• Antimicrobial stewardship
• Critical care
• Prescription drug overuse
• Sepsis
• Septic shock

• Humans
• Retrospective Studies
• Female
• Male
• Middle Aged
• Anti-Bacterial Agents/administration & dosage
• Anti-Bacterial Agents/therapeutic use
• Aged
• Cross Infection/drug therapy
• Cohort Studies
• Sepsis/drug therapy
• Adult
• Withholding Treatment
• Critical Illness
• Shock, Septic/drug therapy

• Antibacterial agents
• Healthcare-associated pneumonia
• Lung injury
• Thoracic injuries

• Humans
• Male
• Female
• Retrospective Studies
• Middle Aged
• Contusions/epidemiology
• Incidence
• Adult
• Critical Illness
• Healthcare-Associated Pneumonia/epidemiology
• Healthcare-Associated Pneumonia/drug therapy
• Anti-Bacterial Agents/administration & dosage
• Lung Injury/epidemiology
• Cohort Studies
• Aged

• DAMPs
• PAMPs
• compensatory anti‐inflammatory response syndrome
• persistent inflammation, immunosuppression, and catabolism syndrome
• systemic inflammatory response syndrome

• Bursera graveolens
• Candida albicans
• Candida glabrata
• Candida parapsilosis
• Dacryodes peruviana
• Melaleuca armillaris
• Mespilodaphne quixos
• essential oil
• skin inflammation

• Mice
• Animals
• Oils, Volatile/chemistry
• Antifungal Agents/chemistry
• Plant Oils/chemistry
• Ecuador
• Candida
• Candida albicans
• Candidiasis/drug therapy
• Candidiasis/microbiology
• Anti-Inflammatory Agents/pharmacology
• Microbial Sensitivity Tests

• outcomes research
• clinical trial design

• Humans
• Aftercare
• Patient Discharge
• Randomized Controlled Trials as Topic
• Resuscitation
• Critical Care

• Medical Research and Materiel Command

• Immunesenescence
• Inflammation
• Sepsis
• Traumatic injury

Background: Accidents and injuries are the leading causes of mortality in young people. CD4+ regulatory T cells (CD4+ Tregs), Th17 cells and platelets could be identified as key players in post-traumatic immunological dysfunction, which is a common cause of late mortality in trauma patients. The mechanisms of activation of these cell types and their interaction remain mostly unclear. Since CD69 is not only a leukocyte marker but has also immunoregulatory functions, we postulate a role for CD69 after trauma. The present study investigates the expression of CD69 on CD4+ Tregs and Th17 cells, as well as the posttraumatic expansion of platelets and hemostatic function. Subgroup analysis was performed to assess the differences between polytrauma patients with and without severe traumatic brain injury (TBI). Methods: In this non-interventional prospective clinical trial, we analyzed sequential blood samples over a period of 10 days from 30 patients after multiple traumas with an ISS ≥ 16. Platelet function was assessed by rotational thromboelastometry (ROTEM analysis). CD4+ Tregs and Th17 cells were stained with surface markers and analyzed by flow cytometry. Results: We were able to demonstrate a significantly increased expression of CD69 on CD4+ Tregs after trauma. Subgroup analysis revealed that the absence of severe TBI is associated with a significantly higher expression of CD69 on CD4+ Tregs and on Th17 cells. Platelets expanded and showed signs of dysfunction, while an overall tendency of posttraumatic hypercoagulation was detected. Conclusions: Our results support the concept of injury-specific immune responses and add to a further understanding of the complex pathophysiology of post-traumatic immune dysfunction.

• CD4+ regulatory T cells
• CD69
• T helper 17 cells
• hemostasis
• neuro-immune interaction
• trauma
• traumatic brain injury

• brain trauma
• intensive care unit
• probiotics
• surgical site infection
• trauma

• Bifidobacterium
• Bifidobacterium animalis
• Double-Blind Method
• Humans
• Lactobacillus acidophilus
• Probiotics/therapeutic use
• Surgical Wound Infection/prevention & control

• CyTOF
• T cell receptor diversity
• Tregs
• single-cell RNA sequencing
• trauma immunology

• Animals
• Cell Proliferation
• Mice
• Receptors, Antigen, T-Cell, alpha-beta
• T-Lymphocytes, Regulatory

• R01 AI092905 NIAID NIH HHS
• R01 AI148232 NIAID NIH HHS
• U01 AI107360 NIAID NIH HHS
• U01 AI138318 NIAID NIH HHS
• National Institutes of Health

CD4+ FoxP3+ regulatory T cells (CD4+ Tregs) are important for the posttraumatic anti-inflammatory host response. As described previously, platelets are able to modulate CD4+ Treg activity in a reciprocally activating interaction following injury. The underlying mechanisms of the posttraumatic interaction between platelets and CD4+ Tregs remain unclear. We investigated the potential influence of CD40L and P-selectin, molecules known to be involved in direct cell contact of these cell types. In a murine burn injury model, the potential interaction pathways were addressed using CD40L- and P-selectin-deficient mice. Draining lymph nodes were harvested following trauma (1 h) and following a sham procedure. Early rapid activation of CD4+ Tregs was assessed by phospho-flow cytometry (signaling molecules (p)PKC-δ and (p)ZAP-70). Platelet function was analyzed performing rotational thromboelastometry (ROTEM). We hypothesized that disruption of the direct cell-cell contact via CD40L and P-selectin would affect posttraumatic activation of CD4+ Tregs and influence the hemostatic function of platelets. Indeed, while injury induced early activation of CD4+ Tregs in wild-type mice (ZAP-70: p = 0.13, pZAP-70: p < 0.05, PKC-δ: p < 0.05, pPKC-δ: p < 0.05), disruption of CD40L-dependent interaction (ZAP-70: p = 0.57, pZAP-70: p = 0.68, PKC-δ: p = 0.68, pPKC-δ: p = 0.9) or P-selectin-dependent interaction (ZAP-70: p = 0.78, pZAP-70: p = 0.58, PKC-δ: p = 0.81, pPKC-δ: p = 0.73) resulted in reduced posttraumatic activation. Furthermore, hemostatic function was impaired towards hypocoagulability in either deficiency. Our results suggest that the posttraumatic activation of CD4+ Tregs and hemostatic function of platelets are affected by direct cell-cell-signaling via CD40L and P-selectin.

• CD4+ regulatory T cells
• adaptive immune response
• cell communication
• hemostasis
• platelets
• trauma

During the last decade, experimental and clinical studies have demonstrated that isolated acute brain injury (ABI) may cause severe dysfunction of peripheral extracranial organs and systems. Of all potential target organs and systems, the lung appears to be the most vulnerable to damage after brain injury (BI). The pathophysiology of these brain–lung interactions are complex and involve neurogenic pulmonary oedema, inflammation, neurodegeneration, neurotransmitters, immune suppression and dysfunction of the autonomic system. The systemic effects of inflammatory mediators in patients with BI create a systemic inflammatory environment that makes extracranial organs vulnerable to secondary procedures that enhance inflammation, such as mechanical ventilation (MV), surgery and infections. Indeed, previous studies have shown that in the presence of a systemic inflammatory environment, specific neurointensive care interventions—such as MV—may significantly contribute to the development of lung injury, regardless of the underlying mechanisms. Although current knowledge supports protective ventilation in patients with BI, it must be born in mind that ABI-related lung injury has distinct mechanisms that involve complex interactions between the brain and lungs. In this context, the role of extracerebral pathophysiology, especially in the lungs, has often been overlooked, as most physicians focus on intracranial injury and cerebral dysfunction. The present review aims to fill this gap by describing the pathophysiology of complications due to lung injuries in patients with a single ABI, and discusses the possible impact of MV in neurocritical care patients with normal lungs.

• Acute respiratory distress syndrome
• Brain damage
• Brain–lung interactions
• Inflammation
• Mechanical ventilation
• Ventilator induced lung injury

• polytrauma
• dysregulated neutrophil function
• pneumonia-induced lung injury

• Acute Lung Injury/blood
• Acute Lung Injury/immunology
• Acute Lung Injury/microbiology
• Acute Lung Injury/pathology
• Animals
• Disease Models, Animal
• Humans
• Lung/immunology
• Lung/microbiology
• Lung/pathology
• Male
• Mice
• Multiple Trauma/blood
• Multiple Trauma/complications
• Multiple Trauma/diagnosis
• Multiple Trauma/immunology
• Neutrophils/immunology
• Neutrophils/metabolism
• Pneumonia, Bacterial/blood
• Pneumonia, Bacterial/immunology
• Pneumonia, Bacterial/microbiology
• Pneumonia, Bacterial/pathology
• Pseudomonas Infections/blood
• Pseudomonas Infections/immunology
• Pseudomonas Infections/microbiology
• Pseudomonas Infections/pathology
• Pseudomonas aeruginosa/immunology
• Reactive Oxygen Species/metabolism
• Trauma Severity Indices

• R35 GM133756 NIGMS NIH HHS

• CyTOF
• MHC-II
• danger
• injury
• memory
• trauma

• Animals
• Biomarkers/metabolism
• Burns/immunology
• Burns/pathology
• Cell Proliferation
• Histocompatibility Antigens Class II/metabolism
• Immunologic Memory
• Lymph Nodes/pathology
• Lymphocyte Activation/immunology
• Mice, Inbred C57BL
• Spleen/pathology
• T-Lymphocytes, Regulatory/immunology
• Wounds and Injuries/immunology
• Wounds and Injuries/pathology
• Mice

• R01 AI092905 NIAID NIH HHS
• R01 AI148232 NIAID NIH HHS
• T32 GM103702 NIGMS NIH HHS

• DAMP
• Danger
• Inflammation
• SAMP
• Trauma

• Alarmins/immunology
• Animals
• Biomarkers
• Disease Models, Animal
• Humans
• Immune System Phenomena
• Inflammation/immunology
• Wounds and Injuries/immunology

• Acute respiratory distress syndrome
• Brain injury
• Brain-heart crosstalk
• Brain-lung crosstalk
• Cardiomyopathy
• Neurogenic pulmonary œdema

• Biomarkers
• Brain
• CRP
• Corticosteroid
• Cortisol
• Injury
• Pneumonia
• Traumatic

• Adolescent
• Adrenal Cortex Hormones/standards
• Adrenal Cortex Hormones/therapeutic use
• Adult
• Aged
• Anti-Bacterial Agents/standards
• Anti-Bacterial Agents/therapeutic use
• Biomarkers/analysis
• Biomarkers/blood
• Brain Injuries, Traumatic/drug therapy
• Brain Injuries, Traumatic/physiopathology
• C-Reactive Protein/analysis
• Double-Blind Method
• Female
• Healthcare-Associated Pneumonia/drug therapy
• Healthcare-Associated Pneumonia/physiopathology
• Humans
• Hydrocortisone/analysis
• Hydrocortisone/blood
• Male
• Middle Aged
• Odds Ratio
• Pneumonia/drug therapy
• Pneumonia/physiopathology
• Predictive Value of Tests
• ROC Curve

• . The French Society of Anesthesiology and Intensive care (SFAR) and institutional funds

Systemic inflammation induced by sterile or infectious insults is associated with an enhanced susceptibility to life-threatening opportunistic, mostly bacterial, infections due to unknown pathogenesis. Natural killer (NK) cells contribute to the defence against bacterial infections through the release of Interferon (IFN) γ in response to Interleukin (IL) 12. Considering the relevance of NK cells in the immune defence we investigated whether the function of NK cells is disturbed in patients suffering from serious systemic inflammation.

NK cells from severely injured patients were analysed from the first day after the initial inflammatory insult until the day of discharge in terms of IL-12 receptor signalling and IFN-γ synthesis.

During systemic inflammation, the expression of the IL-12 receptor β2 chain, phosphorylation of signal transducer and activation 4, and IFN-γ production on/in NK cells was impaired upon exposure to Staphylococcus aureus. The profound suppression of NK cells developed within 24 h after the initial insult and persisted for several weeks. NK cells displayed signs of exhaustion. Extrinsic changes were mediated by the early and long-lasting presence of growth/differentiation factor (GDF) 15 in the circulation that signalled through the transforming growth factor β receptor I and activated Smad1/5. Moreover, the concentration of GDF-15 in the serum inversely correlated with the IL-12 receptor β2 expression on NK cells and was enhanced in patients who later acquired septic complications.

GDF-15 is associated with the development of NK cell dysfunction during systemic inflammation and might represent a novel target to prevent nosocomial infections.

The study was supported by the Department of Orthopaedics and Trauma Surgery, University Hospital Essen.

• Immunosuppression
• Interferon gamma
• Interleukin 12
• Natural killer cells
• Opportunistic infections
• Transforming growth factor receptor

The aim of this investigation was to assess expression of programmed death-1 (PD-1) and inflammatory status after hip fracture surgery in aged mice and to evaluate the effect of anti-PD-1 antibody intervention. Male C57BL/6 mice aged 22-28 months underwent hip fracture and femoral intramedullary pinning or a sham procedure. Expression of PD-1 was measured on CD4⁺ and CD8⁺ T cells. Additionally, the effects of anti-PD-1 antibody on lymphocyte apoptosis, cytokine production, bacterial clearance, and survival were determined. Expression of PD-1 on T cells was upregulated in mice after hip fracture and surgery compared to sham controls. Administration of anti-PD-1 antibody prevented T lymphocyte apoptosis, increased IFN-γ production in splenocytes, and decreased systemic inflammation. Antibody blockade of PD-1 significantly decreased susceptibility to bacteria and improved survival rates of aged mice after hip fracture and surgery followed by the induction of Pseudomonas aeruginosa pneumonia. This study showed that hip fracture and surgical trauma cause significant increases in PD-1 expression in aged mice. Antibody blockade of PD-1 partially reverses T cell apoptosis, decreases the systemic inflammatory response and susceptibility to bacteria, and reduces mortality.

• Albumin
• CRP
• Cytokines
• PCT
• Posttraumatic osteomyelitis
• T regulatory cells CD4+CD25+
• Tibial fracture

Trauma is known to lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), which is often a cause of late deaths after injury. SIRS and MODS have been objectively measured using scoring systems. This prospective observational study was carried out in a tertiary care hospital in India to evaluate SIRS and MODS following trauma in terms of their incidence, the associated risk factors and the effect on the outcome.

All adult patients with major life- and limb-threatening trauma were included. Patients who died within 24 h, those with severe head injury, known comorbidity, immunocompromised state, on immunosuppressants or pregnancy were excluded. SIRS and MODS scores were recorded after initial management (baseline score), on days 3 and 6 of admission. SIRS was defined as SIRS score of ≥2 and MODS was defined as MODS score of ≥1.

Two hundred patients were enrolled. SIRS was noted in 156 patients (78%). MODS was noted in 145 (72.5%) patients. Overall mortality was 39 (19.5%). Both SIRS and MODS scores were significantly associated with age >60 yr, blunt injury, (lower) revised trauma score hypotension on admission and (higher) injury severity score, but not with gender, pre-hospital time or operative treatment.

Both SIRS and MODS scores were associated with longer Intensive Care Unit (ICU) stay, more ICU interventions and higher mortality. Incidence of MODS was significantly higher in patients with SIRS. Both scores showed rising trend with time in non-survivors and a decreasing trend in survivors. The serial assessment of scores can help prognosticate outcome and also allocate appropriate critical care resources to patients with rising scores.

Trauma is one of the leading causes of death and disability in the world. Multiple trauma or isolated traumatic brain injury are both indicative of human tissue damage. In the early phase after trauma, damage-associated molecular patterns (DAMPs) are released and give rise to sterile systemic inflammatory response syndrome (SIRS) and organ failure. Later, protracted inflammation following sepsis will favor hospital-acquired infection and will worsen patient’s outcome through immunosuppression. Throughout medical care or surgical procedures, severe trauma patients will be subjected to endogenous or exogenous DAMPs. In this review, we summarize the current knowledge regarding DAMP-mediated SIRS or immunosuppression and the clinical consequences in terms of organ failure and infections.

• critical care
• damage-associated molecular pattern
• hospital-acquired infection
• posttraumatic immunosuppression
• remote organ dysfunction
• transfusion

• Injury
• mortality
• predicting factors
• trauma

Systemic inflammatory response syndrome (SIRS) may be related to poor outcomes after intracerebral hemorrhage (ICH).

The Ethnic/Racial Variations of Intracerebral Hemorrhage study is an observational study of ICH in whites, blacks, and Hispanics throughout the United Sates. SIRS was defined by standard criteria as 2 or more of the following on admission: (1) body temperature <36°C or >38°C, (2) heart rate >90 beats per minute, (3) respiratory rate >20 breaths per minute, or (4) white blood cell count <4,000/mm³ or >12,000/mm³. The relationship among SIRS, infection, and poor outcome (modified Rankin Scale [mRS] 3–6) at discharge and 3 months was assessed.

Of 2,441 patients included, 343 (14%) met SIRS criteria at admission. Patients with SIRS were younger (58.2 vs 62.7 years; p < 0.0001) and more likely to have intraventricular hemorrhage (IVH; 53.6% vs 36.7%; p < 0.0001), higher admission hematoma volume (25.4 vs 17.5 mL; p < 0.0001), and lower admission Glasgow Coma Scale (GCS; 10.7 vs 13.1; p < 0.0001). SIRS on admission was significantly related to infections during hospitalization (adjusted odds ratio [OR] 1.36, 95% confidence interval [CI] 1.04–1.78). In unadjusted analyses, SIRS was associated with poor outcomes at discharge (OR 1.96, 95% CI 1.42–2.70) and 3 months (OR 1.75, 95% CI 1.35–2.33) after ICH. In analyses adjusted for infection, age, IVH, hematoma location, admission GCS, and premorbid mRS, SIRS was no longer associated with poor outcomes.

SIRS on admission is associated with ICH score on admission and infection, but it was not an independent predictor of poor functional outcomes after ICH.

• canine
• hit by car
• motor
• trauma
• vehicle
• vehicular

• Burns
• Cohort
• Infections
• Long-term health
• Population-based

• Adolescent
• Adult
• Burns/epidemiology
• Case-Control Studies
• Child
• Female
• Gastroenteritis/epidemiology
• Gastroenteritis/mortality
• Hospitalization/statistics & numerical data
• Humans
• Incidence
• Infections/epidemiology
• Infections/mortality
• Information Storage and Retrieval
• Longitudinal Studies
• Male
• Middle Aged
• Multivariate Analysis
• Proportional Hazards Models
• Respiratory Tract Infections/epidemiology
• Respiratory Tract Infections/mortality
• Retrospective Studies
• Skin Diseases, Infectious/epidemiology
• Skin Diseases, Infectious/mortality
• Soft Tissue Infections/epidemiology
• Soft Tissue Infections/mortality
• Western Australia
• Young Adult

Burn injury initiates an acute inflammatory response that subsequently drives wound repair. However, acute disruption to the immune response is also common, leading to susceptibility to sepsis and increased morbidity and mortality. Despite increased understanding of the impact of burn injury on the immune system in the acute phase, little is known about long-term consequences of burn injury on immune function. This study was established to determine whether burn injury has long-term clinical impacts on patients’ immune responses.

Using a population-based retrospective longitudinal study and linked hospital morbidity and death data from Western Australia, comparative rates of hospitalisation for respiratory infections in burn patients and a non-injured comparator cohort were assessed. In addition, a mouse model of non-severe burn injury was also used in which viral respiratory infection was induced at 4 weeks post-injury using a mouse modified version of the Influenza A virus (H3NN; A/mem/71-a).

The burn injured cohort contained 14893 adult patients from 1980–2012 after removal of those patients with evidence of smoke inhalation or injury to the respiratory tract. During the study follow-up study a total of 2,884 and 2,625 respiratory infection hospital admissions for the burn and uninjured cohorts, respectively, were identified. After adjusting for covariates, the burn cohort experienced significantly elevated admission rates for influenza and viral pneumonia (IRR, 95%CI: 1.73, 1.27–2.36), bacterial pneumonia (IRR, 95%CI: 2.05, 1.85–2.27) and for other types of upper and lower respiratory infections (IRR, 95% CI: 2.38, 2.09–2.71). In the mouse study an increased viral titre was observed after burn injury, accompanied by a reduced CD8 response and increased NK and NKT cells in the draining lymph nodes. This data suggests burn patients are at long-term increased risk of infection due to sustained modulation of the immune response.

Major pulmonary disorders may occur after brain injuries as ventilator-associated pneumonia, acute respiratory distress syndrome or neurogenic pulmonary edema. They are key points for the management of brain-injured patients because respiratory failure and mechanical ventilation seem to be a risk factor for increased mortality, poor neurological outcome and longer intensive care unit or hospital length of stay. Brain and lung strongly interact via complex pathways from the brain to the lung but also from the lung to the brain. Several hypotheses have been proposed with a particular interest for the recently described “double hit” model. Ventilator setting in brain-injured patients with lung injuries has been poorly studied and intensivists are often fearful to use some parts of protective ventilation in patients with brain injury. This review aims to describe the epidemiology and pathophysiology of lung injuries in brain-injured patients, but also the impact of different modalities of mechanical ventilation on the brain in the context of acute brain injury.

• Brain-lung crosstalk
• Brain injury
• Lung injury
• Protective ventilation
• Double hit model

• CARS
• MODS
• PICS
• SIRS
• innate immune response
• sepsis

• Definition
• Polytrauma

• CARS
• SIRS
• injury
• macrophage
• regulatory T cells (Tregs)

• Anaesthesiology
• Anesthésiologie
• Choc hémorragique
• Cortico-surrenal
• Cortico-surrénale
• Etomidate
• Haemorrhagic shock
• Hydrocortisone
• Immunity
• Immunité
• Immunosuppression
• Ketamine
• Kétamine
• Propofol
• Resuscitation
• Réanimation
• Trauma
• Étomidate

• Abbreviated Injury Scale
• Adult
• Female
• Hospital Mortality
• Humans
• Intensive Care Units
• Male
• Middle Aged
• Multiple Trauma/classification
• Multiple Trauma/diagnosis
• Prognosis
• Prospective Studies
• Systemic Inflammatory Response Syndrome/classification
• Systemic Inflammatory Response Syndrome/diagnosis
• Trauma Centers
• Traumatology