Irene Cortes Puch

• National Institutes of Health

Chronic pain represents a significant unmet medical need, affecting one‐fifth of the U.S. population. EC5026 is a small molecule inhibitor of the enzyme soluble epoxide hydrolase (sEH) which is being developed as a novel non‐opioid, non‐NSAID analgesic. EC5026 prolongs the action of epoxy fatty acids, endogenous analgesic lipid mediators that are r...

Background Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on syste...

Background Early mobility interventions in intensive care units (ICUs) are safe and improve outcomes in subsets of critically ill adults. However, implementation varies, and the optimal mobility dose remains unclear. Objective To test for associations between daily dose of out-of-bed mobility and patient outcomes in different ICUs. Methods In thi...

Background: The ratio of oxygen saturation index (ROX index; or SpO2 /FIO2 /breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unkno...

Background: Comparative effectiveness research is meant to determine which commonly employed medical interventions are most beneficial, least harmful, and/or most costly in a real-world setting. While the objectives for comparative effectiveness research are clear, the field has failed to develop either a uniform definition of comparative effectiv...

Background: Despite decades of research on predictors of extubation success, use of ventilatory support after extubation is common and 10-20% of patients require re-intubation. Proportional assist ventilation (PAV) mode automatically calculates estimated total work of breathing (total WOB). Here, we assessed the performance of total WOB to predict...

OBJECTIVE: To determine whether contemporaneous practices are adequately represented in recent critical care comparative effectiveness research studies. DESIGN: All critical care comparative effectiveness research trials published in the New England Journal of Medicine from April 2019 to March 2020 were identified. To examine studies published in o...

The acute respiratory distress syndrome (ARDS) is a severe form of hypoxemic respiratory failure with in-hospital mortality of 35-46%. High mortality is thought to be related in part to challenges in making a prompt diagnosis, which may in turn delay implementation of evidence-based therapies. A deep neural network (DNN) algorithm utilizing unbiase...

Polyunsaturated fatty acids are metabolized into regulatory lipids important for initiating inflammatory responses in the event of disease or injury and for signaling the resolution of inflammation and return to homeostasis. The epoxides of linoleic acid (leukotoxins) regulate skin barrier function, perivascular and alveolar permeability and have b...

This report describes the development of an orally active analgesic that resolves inflammation and neuropathic pain without the addictive potential of opioids. EC5026 acts on the cytochrome P450 branch of the arachidonate cascade to stabilize epoxides of polyunsaturated fatty acids (EpFA), which are natural mediators that reduce pain, resolve infla...

To develop and characterize a machine learning algorithm to discriminate acute respiratory distress syndrome from other causes of respiratory failure using only ventilator waveform data. Design: Retrospective, observational cohort study. Setting: Academic medical center ICU. Patients: Adults admitted to the ICU requiring invasive mechanical v...

Future healthcare systems will rely heavily on clinical decision support systems (CDSS) to improve the decision-making processes of clinicians. To explore the design of future CDSS, we developed a research-focused CDSS for the management of patients in the intensive care unit that leverages Internet of Things devices capable of collecting streaming...

Severe coronavirus disease (COVID-19) is characterized by pulmonary hyper-inflammation and potentially life-threatening “cytokine storms”. Controlling the local and systemic inflammatory response in COVID-19 may be as important as anti-viral therapies. Endogenous lipid autacoid mediators, referred to as eicosanoids, play a critical role in the indu...

Background: In experimental canine septic shock, depressed circulating granulocyte counts were associated with a poor outcome and increasing counts with prophylactic granulocyte colony-stimulating factor (G-CSF) improved outcome. Therapeutic G-CSF, in contrast, did not improve circulating counts or outcome, and therefore investigation was undertak...

Background: During sepsis, higher plasma cell-free hemoglobin (CFH) levels portend worse outcomes. In sepsis models, plasma proteins that bind CFH improve survival. In our canine antibiotic-treated Staphylococcus aureus pneumonia model, with and without red blood cell (RBC) exchange transfusion, commercial human haptoglobin (Hp) concentrates bound...

Dysfunction in the nitric oxide (NO) signaling pathway can lead to the development of pulmonary hypertension (PH) in mammals. Discovery of an alternative pathway to NO generation involving reduction from nitrate to nitrite and to NO has motivated the evaluation of nitrite as an alternative to inhaled NO for PH. In contrast, inhaled nitrate has not...

Algorithmic classifiers are crucial components of clinical decision support (CDS) systems needed to advance healthcare delivery. Robust CDS systems must be derived and validated via creation of multi-reviewer adjudicated gold standard datasets. Manual annotation of physiologic data such as mechanical ventilator waveform data (VWD) can be time-consu...

BACKGROUND Storage temperature is a critical factor for maintaining red‐blood cell (RBC) viability, especially during prolonged cold storage. The target range of 1 to 6°C was established decades ago and may no longer be optimal for current blood‐banking practices. STUDY DESIGN AND METHODS Human and canine RBCs were collected under standard conditi...

During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alt...

Aim To evaluate the risks of restrictive red blood cell transfusion strategies (haemoglobin 7–8 g dL⁻¹) in patients with and without known cardiovascular disease (CVD). Background Recent guidelines recommend restrictive strategies for CVD patients hospitalised for non‐CVD indications, patients without known CVD and patients hospitalised for CVD co...

Background: No studies have been performed comparing intravenous (IV) iron with transfused red blood cells (RBCs) for treating anemia during infection. In a previous report, transfused older RBCs increased free iron release and mortality in infected animals when compared to fresher cells. We hypothesized that treating anemia during infection with...

Objective The adequacy of informed consent in the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial (SUPPORT) has been questioned. SUPPORT investigators and publishing editors, heads of government study funding agencies, and many ethicists have argued that informed consent was adequate because the two oxygen saturation target range...

Background and objectives: Preclinical studies generated the hypothesis that older stored red blood cells (RBCs) can increase transfusion risks. To examine the most updated and complete clinical evidence and compare results between two trial designs, we assessed both observational studies and randomized controlled trials (RCTs) studying the effect...

BACKGROUND Massive exchange transfusion of 42-day-old red blood cells (RBCs) in a canine model of Staphylococcus aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin-bound iron (TBI), non–transferrin-bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before tra...

In canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell-free hemoglobin (CFH) and non-transferrin-bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury an...

The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. Intra-tracheal inoculation of a known amount of bacteria has been successfully used to reproduce the pathogenesis of pneumonia which then develops into sepsis. Monitoring hemodynamic parameters and provid...

The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life supportive measures. Treatment with dexamethasone, a glucocorti...

In experimental pneumonia we found that transfused older blood increased mortality and lung injury that was associated with increased in vivo hemolysis and elevated plasma cell-free hemoglobin (CFH), non-transferrin-bound iron (NTBI), and plasma labile iron (PLI) levels. In this study, we additionally analyze identically treated animals that receiv...

Key Points Washing older blood before transfusion reduces plasma iron, improving outcomes from established infection in canines. In contrast, washing fresh blood before transfusion increases in vivo plasma CFH release, worsening outcomes.

Background Cell-free hemoglobin (Hb) in the vasculature leads to vasoconstriction and injury. Proposed mechanisms have been based on nitric oxide (NO) scavenging by oxyhemoglobin (oxyHb) or processes mediated by oxidative reactions of methemoglobin (metHb). To clarify this, we tested the vascular effect and fate of oxyHb or metHb infusions. Study D...

Rationale: A revised definition of clinical criteria for acute respiratory distress syndrome (ARDS), the Berlin definition, was recently established to classify patients according to their severity. Objective: To evaluate the accuracy of these clinical criteria using diffuse alveolar damage (DAD) at autopsy as the reference standard. Methods:...

Purpose of review: The decision to extubate is a crucial moment for intubated patients. In most cases, the transition to spontaneous breathing is uneventful, but in some patients, it implies a more challenging decision. Both extubation delay and especially the need for reintubation are associated with poor outcomes. We aim to review the recent lit...

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that affects patients admitted in the Intensive Care Units (ICUs) under mechanical ventilation. ARDS is a process of non-hydrostatic pulmonary edema and hypoxemia associated with a variety of conditions, resulting in a direct (e.g., pneumonia) or indirect (e.g., sepsis) lung...

The concept of exposing vast numbers of critically ill patients to broad-spectrum multiple-drug cocktails runs counter to existing theoretical models. The dynamics of resistance are driven by three mechanisms: import; acquisition; de novo development. Gut overgrowth is a risk factor for de novo resistance development. Each mechanism is responsible...

Solid organ and bone marrow recipients are highly at risk of infection related to immunosuppressant therapy, which is necessary to avoid transplant rejection. The approach to this problem must be multifactorial, with general and pharmacologic measures. In the early post-transplant period, the pattern of infections and the microorganisms involved ar...

To describe the incidence, risk factors, and impact on mortality of acute kidney injury (AKI) in patients with 2009 influenza A (H1N1) viral pneumonia requiring mechanical ventilation. Observational cohort study. AKI was defined as risk, injury or failure, according to the RIFLE classification. Early and late AKI were defined as AKI occurring on in...

Weaning describes the process of liberating the patient from mechanical ventilation. It is a withdrawal or discontinuation process that covers the transition from mechanical support to spontaneous breathing. In most patients, this transition is quick and uneventful once we realise that the respiratory failure has improved and the patient is ready f...

There has been a remarkable increase in prescription rates of antipsychotics in children and adolescents in recent years. Their side effects are a neglected area of research in this population, despite its vulnerability. In this cross-sectional study, we compared the presence of side effects in 60 children and adolescents who had taken antipsychoti...