• Elderly hip fractures
• Mortality
• NLR
• SII
• SIRI
• Walking independence

• 82072447 National Natural Science Foundation of China
• 82272578 National Natural Science Foundation of China
• H2023206519 Yanzhao Young Scientist Project of Hebei Natural Science Foundation

• Nerve block
• Pain management
• Trauma centers

• Humans
• Nerve Block/methods
• Pain Management/methods
• Ultrasonography, Interventional
• Trauma Centers
• Supine Position
• Extremities/injuries
• Extremities/innervation
• Patient Positioning

• Humans
• Nomograms
• Retrospective Studies
• Intraabdominal Infections/diagnosis
• Intraabdominal Infections/etiology
• Abdominal Injuries/complications
• Abdominal Injuries/diagnosis
• Abdominal Injuries/surgery
• Wounds, Nonpenetrating/complications
• Wounds, Nonpenetrating/diagnosis
• Wounds, Nonpenetrating/surgery

• Compensatory anti-inflammatory response syndrome (CARS)
• Cytokines
• Immunosuppression
• SARS-CoV-2
• Systemic inflammatory response syndrome (SIRS)
• Trauma

• Multiple trauma
• Neutropenia
• Neutrophils
• Survival
• Trauma Severity Indices
• Wounds and Injuries

• endotheliopathy
• extracellular vesicles
• shock
• trauma

• CD11b
• CD68
• SIRPα
• Siglec-F
• innate immune system
• neutrophil phenotype
• post-traumatic sepsis

• Japan Society for the Promotion of Science

• hematology - platelets
• hemostasis
• platelet transfusion

• Blood Platelet Disorders/etiology
• Blood Platelet Disorders/therapy
• Blood Platelets
• Hemostasis
• Humans
• Platelet Transfusion

• R01 HL121212 NHLBI NIH HHS
• R01 HL129179 NHLBI NIH HHS

• immunology
• innate immune cells
• sterile injury

Hematoma expansion can be related to increased mortality and poor clinical outcomes in patients with intracerebral hemorrhage (ICH). So, early identification and prevention of hematoma expansion can be considered as an important therapeutic aim. This study aimed to evaluate the hypothesis that the neutrophil to lymphocyte ratio (NLR) is associated with hematoma expansion in ICH patients.

We retrospectively evaluated the clinical data of a total of 221 patients with ICH who were treated in our department between April 2018 and April 2021. The demographic, clinical, radiological, and laboratory test data including the NLR upon admission were investigated. A binary logistic regression analysis was used to assess the independent associations between different variables and hematoma expansion.

A total of 221 patients with ICH were included. There were 122 (55.2%) males and 99 (44.8%) females. The mean age (years) at admission was 66.43 ± 8.28.

The hematoma expansion occurred in 57 (25.8%) cases. The results of the multivariate analysis showed that hematoma volume at baseline (OR, 3.12; 95% CI 1.78–5.02; P < 0.001), admission systolic blood pressure (OR, 2.87; 95% CI 1.79–4.34; P = 0.013), Glasgow Coma Scale (GCS) (OR, 1.94; 95% CI 1.45–2.93; P = 0.020), and NLR (OR, 1.74; 95% CI 1.16–2.60; P = 0.032) were correlated with hematoma expansion in these patients.

Our findings suggest that NLR can be a predictor of hematoma expansion in patients with ICH. This cost-effective and easily available biomarker could be used to early prediction of hematoma expansion in these patients.

• Glasgow Coma Scale
• Hematoma expansion
• Intracerebral hemorrhage
• Neutrophil-to-lymphocyte ratio

• Glasgow outcome scale
• Neutrophil-to-lymphocyte ratio
• Prognosis
• Traumatic brain injury

• COVID-19
• T cell
• cytokine
• prognosis
• trauma

• COVID-19/complications
• COVID-19/diagnosis
• COVID-19/immunology
• Cytokines/metabolism
• Humans
• Inflammation Mediators/metabolism
• Prognosis
• SARS-CoV-2/physiology
• T-Lymphocyte Subsets/immunology
• Th1 Cells/immunology
• Wounds and Injuries/complications
• Wounds and Injuries/diagnosis
• Wounds and Injuries/immunology

• Shahid Beheshti University of Medical Sciences

• ALI (acute lung injury)
• ARDS (acute respiratory distress syndrome)
• COVID-19
• DAMPs (damage-associated molecular patterns)
• NETs (neutrophil extracellular traps)
• Thromboinflammation
• infections and sepsis
• sterile inflammatory response

• Acute Lung Injury/pathology
• Extracellular Traps/metabolism
• Humans
• Inflammation/metabolism
• Neutrophils/metabolism
• Thrombosis/metabolism

• P01 AI116501 NIAID NIH HHS
• R01 HL094601 NHLBI NIH HHS
• R01 HL157407 NHLBI NIH HHS

• COVID-19
• biomarkers
• critical illness
• immunologic
• immunosuppression
• immunotherapy
• monitoring
• sepsis
• therapy
• trauma

Thoracic traumas with extra-thoracic injuries result in an immediate, complex host response. The immune response requires tight regulation and can be influenced by additional risk factors such as obesity, which is considered a state of chronic inflammation. Utilizing high-dimensional mass and regular flow cytometry, we define key signatures of obesity-related alterations of the immune system during the response to the trauma. In this context, we report a modification in important components of the splenic response to the inflammatory reflex in obese mice. Furthermore, during the response to trauma, obese mice exhibit a prolonged increase of neutrophils and an early accumulation of inflammation associated CCR2⁺CD62L⁺Ly6C^hi monocytes in the blood, contributing to a persistent inflammatory phase. Moreover, these mice exhibit differences in migration patterns of monocytes to the traumatized lung, resulting in decreased numbers of regenerative macrophages and an impaired M1/M2 switch in traumatized lungs. The findings presented in this study reveal an attenuation of the inflammatory reflex in obese mice, as well as a disturbance of the monocytic compartment contributing to a prolonged inflammation phase resulting in fewer phenotypically regenerative macrophages in the lung of obese mice.

• immune response
• inflammatory reflex
• mass cytometry (CyTOF)
• monocyte compartment
• obesity
• severe trauma

• Animals
• Caspase 1
• Cognitive Dysfunction/drug therapy
• Cognitive Dysfunction/etiology
• Humans
• Microglia
• NLR Family, Pyrin Domain-Containing 3 Protein
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid

Patients with prolonged and intense neutrophilia after spinal surgery are at high risk of developing surgical site infection (SSI). To date, there is no standard method for the objective assessment of the intensity and duration of neutrophilia. Thus, this retrospective observational study aimed to test a new index (I-index), developed by combining the duration and intensity of neutrophilia, as a predictor of SSI.

I-index was calculated based on the postoperative neutrophil percentage. A total of 17 patients with SSI were enrolled as cases, and 51 patients without SSI were selected as controls. The groups were matched at a ratio of 1:3 by age, sex, and surgery type. The differences in the I-index were compared between the groups. Moreover, we checked the cumulative I-index (c-I-index), which we defined as the area under the neutrophil curve from postoperative day 1 until the first clinical manifestation of SSI in each case. Furthermore, a cutoff for SSI was defined using the receiver operating characteristic curve.

The median I-index-7, I-index-14, and c-I-index were significantly higher in the SSI group than those in the control group. For a cutoff point of 42.1 of the I-index-7, the sensitivity and specificity were 0.706 and 0.882, respectively. For a cutoff point of 45.95 of the I-index-14, the sensitivity and specificity were 0.824 and 0.804, respectively. For a cutoff point of 45.95 of the c-I-index, the sensitivity and specificity were 0.824 and 0.804, respectively.

We devised a new indicator of infection, i.e., the I-Index and c-I-index, and confirmed its usefulness in predicting SSI.

• I-index
• Neutrophil curve
• Predictor
• Receiver operating characteristic curve
• Spinal surgery
• Surgical site infection

Background: Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection, are divided into three different subsets according to their CD16/CD62L and CD16/CD14 expression, respectively. Their differential functions have not yet been clearly understood. Thus, we evaluated the phenotypic changes of neutrophil and monocyte subsets among their functionality regarding oxidative burst and the phagocytic capacity in severely traumatized patients. Methods: Peripheral blood was withdrawn from severely injured trauma patients (TP; n = 15, ISS ≥ 16) within the first 12 h post-trauma and from healthy volunteers (HV; n = 15) and stimulated with fMLP and PMA. CD16^dimCD62L^bright (immature), CD16^brightCD62L^bright (mature) and CD16^brightCD62L^dim (CD62L^low) neutrophil subsets and CD14^brightCD16⁻ (classical), CD14^brightCD16⁺ (intermediate) and CD14^dimCD16⁺ (non-classical) monocyte subsets of HV and TP were either directly analyzed by flow cytometry or the examined subsets of HV were sorted first by fluorescence-activated cell sorting and subsequently analyzed. Subset-specific generation of reactive oxygen species (ROS) and of E. coli bioparticle phagocytosis were evaluated. Results: In TP, the counts of immature neutrophils were significantly increased vs. HV. The numbers of mature and CD62L^dim neutrophils remained unchanged but the production of ROS was significantly enhanced in TP vs. HV and the stimulation with fMLP significantly increased the generation of ROS in the mature and CD62L^dim neutrophils of HV. The counts of phagocyting neutrophils did not change but the mean phagocytic capacity showed an increasing trend in TP. In TP, the monocytes shifted toward the intermediate phenotype, whereas the classical and non-classical monocytes became less abundant. ROS generation was significantly increased in all monocyte subsets in TP vs. HV and PMA stimulation significantly increased those level in both, HV and TP. However, the PMA-induced mean ROS generation was significantly lower in intermediate monocytes of TP vs. HV. Sorting of monocyte and neutrophil subsets revealed a significant increase of ROS and decrease of phagocytic capacity vs. whole blood analysis. Conclusions: Neutrophils and monocytes display a phenotypic shift following severe injury. The increased functional abnormalities of certain subsets may contribute to the dysbalanced immune response and attenuate the antimicrobial function and thus, may represent a potential therapeutic target. Further studies on isolated subsets are necessary for evaluation of their physiological role after severe traumatic injury.

• CD14
• CD16
• CD62L
• PMA
• fMLP
• phagocytosis
• reactive oxygen species
• traumatic injury

Immune dysfunction following major traumatic injury is complex and strongly associated with significant morbidity and mortality through the development of multiple organ dysfunction syndrome (MODS), persistent inflammation, immunosuppression, and catabolism syndrome and sepsis. Neutrophils are thought to be a pivotal mediator in the development of immune dysfunction.

To provide a review with a systematic approach of the recent literature describing neutrophil kinetics and functional changes after major trauma in humans and discuss hypotheses as to the mechanisms of the observed neutrophil dysfunction in this setting.

Medline, Embase and PubMed were searched on January 15, 2021. Papers were screened by two reviewers and those included had their reference list hand searched for additional papers of interest. Inclusion criteria were adults > 18 years old, with an injury severity score > 12 requiring admission to an intensive care unit. Papers that analysed major trauma patients as a subgroup were included.

Of 107 papers screened, 48 were included in the review. Data were heterogeneous and most studies had a moderate to significant risk of bias owing to their observational nature and small sample sizes. Key findings included a persistently elevated neutrophil count, stereotyped alterations in cell-surface markers of activation, and the elaboration of heterogeneous and immunosuppressive populations of cells in the circulation. Some of these changes correlate with clinical outcomes such as MODS and secondary infection. Neutrophil phenotype remains a promising avenue for the development of predictive markers for immune dysfunction.

Understanding of neutrophil phenotypes after traumatic injury is expanding. A greater emphasis on incorporating functional and clinically significant markers, greater uniformity in study design and assessment of extravasated neutrophils may facilitate risk stratification in patients affected by major trauma.

• Neutrophils
• Multiple trauma
• Immunophenotypes
• Inflammation
• Systemic inflammatory response syndrome
• Intensive care units

• Chronic diseases
• Dynamics
• Neutrophil memory

Organ damages following hemorrhagic shock (HS) have been partly attributed to an immunological dysfunction. The current challenge in the management of HS patients is to prevent organ injury-induced morbidity and mortality which currently has not etiological treatment available. Mesenchymal stromal cells (MSC) are used in clinical cell therapy for immunomodulation and tissue repair. In vitro priming is often used to improve the immunomodulation efficiency of MSC before administration.

Assess the effect of naive MSC (MSCn) or interleukin (IL)-1β primed (MSCp) treatment in a context of HS-induced organ injury.

Rats underwent fixed pressure HS and were treated with allogenic MSCn or MSCp. Liver and kidney injuries were evaluated 6h later by histological and biochemical analysis. Whole blood was collected to measure leukocytes phenotypes. Then, in vitro characterization of MSCn or MSCp was carried out.

Plasma creatinine, blood urea nitrogen, and cystatin C were decrease by MSCp infusion as well as kidney injury molecule (KIM)-1 on histological kidney sections. Transaminases, GGT, and liver histology were normalized by MSCp. Systemic cytokines (IL-1α, IL-6, and IL-10) as well as CD80, 86, and PD-1/PDL-1 axis were decreased by MSCp on monocytes and granulocytes. In vitro, MSCp showed higher level of secreted immunomodulatory molecules than MSCn.

An early administration of MSCp moderates HS-induced kidney and liver injury. IL-1β priming improves MSC efficiency by promoting their immunomodulatory activity. These data provide proof of concept that MSCp could be a therapeutic tool to prevent the appearance of organs injury following HS.

The online version contains supplementary material available at 10.1186/s13287-021-02505-4.

• Hemorrhagic shock
• IL-1β
• Immunomodulation
• Mesenchymal stromal cells
• Multiple organ dysfunction syndrome
• Priming

• dogs
• flow cytometry
• inflammation
• phagocyte
• phagocytosis
• respiratory burst

Severe burn injury causes local and systemic immune responses that can persist up to months, and can lead to systemic inflammatory response syndrome, organ damage and long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying mechanisms is essential. In this longitudinal study, we analyzed the temporal peripheral blood immune profile of 20 burn wound patients admitted to the intensive care by flow cytometry and secretome profiling, and compared this to data from 20 healthy subjects. The patient cohort showed signs of systemic inflammation and persistently high levels of pro-inflammatory soluble mediators, such as IL-6, IL-8, MCP-1, MIP-1β, and MIP-3α, were measured. Using both unsupervised and supervised flow cytometry techniques, we observed a continuous release of neutrophils and monocytes into the blood for at least 39 days. Increased numbers of immature neutrophils were present in peripheral blood in the first three weeks after injury (0.1–2.8 × 10⁶/ml after burn vs. 5 × 10³/ml in healthy controls). Total lymphocyte numbers did not increase, but numbers of effector T cells as well as regulatory T cells were increased from the second week onward. Within the CD4⁺ T cell population, elevated numbers of CCR4⁺CCR6^- and CCR4⁺CCR6⁺ cells were found. Altogether, these data reveal that severe burn injury induced a persistent innate inflammatory response, including a release of immature neutrophils, and shifts in the T cell composition toward an overall more pro-inflammatory phenotype, thereby continuing systemic inflammation and increasing the risk of secondary complications.

• burn injury
• flow cytometry
• immune response
• inflammation
• lymphocytes
• monocytes
• neutrophils
• systemic

Severe trauma is believed to disrupt the homeostasis of the immune system, and lead to dramatic changes in the circulating immune-cell count (ICC). The latter fluctuates widely over time. Knowledge about the relationship between these dramatic changes and dynamic fluctuations and the late prognosis of trauma patients is sparse. We investigated the relationship between the trajectory of alterations in the circulating ICC within 7 days in severe-trauma patients and subsequent sepsis and mortality.

A retrospective analysis of 917 patients with an Injury Severity Score ≥16 was undertaken. The absolute neutrophil, lymphocyte, and monocyte counts (ANC, ALC, and AMC, respectively) on days 1, 3, and 7 (D1, D3, and D7, respectively) after trauma, and whether sepsis or death occurred within 60 days, were recorded. As the disordered circulating ICCs fluctuated widely, their time-varying slopes (D3/D1 and D7/D3) were calculated. Patients were divided into “sepsis” and “non-sepsis” groups, as well as “alive” and “death” groups. Comparative studies were conducted between every two groups. Univariate and multivariate logistic regression analyses were used to identify variables related to the risk of sepsis and mortality. Receiver operating characteristic curves were plotted to assess the predictive value of various risk factors.

More severe trauma caused more pronounced increases in the ANC and slower recovery of the ALC within 7 days. The ALC (D3), ANC (D7), ALC (D3/D1), and ANC (D7/D3) were independent risk factors for sepsis. The ALC (D3), ALC (D7), AMC (D7), and ALC (D3/D1) were independent risk factors for mortality. A combination of the ALC (D3) and ALC (D3/D1) exerted a good predictive value for sepsis and death.

The trajectory of alterations in the circulating ICC in the early stage after trauma is related to subsequent sepsis and mortality.

• lymphocyte
• monocyte
• mortality
• neutrophil
• sepsis
• trauma

• Femur fracture
• Integrin
• Intramedullary nailing
• Isolated trauma
• Neutrophil
• Selectin

• Bedside
• Infections
• Intensive care
• Monitoring
• Neutrophils
• Point-of-care
• Trauma