Central Venous Pressure as a Predictor of Fluid Responsiveness: Is This All You Need?

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Restored perfusion and reduced inflammation in the infarcted heart after grafting stem cells with a hyaluronan-based scaffold

The aim of this study is to investigate the blood perfusion and the inflammatory response of the myocardial infarct area after transplanting a hyaluronan-based scaffold (HYAFF\uae11) with bone marrow mesenchymal stem cells (MSCs). Nine-week-old female pigs were subjected to a permanent left anterior descending coronary artery ligation for 4 weeks. According to the kind of the graft, the swine subjected to myocardial infarction were divided into the HYAFF\uae11, MSCs, HYAFF\uae11/MSCs and untreated groups. The animals were killed 8 weeks after coronary ligation. Scar perfusion, evaluated by Contrast Enhanced Ultrasound echography, was doubled in the HYAFF\uae11/MSCs group and was comparable with the perfusion of the healthy, non-infarcted hearts. The inflammation score of the MSCs and HYAFF\uae11/MSCs groups was near null, revealing the role of the grafted MSCs in attenuating the cell infiltration, but not the foreign reaction strictly localized around the fibres of the scaffold. Apart from the inflammatory response, the native tissue positively interacted with the HYAFF\uae11/MSCs construct modifying the extracellular matrix with a reduced presence of collagene and increased amount of proteoglycans. The border-zone cardiomyocytes also reacted favourably to the graft as a lower degree of cellular damage was found. This study demonstrates that the transplantation in the myocardial infarct area of autologous MSCs supported by a hyaluronan-based scaffold restores blood perfusion and almost completely abolishes the inflammatory process following an infarction. These beneficial effects are superior to those obtained after grafting only the scaffold or MSCs, suggesting that a synergic action was achieved using the cell-integrated polymer construct

Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study

Background Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. Methods This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. Results Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO(2) ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 x 10(27); p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO(2) ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). Conclusions DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021)

Comparison between Culture Conditions Improving Growth and Differentiation of Blood and Bone Marrow Cells Committed to the Endothelial Cell Lineage

The aim of this study was to compare different cell sources and culture conditions to obtain endothelial progenitor cells (EPCs) with predictable antigen pattern, proliferation potential and in vitro vasculogenesis. Pig mononuclear cells were isolated from blood (PBMCs) and bone marrow (BMMCs). Mesenchymal stem cells (MSCs) were also derived from pig bone marrow. Cells were cultured on fibronectin in the presence of a high concentration of VEGF and low IGF-1 and FGF-2 levels, or on gelatin with a lower amount of VEGF and higher IGF-1 and FGF-2 concentrations. Endothelial commitment was relieved in almost all PBMCs and BMMCs irrespective of the protocol used, whilst MSCs did not express a reliable pattern of EPC markers under these conditions. BMMCs were more prone to expand on gelatin and showed a better viability than PBMCs. Moreover, about 90% of the BMMCs pre-cultured on gelatin could adhere to a hyaluronan-based scaffold and proliferate on it up to 3 days. Pre-treatment of BMMCs on fibronectin generated well-shaped tubular structures on Matrigel, whilst BMMCs exposed to the gelatin culture condition were less prone to form vessel-like structures. MSCs formed rough tubule-like structures, irrespective of the differentiating condition used. In a relative short time, pig BMMCs could be expanded on gelatin better than PBMCs, in the presence of a low amount of VEGF. BMMCs could better specialize for capillary formation in the presence of fibronectin and an elevated concentration of VEGF, whilst pig MSCs anyway showed a limited capability to differentiate into the endothelial cell lineage

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Different strategies for mechanical VENTilation during CardioPulmonary Bypass (CPBVENT 2014): Study protocol for a randomized controlled trial

Background: There is no consensus on which lung-protective strategies should be used in cardiac surgery patients. Sparse and small randomized clinical and animal trials suggest that maintaining mechanical ventilation during cardiopulmonary bypass is protective on the lungs. Unfortunately, such evidence is weak as it comes from surrogate and minor clinical endpoints mainly limited to elective coronary surgery. According to the available data in the academic literature, an unquestionable standardized strategy of lung protection during cardiopulmonary bypass cannot be recommended. The purpose of the CPBVENT study is to investigate the effectiveness of different strategies of mechanical ventilation during cardiopulmonary bypass on postoperative pulmonary function and complications. Methods/design: The CPBVENT study is a single-blind, multicenter, randomized controlled trial. We are going to enroll 870 patients undergoing elective cardiac surgery with planned use of cardiopulmonary bypass. Patients will be randomized into three groups: (1) no mechanical ventilation during cardiopulmonary bypass, (2) continuous positive airway pressure of 5 cmH2O during cardiopulmonary bypass, (3) respiratory rate of 5 acts/min with a tidal volume of 2-3 ml/Kg of ideal body weight and positive end-expiratory pressure of 3-5 cmH2O during cardiopulmonary bypass. The primary endpoint will be the incidence of a PaO2/FiO2ratio <200 until the time of discharge from the intensive care unit. The secondary endpoints will be the incidence of postoperative pulmonary complications and 30-day mortality. Patients will be followed-up for 12 months after the date of randomization. Discussion: The CPBVENT trial will establish whether, and how, different ventilator strategies during cardiopulmonary bypass will have an impact on postoperative pulmonary complications and outcomes of patients undergoing cardiac surgery. Trial registration: ClinicalTrials.gov, ID: NCT02090205. Registered on 8 March 2014

Fluid management in cardiac surgery patients: Pitfalls, challenges and solutions

Fluid administration is a powerful tool for hemodynamic stabilization as it increases preload and improves cardiac function in fluid-responsive patients. However, there are various types of fluid to choose from. The use of colloids and crystalloids in non-cardiac Intensive Care Units (ICU) has been reported, showing controversial results. Many trials on sepsis in a non-cardiac ICU setting show that colloids, in particular hydroxyethyl starches and gelatins, might have a detrimental effect on kidney function, and on major outcomes such as mortality. Many small randomized clinical trials focusing on coagulation and bleeding show controversial results regarding fluid safety during the perioperative period in cardiac surgery, and in the cardiac ICU. No definitive data are available on the superiority of one fluid compared with another for fluid replacement after cardiac surgery. Only few data are available regarding the impact of fluids on kidney function in the cardiac ICU. On the other hand, there is much evidence showing that fluid administration requires strict protocols and close monitoring. Improved clinical outcomes are evident in protocols for goal-directed therapy. In conclusion, the application of a close monitoring and a pre-defined goal-directed protocol are far more important than the choice of a single fluid. This review examines the available evidence on fluid management in cardiac surgery and in the ICU, and analyzes the key steps of fluid strategy in these settings

Clinical practice in perioperative monitoring in adult cardiac surgery. is there a standard of care? results from an national survey

This study was to investigate and define what isconsidered as a current clinical practice in hemodynamicmonitoring and vasoactive medication use after cardiacsurgery in Italy. A 33-item questionnaire was sent to allintensive care units (ICUs) admitting patients after cardiacsurgery. 71 out of 92 identified centers (77.2 %) returned acompleted questionnaire. Electrocardiogram, invasiveblood pressure, central venous pressure, pulse oximetry,diuresis, body temperature and blood gas analysis wereidentified as routinely used hemodynamic monitoring,whereas advanced monitoring was performed with pul-monary artery catheter or echocardiography. Crystalloidswere the fluids of choice for volume replacement (86.8 %of Centers). To guide volume management, central venouspressure (26.7 %) and invasive blood pressure (19.7 %)were the most frequently used parameters. Dobutaminewas the first choice for treatment of left heart dysfunction(40 %) and epinephrine was the first choice for right heartdysfunction (26.8 %). Half of the Centers had an internalprotocol for vasoactive drugs administration. Intra-aorticballoon pump and extra-corporeal membrane oxygenationwere widely available among Cardiothoracic ICUs.Angiotensin-converting enzyme inhibitors were suspendedin 28 % of the Centers. The survey shows what is con-sidered as standard monitoring in Italian Cardiac ICUs.Standard, routinely used monitoring consists of ECG,SpO2, etCO2, invasive BP, CVP, diuresis, body tempera-ture, and BGA. It also shows that there is large variabilityamong the various Centers regarding hemodynamic mon-itoring of fluid therapy and inotropes administration. Fur-ther research is required to better standardize and define theindicators to improve the standards of intensive care aftercardiac surgery among Italian cardiac ICU