Search Results (361)

Human serum albumin (HSA) is one of the main proteins in human blood plasma and serves as a molecular “taxi” transporting various compounds, including organic compounds, drugs, metal ions, etc., through the circulatory system throughout the human body. As with any other proteins, HSA hydration plays an important role in maintaining its structure and functioning as well as influencing its ability to bind to ligands. This contribution presents, for the first time, a generalized picture of hydration of this biomacromolecule obtained within the framework of the 3D-RISM (three-dimensional Reference Interaction Site Model) theory of solvation. Based on 3D isodensity maps and structural parameters (hydration numbers, hydration layer thickness, fraction of hydrogen bonds, SASA, etc.), the most probable model of HSA hydration structure was reconstructed. With the description of HSA hydration, two important issues were also addressed in detail. The first is the correct determination of the hydration layer thickness, a common problem in protein science. The second is the possible state and behavior of hydration water in HSA–ligand binding. The presented results provide a deeper understanding of the relationship between solvent and HSA, which brings new knowledge to the understanding of protein hydration. Full article

Background: Orthotopic heart transplantation (OHT) remains the gold standard for end-stage heart failure, yet individualized risk assessment for postoperative mortality remains challenging. We aimed to develop and interpret random forest-based models for predicting 30-day and 1-year mortality and to examine whether the key predictors differ between the 30-day and 1-year models. Methods: We analyzed 581 patients who underwent OHT between 2012 and 2024. The 30-day and 1-year mortality rates were 9.9% and 17.6%, respectively. Eighty-seven preoperative and forty-eight postoperative variables were considered as input features for model development. Random forest models were trained and validated using five-fold cross-validation, and explainability was assessed using SHapley Additive exPlanations (SHAP). Results: Using preoperative features only, the random forest models achieved AUCs of 0.62 (95% CI, 0.48–0.75) for 30-day and 0.67 (95% CI, 0.56–0.78) for 1-year mortality. SHAP analysis revealed that early mortality predictions were primarily driven by features reflecting acute physiological stress—hepatic dysfunction, inflammation, and hemodynamic instability—whereas long-term predictions were increasingly influenced by renal function, metabolic reserve, and frailty. Incorporating postoperative features improved performance (AUC 0.98 [95% CI, 0.97–0.99] and 0.86 [95% CI, 0.80–0.92], respectively), with model predictions dominated by the severity and persistence of organ dysfunction: short-term risk driven by hepatic injury, hemodynamic compromise, and critical illness, and long-term risk by sustained hepatic and renal impairment, metabolic resilience, and duration of circulatory support. Conclusions: Random forest models integrating preoperative and immediate postoperative data could predict short- and mid-term mortality after OHT. SHAP analysis demonstrated temporal shifts in the most important predictors, supporting the role of dynamic, data-driven risk assessment in transplant care. Full article

Background: Foam rolling has become an increasingly popular self-myofascial release (SMR) technique among athletes to prevent injuries, improve recovery, and increase athletic performance. This study investigated how SMR improves mechanical and movement efficiency in recreational road cyclists. Methods: We conducted an exploratory randomized controlled trial (RCT) to investigate the effects of SMR using a foam roller on biomechanical and physiological performance parameters over a six-month period. A total of 32 male participants, aged 26–57 years, with a mean Body Mass Index (BMI) of 24.0 kg/m² (SD = 2.2), were randomly assigned to either an intervention group (n = 16), which incorporated a standardized SMR program into their post-exercise recovery, or a control group (n = 16), which followed the same cycling protocol without SMR. The training program included heart rate-controlled strength endurance intervals. As the primary target, the variables we investigated included torque effectiveness, leg force symmetry, and pedal smoothness. Secondary measurements included submaximal oxygen uptake (VO₂) as well as bioelectrical variables, which we analyzed using classic, repeated-measures ANOVA models and descriptive statistical methods. Results: The analysis revealed significant interaction effects in favor of the intervention group for torque effectiveness (η²_p = 0.434), leg strength symmetry (η²_p = 0.303), and pedal smoothness (η²_p = 0.993). No significant group × time interactions were found for submaximal VO₂ or bioelectrical parameters. Conclusions: Our findings indicate that foam rolling may serve as an effective adjunct to endurance training by enhancing functional neuromuscular performance in cyclists, particularly in torque control and pedal coordination. Its impact on aerobic efficiency and muscle composition appears to be minimal. The results support theoretical models that attribute SMR benefits to proprioceptive, circulatory, and neuromuscular mechanisms rather than structural tissue adaptations. Full article

Background and Objectives: The use of controlled donation after circulatory death (cDCD) donors has significantly increased during the past decades and successfully expanded the donors’ pool. However, warm ischemia may have detrimental effects on graft function. Italian Law requires a no-touch period of at least 20 min, which is much longer compared to the 5 min accepted in most European countries. Materials and Methods This is an Italian single-centre retrospective review of all cDCD procedures performed from April 2021 to June 2025. Patients with severe brain injury undergoing withdrawal of life-sustaining therapy (WLST) were considered for cDCD. After cardiac arrest and a no-touch period of 20 min, organ reperfusion was performed using abdominal or thoraco-abdominal normothermic regional perfusion (NRP) through femoral vessels cannulation. The primary endpoint was 30-day graft survival; secondary endpoints included: incidence of primary non-function (PNF) and non-anastomotic biliary stricture (NAS) in liver transplantation, PNF and delayed graft function (DGF) in kidney transplantation, primary graft dysfunction (PGD) in heart and lung transplantation, and recipient’s survival. Results: A total of 52 patients, 33 (63%) males, median age 74 (65–79) years, underwent WLST during the study period and were included in the cDCD program. Median functional warm ischemic time (WIT), total WIT, asystolic phase, and NRP duration were 37 (34–40), 40 (37–42), 24 (23–26), and 192 (166–212) min, respectively. A total of 123 organs (46 livers, 61 kidneys, 8 hearts, and 8 lungs) were considered suitable for transplantation, procured, and successfully transplanted in 115 recipients. We report the early and mid-term outcomes of 84 recipients, including 41 liver recipients, 32 kidney recipients, and 8 heart recipients transplanted at the Azienda Ospedaliera Universitaria Integrata of Verona, and 3 lung recipients transplanted at the Azienda Ospedale Università of Padova. The 30-day graft survival was 95% in liver recipients, 97% in kidney recipients, and 100% in heart and lung recipients. PNF was observed in two liver recipients, and PGD in two lung recipients. DGF was recorded in 3 (9%) kidney recipients. Six recipients died during the follow-up, and the mean survival time was 3.9 ± 0.1 years. Conclusions: Solid organ transplantation using cDCD donors is feasible and provides excellent early and mid-term results despite longer donor asystolic times. Larger data and longer follow-up are necessary to confirm these promising results. Full article

Background: Uncontrolled donation after circulatory death (uDCD) remains underutilized globally, despite critical organ shortages. We report outcomes from Israel’s uDCD kidney transplant program compared with the matched donation after brain death (DBD) recipients. Methods: This retrospective cohort study analyzed all uDCD kidney transplants performed at the Rabin Medical Center between January 2018 and December 2024, compared with DBD transplants during the same period. Propensity score matching (1:3 ratio) was performed using recipient demographics, comorbidities, and donor characteristics. Primary outcomes included delayed graft function (DGF), graft failure, and patient survival. Results: Among 92 kidney transplants, 21 (22.8%) were from uDCD donors. After propensity-matching (21 uDCD, 63 DBD), significant baseline differences persisted: uDCD recipients were younger (47.2 ± 11.8 vs. 57.5 ± 10.9 years, p < 0.001) despite a similar dialysis vintage (7.2 ± 3.2 vs. 7.7 ± 3.7 years, p = 0.569). Warm ischemia time was 58.5 ± 12.3 vs. 3.0 ± 0.0 min (p < 0.001), and cold ischemia time was longer in uDCD (13.7 ± 5.9 vs. 8.4 ± 2.5 h, p < 0.001). DGF occurred in 90.5% of uDCD versus 54.1% of DBD recipients (p = 0.006). Graft failure was markedly higher in uDCD (28.6% vs. 1.6%, p = 0.001), yet mortality was lower (14.3% vs. 27.9%, p = 0.339). After a median follow-up of 60 months (IQR 48–72) for both groups, the death-censored 5 year graft survival rate was 71.4% for uDCD versus 98.4% for DBD (p < 0.001). Conclusions: Despite higher rates of DGF and graft failure, uDCD kidney transplantation demonstrated an acceptable 5 year patient survival rate in carefully selected younger recipients. These findings support cautious expansion of uDCD programs with rigorous recipient selection criteria and realistic outcome expectations. Full article

The prevalence of advanced heart failure (AdHF) is increasing globally, driven by population aging and improved survival rates in chronic heart failure (CHF). Durable Mechanical Circulatory Support (DMCS), particularly Left Ventricular Assist Devices (LVADs), has become a cornerstone in AdHF management. However, its successful implantation requires a comprehensive preoperative evaluation integrating cardiac, hemodynamic, and systemic assessments. Echocardiography and cardiac magnetic resonance (CMR) provide critical data for risk stratification—e.g., LV ejection fraction < 25%, LV end-diastolic diameter < 60 mm, or free wall RV longitudinal strain (fwRVLS) > −14% predict poorer outcomes. Right heart catheterization (RHC) identifies hemodynamic contraindications (PVR > 6 WU, PAPi < 1.5, cardiac index < 2 L/min/m²), while cardiopulmonary exercise testing (CPET) remains pivotal for assessing functional reserve (peak VO₂ < 12 mL/kg/min or <50% predicted). Systemic assessment must address renal, hepatic, oncologic, and psychiatric comorbidities that influence surgical risk. Integrating these multimodal data within a multidisciplinary framework—spanning cardiologists, cardiac surgeons, anesthesiologists, and psychologists—optimizes selection and outcomes for DMCS candidates. Full article

Introduction: Evaluating cardiovascular function is crucial in the care of critically ill patients. Recent advancements in continuous cardiac output (CO) monitoring have led to the emergence of several arterial pulse contour devices. To effectively compare the accuracy of these devices, a comprehensive assessment is necessary. However, no experimental studies were found that have evaluated these devices in a controlled setting. Methods: In this innovative bench study, we used a Donovan mock circulatory system in conjunction with a total artificial heart (TAH-t) to simultaneously generate several comparable arterial waveforms and compared CO estimates from three different pulse contour devices: FloTrac™ (Vigileo™, v1.8 4th generation, Edwards LifeSciences, Irvine, CA, USA), proAQT™ (PulsioFlex™, Pulsion Medical Systems, Munich, Germany), and LiDCO™ Plus (LiDCO™, LidCO Ltd., Cambridge, UK). These devices underwent several hemodynamic challenges (HCs), including decreased preload, decreased afterload, and increased heart rate. To evaluate the degree of agreement between the devices, we performed a Bland–Altman analysis for the paired devices. The interclass comparison, error percentage, and variation coefficient for each device were also assessed. Results: The present study first tested the comparability between the three additional arterial line waveforms, and the arterial control line was simultaneously generated with the hemodynamic simulation bench. Comparing the reference values of the dP/dt and sAUC pulse pressure, we found no clinically significant difference between the simultaneously generated arterial waveforms. The different pulse contour devices were then each connected to the arterial lines, with the performance of HCs. HC1 with a decreased preload revealed that CO estimates significantly decreased compared to the baseline values: 3.2 ± 0.06 L.min⁻¹, 4.7 ± 0.05, 4.3 ± 0.07, and 4.0 ± 0.05 for reference methods FloTrac™, PulsioFlex™, and LiDCO™, respectively. HC2 with an increased heart rate revealed CO estimates with FloTrac™, PulsioFlex™, and LiDCO™—6.0 ± 0.03, 6.6 ± 0.06, and 6.0 ± 0.05 L.min⁻¹, respectively—when the CO estimate was 5.6 ± 0.2. HC3 with a decreased afterload that significantly increased CO estimates compared to the baseline with FloTrac™, PulsioFlex™, and LiDCO™—7.0 ± 0.18, 6.6 ± 0.15, and 7.1 ± 0.30 L.min⁻¹, respectively—when the CO estimate with the reference method did not change significantly (from 5.90 ± 0.13 to 5.94 ± 0.11 p = 0.26). The devices’ degree of agreement was estimated with Bland–Altman analysis. Conclusions: The Donovan Mock Circulatory System with SynCardia TAH-t can be used as an innovative experimental hemodynamic simulation bench. It was proven to be stable, accurate, and reliable in generating several controlled pulse pressure waveforms, while many parameters could be changed, such as the preload, heart rate, or afterload. This enables a simultaneous evaluation of different pulse contour devices submitted to several HCs. This is of interest for clinicians to better understand the underlying principles and realistically compare the performance and potentially inherent limitations of pulse contour devices experimentally in a controlled simulated environment. Full article

Background: Septic shock remains a major cause of mortality in critical care, driven by profound vasoplegia, myocardial depression and refractory circulatory collapse. Conventional therapy occasionally fails to restore adequate perfusion, leading to life-threatening multi-organ failure. Methods: This narrative review examines current evidence on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) as a salvage strategy for refractory septic shock, focusing on the pathophysiological rationale, patient selection, timing of initiation and hemodynamic management. Results: Data from observational studies and registry analyses suggest that V-A ECMO may improve survival in patients with septic cardiomyopathy (SCM), with reported survival rates approaching 40% in selected adult cohorts and over 50% in pediatric populations. Early initiation, phenotype-guided selection and precise hemodynamic titration are critical to optimize outcomes. Conclusions: The role of ECMO in septic shock remains controversial and should be restricted to experienced centers and well-defined phenotypes. Future research must refine selection criteria, standardize support strategies and evaluate long-term functional recovery beyond survival. Full article

The heart is the body’s core pump. Heart failure impairs the heart’s ability to pump blood, leading to circulatory disorders. The artificial heart (blood pump) is an important mechanical circulatory support device that can partially or completely substitute cardiac pumping function, potentially improving hemodynamic performance and alleviating symptoms of heart failure. A combination of computational fluid dynamics simulation and hydraulic performance testing was used to study key parameters of the impeller, including blade count, blade wrap angle, impeller flow path, and diversion cone height. The goal was to reduce hemolysis risk and enhance pumping efficiency. Increasing the blade count raised the head, with optimal efficiency achieved at seven blades. A larger blade wrap angle decreased the head but improved efficiency. Synchronizing the flow path and diversion cone height at 4.1 mm maximized the head. Under various rotational speeds, the studied hemolysis index remained well below 0.1 g/100 L. Both experimental and simulation data were validated against each other, meeting the required error tolerances. The studied blood pump meets the design specifications. At an operating condition of 5 L/min flow rate and 2800 rpm, the pump achieves the required head and hemolysis criteria with a margin of safety. Full article

Cardiogenic shock (CS) is a complex, life-threatening syndrome characterized by inadequate tissue perfusion due to impaired cardiac function. Acute myocardial infarction (AMI) and acute decompensated heart failure are the leading causes, with mortality remaining high despite advances in revascularization and supportive care. The Society for Cardiovascular Angiography and Interventions (SCAI) classification allows risk stratification and guides clinical decision making by capturing the spectrum of shock severity. Percutaneous mechanical circulatory support (pMCS) devices, such as the intra-aortic balloon pump (IABP) and Impella, aim to stabilize hemodynamics by augmenting cardiac output and unloading the left ventricle. However, randomized trials and meta-analyses have not demonstrated a consistent survival advantage of Impella over IABP, while reporting higher rates of bleeding and vascular complications. Landmark trials, including ECLS-SHOCK and DanGer, have provided conflicting results, likely reflecting differences in baseline severity and timing of device implantation. Veno-arterial extracorporeal membrane oxygenator (VA-ECMO) offers full cardiopulmonary support but increases left ventricular afterload, potentially worsening myocardial injury. Combined strategies such as ECPELLA (Impella + VA-ECMO) or ECMO + IABP may mitigate left ventricle (LV) overload and improve bridging to recovery or advanced therapies, although evidence remains largely observational and complication rates are considerable. In right-sided or biventricular failure, tailored options (e.g., Impella RP, Bi-Pella) guided by invasive hemodynamics may be required. Current evidence suggests that pMCS benefits are limited to carefully selected subgroups, underscoring the importance of early diagnosis, prompt referral, and individualized intervention. Robust randomized data are still needed to define the optimal role of pMCS in AMI-related CS. Full article

Background: Despite advances in temporary mechanical circulatory support (tMCS), patients with cardiogenic shock (CS) who are treated with a microaxial flow pump (mAFP; Impella^®, Abiomed) still have a high mortality rate. A dysregulated systemic inflammatory response significantly contributes to multiorgan failure in this population. CytoSorb^® hemadsorption has emerged as a potential adjunctive therapy for modulating inflammation, but data on its use in CS are limited. Methods: This retrospective, single-center study used propensity score matching analysis (1:1 matching; n = 15 per group) to compare the outcomes of patients receiving mAFP support with and without concomitant CytoSorb therapy. Baseline data (T0), including comorbidities and clinical status at ICU admission, were collected for all patients. In the CytoSorb group, data were collected at two additional time points: 24 h before the start of CytoSorb therapy (T1), and 24 h after its completion (T2). At these time points, laboratory values and parameters on respiratory, hemodynamic, and organ function were assessed. Corresponding data were also collected for matched patients in the non-CytoSorb group at equivalent time points relative to their matched counterparts. Results: In the propensity score-matched cohort, patients treated with CytoSorb exhibited significant improvements between T1 and T2. Specifically, reductions were observed in the vasoactive-inotropic score (p = 0.035), procalcitonin levels (p = 0.041), peak inspiratory pressure (p = 0.036), and positive end-expiratory pressure (p = 0.016). Flow rates through the mAFP declined significantly (p = 0.014), suggesting stabilization of hemodynamics. These changes were not observed in the non-CytoSorb group, where most parameters remained unchanged or exhibited less pronounced trends. We observed a lower in-hospital mortality rate in the CytoSorb group (33.3% versus 46.7%), though the difference was not significant, potentially due to limited statistical power. Conclusions: CytoSorb hemadsorption in mAFP-supported CS was associated with improved hemodynamic stability and reduced inflammatory burden. These findings suggest a potential therapeutic benefit of adjunctive hemadsorption in this high-risk population. Full article

Chronic kidney disease (CKD) affects over 10% of the global population, with end-stage renal disease (ESRD) necessitating renal replacement therapy. Kidney transplantation remains the optimal treatment for ESRD. However, the global donor kidney shortage crisis has led to increased reliance on deceased donor kidneys. Donors are classified as either donation after brain death (DBD) or donation after circulatory death (DCD), each associated with distinct ischemic injuries that impact graft function. Ischemia–reperfusion injury (IRI) plays a pivotal role in transplant outcomes, triggering oxidative stress, inflammation, and endothelial dysfunction. While static cold storage (SCS) remains the gold standard for organ preservation, alternative strategies such as hypothermic or normothermic machine perfusion (HMP and NMP), use of oxygen carriers during storage, and supplemental compounds to storage solutions have emerged, offering potential benefits in preserving graft viability. This review explores the cellular and molecular mechanisms of ischemic injury in deceased donor kidneys, preservation strategies tested in preclinical models, and emerging therapeutic interventions aimed at improving adverse post-transplant outcomes. Full article

Septic shock has an unacceptably high mortality rate and unmet need for new therapeutics. Murine models are crucial for research, yet methodologies often differ. This study characterised standard- and high-grade caecal ligation and puncture (CLP) murine models of septic shock by integrating ultraminiature arterial telemetry with comprehensive plasma biomarker analysis. Standard-grade and high-grade CLP was performed in 8–10 week old, male C57BL/6 mice (n = 98), with a subset implanted with arterial telemetry to monitor real-time circulatory function. Plasma markers of inflammation and organ damage were measured at multiple intervals up to 168 h post-CLP. Standard-grade and high-grade CLP showed distinct progressions; episodes of hypotension began 5–6 h after CLP in 30% of standard-grade and all high-grade CLP mice, with respective 168 h mortality of 40% and 71%. Recurrent episodes of hypotension 5–39 h after CLP were universally lethal. The coincidence of hypotension and elevated plasma lactate defined the onset of septic shock after high-grade CLP, which was always lethal. Inflammatory cytokines and markers of liver, renal, and cardiac damage were markedly elevated to 168 h after high-grade CLP, in contrast to standard-grade CLP, which returned to baseline by 48 h. Elevated plasma IL-6, TNFα, and corticosterone, along with reduced albumin, were significantly correlated with mortality. In conclusion, this research refines murine CLP models by providing a precise, dynamic map of the progression to septic shock. The high-grade CLP model consistently models early and late-stage physiological deterioration and serves as a robust model for evaluating the efficacy of novel therapies aimed at human septic shock. Full article

Hemodynamic monitoring is fundamental in the management of critically ill patients with acute circulatory failure. The invasiveness of conventional devices, however, often limits their applicability in the emergency department (ED). Recent advances have introduced non-invasive modalities (including echocardiography, bioreactance, and plethysmography) that extend the use of hemodynamic assessment beyond the intensive care unit. Among various available techniques, bedside ultrasound (Point-of-Care Ultrasound, POCUS) emerges as a particularly versatile tool for rapid and comprehensive assessment of cardiac function and volume status. When integrated with continuous technologies such as bioreactance or pulse contour analysis, it allows for the adoption of more dynamic and personalized fluid management strategies. Currently, a multimodal and patient-centered approach represents the most effective paradigm for non-invasive hemodynamic evaluation in the emergency setting. This strategy enhances diagnostic accuracy and enables timely interventions guided by pathophysiological principles. Despite the inherent limitations of each technique, their integration provides emergency physicians with real-time information, with potential benefits on clinical outcomes and resource utilization. This review aims to outline the pathophysiological rationale for adopting non-invasive monitoring in the ED and to critically evaluate the advantages and limitations of each technique, providing emergency physicians with a concise framework to guide clinical practice. Full article

Background/Objectives: Mechanical circulatory support (MCS) is increasingly utilized for the management of acute decompensated heart failure (HF) and cardiogenic shock (CS). The primary goals of MCS are to restore systemic perfusion, reduce cardiac workload, and support end-organ function. A thorough understanding of cardiovascular physiology in patients supported by MCS is essential for clinical decision-making. This review summarizes current evidence on the physiological effects of various MCS devices, key monitoring techniques, patient management, and explores the emerging role of artificial intelligence (AI) in this field. Main Text: Short-term MCS devices include intra-aortic balloon pumps (IABP), percutaneous left-sided devices such as Impella (Abiomed, Danvers, MA, USA) and TandemHeart (LivaNova, London, UK), percutaneous right-sided support devices like Protek Duo (LivaNova, London, UK) and Impella RP Flex (Abiomed, Danvers, MA, USA), and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Long-term support is mainly provided by left ventricular assist devices (LVADs), including the HeartMate 3 (Abbott Laboratories, Chicago, IL, USA). Optimal MCS application requires an understanding of device-specific cardiovascular interactions and expertise in appropriate monitoring tools to assess device performance and patient response. The choice of device, timing of initiation, and patient selection must be individualized, with careful consideration of ethical implications. The integration of AI offers significant potential to advance clinical care by improving complication prediction, enabling real-time optimization of device settings, and refining patient selection criteria. Conclusions: MCS is a rapidly evolving field that requires a comprehensive understanding of cardiovascular interactions, careful selection of monitoring strategies, and individualized clinical management. Future research should address current device limitations, clarify device-specific clinical applications, and assess the validity of AI-driven technologies. Full article