Salivary lactate and 8-isoprostaglandin F2α as potential non-invasive biomarkers for monitoring heart failure: a pilot study.

Heart failure (HF) is a cardiovascular disease affecting about 26 million people worldwide costing about $100 billons per year. HF activates several compensatory mechanisms and neurohormonal systems, so we hypothesized that the concomitant monitoring of a panel of potential biomarkers related to such conditions might help predicting HF evolution. Saliva analysis by point-of-care devices is expected to become an innovative and powerful monitoring approach since the chemical composition of saliva mirrors that of blood. The aims of this study were (i) to develop an innovative procedure combining MEPS with UHPLC-MS/MS for the simultaneous determination of 8-isoprostaglandin F2α and cortisol in saliva and (ii) to monitor lactate, uric acid, TNF-α, cortisol, α-amylase and 8-isoprostaglandin F2α concentrations in stimulated saliva samples collected from 44 HF patients during their hospitalisation due to acute HF. Limit of detection of 10 pg/mL, satisfactory recovery (95-110%), and good intra- and inter-day precisions (RSD ≤ 10%) were obtained for 8-isoprostaglandin F2α and cortisol. Salivary lactate and 8-isoprostaglandin F2α were strongly correlated with NT-proBNP. Most patients (about 70%) showed a significant decrease (a factor of 3 at least) of both lactate and 8-isoprostaglandin F2α levels at discharge, suggesting a relationship between salivary levels and improved clinical conditions during hospitalization.

Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease.

OBJECTIVES: We explored the role of oxidative stress and inflammatory molecules as potential Parkinson (PD) biomarkers and correlated biological with non-motor abnormalities (olfactory impairment and dysautonomia), in patients with idiopathic REM behavior disorder (iRBD) (prodromal PD) and established PD. METHODS: We recruited 11 iRBD and 15 patients with idiopathic PD (Hohen&Yahr 1-3, on L-DOPA and dopamine agonists combination therapy) and 12 age- and sex-matched controls (CTRL). We measured total olfactory score (TOS), autonomic function [deep breathing (DB), lying to standing (LS) and Valsalva manoeuvre (VM) ratios], blood reduced glutathione (Br-GSH), oxidative stress and inflammatory markers (neopterin). RESULTS: Anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but absent in CTRL. Orthostatic hypotension was more common among iRBD (73%) and PD (60%) than in CTRL (25%). By univariable ordinal logistic regression, TOS, Br-GSH, LS and VM ratio worsened from CTRL to iRBD and PD groups. Only reduced Br-GSH levels (p=0.037, OR=0.994; 95%CI 0.988-1.000) were independently associated to PD. TOS correlated with Br-GSH (R=0.34, p=0.037), VM ratio (R=0.43, p=0.015), and neopterin (rho=0.39, p=0.016). CONCLUSIONS: Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular dysautonomia, a useful biomarker for an integrative, early diagnosis of PD.

Hemodynamic Effects of Ventricular Assist Device Implantation on Norwood, Glenn, and Fontan Circulation: A Simulation Study.

The growing population of failing single-ventricle (SV) patients might benefit from ventricular assist device (VAD) support as a bridge to heart transplantation. However, the documented experience is limited to isolated case reports. Considering the complex and different physiopathology of Norwood, Glenn, and Fontan patients and the lack of established experience, the aim of this work is to realize and test a lumped parameter model of the cardiovascular system able to simulate SV hemodynamics and VAD implantation effects to support clinical decision. Hemodynamic and echocardiographic data of 30 SV patients (10 Norwood, 10 Glenn, and 10 Fontan) were retrospectively collected and used to simulate patients' baseline. Then, the effects of VAD implantation were simulated. Simulation results suggest that the implantation of VAD: (i) increases the cardiac output and the mean arterial systemic pressure in all the three palliation conditions (Norwood 77.2 and 19.7%, Glenn 38.6 and 32.2%, and Fontan 17.2 and 14.2%); (ii) decreases the SV external work (Norwood 55%, Glenn 35.6%, and Fontan 41%); (iii) decreases the pressure pulsatility index (Norwood 65.2%, Glenn 81.3%, and Fontan 64.8%); (iv) increases the pulmonary arterial pressure in particular in the Norwood circulation (Norwood 39.7%, Glenn 12.1% and Fontan 3%); and (v) decreases the atrial pressure (Norwood 2%, Glenn 10.6%, and Fontan 8.6%). Finally, the VAD work is lower in the Norwood circulation (30.4 mL·mm Hg) in comparison with Fontan (40.3 mL·mm Hg) and to Glenn (64.5 mL·mm Hg) circulations. The use of VAD in SV physiology could be helpful to bridge patients to heart transplantations by increasing the CO and unloading the SV with a decrement of the atrial pressure and the SV external work. The regulation of the pulmonary flow is challenging because the Pap is increased by the presence of VAD. The hemodynamic changes are different in the different SV palliation step. The use of numerical models could be helpful to support patient and VAD selection to optimize the clinical outcome.

Simulation of acute haemodynamic outcomes of the surgical strategies for the right ventricular failure treatment in pediatric LVAD.

BACKGROUND: Right ventricular failure (RVF) is one of the major complications during LVAD. Apart from drug therapy, the most reliable option is the implantation of RVAD. However, BIVAD have a poor prognosis and increased complications. Experiments have been conducted on alternative approaches, such as the creation of an atrial septal defect (ASD), a cavo-aortic shunt (CAS) including the LVAD and a cavo-pulmonary connection (CPC). This work aims at realizing a lumped parameter model (LPM) to compare the acute hemodynamic effects of ASD, CPC, CAS, RVAD in LVAD pediatric patients with RVF. METHODS: Data of 5 pediatric patients undergoing LVAD were retrospectively collected to reproduce patients baseline hemodynamics with the LPM. The effects of continuous flow LVAD implantation complicated by RVF was simulated and then the effects of ASD, CPC, CAS and RVAD treatments were simulated for each patient. RESULTS: The model successfully reproduced patients' baseline and the hemodynamic effects of the surgical strategies. Simulating the different surgical strategies, an unloading of the right ventricle and an increment of left ventricular preload were observed with an improvement of the hemodynamics (total cardiac output: ASD +15%, CPC +10%, CAS +70% RVAD +20%; right ventricular external work: ASD -19%, CPC -46%, CAS -76%, RVAD -32%; left ventricular external work: ASD +12%, CPC +28%, RVAD +64%). CONCLUSIONS: The use of numerical model could offer an additional support for clinical decision-making, also potentially reducing animal experiments, to compare the outcome of different surgical strategies to treat RVF in LVAD.

Inflammation blood and tissue factors of plaque growth in an experimental model evidenced by a systems approach.

PURPOSE: The multifactorial pathogenesis of coronary atherosclerotic lesion formation has been investigated in a swine model of high cholesterol diet induced atherogenesis and data processed by a systems approach. METHODS: Farm pigs were fed on standard or high cholesterol diet of 8 and 16 weeks duration. Plasma assessment of total cholesterol, HDL, LDL, and ELISA of some cytokines and ICAM-1 were performed on baseline and end-diet samples. Segments of the right coronary artery were incubated for 24 h in serum-free medium to collect secreted proteins and their expression analyzed by mass spectrometry. Data of plasma and tissue factors were processed by a statistical systems inference approach: both histologic parameters of coronary intimal thickness (IT) and of lesion area (LA) were chosen as dependent variables (coronary atherosclerotic burden). RESULTS: Relations among plasma adhesion molecules, cytokines, lipoproteins, tissue proteins and histology indexes were integrated in a model regression scheme. Bayesian model averaging (BMA) variable selection was chosen as a method to identify relevant factors associated to atherosclerotic burden: TNFα was identified as an associated plasma marker, oxLDL and HDL as relevant lipoproteins; macrophage function related antioxidant Catalase enzyme, lysosome associated Cathepsin D, S100-A10, and Transforming growth factor-beta-induced protein ig-h3 were identified and selected as associated to atherogenesis outcome. CONCLUSIONS: The results of this systems approach are consistent with the hypothesis that, in high cholesterol diet-induced experimental atherogenesis, the interaction between plasma cytokines, lipoproteins and artery-specific proteins, influences lesion initiation and growth. In particular, some macrophage function related proteins are found significantly and positively associated to atherosclerotic burden, suggesting a novel molecular framework into the atherogenesis-inflammatory disorder.

Simulation of apical and atrio-aortic VAD in patients with transposition or congenitally corrected transposition of the great arteries.

PURPOSE: VADs could be used for transportation of the great arteries (TGA) and for congenitally corrected transposition (ccTGA) treatment. A cardiovascular numerical model (NM) may offer a useful clinical support in these complex physiopathologies. This work aims at developing and preliminarily verifying a NM of ccTGA and TGA interacting with VADs. METHODS: Hemodynamic data were collected at the baseline (BL) and three months (FUP) after apical (atrio-aortic) VAD implantation in a TGA (ccTGA) patient and used in a lumped parameter NM to simulate the patient's physiopathology. Measured (MS) and simulated (SIM) data were compared. RESULTS: MS and SIM data are in accordance at the BL and at FUP. Cardiac output (l/min): BL_m = 2.9 ± 0.4, BL_s = 3.0 ± 0.3; FUP_m = 4.2 ± 0.2, FUP_s = 4.1 ± 0.1. Right atrial pressure (mmHg): BL_m = 21.4 ± 4.1, BL_s = 18.5 ± 4.5; FUP_m = 13 ± 4, FUP_s = 14.8 ± 3.6. Pulmonary arterial pressure (mmHg): BL_m = 56 ± 6.3,BL_s = 57 ± 2, FUP_m = 37.5 ± 7.5, FUP_s = 35.5 ± 5.9. Systemic arterial pressure (mmHg): BL_m = 71 ± 2, BL_s = 74.6 ± 2.1; FUP_m = 84 ± 9, FUP_s = 81.9 ± 9.8. CONCLUSIONS: NM can simulate the effect of a VAD in complex physiopathologies, with the inclusion of changes in circulatory parameters during the acute phase and at FUP. The simulation of differently assisted physiopathologies offers a useful support for clinicians.

Adverse event prediction in patients with left ventricular assist devices.

This work presents the Treatment Tool, which is a component of the Specialist's Decision Support Framework (SDSS) of the SensorART platform. The SensorART platform focuses on the management of heart failure (HF) patients, which are treated with implantable, left ventricular assist devices (LVADs). SDSS supports the specialists on various decisions regarding patients with LVADs including decisions on the best treatment strategy, suggestion of the most appropriate candidates for LVAD weaning, configuration of the pump speed settings, while also provides data analysis tools for new knowledge extraction. The Treatment Tool is a web-based component and its functionality includes the calculation of several acknowledged risk scores along with the adverse events appearance prediction for treatment assessment.

Knowledge Editor and execution engine development for optimal ventricular assist device weaning.

In this work, the weaning module of the SensorART specialist decision support system (SDSS) is presented. SensorART focuses on the treatment of patients suffering from end-stage heart failure (HF). The use of a ventricular assist device (VAD) is the main treatment for HF patients. However in certain cases, myocardial function recovers and VADs can be explanted after the patient is weaned. In that framework an efficient module is developed responsible for the selection of the most suitable candidates for VAD weaning. In this study we describe all technical specifications concerning its two main sub-modules of the weaning module, of the Clinical Knowledge Editor and the Knowledge Execution Engine.

Automated knowledge-based fuzzy models generation for weaning of patients receiving ventricular assist device (VAD) therapy.

The SensorART project focus on the management of heart failure (HF) patients which are treated with implantable ventricular assist devices (VADs). This work presents the way that crisp models are transformed into fuzzy in the weaning module, which is one of the core modules of the specialist's decision support system (DSS) in SensorART. The weaning module is a DSS that supports the medical expert on the weaning and remove VAD from the patient decision. Weaning module has been developed following a "mixture of experts" philosophy, with the experts being fuzzy knowledge-based models, automatically generated from initial crisp knowledge-based set of rules and criteria for weaning.

Nutrición parenteral total en niños con diarrea prolongada / Total parenteral nutrition in a child with

Aranceta, M.; Leal. V.; Trivella, M.; Chávez, A.; y Westinner, J. Nutrición parenteral total en niños con diarrea prolongada. Salus Militiae. 1987; 12. Fue utilizado en 3 niños menores de 3 meses quienes cumplian con los requisitos de 1) Diarrea de más de 2 semanas; 2) Repuestas satisfactorias al tratamineto convencional; 3) Déficit ponderal; 4) Hiperalbuminemia. Los resultados fueron satisfactorios y no hubo complicaciones