infrared spectroscopy values were close to 40% at ICU admission with a significant stable increase to 50% after 12 hours (P < .05). Median lactate level was 13 mmol/L at ICU admission but showed a trend to a rapid and significant decrease after 12 hours (P < .05). Median urine output was surprisingly elevated, always remaining between 5.2 and 6.2 mL/kg/h throughout the postoperative period. Survival rate was 85% at 30 days (17/20 patients) and 75% (15/20) at hospital discharge. Levosimendan infusion in a cohort of neonates with univentricular anatomy was safe and potentially beneficial on postoperative hemodynamic and metabolic parameters.

Fenoldopam in newborn patients undergoing cardiopulmonary bypass: controlled clinical trial.

We determined if low dose fenoldopam in neonates already receiving conventional diuretics improves urine output, fluid balance, acute kidney injury incidence (AKI) and time to extubation. A prospective controlled clinical trial in a pediatric cardiac intensive care unit on 40 neonates undergoing cardiac surgery with cardiopulmonary bypass, excluding simple ventricular septal defect and atrial septal defect. Fenoldopam was infused at a low dose of 0.1 microg/kg/min soon after anesthesia induction and infusion prolonged for 72 h in 20 patients. Twenty neonates with standardized perioperative therapy except fenoldopam administration served as controls. Demographic, hemodynamic, daily urine output, creatinine, creatinine clearance, serum and urinary sodium and potassium were recorded. Inotropic score (IS) was calculated as a surrogate for the degree of hemodynamic impairment. Low dose fenoldopam infusion did not show beneficial effects in renal function. The treatment did not significantly affect IS value, AKI incidence, fluid balance control, time to sternal closure, time to extubation and time to intensive care unit discharge. Low dose fenoldopam in neonates undergoing cardiac surgery with CPB did not produce effects on urine output, fluid balance and AKI incidence. Fenoldopam was well tolerated and did not negatively affect hemodynamics and vasopressor support.