A dose-adjusted, open-label, pilot study of the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.

Increased circulating histones correlate with sepsis severity and are a potential therapeutic target. Pre-clinical studies showed benefit with a histone-neutralizing polyanion molecule (STC3141). We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.

Targeting NETosis in Acute Brain Injury: A Systematic Review of Preclinical and Clinical Evidence.

Acute brain injury (ABI) remains one of the leading causes of death and disability world-wide. Its treatment is challenging due to the heterogeneity of the mechanisms involved and the variability among individuals. This systematic review aims at evaluating the impact of anti-histone treatments on outcomes in ABI patients and experimental animals and defining the trend of nucleosome levels in biological samples post injury.

Circulating Nucleosomes as a Novel Biomarker for Sepsis: A Scoping Review.

Circulating nucleosome levels are commonly elevated in physiological and pathological conditions. Their potential as biomarkers for diagnosing and prognosticating sepsis remains uncertain due, in part, to technical limitations in existing detection methods. This scoping review explores the possible role of nucleosome concentrations in the diagnosis, prognosis, and therapeutic management of sepsis.

NHH promotes Sepsis-associated Encephalopathy with the expression of AQP4 in astrocytes through the gut-brain Axis.

Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE.

Ketone Bodies after Cardiac Arrest: A Narrative Review and the Rationale for Use.

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain.

The impact of the new acute respiratory distress syndrome (ARDS) criteria on Berlin criteria ARDS patients: a multicenter cohort study.

Objective: The European Society of Intensive Care Medicine (ESICM) recently recommended changes to the criteria of acute respiratory distress syndrome (ARDS), patients with high-flow oxygen were included, however, the effect of these changes remains unclear. Our objectives were to evaluate the performance of these new criteria and to compare the outcomes of patients meeting the new ARDS criteria with those meeting the Berlin ARDS criteria.

Methods: This was a retrospective cohort.

Pulse wave analysis as a tool for the evaluation of resuscitation therapy in septic shock.

. Pulse wave analysis (PWA) can provide insights into cardiovascular biomechanical properties. The use of PWA in critically ill patients, such as septic shock patients, is still limited, but it can provide complementary information on the cardiovascular effects of treatment when compared to standard indices outlined in international guidelines.

Evaluation of a new magnetically suspended centrifugal neonatal pump in healthy animals using a veno-venous extracorporeal membrane oxygenation configuration.

Background: The objective of this animal study was to evaluate the hemodynamic performance of a new centrifugal pump for extra-corporeal membrane oxygenation (ECMO) support in neonates.

Methods: Six healthy swines were supported with veno-venous ECMO with the New Born ECMOLife centrifugal pump (Eurosets, Medolla, Italy) at different flow rates: 0.25, 0.

Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest.

Introduction: Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA.

The use of induced hypothermia in extracorporeal membrane oxygenation: A narrative review.

Despite venovenous or venoarterial extracorporeal membrane oxygenation (ECMO) being increasingly used in patients with severe acute respiratory disease syndrome, severe cardiogenic shock, and refractory cardiac arrest, mortality rates still remain high mainly because of the severity of the underlying disease and the numerous complications associated with initiation of ECMO. Induced hypothermia might minimize several pathological pathways present in patients requiring ECMO; even though numerous studies conducted in the experimental setting have reported promising results, there are currently no recommendations suggesting the routine use of this therapy in patients requiring ECMO. In this review, we summarized the existing evidence on the use of induced hypothermia in patients requiring ECMO.

The Effects of Temperature Management on Brain Microcirculation, Oxygenation and Metabolism.

Purpose: Target temperature management (TTM) is often used in patients after cardiac arrest, but the effects of cooling on cerebral microcirculation, oxygenation and metabolism are poorly understood. We studied the time course of these variables in a healthy swine model.

Methods: Fifteen invasively monitored, mechanically ventilated pigs were allocated to sham procedure (normothermia, NT; = 5), cooling (hypothermia, HT, = 5) or cooling with controlled oxygenation (HT-Oxy, = 5).

Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock.

Background: Angiotensin II is one of the vasopressors available for use in septic shock. However, its effects on the septic myocardium remain unclear. The aim of the study was to compare the effects of angiotensin II and norepinephrine on cardiac function and myocardial oxygen consumption, inflammation and injury in experimental septic shock.

Sepsis modulates cortical excitability and alters the local and systemic hemodynamic response to seizures.

Non-convulsive seizures and status epilepticus are frequent and associated with increased mortality in septic patients. However, the mechanism through which seizures impact outcome in these patients is unclear. As previous studies yielded an alteration of neurovascular coupling (NVC) during sepsis, we hypothesized that non-convulsive seizures, might further impair NVC, leading to brain tissue hypoxia.

Effects of Reversal of Hypotension on Cerebral Microcirculation and Metabolism in Experimental Sepsis.

The effects of reversal of hypotension on the cerebral microcirculation, oxygenation, and metabolism in septic shock remain unclear. In 12 sheep, peritonitis was induced by injection of feces into the abdominal cavity. At the onset of septic shock (mean arterial pressure (MAP) < 65 mmHg, unresponsive to fluid challenge), a norepinephrine infusion was titrated in eight sheep to restore a MAP ≥ 75 mmHg; the other four sheep were kept hypotensive.

A comprehensive neuromonitoring approach in a large animal model of cardiac arrest.

Background: Anoxic brain injuries represent the main determinant of poor outcome after cardiac arrest (CA). Large animal models have been described to investigate new treatments during CA and post-resuscitation phase, but a detailed model that includes extensive neuromonitoring is lacking.

Method: Before an electrically-induced 10-minute CA and resuscitation, 46 adult pigs underwent neurosurgery for placement of a multifunctional probe (intracranial pressure or ICP, tissue oxygen tension or PbtO and cerebral temperature) and a bolt-based technique for the placement and securing of a regional blood flow probe and two sEEG electrodes; two modified cerebral microdialysis (CMD) probes were also inserted in the frontal lobes and accidental misplacement was prevented using a perforated head support.

Early Hyperdynamic Sepsis Alters Coronary Blood Flow Regulation in Porcine Fecal Peritonitis.

Sepsis is a common condition known to impair blood flow regulation and microcirculation, which can ultimately lead to organ dysfunction but such contribution of the coronary circulation remains to be clarified. We investigated coronary blood flow regulatory mechanisms, including autoregulation, metabolic regulation, and endothelial vasodilatory response, in an experimental porcine model of early hyperdynamic sepsis. Fourteen pigs were randomized to sham ( = 7) or fecal peritonitis-induced sepsis ( = 7) procedures.

Cerebral and systemic hemodynamic effect of recurring seizures.

The increase in neuronal activity induced by a single seizure is supported by a rise in the cerebral blood flow and tissue oxygenation, a mechanism called neurovascular coupling (NVC). Whether cerebral and systemic hemodynamics are able to match neuronal activity during recurring seizures is unclear, as data from rodent models are at odds with human studies. In order to clarify this issue, we used an invasive brain and systemic monitoring to study the effects of chemically induced non-convulsive seizures in sheep.

Quantification of Cardiac Kinetic Energy and Its Changes During Transmural Myocardial Infarction Assessed by Multi-Dimensional Seismocardiography.

Seismocardiography (SCG) records cardiac and blood-induced motions transmitted to the chest surface as vibratory phenomena. Evidences demonstrate that acute myocardial ischemia (AMI) profoundly affects the SCG signals. Multidimensional SCG records cardiac vibrations in linear and rotational dimensions, and scalar parameters of kinetic energy can be computed.