Combined anatomic and physiologic scoring systems for predicting in-hospital mortality in ICU patients with severe trauma: A multicenter observational cohort study

Objective: To evaluate the ability of new injury severity score (NISS), acute physiology and chronic health evaluation II (APACHE II), Glasgow coma scale (GCS), a combination of NISS and GCS, a combination of APACHE II and GCS, a combination of NISS and APACHE II to predict all-cause mortality of patients with severe trauma in mainland China. Methods: This was a multicenter observational cohort study conducted in the ICU of the Chonggang General Hospital, Daping Hospital of the Army Medical University and Affiliated Hospital of Zunyi Medical College from January 2012 to August 2016. The score of NISS, APACHE II, GCS, a combination of NISS and GCS, a combination of APACHE II and GCS, a combination of NISS and APACHE II were calculated based on data from the first 24 hours of ICU admission. Data were processed with Student's t-test, chi-square test, and receiver operating characteristic (ROC) curve of six scoring systems. Calibration was assessed with the Hosmer-Lemeshow test. The primary endpoint was death from any cause during ICU stay. Results: A total of 852 and 238 patients with severe trauma were assigned to the derivation group and validation group, respectively. Area under the ROC curve (AUC) was 0.826 [95% confidence interval (CI)=0.794-0.855)] for NISS, 0.802 (95% CI=0.768-0.832) for APACHE II, 0.808 (95% CI=0.774-0.838) for NGCS, 0.859 (95% CI=0.829 -0.886) for NISS+NGCS, 0.864 (95% CI=0.835-0.890) for APACHE II +NGCS, 0.896 (95% CI=0.869-0.929) for NISS+APACHE II in the derivation cohort. Similarly, the score of NISS+APACHE II was also better than the other five scores in the validation cohort (AUC=0.782; 95% CI=0.725-0.833) and had a good calibration (P=0.41). Conclusions: Taking into account anatomical and physiological parameters completely, the combination of NISS and APACHE II performs better than NISS, APACHE II, NGCS, NISS+NGCS, APACHE II +NGCS for predicting mortality in ICU severe trauma patients. It is needful to develop models that contain various types of accessible predictors (demographic variables, injury cause/mechanism, physiological and anatomical variables, etc.) as comprehensive as possible.

Exogenous agmatine inhibits lipopolysaccharide-induced activation and dysfunction of human umbilical vein endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate whether exogenous agmatine inhibits lipopolysaccharide (LPS)-induced activation and dysfunction of human umbilical vein endothelial cells (HUVECs) by modulating nuclear factor-κB (NF-κB) and MAPK signal pathways and the production of reactive oxygen species (ROS).</p><p><b>METHODS</b>Cultured HUVECs were treated with agmatine at the optimized concentration of 1.0 mmolγL, LPS (10 µgγmL), and LPS + agmatine, with or without pretreatment with the inhibitors of NF-κB (PDTC), p38 (SB203580), and ERK (PD98059) for 1 h. The levels of soluble vascular cell adhesion molecule 1 (VCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and monocyte chemoattractant protein 1 (MCP-1) in the supernatant were determined using ELISA, and their mRNA expressions, along with heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO-1), were assessed using real-time PCR. ROS production in the cells was determined using 2, 7-dichlorofluoresce in diacetate (DCFH-DA) as the fluorescence probe. The protein expressions of VCAM-1, ICAM-1, p65, phospho-p65 (p-p65), IκBα, p-IκBα, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected using Western blotting.</p><p><b>RESULTS</b>LPS stimulation for 6 and 24 h significantly increased the levels of sVCAM-1, sICAM-1, sE-selectin and MCP-1 in the supernatant, intracellular ROS production, and the mRNA expressions of these molecules (P<0.05). Intervention with 1 mmolγL agmatine, similar with pretreatment with p38, ERK and NF-κB inhibitors, obviously inhibited such effects of LPS in HUVECs (P<0.05). Agmatine significantly up-regulated the mRNA expression of HO-1 (P<0.05), inhibited LPS-induced phosphorylation of p38, ERK, nuclear p65 and cytoplasmic IκBα, and up-regulated the protein expression of cytoplasmic IκBα.</p><p><b>CONCLUSION</b>Agmatine inhibits LPS-induced activation and dysfunction of HUVECs by modulating NF-κB and MAPK signal pathways to down-regulate the expressions of adhesion molecules and chemokines and by up-regulating the expression of HO-1 to reduce ROS production.</p>

Role of speckle tracking imaging in the assessment of myocardial regional ventricular function in experimental blunt cardiac injury / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>To evaluate the usefulness and information collecting ability of speckle tracking imaging techniques in the assessment of myocardial regional ventricular contractility in a rabbit model with blunt cardiac injury.</p><p><b>METHODS</b>Fifteen healthy New Zealand rabbits weighing (2.70 ±0.28) kg were anesthetized (3% pentobarbital sodium/i.v) and impacted using the BIM-II biological impact machine to induce myocardial contusion (MC). Hemodynamic parameters, such as heart rate, systolic pressure, mean arterial pressure, diastolic pressure and central venous pressure, were determined before and after MC. Further, parameters reflecting left ventricular functions, such as left ventricular end systolic pressure, left ventricular end diastolic pressure, isovolumic pressure (IP) and the maximal increasing/decreasing rate of left intraventricular pressure (±dp/dtmax), were also determined before and after MC. Left ventricular functions were determined either by two dimensional transthoracic echocardiography or by speckle tracking imaging for segmental abnormal ventricular wall motions.</p><p><b>RESULTS</b>Heart rate, systolic pressure, diastolic pressure and mean arterial pressure decreased significantly but transiently, while central venous pressure markedly increased after MC. In contrast to significant changes in diastolic functions, there was no significant change in cardiac systolic functions after MC. The speckle tracking imaging demonstrated that strain values of different myocardial segment significantly decreased post impact, and that of the ventricular segment decreased from segment to segment.</p><p><b>CONCLUSION</b>Speckle tracking imaging is useful and informative to assess myocardial regional dysfunctions post MC.</p>

Effect of sirolimus on capacity of splenic dendritic cells from traumatized mice in inducing T cell responses ex vivo / 中华烧伤杂志

<p><b>OBJECTIVE</b>To study the ex vivo effect of sirolimus on capacity of splenic dendritic cells (DC) from traumatized mice in inducing T cell responses.</p><p><b>METHODS</b>Twenty-four BALB/c mice were divided into control group and trauma group according to the random number table, with 12 mice in each group. Mice in trauma group were bled followed by closed femur fracture after anaesthesia, while mice in control group were only anaesthetized without injury. Twenty-four hours later DC were isolated from spleens and divided into 4 subgroups: sirolimus devoid control (trauma) groups [consisted of cells from control (trauma) groups, without sirolimus treatment] and sirolimus treated control (trauma) groups [consisted of cells from control (trauma) groups, treated with 10 microg/L sirolimus for 6 hours]. Then their autophagic activity, DC-induced mixed lymphocyte reaction (MLR) were measured and recorded as fluorescence intensity (FI) value and absorbance value respectively. The expression of major histocompatibility complex class (MHC) II and costimulatory molecules CD40, CD80, and CD86 on DC surface were measured with flow cytometry. IL-12p40, IL-12p70 and IL-10 levels in lipopolysaccharide-stimulated DC supernatants were determined by ELISA. Data were processed with one-way analysis of variance.</p><p><b>RESULTS</b>(1) Compared with those of sirolimus devoid control group (FI value = 22 +/- 6), DC autophagic activity (FI value = 13 +/- 2) and DC-induced MLR in mice from sirolimus devoid trauma group were significantly weakened (F = 212.836, P < 0.05). Compared with those of sirolimus devoid control (trauma) groups, DC autophagic activity in mice from sirolimus treated control (trauma) groups (FI = 45 +/- 8, 44 +/- 8 respectively) were significantly strengthened (F = 212.836, P < 0.05 or P < 0.01). MLR in mice from sirolimus treated trauma group was stronger than that from sirolimus devoid trauma group (with F value respectively 101.426, 86.533, P values all below 0.05). (2) Compared with those of sirolimus devoid control group [MHC II (85 +/- 6)%, CD40 (8 +/- 1)%], the expressions of MHCII [(60 +/- 9)%] and CD40 [(4 +/- 1)%] on DC surface from sirolimus devoid trauma group were significantly reduced (with F value respectively 37.918, 40.426, P values all below 0.05). The expression of MHCII from sirolimus treated trauma group [(78 +/- 7)%] was higher than that from sirolimus devoid trauma group (F = 37.918, P < 0.05). (3) IL-12p40, IL-12p70 secretion by DC from sirolimus devoid trauma group [(120 +/- 13), (10 +/- 3) pg/mL] were significantly reduced as compared with those from sirolimus devoid control group [(200 +/- 25), (20 +/- 6) pg/mL, with F value respectively 218.646, 310.253, P values all below 0.05]. Compared with those from sirolimus devoid control (trauma) groups, IL-12p40 [(560 +/- 34), (540 +/- 29) pg/mL], IL-12p70 [(55 +/- 8), (60 +/- 11) pg/mL] secretion by DC from sirolimus treated control (trauma) groups were obviously enhanced (with F value respectively 218.646, 310.253, P values all below 0.01), while IL-10 secretion levels were significantly decreased (F = 246.108, P < 0.01).</p><p><b>CONCLUSIONS</b>Sirolimus can partially ameliorate DC functions ex vivo in traumatized mice, and further enhance the capacity of DC in inducing T cell responses.</p>

Circulating fibrocytes: a potent cell population in antigen-presenting and wound healing / 中华创伤杂志(英文版)

Fibrocytes are bone marrow-derived mesenchymal progenitors that co-express hematopoietic cell antigens and markers of monocytic lineage as well as fibroblast products. During wound healing, fibrocytes have been found to possess the ability of antigen-presentation to naive T cells in the inflammatory phase. Moreover, they can promote the endothelial cell proliferation, migration and angiogenesis by secreting several proteins. Fibrocytes can further differentiate into mature mesenchymocyte lineage, such as fibroblasts, myofibroblasts and adipocytes, and they may represent the systemic source of myofibroblasts that exert a contractile force required to close tissue wounds. A deep understanding of the mechanism involved in fibrocyte migration and differentiation may lead to the development of a novel theory of normal physiology and pathology.

Stimulating effect of sera from severe trauma patients on NF-kappaB activity in macrophage and its relationship with patients prognosis / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the stimulating effect of sera from severe multiple trauma patients within 24 h post trauma on nuclear factor-kappaB (NF-kappaB) activity in macrophage and their relationship with patients prognosis.</p><p><b>METHODS</b>Peripheral blood of 47 patients with multiple traumas with injury severity score (ISS) > or = 16 and 24 healthy volunteers were obtained, and sera samples were isolated. And 24 h after transfection of the recombinant NF-kappaB plasmid containing luciferase reporter gene into the mouse macrophage line (RAW 264.7), the cells were stimulated by sera from different patients for 6 h, then stimulating effect of sera on NF-kappaB was assessed by luciferase activity. The concentrations of interleukin-1 beta, tumor necrosis factor alpha, interleukin-10, interleukin-1 receptor antagonist, and soluble tumor necrosis factor receptor I were detected with ELISA kits.</p><p><b>RESULTS</b>The stimulating activity of sera from trauma patients on NF-kappaB was increased significantly, and it was higher in MODS group, non-survivor group than that in non-MODS, survivor group respectively. The level of activity was correlated positively with APACHE II score, while it did not have relationship to the cytokine or endogenous antagonist levels. The area under the receiver operating characteristic curve (ROC) of NF-kappaB activity for predicting MODS and mortality was significantly higher than that of APACHE II score.</p><p><b>CONCLUSION</b>Early measurement of NF-kappaB stimulating activity of sera from severe multiple trauma patients may have the value to predict occurrence of MODS and mortality.</p>

Reduced capacity of dendritic cells from trauma-hemorrhage mice in initiating delayed-type hypersensitivity to fluorescein isothiocyanate / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the role of dendritic cells (DCs) in initiating delayed-type hypersensitivity (DTH) to fluorescein isothiocyanate (FITC) after trauma-hemorrhage in mice.</p><p><b>METHODS</b>Inbred BALB/c mice (6-8 weeks old, male) were epicutaneously sensitized with FITC 12 hours, 1 day, 2 days, 4 days and 7 days after closed bilateral femur fractures combined with hemorrhage. And 5 days after sensitization, DTH was evaluated by ear swelling after a challenge of FITC. Draining lymph node cells were examined for the percentages of FITC-positive cells, cluster of differentiation (CD)11c-positive cells and major histocompatibility complex II (MHC II)-positive cells by means of flow cytometry. In vitro proliferative responses of syngeneic lymphocytes and in vivo passive transfer of DTH to naive recipients induced by isolated DCs from the draining lymph nodes were determined.</p><p><b>RESULTS</b>The time of DTH to FITC decreased more significantly in the mice with trauma-hemorrhage (12 hours to 4 days) than in the mice with sham injury. After sensitization, the relative percentages of FITC+ cells, FITC+/CD11c+ cells and FITC+/CD11c+/MHC II+ cells from the draining lymph nodes were all significantly reduced following injury. And the capacity of DCs from the draining lymph nodes in stimulating proliferative responses of lymphocytes and transferring DTH to naive recipients were also inhibited after injury.</p><p><b>CONCLUSIONS</b>Trauma-hemorrhage induces repressive DTH in mice, which may be attributed, at least partially, to the reduced trafficking of DCs into the draining lymph nodes and insufficient maturation during DC migration.</p>

Roles of dendritic cells in mediating decreased delayed type hypersensitivity responses after trauma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effects of hemorrhage combined with closed fracture on delayed type hypersensitivity (DTH) responses in mice and to explore the relevant mechanisms.</p><p><b>METHODS</b>DTH responses were induced with 2, 4-dinitro-1-fluorobenzene (DNFB) or fluorescein isothiocyanate (FITC) skin painting after injury, and single cell suspensions from pooled inguinal lymph nodes were analyzed by flow cytometry for FITC+ cells and dendritic cells (DC). The ability of cells from pooled inguinal lymph nodes was tested 24 hours after skin painting with DNFB in transferring sensitization for DTH to DNFB.</p><p><b>RESULTS</b>The DTH responses after injury decreased significantly compared with that of sham-injured mice (P<0.01). Flow cytometry showed that FITC+ cells, FITC+/CD11c+ cells, and FITC+/CD11c+ / major histocompatibility complex II+ cells were all significantly decreased after trauma (P<0.01). The ability of cells to transfer sensitization for DTH to DNFB also declined (P<0.01).</p><p><b>CONCLUSION</b>Hemorrhage combined with closed fracture decreases the DTH responses in mice, which may be attributed to the reduced antigen-presenting capacity of DC in the injured mice.</p>

Clinical significance of scoring system for systemic inflammatory response syndrome / 中华创伤杂志(英文版)

The concepts of systemic inflammatory response syndrome (SIRS) and scoring system were defined by the journal of Bone in 1992. SIRS was described as occurrence of two or more clinical criteria in four ones (fever or hypothermia, tachypnea, tachycardia, and leukocytosis). An early diagnosis and estimation of systemic inflammation in patients is helpful for treatment selection. This paper reviews the application of SIRS scoring system, which has been extensively validated for large groups of critical care patients with severe injury and critical surgical diseases. Recent studies have documented SIRS score as a significant predictive parameter of adverse outcome in critical care patients. Furthermore, some studies also give us a suggestion on how to reduce the overload systemic response.

Effects of extracellular signal-regulated kinase inhibition by AG126 on tissue tumor necrosis factor-alpha expression and multiple organ dysfunction in rats with postburn Staphylococcus aureus sepsis / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of extracellular signal-regulated kinase (ERKs) inhibition by AG126 on tissue tumor necrosis factor-alpha (TNF-alpha) expression and multiple organ dysfunction in rats with postburn Staphylococcus aureus sepsis and its potential signal regulating mechanism.</p><p><b>METHODS</b>To reproduce postburn sepsis model, male Wistar rats were inflicated with 20% total body surface area third-degree scald followed by Staphylococcus aureus challenge. 34 rats were randomly divided into four groups as follows: normal control group (n = 6), scald control group (n = 6), postburn sepsis group (n = 12), and AG126 treatment group (n = 10). Tissue samples from the liver, kidneys and lungs were collected to determine phosphorylated ERKs by Western blot analysis, and TNF-alpha mRNA expression as well as its protein levels.</p><p><b>RESULTS</b>It was revealed that phosphorylated ERKs in the liver, lungs, and kidneys from postburn septic animals were up-regulated rapidly at 0.5 - 2.0 hours, being 1.94-fold (P < 0.05), 2.86-fold (P < 0.01), and 1.41-fold at 2.0 hours compared to normal controls, respectively. Treatment with AG126 could significantly reduce phosphorylated ERKs in lung tissue by 70.6% (P < 0.01) at 2.0 hours postburn sepsis, and almost completely inhibited ERKs activation in the liver and kidneys at various time points. Meanwhile, both TNF-alpha mRNA and protein expressions in the liver, lungs, and kidneys were significantly decreased in AG126-treated group following septic challenge (P < 0.05 or 0.01). In addition, 2.0 hours after Staphylococcus aureus infection, treatment with AG126 markedly improved hepatic and renal function parameters, including serum ALT, AST, Cr, as well as BUN levels (P < 0.05 or 0.01), together with significant decrease in pulmonary myeloperoxidase activity, compared to those without AG126 treatment.</p><p><b>CONCLUSION</b>These data suggested that ERKs signal transduction might be involved in the pathogenesis of systemic inflammatory response and multiple organ dysfunction in postburn gram-positive bacterial sepsis. Early treatment with AG126 could significantly down-regulate TNF-alpha mRNA expression as well as protein levels in vital organs and attenuate multiple organ dysfunction induced by scald injury combined with Staphylococcus aureus challenge.</p>

Effect of decoy-oligodeoxynucleotides on expression of inflammation mediators in pMPhi cells from rats / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the effect of decoy-oligodeoxynucleotides (decoy-ODNs) in dumbbell shape with the oligodeoxynucleotide sequence similar to nuclear factor kappa B (NF-kappaB) cis-elements on expression of inflammation mediators in pMPhi cells from rats.</p><p><b>METHODS</b>With carriers of cationic liposomes, decoy-ODNs were transfected into pMPhi cells of rats. Then the inhibiting effects of the decoy-ODNs on tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and IL-10 were analyzed.</p><p><b>RESULTS</b>Decoy-ODNs could decrease the expression of TNFalpha and IL-6 in dose-dependent fashion but had weaker inhibiting effect on IL-10.</p><p><b>CONCLUSIONS</b>Decoy-ODNs targeting NF-kappaB can decrease the expression of inflammatory mediators in pMPhi cells from rats.</p>

Serum levels of HMGB-1 and organ dysfunction and death in patients with multiple trauma / 中华创伤杂志

Objective To study the changes of serum level of high mobility group box-1(HMGB- 1)in patients with multiple trauma in order to forecast organ dysfunction(OD)and deaths.Methods The optical densities of HMGB-1 in serum of 35 patients with multiple trauma were determined on 1st,3rd, and 7th days after trauma,and the incidence of organ dysfunction and deaths were evaluated,then analyzed statistically to learn the relation between the serum levels of HMGB-1 and deaths with an attempt of predic- ting the incident of organ dysfunction and deaths.Results (1)As OD was concerned,there was a statis- tically significant difference in optical density of HMGB-1 on 1st and 3rd days between the two groups of multiple injury patients(t=4.411,P