jean-Francois Pittet

University of Alabama at Birmingham | UAB · Department of Anesthesiology

Background Bacterial pneumonia and sepsis are both common causes of end-organ dysfunction, especially in immunocompromised and critically ill patients. Pre-clinical data demonstrate that bacterial pneumonia and sepsis elicit the production of cytotoxic tau and amyloids from pulmonary endothelial cells, which cause lung and brain injury in naïve ani...

Physiological hemostasis is a balance between pro- and anticoagulant pathways, and in sepsis, this equilibrium is disturbed, resulting in systemic thrombin generation, impaired anticoagulant activity, and suppression of fibrinolysis, a condition termed sepsis-induced coagulopathy (SIC). SIC is a common complication, being present in 24% of patients...

Purpose: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. Methods: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new on...

Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated g...

Purpose: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. Methods: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new on...

Purpose: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. Methods: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new on...

Purpose Chronic kidney disease (CKD) is a significant health care burden worldwide. However, little is known about its development after major surgery. Methods We conducted an international prospective, observational, multi-center study in 30 countries among patients undergoing major surgery. The primary study endpoint was the incidence of CKD (de...

Pulmonary microvascular endothelial cells contribute to integrity of the lung gas exchange interface and they are highly glycolytic. While glucose and fructose represent discrete substrates available for glycolysis, pulmonary microvascular endothelial cells prefer glucose over fructose and the mechanisms involved in this selection are unknown. 6-Ph...

Background: There is a lack of reported clinical outcomes after opioid use in acute trauma patients undergoing anesthesia. Data from the Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study were analyzed to examine opioid dose and mortality. We hypothesized that higher dose opioids during anesthesia were associated with lower m...

The year 2022 marks the 100th anniversary of Anesthesia & Analgesia, the longest-running anesthesiology publication in the world. Founded in 1922 as Current Researches in Anesthesia & Analgesia by the visionary and charismatic Francis McMechan, MD, the journal served as a reliable mirror for the key scientific and political issues facing the nascen...

Patients who recover from nosocomial pneumonia oftentimes exhibit long-lasting cognitive impairment comparable to what is observed in Alzheimer's Disease patients. We previously hypothesized that the lung endothelium contributes to infection-related neurocognitive dysfunction, since bacteria-exposed endothelial cells release a form(s) of cytotoxic...

Acute kidney injury (AKI) may be induced by different causes, including renal ischemia-reperfusion injury and sepsis, which represent the most common reasons for AKI in hospitalized patients. AKI is defined by reduced urine production and/or increased plasma creatinine. However, this definition does not address the molecular mechanisms of different...

The Gram-negative, opportunistic pathogen Pseudomonas aeruginosa utilizes a type III secretion system to inject exoenzyme effectors into a target host cell. Of the four best-studied exoenzymes, ExoU causes rapid cell damage and death. ExoU is a phospholipase A2 (PLA2) that hydrolyses host cell membranes, and P. aeruginosa strains expressing ExoU ar...

Patients who recover from nosocomial pneumonia oftentimes exhibit long-lasting cognitive impairment comparable to what is observed in Alzheimer’s Disease patients. We previously hypothesized that the lung endothelium contributes to infection-related neurocognitive dysfunction, since bacteria-exposed endothelial cells release a form(s) of cytotoxic...

Pseudomonas (P.) aeruginosa is an opportunistic pathogen that causes serious infections and hospital-acquired pneumonia in immunocompromised patients. P. aeruginosa accounts for up to 20% of all cases of hospital-acquired pneumonia, with an attributable mortality rate of ~30–40%. The poor clinical outcome of P. aeruginosa-induced pneumonia is ascri...

Pneumonia causes short‐ and long‐term cognitive dysfunction in a high proportion of patients, although the mechanism(s) responsible for this effect are unknown. Here, we tested the hypothesis that pneumonia‐elicited cytotoxic amyloid and tau variants: (1) are present in the circulation during infection; (2) lead to impairment of long‐term potentiat...

Low tidal volume ventilation protects the lung in mechanically ventilated patients. The impact of the accompanying permissive hypoxemia and hypercapnia on endothelial cell recovery from injury is poorly understood. Carbonic anhydrase IX (CA IX) is expressed in pulmonary microvascular endothelial cells (PMVECs), where it contributes to CO2 and pH ho...

Despite the high morbidity and mortality among patients with extensive cutaneous burns in the intensive care unit due to the development of acute respiratory distress syndrome, effective therapeutics remain to be determined. This is primarily because the mechanisms leading to acute lung injury (ALI) in these patients remain unknown. We test the hyp...

Purpose Nosocomial infection contributes to adverse outcome after brain injury. This study investigates whether autonomic nervous system activity is associated with a decreased host immune response in patients following stroke or traumatic brain injury (TBI). Methods A prospective study was performed in adult patients with TBI or stroke who were a...

Traumatic brain injury (TBI) is the leading cause of injury-related death and disability in patients under the age of 46 years. Survivors of the initial injury often endure systemic complications such as pulmonary infection, and Pseudomonas aeruginosa is one of the most common causes of nosocomial pneumonia in intensive care units. Female patients...

Purpose: Nosocomial infection contributes to adverse outcome after brain injury. This study investigates whether autonomic nervous system activity is associated with a decreased host immune response in patients following stroke or traumatic brain injury (TBI). Methods: A prospective study was performed in adult patients with TBI or stroke who were...

Objectives: Results from preclinical and adult sepsis studies suggest that the balance of circulating angiopoietin-1 and -2 levels, represented as angiopoietin-2/-1 ratios, plays a pivotal role in mediating vascular dysfunction and organ injury during sepsis. However, the relationship of plasma angiopoietins with organ injury and clinical outcomes...

Trauma and sepsis are frequent causes of immunosuppression and risk of secondary bacterial infections and mortality among critically ill patients. Reduced activity of neutrophil NADPH oxidase 2 (NOX2) and impaired bacterial killing are among the major indices of immunosuppression. We hypothesize that NOX2-decoy peptides disrupt the inhibition of ne...

Pseudomonas aeruginosa is an opportunistic pathogen that causes pneumonia in immunocompromised and intensive care unit (ICU) patients. During host infection, P. aeruginosa upregulates the type III secretion system (T3SS), which is used to intoxicate host cells with exoenzyme (Exo) virulence factors. Of the four known Exo virulence factors (U, S, T...

Pseudomonas aeruginosa infection elicits the production of cytotoxic amyloids from lung endothelium, yet molecular mechanisms of host‐pathogen interaction that underlie the amyloid production are not well understood. We examined the importance of type III secretion system (T3SS) effectors in the production of cytotoxic amyloids. P aeruginosa posses...

Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The Type III secretion system (T3SS) of P. aeruginosa mediates many of the adverse effects of infection with this pathogen including increased lung permeability in a toll-like receptor 4/Rho A/plasminogen activator...

Pulmonary edema associated with increased vascular permeability is a severe complication of Pseudomonas (P.) aeruginosa‐induced acute lung injury. The mechanisms underlying P aeruginosa‐induced vascular permeability are not well understood. In the present study, we investigated the role of neuronal Wiskott Aldrich syndrome protein (N‐WASP) in modul...

[This corrects the article DOI: 10.1371/journal.pmed.1002522.].

Increases in plasma von Willebrand Factor (VWF) and decrease in its respective activity of cleaving metalloprotease ADAMTS13 (A13) have been implicated in the disease process in thrombotic thrombocytopenic purpura, MI, ischemic stroke, and sepsis. We have recently demonstrated that pediatric trauma patients with markedly low A13 levels have increas...

Rationale: Pseudomonas aeruginosa is the prevalent agent of ventilator-associated pneumonia and utilizes a type III secretion system (T3SS) to inject exoenzymes into host cells. The T3SS effector ExoY is expressed by ∼95% of P. aeruginosa clinical isolates; however, its relevance in the clinical setting remains unclear. During infection with ExoY-i...

Background: Aneurysmal subarachnoid hemorrhage (aSAH) has high fatality and permanent disability rates due to the severe damage to brain cells and inflammation. The SERPINE1 gene that encodes PAI-1 for the regulation of tissue plasminogen activator is considered an important therapeutic target for aSAH. Methods: Six SNPs in the SERPINE1 gene (in...

Patients with nosocomial pneumonia exhibit elevated levels of neurotoxic amyloid and tau proteins in the cerebrospinal fluid (CSF). In vitro studies indicate that pulmonary endothelium infected with clinical isolates of either Pseudomonas aeruginosa, Klebsiella pneumoniae, or Staphylococcus aureus produces and releases cytotoxic amyloid and tau pro...

BACKGROUND The mortality of trauma patients requiring massive transfusion to treat hemorrhagic shock approaches 17% at 24 hours and 26% at 30 days. The use of stored RBCs is limited to less than 42 days, so older RBCs are delivered first to rapidly bleeding trauma patients. Patients who receive a greater quantity of older RBCs may have a higher ris...

Acute kidney injury (AKI) is a serious condition that affects critically ill patients admitted to the ICU. In this study, we report the association between right ventricle shape and AKI in a cohort of burn and trauma patients. This study is a retrospective review of trauma and burn patients who were admitted to our ICU between 2013 and 2016 who und...

Background: Although the association of neutrophil proportions with mortality in trauma patients has recently been shown, there is a paucity of research on the association with other outcomes. We sought to investigate the association of neutrophil proportions with organ failure in critically-ill trauma patients. Methods: We reviewed a randomly-sele...

Study objective: The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion. Methods: We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in t...

We have recently reported that following bacterial infection with Pseudomonas aeruginosa , injury to the pulmonary endothelium induces tau hyperphosphorylation and release as a cytotoxic amyloid protein. Further, cytotoxic amyloid production requires an intact type 3 secretion system (PA103 strain), because a non‐functional type 3 secretion system...

Background: Angiopoietin-1 (Agpt-1) and Agpt-2 are cytokine regulators of vascular endothelial integrity. Elevated plasma Agpt-2 levels and ratios of Agpt-2:Agpt-1 are associated with adverse outcomes in adult trauma and pediatric sepsis populations. However, the behavior of the angiopoietins after pediatric trauma has not been characterized, and...

Background: The Centers for Disease Control and Prevention replaced the definition for ventilator-associated pneumonia with an algorithm comprised of three categories-ventilator associated condition (VAC), infection -related ventilator associated complication (IVAC) and possible ventilator associated pneumonia (PVAP). We sought to compare the outc...

Decrease of plasma activity of ADAMTS13, a metalloenzyme that cleaves von Willebrand factor (VWF) and prevents adhesion and aggregation of platelets, has been reported early after onset of systemic inflammation resulting from infections and after severe trauma. Here, we determined whether trauma-induced systemic (sterile) inflammation would be asso...

Background Trauma is the leading cause of death and disability in patients aged 1–46 y. Severely injured patients experience considerable blood loss and hemorrhagic shock requiring treatment with massive transfusion of red blood cells (RBCs). Preclinical and retrospective human studies in trauma patients have suggested that poorer therapeutic effic...

Raw data presented in Figs 1–6. (XLSX)

Acid (HCl) aspiration during anesthesia may lead to acute lung injury. There is no effective therapy. We hypothesized that HCl, instilled intratracheally in C57BL/6 mice results in the formation of low molecular weight hyaluronan (L-HA), which activates RhoA and ROCK, causing airway hyperresponsiveness (AHR) and increased permeability. Furthermore,...

Background Little data is available in the literature about the role of end tidal oxygen in critically ill patients. We sought to identify the association between the level of respiratory oxygen and clinical outcomes in critically-ill ventilated trauma and burn patients. Methods A retrospective cohort of 55 trauma and burn patients from 2010 to 20...

Abstract Background Conventional echocardiographic technique for assessment of volume status and cardiac contractility utilizes left ventricular end-diastolic area (LVEDA) and fractional area of change (FAC), respectively. Our goal was to find a technically reliable yet faster technique to evaluate volume status and contractility by measuring left...

Background: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study evaluated the effects of plasma and platelets on hemostasis and mortality after hemorrhage. The pulmonary consequences of resuscitation strategies that mimic whole blood, remain unknown. Methods: A secondary analysis of the PROPPR study was performed. Injured...

Background: The Centers for Disease Control and Prevention (CDC) replaced its definition for ventilator-associated pneumonia (VAP) in 2013. The aim of the current study is to compare the outcome of burn patients with ventilator associated events (VAEs). Methods: Burn patients with at least two days of ventilator support were identified from the...

Data fabrication and scientific misconduct have been recently uncovered in the anesthesia literature, partly via the work of John Carlisle. In a recent article in Anaesthesia, Carlisle analyzed 5087 randomized clinical trials from anesthesia and general medicine journals from 2000 to 2015. He concluded that in about 6% of studies, data comparing ra...

In this research agenda on the acute and critical care management of trauma patients, we concentrate on the major factors leading to death, namely haemorrhage and traumatic brain injury (TBI). In haemostasis biology, the results of randomised controlled trials have led to the therapeutic focus moving away from the augmentation of coagulation factor...

Objectives: The National Healthcare Safety Network (NHSN) replaced its old definition for ventilator associated pneumonia (VAP) with ventilator associated events (VAEs) in 2013. Little data is available comparing the two definitions in burn patients. Methods: Data from 2011-2014 were collected on burn patients mechanically ventilated for at leas...

Background: The release of damage-associated molecular pattern molecules (DAMPs) in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have...

Background The Centers for Disease Control and Prevention’s (CDC) NHSN replaced its old definition for ventilator-associated pneumonia (VAP) with the ventilator-associated events (VAEs) algorithm in 2013. We sought to compare the outcome of trauma patients meeting the definitions for VAP in the two modules. Methods Trauma patients with blunt or pe...

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Even when patients survive the initial insult, there is significant morbidity and mortality secondary to subsequent pulmonary edema, acute lung injury and nosocomial pneumonia. While the relationship between TBI and secondary pulmonary complications is recognized, l...

Patients who recover from pneumonia subsequently have elevated rates of death after hospital discharge as a result of secondary organ damage, the causes of which are unknown. We used the bacterium Pseudomonas aeruginosa, a common cause of hospital-acquired pneumonia, as a model for investigating this phenomenon. We show that infection of pulmonary...

Background: The role of echocardiographic indices of preload and contractility in predicting outcomes is unknown. We report the association of end diastolic area (EDA) and fractional area of change (FAC) with mortality in a cohort of trauma and burn patients. Methods: Data on 86 patients admitted to a tertiary care center between July 2013 and J...

Background: Acute traumatic coagulopathy occurs in both pediatric and adult trauma patients and is associated with an increased risk of mortality. Trauma patients not only have increased risk for hemorrhagic complications, but also are at increased risk for thrombosis due to multiple factors including local tissue injury, inflammation, and immobili...

Background: The Perioperative Surgical Home (PSH) seeks to remedy the currently highly fragmented and expensive perioperative care in the United States. The 2 specific aims of this health services research study were to assess the association between the preoperative and postoperative elements of an initial PSH model and a set of (1) clinical, qua...

Cell-free heme (CFH) and hemoglobin (Hb) have emerged as distinct mediators of acute injury characterized by inflammation and microcirculatory dysfunction in hemolytic conditions and critical illness. Several reports have shown changes in Hb and CFH in specific pathophysiological settings. Using PBS, plasma from patients with sickle cell disease, a...

Emergency surgery is associated with increased postoperative complications and mortality. Few patients are more poorly prepared for surgery than those who come to the operating room from the emergency department or trauma bay, in need of an urgent operative procedure. The physiology of these patients may be abnormal upon presentation due to multipl...

Alterations in metabolic and bioenergetic homeostasis contribute to sepsis-mediated organ injury. However, how AMP-activated protein kinase (AMPK), a major sensor and regulator of energy expenditure and production, affects development of organ injury and loss of innate capacity during polymicrobial sepsis remains unclear. In the present experiments...

Introduction: Early trauma-induced coagulopathy may increase susceptibility to nosocomial infections like ventilator-associated pneumonia. However, the relationship between Trauma- induced coagulopathy and the development of Ventilator- associated pneumonia in spinal cord injury patients has not been evaluated. Methods: We conducted a 5-year ret...

There is a lack of evidence-based approach regarding the best practice for airway management in patients with a traumatized airway. General recommendations for the management of the traumatized airway are summarized in table 5. Airway trauma may not be readily apparent, and its evaluation requires a high level of suspicion for airway disruption and...

In the United States trauma is the leading cause of mortality among those under the age of 45, claiming approximately 192,000 lives each year. Significant personal disability, lost productivity and long term healthcare needs are common and contribute 580 billion dollars in economic impact each year. Improving resuscitation strategies and the early...

Transfusion of stored red blood cells (RBCs) is associated with increased morbidity and mortality in trauma patients. Pro-oxidant, pro-inflammatory, and nitric oxide (NO) scavenging properties of stored RBCs are thought to underlie this association. In this study we determined the effects of RBC washing and nitrite and antiheme therapy on stored RB...

Transfusion of stored red blood cells (RBCs) is associated with increased morbidity and mortality in trauma patients. Pro-oxidant, pro-inflammatory and nitric oxide (NO) scavenging properties of stored RBC are thought to underlie this association. In this study we determined the effects of RBC washing, nitrite and anti-heme therapy on stored RBC-de...

Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. To determine th...

Optimizing hemostasis with antifibrinolytics is becoming a common surgical practice. Large clinical studies have demonstrated efficacy and safety of tranexamic acid (TXA) in the trauma population to reduce blood loss and transfusions. Its use in patients without pre-existing coagulopathies is debated, as thromboembolic events are a concern. In this...

Sepsis, defined by the presence of infection and host inflammation, is a lethal clinical syndrome with an increasing mortality rate worldwide. In severe disease, the coagulation system becomes diffusely activated, with consumption of multiple clotting factors resulting in disseminated intravascular coagulation (DIC). When present, DIC portends a hi...

Patients with acute respiratory distress syndrome who retain maximal alveolar fluid clearance (AFC) have better clinical outcomes. The release of endogenous catecholamines associated with shock or the administration of β2-adrenergic receptor (β2AR) agonists enhances AFC via a 3'-5'-cyclic adenosine monophosphate-dependent mechanism. The authors hav...

Hypotensive resuscitation is a component of damage control resuscitation, the evolving approach to resuscitation in severely injured trauma patients. Resuscitation strategies used in treating severely injured trauma patients have changed dramatically over the last 20 years. The purpose of this review is to examine the current literature pertaining...

Trauma is the leading cause of death among people under the age of 44. Hemorrhage is a major contributor to deaths related to trauma in the first 48 h. Accordingly, the management of these patients is a time-sensitive and critical affair that anesthesiologists responsible for surgical resuscitation will face. Coagulopathy associated with trauma exi...

Chlorine (Cl2) is a highly reactive oxidant gas that, when inhaled, may cause acute lung injury culminating in death from respiratory failure. In this study, we tested the hypothesis that exposure of mice to Cl2 causes intra-alveolar and systemic activation of the coagulation cascade that plays an important role in development of lung injury. C57BL...

Chlorine (Cl 2 ) is a toxic oxidative gas that can cause acute lung injury (ALI) and death when inhaled at high concentrations for extended periods of time. Used in the production of pharmaceuticals, Cl 2 exposure can occur in industrial or transportation accidents, which are common enough to pose a serious health risk. Cl 2 insult results in coagu...

The heat-shock response (HSR) protects from insults, such as ischemia-reperfusion injury, by inhibiting signaling pathways activated by sterile inflammation. However, the mechanisms by which the HSR activation would modulate lung damage and host response to a bacterial lung infection remain unknown. HSR was activated with whole-body hyperthermia or...

Trauma remains the leading cause of morbidity and mortality in the United States among children from the age 1 year to 21 years old. The most common cause of lethality in pediatric trauma is traumatic brain injury (TBI). Early coagulopathy has been commonly observed after severe trauma and is usually associated with severe hemorrhage and/or traumat...

Recent studies have changed our understanding of the timing and interactions of the inflammatory processes and coagulation cascade following severe trauma. This review highlights this information and correlates its impact on the current clinical approach for fluid resuscitation and treatment of coagulopathy for trauma patients. Severe trauma is ass...

High mobility group box 1 (HMGB1) protein is a danger-signaling molecule, known to activate an inflammatory response via TLR4 and RAGE. HMGB1 can be either actively secreted or passively released from damaged alveolar epithelial cells. Previous studies have shown that IL-1β, a critical mediator acute lung injury in humans that is activated by HMGB1...