• Epidemiology
• Multiple organ failure
• Polytrauma
• Trauma
• Trauma Center

• Humans
• Multiple Organ Failure/epidemiology
• Multiple Organ Failure/mortality
• Male
• Prospective Studies
• Female
• Middle Aged
• New South Wales/epidemiology
• Multiple Trauma/epidemiology
• Multiple Trauma/complications
• Adult
• Incidence
• Trauma Centers
• Aged
• Injury Severity Score
• Risk Factors

• The University of Newcastle (Australia)

• Humans
• Middle Aged
• Abscess
• Biomarkers
• Hospital Mortality
• Procalcitonin
• Prognosis
• Retrospective Studies
• ROC Curve
• Sepsis/complications
• Sepsis/diagnosis
• Shock, Septic
• Systemic Inflammatory Response Syndrome
• Urinary Tract Infections/complications
• Urinary Tract Infections/diagnosis

• Hemorrhagic shock-resuscitation
• Ischemia–reperfusion injury
• Mitochondria
• Mitochondrial quality control
• Parkin-dependent mitophagy

• Antimicrobial stewardship
• ECMO
• Infections
• Injury severity score
• Trauma

• damage control surgery
• exsanguination
• fluid load test
• hemorrhagic shock
• hypotensive resuscitation
• titrated-to-response anesthesia

• blunt injuries
• extracorporeal membrane oxygenation
• penetrating injuries
• trauma outcomes

• Extracorporeal Membrane Oxygenation/methods
• Humans
• Injury Severity Score
• Retrospective Studies
• Survival Rate
• Wounds, Nonpenetrating/surgery
• Wounds, Penetrating/surgery

(1) Background: Current findings emphasize the potential contribution of platelets to the immunological response after severe trauma. As clinical relevance remains unclear, this study aims to analyze the correlation between platelets and lung dysfunction in severely injured patients. (2) Methods: We retrospectively enrolled all multiple trauma patients presenting to our level 1 trauma center from 2015 to 2016 with an Injury-Severity Score (ISS) ≥ 16. Apart from demographic data, platelet counts and PaO₂/FiO₂ as an approximate indicator for lung physiology were analyzed and correlated on subsequent days after admission. (3) Results: 83 patients with a median ISS of 22 (IQR 18–36) were included. Compared to day 1, platelet counts were decreased on day 3 (p ≤ 0.001). Platelet counts were significantly lower on day 3 in patients with an ISS ≥ 35 (p = 0.011). There were no differences regarding PaO₂/FiO₂ index. Correlation analysis revealed a positive link between increased platelet counts and PaO₂/FiO₂ index on day 1 only in severely injured patients (p = 0.007). (4) Conclusions: This work supports the concept of platelets modulating the posttraumatic immune response by affecting lung dysfunction in the early phase after multiple trauma in dependence of injury severity. Our findings contribute to the understanding of the impact of platelets on systemic processes in multiple trauma patients.

• immune system
• platelets
• posttraumatic hyperinflammation
• posttraumatic lung dysfunction
• posttraumatic organ failure
• trauma

• Animals
• Disease Models, Animal
• Female
• Gonadal Steroid Hormones/therapeutic use
• Humans
• Male
• Sex Factors
• Shock, Hemorrhagic/drug therapy
• Shock, Hemorrhagic/etiology
• Wounds and Injuries/complications
• Wounds and Injuries/therapy

• Acute lung injury
• Acute respiratory distress syndrome
• Ischaemia–reperfusion injury
• Ischaemic conditioning
• Lung ischaemia–reperfusion

Severe trauma is the principal cause of death among young people worldwide. Hemorrhagic shock is the leading cause of death after severe trauma. Traumatic hemorrhagic shock (THS) is a complex phenomenon associating an absolute hypovolemia secondary to a sudden and significant extravascular blood loss, tissue injury, and, eventually, hypoxemia. These phenomena are responsible of secondary injuries such as coagulopathy, endotheliopathy, microcirculation failure, inflammation, and immune activation. Collectively, these dysfunctions lead to secondary organ failures and multi-organ failure (MOF). The development of MOF after severe trauma is one of the leading causes of morbidity and mortality, where immunological dysfunction plays a central role. Damage-associated molecular patterns induce an early and exaggerated activation of innate immunity and a suppression of adaptive immunity. Severe complications are associated with a prolonged and dysregulated immune–inflammatory state. The current challenge in the management of THS patients is preventing organ injury, which currently has no etiological treatment available. Modulating the immune response is a potential therapeutic strategy for preventing the complications of THS. Mesenchymal stromal cells (MSCs) are multipotent cells found in a large number of adult tissues and used in clinical practice as therapeutic agents for immunomodulation and tissue repair. There is growing evidence that their efficiency is mainly attributed to the secretion of a wide range of bioactive molecules and extracellular vesicles (EVs). Indeed, different experimental studies revealed that MSC-derived EVs (MSC-EVs) could modulate local and systemic deleterious immune response. Therefore, these new cell-free therapeutic products, easily stored and available immediately, represent a tremendous opportunity in the emergency context of shock. In this review, the pathophysiological environment of THS and, in particular, the crosstalk between the immune system and organ function are described. The potential therapeutic benefits of MSCs or their EVs in treating THS are discussed based on the current knowledge. Understanding the key mechanisms of immune deregulation leading to organ damage is a crucial element in order to optimize the preparation of EVs and potentiate their therapeutic effect.

• acute injury
• extracellular vesicles
• inflammation
• mesenchymal stromal cell
• multi-organ failure
• traumatic hemorrhagic shock

• extracorporeal membrane oxygenation
• traumatic brain injury

• apoptosis
• hyperbaric oxygenation
• microcirculation
• sepsis
• survival rate

Many factors of trauma care have changed in the last decades. This review investigated the effect of these changes on global all-cause and cause-specific mortality in polytrauma patients admitted to the intensive care unit (ICU). Moreover, changes in trauma mechanism over time and differences between continents were analyzed.

A systematic review of literature on all-cause mortality in polytrauma patients admitted to ICU was conducted. All-cause and cause-specific mortality rates were extracted as well as trauma mechanism of each patient. Poisson regression analysis was used to model time trends in all-cause and cause-specific mortality.

Thirty studies, which reported mortality rates for 82,272 patients, were included and showed a decrease of 1.8% (95% CI 1.6–2.0%) in all-cause mortality per year since 1966. The relative contribution of brain injury-related death has increased over the years, whereas the relative contribution of death due to multiple organ dysfunction syndrome (MODS), acute respiratory distress syndrome, and sepsis decreased. MODS was the most common cause of death in North America, and brain-related death was the most common in Asia, South America, and Europe. Penetrating trauma was most often reported in North America and Asia.

All-cause mortality in polytrauma patients admitted to the ICU has decreased over the last decades. A shift from MODS to brain-related death was observed. Geographical differences in cause-specific mortality were present, which may provide region-specific learning possibilities resulting in improvement of global trauma care.

• Intensive care unit
• Mortality
• Polytrauma patients
• Trauma care

• Extracorporeal membrane oxygenation (ECMO)
• Systematic review
• Trauma

• Extracorporeal Membrane Oxygenation
• Humans
• Wounds and Injuries/therapy

Microcirculatory perfusion disturbances following hemorrhagic shock and fluid resuscitation contribute to multiple organ dysfunction and mortality. Standard fluid resuscitation is insufficient to restore microcirculatory perfusion; however, additional therapies are lacking. We conducted a systematic search to provide an overview of potential non‐fluid‐based therapeutic interventions to restore microcirculatory perfusion following hemorrhagic shock.

A structured search of PubMed, EMBASE, and Cochrane Library was performed in March 2020. Animal studies needed to report at least one parameter of microcirculatory flow (perfusion, red blood cell velocity, functional capillary density).

The search identified 1269 records of which 48 fulfilled all eligibility criteria. In total, 62 drugs were tested of which 29 were able to restore microcirculatory perfusion. Particularly, complement inhibitors (75% of drugs tested successfully restored blood flow), endothelial barrier modulators (100% successful), antioxidants (66% successful), drugs targeting cell metabolism (83% successful), and sex hormones (75% successful) restored microcirculatory perfusion. Other drugs consisted of attenuation of inflammation (100% not successful), vasoactive agents (68% not successful), and steroid hormones (75% not successful).

Improving mitochondrial function, inhibition of complement inhibition, and reducing microvascular leakage via restoration of endothelial barrier function seem beneficial to restore microcirculatory perfusion following hemorrhagic shock and fluid resuscitation.

• animal models
• capillary perfusion
• fluid resuscitation
• hemorrhagic shock

• biomarkers
• blunt trauma
• dynamic network analysis
• fuzzy C-means clustering
• intensive care unit
• multiple organ dysfunction

• P50 GM053789 NIGMS NIH HHS

Inflammation is recognized as an important contributor of ischemia/reperfusion (I/R) damage after ischemic stroke. Sphingomyelin synthase 2 (SMS2), the key enzyme for the biosynthesis of sphingomyelin, can function as a critical mediator of inflammation. In the present study, we investigated the role of SMS2 in a mouse model of cerebral I/R.

Cerebral I/R was induced by 60‐minute transient middle cerebral artery occlusion in SMS2 knockout (SMS2^‐/‐) mice and wild‐type mice. Brain injury was determined by neurological deficits and infarct volume at 24 and 72 hours after transient middle cerebral artery occlusion. Microglia activation and inflammatory factors were detected by immunofluorescence staining, flow cytometry, western blot, and RT‐PCR. SMS2 deficiency significantly improved neurological function and minimized infarct volume at 72 hours after transient middle cerebral artery occlusion. The neuroprotective effects of SMS2 deficiency were associated with (1) suppression of microglia activation through Toll‐like receptor 4/nuclear factor kappa‐light‐chain‐enhancer of activated B cells pathway and (2) downregulation of the level of galactin‐3 and other proinflammatory cytokines. The mechanisms underlying the beneficial effects of SMS2 deficiency may include altering sphingomyelin components in lipid raft fractions, thus impairing the recruitment of Toll‐like receptor 4 to lipid rafts and subsequently reducing Toll‐like receptor 4/myeloid differentiation factor 2 complex formation on the surface of microglia.

SMS2 deficiency ameliorated inflammatory injury after cerebral I/R in mice, and SMS2 may be a key modulator of Toll‐like receptor 4/nuclear factor kappa‐light‐chain‐enhancer of activated B cells activation by disturbing the membrane component homeostasis during cerebral I/R.

• Toll‐like receptor 4
• cerebral ischemic reperfusion
• inflammation
• lipid rafts
• sphingomyelin synthase 2

• transcriptomics
• spinal cord injury

• Animals
• Chronic Disease
• Liver/metabolism
• Motor Activity
• Physical Conditioning, Animal
• Rats
• Spinal Cord Injuries/metabolism
• Spinal Cord Injuries/physiopathology
• Transcriptome

• R01 NS094741 NINDS NIH HHS
• R01 NS112304 NINDS NIH HHS
• P20 GM103436 NIGMS NIH HHS
• R56 NS052292 NINDS NIH HHS
• P30 GM103507 NIGMS NIH HHS
• U.S. Department of Health & Human Services | National Institutes of Health (NIH)
• Leona M. and Harry B. Helmsley Charitable Trust (Helmsley Charitable Trust)
• Commonwealth of Kentucky Challenge for Excellence
• Commonwealth of Kentucky Challenge for Excellence Norton Healthcare

• Animals
• Male
• Rats
• Apoptosis
• Biomarkers/metabolism
• Caspases/metabolism
• Disease Models, Animal
• Inflammation/metabolism
• Rats, Wistar
• Resuscitation
• Shock, Hemorrhagic/metabolism
• Shock, Hemorrhagic/therapy
• Uric Acid/metabolism

• cancer
• damage-associated molecular pattern
• extracellular vesicle
• inflammation
• polymer
• thrombosis
• transplantation
• trauma

• LRR-
• NOD-
• and pyrin domain-containing 3
• inflammasome
• inflammation
• interleukin-1β
• ischemia–reperfusion
• lung injury
• neutrophil activation

• Adult
• Aged
• Aged, 80 and over
• Animals
• Cohort Studies
• Disease Models, Animal
• Female
• Gene Expression Regulation
• Humans
• Immunity, Humoral
• Interleukin-33/blood
• Interleukin-33/metabolism
• Interleukin-5/genetics
• Interleukin-5/immunology
• Lung/immunology
• Lymphocytes/immunology
• Male
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Retrospective Studies
• Shock, Hemorrhagic/complications
• Shock, Hemorrhagic/immunology
• Wounds and Injuries/etiology
• Wounds and Injuries/genetics
• Wounds and Injuries/immunology
• Young Adult

• P50 GM053789 NIGMS NIH HHS
• R01 HL122489 NHLBI NIH HHS
• R35 GM127027 NIGMS NIH HHS
• T32 GM008516 NIGMS NIH HHS
• National Institutes of Health
• National Natural Science Foundation of China

• Extracorporeal life support (ECLS)
• Extracorporeal membrane oxygenation (ECMO)
• Injury severity score (ISS)
• Major trauma
• Outcome

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Critical Care
• Extracorporeal Membrane Oxygenation
• Female
• Humans
• Length of Stay
• Male
• Middle Aged
• Outcome Assessment, Health Care
• Retrospective Studies
• Survival Rate
• Wounds and Injuries/mortality
• Wounds and Injuries/therapy
• Young Adult

• SOCS-1
• Xuebijing injection
• sepsis

• Acute kidney injury
• Cyclooxygenase
• Obstructive nephropathy
• Prostaglandin E2
• Water balance

The mechanisms of sepsis mortality remain undefined. While there is some evidence of organ damage, it is not clear whether this damage alone is sufficient to cause death. Therefore, we aimed to examine contribution of organ injury/dysfunction to early deaths in the mouse abdominal sepsis.

Female OF-1 mice underwent either medium-severity cecal ligation and puncture (CLP-Only) or non-lethal CLP-ODam (CLP with cisplatin/carbontetrachloride to induce survivable hepatotoxicity and nephrotoxicity). In the first experiment, blood was collected daily from survivors (SUR; CLP-Only and CLP-ODam groups) or until early death (DIED; CLP-Only). In the second experiment (CLP-Only), early outcome was prospectively predicted based on body temperature (BT) and pairs of mice predicted to survive (P-SUR) and die (P-DIE) were sacrificed post-CLP. The overall magnitude of organ injury/dysfunction was compared in retrospectively and prospectively stratified mice.

At day 7 post-CLP, survival in CLP-Only was 48%, while CLP-ODam was non-lethal. In CLP-Only mice within 24 h of death, urea increased to 78 (versus 40 mg/dl in SUR), ALT to 166 (vs. 108 U/l), LDH to 739 (vs. 438 U/l) and glucose declined to 43 (vs. 62 mg/dl). In CLP-ODam, hypoglycemia was exacerbated (by 1.5-fold) and ALT and LDH were 20- and 8-fold higher versus DIED (CLP-Only) mice. In CLP-Only, predicted deaths (P-DIE) were preceded by a significant rise only in cystatin C (268 vs. 170 ng/ml in P-SUR) but not in creatinine and troponin I. Respiratory function of mitochondria in the liver and kidney of P-SUR and P-DIE CLP-Only mice was not impaired (vs. controls) and ATP level in organs remained similar among all groups. Histologic injury scores in the liver, kidney, heart and lung showed no major disparities among dying, surviving and control mice.

In CLP-Only mice, although the deregulation of parameters indicative of organ injury/dysfunction was greater in dying versus surviving mice, it never exceeded the changes in surviving CLP-ODam animals, and it was not followed by histopathological damage and/or mitochondrial dysfunction. This shows that interpretation of the contribution of the organ injury/dysfunction to early deaths in the CLP model is not straightforward and depends on the pathophysiological origin of the profiled disturbances.

The online version of this article (doi:10.1186/s40635-015-0048-z) contains supplementary material, which is available to authorized users.

Cecal ligation and puncture (CLP) is an experimental polymicrobial sepsis induced systemic inflammation that leads to acute organ failure. Aim of our study was to evaluate the effects of SP600125, a specific c-Jun NH₂-terminal kinase (JNK) inhibitor, to modulate the early and late steps of the inflammatory cascade in a murine model of CLP-induced sepsis. CB57BL/6J mice were subjected to CLP or sham operation. Animals were randomized to receive either SP600125 (15 mg/kg) or its vehicle intraperitoneally 1 hour after surgery and repeat treatment every 24 hours. To evaluate survival, a group of animals was monitored every 24 hours for 120 hours. Two other animals were sacrificed 4 or 18 hours after surgical procedures; lung and liver samples were collected for biomolecular and histopathologic analysis. The expression of p-JNK, p-ERK, TNF-α, HMGB-1, NF-κB, Ras, Rho, Caspase 3, Bcl-2, and Bax was evaluated in lung and liver samples; SP600125 improved survival, reduced CLP induced activation of JNK, NF-κB, TNF-α, and HMGB-1, inhibited proapoptotic pathway, preserved Bcl-2 expression, and reduced histologic damage in both lung and liver of septic mice. SP600125 protects against CLP induced sepsis by blocking JNK signalling; therefore, it can be considered a therapeutic approach in human sepsis.

• ARDS
• Hemorrhagic shock
• Inflammation
• Oleic acid

• Acute Lung Injury/blood
• Acute Lung Injury/etiology
• Animals
• Cytokines/blood
• Disease Models, Animal
• Male
• Mice, Inbred C57BL
• Oleic Acids
• Respiratory Distress Syndrome/blood
• Respiratory Distress Syndrome/etiology
• Shock, Hemorrhagic/blood
• Shock, Hemorrhagic/complications

• Acute respiratory distress syndrome
• Noninvasive ventilation
• Pulmonary contusion
• Respiratory failure
• Trauma

• Central venous hemorrhage
• Hepatic hemorrhage
• Hepatocyte proliferation
• Interleukin 6
• Ischemia–reperfusion
• Swine

• Critical care
• Length of stay modeling
• Mortality prediction
• Sequential organ failure score
• Support vector machines

Tuberculosis (TB) is a rare but known cause of acute respiratory distress syndrome (ARDS). The role of inflammatory cytokines in the progression of ARDS in TB patients is unknown.

In this study we investigated the possible link between the levels of inflammatory cytokines in bronchoalveolar lavage (BAL) in patients with TB or ARDS alone or in patients with TB-induced ARDS (ARDS + TB).

90 patients were studied: 30 with TB alone, 30 with ARDS alone and 30 with ARDS + TB. BAL was collected by fiberoptic bronchoscopy and the concentrations of interleukin(IL)-6, CXCL8, TNF-α and IL-1β and the amounts of total protein were measured by ELISA and bicinchoninic acid assay (BCA) methods respectively. The correlation between disease severity measured by Murray scores, SOFA and APACHE II analysis and BAL mediators and cells was also determined.

CXCL8 levels in BAL were significantly higher in the ARDS + TB group compared to TB and ARDS alone groups. Disease severity in the ARDS + TB group as determined by Murray score correlated with BAL CXCL8 and neutrophils but not with IL-6, IL-1β and TNF-α concentrations. In addition, CXCL8 levels and neutrophils were increased in non-miliary TB versus miliary TB. This difference in CXCL8 was lost in the presence of ARDS.

BAL CXCL8 levels were significantly higher in patients with ARDS induced by TB and could suggest an important role of CXCL8 in the pathogenesis of this form of ARDS. This further suggests that CXCL8 inhibitors or blockers may be useful to control the onset and/or development of these combined diseases.

• ARDS
• CXCL8 and neutrophils
• TB

• Biological markers
• Immune monitoring
• Multiple organ failure
• Second hit
• Surgery
• Trauma

• Biomarkers/metabolism
• Cytokines/metabolism
• Fractures, Bone/complications
• Fractures, Bone/mortality
• Fractures, Bone/surgery
• Humans
• Multiple Organ Failure/etiology
• Multiple Organ Failure/immunology
• Multiple Organ Failure/mortality
• Multiple Trauma/complications
• Multiple Trauma/immunology
• Multiple Trauma/mortality
• Multiple Trauma/surgery
• Perioperative Period
• Predictive Value of Tests
• Sepsis/etiology
• Sepsis/immunology
• Sepsis/mortality
• Systemic Inflammatory Response Syndrome/etiology
• Systemic Inflammatory Response Syndrome/immunology
• Systemic Inflammatory Response Syndrome/mortality
• Treatment Outcome

Probiotic use to prevent nosocomial gastrointestinal and potentially respiratory tract infections in critical care has shown great promise in recent clinical trials of adult and pediatric patients. Despite well-documented benefits of probiotic use in intestinal disorders, the potential for probiotic treatment to reduce lung injury following infection and shock has not been well explored.

Evaluate if Lactobacillus rhamnosus GG (LGG) or Bifidobacterium longum (BL) treatment in a weanling mouse model of cecal ligation and puncture (CLP) peritonitis will protect against lung injury.

3 week-old FVB/N mice were orally gavaged with 200 µl of either LGG, BL or sterile water (vehicle) immediately prior to CLP. Mice were euthanized at 24 h. Lung injury was evaluated via histology and lung neutrophil infiltration was evaluated by myeloperoxidase (MPO) staining. mRNA levels of IL-6, TNF-α, MyD88, TLR-4, TLR-2, NFΚB (p50/p105) and Cox-2 in the lung analyzed via real-time PCR. TNF-α and IL-6 in lung was analyzed via ELISA.

LGG and BL treatment significantly improved lung injury following experimental infection and sepsis and lung neutrophil infiltration was significantly lower than in untreated septic mice. Lung mRNA and protein levels of IL-6 and TNF-α and gene expression of Cox-2 were also significantly reduced in mice receiving LGG or BL treatment. Gene expression of TLR-2, MyD88 and NFΚB (p50/p105) was significantly increased in septic mice compared to shams and decreased in the lung of mice receiving LGG or BL while TLR-4 levels remained unchanged.

Treatment with LGG and BL can reduce lung injury following experimental infection and sepsis and is associated with reduced lung inflammatory cell infiltrate and decreased markers of lung inflammatory response. Probiotic therapy may be a promising intervention to improve clinical lung injury following systemic infection and sepsis.

• Animals
• Bifidobacterium/immunology
• Cyclooxygenase 2/metabolism
• Interleukin-6/metabolism
• Lacticaseibacillus rhamnosus/immunology
• Lung Injury/immunology
• Lung Injury/microbiology
• Lung Injury/prevention & control
• Mice
• Neutrophil Infiltration
• Pneumonia/immunology
• Pneumonia/microbiology
• Pneumonia/prevention & control
• Probiotics/therapeutic use
• Sepsis/complications
• Sepsis/immunology
• Toll-Like Receptors/metabolism
• Tumor Necrosis Factor-alpha/metabolism

• R01 GM078312 NIGMS NIH HHS

• and vascular permeability
• lung injury
• obesity
• reactive oxygen species
• trauma

Mortality from trauma remains a major challenge despite recent substantial improvements in acute trauma care. In trauma care patient resuscitation to correct hypotension from volume loss still majorly relies on use of physiological parameters such as blood pressure, pulse rate, respiratory rate, urine output and oxygen saturation. In resource limited settings these methods may not be sufficient to detect occult tissue hypoxia and the accompanying metabolic derangements.

A prospective observational study carried out at a level I urban Trauma centre; Accident and Emergency unit. Major trauma patients were consecutively recruited into the study. Venous blood samples were drawn for analysis of serum electrolytes, serum PH and anion gap. The venous blood gas findings were correlated with patients’ clinical outcome at two weeks. Ethical approval was obtained.

Ninety three major trauma patients were recruited, patients’ age ranged from 12 months to 50 years. Forty nine patients (53%) were acidotic (PH less than 7.32), 39 patients (42%) had low bicarbonate (bicarbonate level less than 21 mmol), 54 patients (58%) had high corrected anion gap (anion gap corrected of 16 or more). Fourteen patients (15%) developed secondary organ failure and 32 (34%) patients died.

Metabolic acidosis is common among major trauma patients, its severity may be related to delay in initiating care. Acid base derangements were predictors of mortality among major trauma patients in this resource limited setting.

• Major trauma
• acidosis
• anion gap
• early outcome
• organ failure