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Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood–air barrier, blood–testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.

Objective To investigate nutritional treatment in the intensive care unit (ICU) of the mainland China. Methods A cross-sectional study was conducted in 116 ICUs of 118 mainland hospitals on April 26th, 2017. All patients of these ICUs were investigated at 0 o'clock on April 26th. Demographic and clinical parameters of those patients on April 25th (the investigation day) were recorded, including the dates of hospitalization, ICU admission and nutrition initiation and clinical outcome on 28 days after the investigation day. Results A total of 1953 patients were collected, including 631 females and 1306 males. The mean age was (64.1±19.3) years old (1950 cases). The means of Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHEⅡ) scores were (10.76±4.35)(1749 cases), (5.65±3.52)(1783 cases), (17.14±7.31)(1792 cases), respectively. The outcomes of 28 days after the investigation day were 1483 survivors (75.9%), 312 non-survivors (16.0%) and 158 cases (8.1%) being lost to follow-up. There were no significant differences between the males and the females in age, severity of disease and clinical outcomes of 28 days but in height and weight. There were 73.7%(1440 cases) of patients with normal or mildly injured gastrointestinal function, 10.8%(210 cases) with moderately or severely injured function, 1.7%(33 cases) with gastrointestinal failure and 13.2%(258 cases) without evaluation. To the investigation day, enteral nutrition (EN) had been initiated in 69.4%(1356 cases) of patients and parenteral nutrition (PN) in 36.4%(711 cases) of patients. There were 1720(88.1%) patients with EN administration on the investigation day. The proportion of patients with nausea, vomit/regurgitation, aspiration, abdominal pain, abdominal distention and diarrhea was 4.8%(93 cases), 5.4%(105 cases), 0.9%(17 cases), 8.7%(170 cases), 27.5%(538 cases) and 4.3%(84 cases) respectively, while that of patients using EN was 3.1%(40 cases), 4.25%(54 cases), 0.79%(10 cases), 4.41%(56 cases), 26.85%(341 cases) and 5.43%(69 cases) correspondingly. The proportion of cases starting EN within 24, 48 and 72 hours after ICU entry was 22.4%(437/1953), 38.6%(754/1953) and 46.6%(911/1953), respectively. The proportion of cases receiving ≥80% estimated energy target (=past body weight ×25 kcal/kg.d) within 3, 7 and 14 days after ICU entry was 12.9%(78/607), 18.7%(189/1010) and 23%(305/1325) respectively, while that of cases with EN was 9.9%(60/607), 15.0%(151/1010) and 18.6%(246/1325) correspondingly. Conclusions Nowadays, most of patients in the mainland ICUs receive nutrition therapy and the EN usage rate is much higher than the PN rate. However, the time of EN initiation and the target-reaching rate of energy are suboptimal and an individualized plan of nutrition therapy is still missing. Details of energy delivery still need to be improved. DOI: 10.11855/j.issn.0577-7402.2019.05.05

Background: Equipoise exists regarding the implementation of evidence-based guidelines for nutritional therapy in critical illness because some previous cluster-randomised controlled trials (cRCTs) demonstrate patient benefits whilst others do not. We aimed to resolve this issue by initiating an appropriately powered cRCT to assess whether active implementation of an evidence-based guideline for nutrition therapy in critical illness could reduce mortality. Methods: We did a multicentre, cluster-randomised, parallel-controlled trial in 97 intensive care units (ICUs) throughout China. We developed an up-to-date, evidence-based nutrition guideline. ICUs randomly allocated to implement the guideline formed a local "intervention team", which actively implemented the guideline using standardized educational materials. ICUs assigned to the control group remained unaware of the guideline. All ICUs enroled critically ill patients who were expected to stay longer than seven days. The primary outcome was all-cause mortality within 28 days of enrolment . Findings Between March, 2018 and July, 2019, we enrolled 1,373 patients at 48 guideline ICUs and 1,399 patients at 49 control ICUs. Implementation of the nutrition guideline resulted in significantly earlier enteral nutrition (EN) initiation (1.20 vs. 1.55 mean days to initiation of EN; difference -0.40 [95% CI, -0.71 to -0.09]; P=0.01) and delayed parenteral nutrition (PN) initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI, 0.44 to 1.67]; P=0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference -1.6% [95% CI -4.3% to 1.2%]; p=0.42) between study groups. Interpretation: Active implementation of an evidence-based guideline can change practice. Our active implementation strategy improved the provision of nutrition therapy to critically ill patients. However, in our cRCT, this improvement in care did not translate to a reduction in mortality. We did not identify any safety concerns associated with the active implementation of our evidence-based guideline for nutrition therapy. Trial Registration: The study was registered in the ISRCTN registry before enrolment commenced (No. ISRCTN12233792). Funding Statement: The study was funded by the Key Research and Development Program Foundation of Jiangsu Province of China (no. BE2015685) and Nutricia, Wuxi, China. Declaration of Interests: Dr. GSD reported receiving academic research grants related to nutrition in critical illness from the Australian National Health and Medical Research Council, Fresenius Kabi Deutschland GmbH and Baxter Healthcare Pty Ltd and speakers honoraria from Fresenius Kabi Deutschland GmbH, Baxter Healthcare Australia, Pty Ltd, Nestle Healthcare, Vevy, Switzerland and Nutricia Pharmaceutical (Wuxi) Co., Ltd. China. Dr. AvZ reports personal fees from Baxter, personal fees from Nestle, personal fees from Fresenius Kabi, grants and personal fees from Nutricia, grants from Cardinal Health grants from Mermaid grants from Lyric, outside the submitted work. Dr. WqL reported receiving speakers honoraria from Nutricia Pharmaceutical (Wuxi) Co., Ltd. China. No other disclosures were reported. Ethics Approval Statement: The study was approved by the local hospital ethics committees of all the participating ICUs. At each site, informed consent was obtained from the patients or their next of kin before enrolment.

Background There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. Methods This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. Results A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2–19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2–3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353–0.599; p

Traumatic brain injury-induced acute lung injury (TBI-ALI) is a serious complication after brain injury for which predictive factors are lacking. In this study, we found significantly elevated blood glutamate concentrations in patients with TBI or multiple peripheral trauma (MPT), and patients with more severe injuries showed higher blood glutamate concentrations and longer durations of elevated levels. Although the increase in amplitude was similar between the two groups, the duration was longer in the patients with TBI. There were no significant differences in blood glutamate concentrations in the patients with MPT with regard to ALI status, but the blood glutamate levels were significantly higher in the patients with TBI-ALI than in those without ALI. Moreover, compared to patients without ALI, patients with TBI showed a clearly enhanced inflammatory response that was closely correlated with the blood glutamate levels. The blood glutamate concentration was also found to be a risk factor (adjusted odds ratio, 2.229; 95% CI, 1.082–2.634) and was a better predictor of TBI-ALI than the Glasgow Coma Scale (GCS) score. These results indicated that dramatically increased blood glutamate concentrations were closely related to the occurrence of TBI-ALI and could be used as a predictive marker for “at-risk” patients.

Objectives To investigate the relationship between sepsis prevalence and disease types in intensive care units (ICUs), as well as the effect of knowledge of the health care workers about the sepsis guidelines on sepsis morbidity and mortality. Methods A one-day cross-sectional survey was conducted in five ICUs in the cities of Chongqing and Guizhou, China. The included patients were divided into three groups: the internal medicine group (Group A), surgery group (Group B), and trauma group (Group C). Sepsis was diagnosed by the 2012 Sepsis Guidelines, and the prevalence and 28-day mortality were statistically analyzed. The relationship between the knowledge of health care workers about sepsis and morbidity and mortality was analyzed. Results Among the enrolled 71 patients, the sepsis prevalence rate was 81.5%, 66.7%, and 87.0% in Groups A, B, and C, respectively. In total, the 28-day mortality rate was 36.4%, 42.9% and 20.0% in Groups A, B, and C, respectively, indicating no significant difference. The sepsis prevalence was 66.7%, 90.0%, 90.9%, 100.0% and 76.9% in the five ICUs. The average cognitive score of each hospital was 68.5 ± 15.4, 65.7 ± 16.7, 69.0 ± 23.3, 25.0 ± 8.4, and 61.4 ± 19.9 points in the five ICUs. Cognitive scores were not associated with prevalence of sepsis, but they were negatively related with sepsis mortality. Conclusions Sepsis prevalence and mortality are not associated with diseases types within ICUs, but the knowledge of sepsis of health care workers is associated with the prognosis of sepsis patients.

Objective To investigate the prevalence and risk factors of post-traumatic sepsis, and to evaluate the rationality of the 1992, 2001 and 2012 international sepsis definitions in diagnosing post-traumatic sepsis in a trauma intensive care unit (ICU) in China. Methods A one-day cross-sectional survey of trauma patients who met the inclusion criteria was conducted from 8:00 a.m., June 16, 2014 to 8:00 a.m., June 17, 2014 in the trauma ICU of Daping Hospital. The survey data included demographic information, clinical characteristics, pertinent scores (APACHE Ⅱ, SOFA, GCS, ISS) and injury mechanism. According to the definition of sepsis as depicted in the 1992, 2001, and 2012 "International Guideline of Sepsis", the patients were divided into A, B and C groups. The infection site, infection pathogens, and key medical treatment were recorded, the infection identified, and the 28day mortality recorded. A positive pathogen culture of respiratory and urinary tracts, blood, cerebrospinal fluid, and wound secretion was adopted as the diagnostic "gold standard" for septic infection. The diagnostic sensitivity and specificity of the three versions of the guidelines were statistically analyzed and the diagnostic feasibility of each definition was assessed. Results A total of 30 trauma patients were enrolled, twenty-three patients met the 1992 sepsis criteria, 22 met the 2001 criteria, and 20 met the 2012 criteria. The prevalence rates were 76.7%, 73.3%, and 66.7%, respectively, and there was no significant statistical difference. Four patients died within 28 days, which was in line with the diagnostic criteria of the three versions of the sepsis criteria. The 28-day mortality in the three sepsis guidelines groups was 17.4%, 18.2%, and 25.0%, respectively, indicating no statistical difference. By adopting culture-positive pathogens as the "gold standard" of septic infection, the diagnostic sensitivity and specificity of the group A was 77.8% and 25.0%, respectively, that of the group B, 82.2% and 41.7%, respectively, and that of the group C, 72.2% and 41.7%, respectively. No statistical difference was found in diagnostic performance among the three versions of sepsis criteria. Conclusion The prevalence of sepsis is high in the ICU trauma patients. There is no difference in diagnostic performance for post-traumatic sepsis among the three versions of the diagnostic criteria. The 1992 international sepsis criteria is relatively simple and may be more feasible for the diagnosis of post-traumatic sepsis. DOI: 10.11855/j.issn.0577-7402.2016.04.07

Objectives: To investigate the effect of non-elastic/elastic abdominal binders on intra-vesical pressure (IVP), physiological functions, and clinical outcomes in laparotomy patients at the perioperative stage. Methods: This prospective study was conducted from May to October 2014 at the Trauma Surgery Department, Daping Hospital, Chongqing, China. Laparotomy patients were randomly divided into non-elastic abdominal binder group (28 patients), and elastic abdominal binder group (29 patients). Binders were applied for 14 days following the operation, or until discharge. Demographic information, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores (prior to the operation, on the first day after operation, the day IVP measurement was stopped, and one day before discharge), and outcomes were recorded. The IVP was measured before the operation to postoperative day 7. Results: There were no significant differences in the demographic information, outcomes, SOFA or APACHE-II scores between the 2 groups. Initial out-of-bed mobilization occurred earlier in the elastic binder group (3.2 ± 2.0 versus 5.0 ± 3.7 days, p =0.028). A greater increase in IVP was observed in the non-elastic binder group than in the elastic binder group (2.9 ± 1.1 versus 1.1 ± 0.7 mm Hg, p =0.000). Conclusion: Elastic binders have relatively little effect on IVP and are more helpful at promoting postoperative recovery than non-elastic binders. Therefore, elastic binders are more suitable for clinical use. Saudi Med J 2016; Vol. 37 (1): 66-72 doi: 10.15537/smj.2016.1.12865 How to cite this article: Zhang HY, Liu D, Tang H, Sun SJ, Ai SM, Yang WQ, et al. The effect of different types of abdominal binders on intra-abdominal pressure . Saudi Med J 2016; 37: 66-72 .

BackgroundAcute lung injury (ALI) is a serious complication of stroke that occurs with a high incidence. Our preclinical results indicated that ALI might be related to blood glutamate levels after brain injury. The purpose of this study was to assess dynamic changes in blood glutamate levels in patients with stroke and to determine the correlation between blood glutamate levels, ALI, and long-term prognosis after stroke.MethodsVenous blood samples were collected from controls and patients with stroke at admission and on the third and seventh day after the onset of stroke. Patients were followed for 3 months. The correlations among blood glutamate levels, severities of stroke and ALI, and long-term outcomes were analyzed, and the predictive values of blood glutamate levels and severity scores for ALI were assessed.ResultsIn this study, a total of 384 patients with stroke were enrolled, with a median age of 59 years. Patients showed significantly increased blood glutamate levels within 7 days of stroke onset (p

Background Intra-abdominal hypertension (IAH) is a disease with high morbidity and mortality among critically ill patients. The study’s objectives were to explore the prevalence of IAH and physicians’ awareness of the 2013 World Society of Abdominal Compartment Syndrome (WSACS) guidelines in Chinese intensive care units (ICUs). Methods A cross-sectional study of four ICUs in Southwestern China was conducted from June 17 to August 2, 2014. Adult patients admitted to the ICU for more than 24 h, with bladder catheter but without obvious intravesical pressure (IVP) measurement contraindications, were recruited. Intensivists with more than 5 years of ICU working experience were also recruited. Epidemiological information, potential IAH risk factors, IVP measurements and questionnaire results were recorded. Results Forty-one patients were selected. Fifteen (36.59 %) had IVP ≥ 12 mmHg. SOFA (Sequential Organ Failure Assessment) hepatic and neurological sub-scores were utilized as independent predictors for IAH via logistic backward analysis. Thirty-seven intensivists participated in the survey (response rate: 80.43 %). The average score of each center was less than 35 points. All physicians believed the IAH prevalence in their departments was no more than 20.00 %. A significant negative correlation was observed between the intensivists’ awareness of the 2013 WSACS guidelines and the IAH prevalence in each center (r = -0.975, P = 0.025). Conclusions The prevalence and independent predictors of IAH among the surveyed population are similar to the reports in the literature. Intensivists generally have a low awareness of the 2013 WSACS guidelines. A systematic guideline training program is vital for improving the efficiency of the diagnosis and treatment of IAH.

Purpose To investigate the prevalence and diagnosis rate of intra-abdominal hypertension (IAH) in a mixed-population intensive care unit (ICU), and to investigate the knowledge of ICU staff regarding the guidelines published by the World Society of Abdominal Compartment Syndrome (WSACS) in 2013. Methods A one-day cross-sectional study based on the WSACS 2013 guidelines was conducted in the general ICU of a tertiary teaching hospital in Chongqing, China. The included patients were divided into intravesical pressure (IVP) measured group and IVP unmeasured group. The epidemiologic data were recorded, and potential IAH risk factors (RFs) were collected based on the guidelines. IVP measurements were conducted by investigators every 4 h and the result was compared to that measured by the ICU staff to evaluate the diagnosis rate. Besides, a questionnaire was used to investigate the understanding of the guidelines among ICU staff. Results Thirty-two patients were included, 14 in the IVP measured group and 18 in the IVP unmeasured group. The prevalence of IAH during the survey was 15.63% (5/32), 35.71% (5/14) in IVP measured group. Only one case of IAH had been diagnosed by the ICU physician and the diagnosis rate was as low as 20.00%. Logistic regression analysis showed that sequential organ failure assessment (SOFA) score was an independent RF for IAH ( OR : 1.532, 95% CI : 1.029–2.282, p = 0.036. Fourteen doctors and 5 nurses were investigated and the response rate was 67.86%. The average scores of the doctors and nurses were 27.14 ± 20.16 and 16.00 ± 8.94 respectively. None of them had studied the WSACS 2013 guidelines thoroughly. Conclusion Patients with a higher SOFA score has a higher incidence of IAH. The IAH prevalence in 14 ICU patients with indwelling catheter was 35.71%. Strengthening the wide and rational use of WSACS guideline is important to improve the diagnosis of IAH.

BACKGROUND Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a major role in the sepsis and multiple organ dysfunction secondary to major trauma. The purpose of this article was to research the clinical relevance of the TNF gene polymorphism in patients with major trauma. METHODS Three hundred six patients with major trauma were prospectively recruited. The TNF gene polymorphisms were genotyped using restriction fragment length polymorphism analysis. Plasma TNF-α levels were determined with enzyme-linked immunosorbent assay. Sepsis morbidity rate and multiple organ dysfunction scores were accessed. RESULTS The TNF-α/-308 polymorphism was shown to be well associated with increased capacity of peripheral leukocytes to produce TNF-α in response to ex vivo lipopolysaccharide stimulation in trauma patients at admission. Results from association study indicated that trauma patients carrying the TNF-α/-308/A allele were more likely complicated with sepsis. CONCLUSIONS The TNF-α/-308 polymorphism might be used as a biomarker for the assessment of outcome of trauma patients, but the TNF-β/252 gene polymorphism might not influence the development of complications in patients with major trauma.

Toll-like receptor 2 (TLR2) signaling plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire TLR2 gene and to investigate their clinical relevance in patients with major trauma. A total of 410 patients with major trauma were prospectively recruited. The htSNPs of the TLR2 gene was determined using HapMap database and linkage disequilibrium analysis. The htSNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The whole peripheral blood samples obtained immediately after admission were stimulated with bacterial lipoprotein and then determined for production of tumor necrosis factor-α, interleukin 8, and interleukin 10. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were accessed. Three SNPs (rs1898830, rs3804099, and rs7656411) were identified as htSNPs for the TLR2 gene. All of them were shown to be high-frequency SNPs in this study cohort. Two of them (rs1898830 and rs3804099) and the haplotype ATT were significantly associated with cytokine production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Only rs3804099, however, was significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma. In addition, the patients with the haplotype ATT had lower sepsis morbidity rate than those without the haplotype ATT. Therefore, three SNPs might act as htSNPs for the entire TLR2 gene in the Chinese population. The rs3804099 and the haplotype ATT might be used as relevant risk estimates for the development of sepsis and MOD in patients with major trauma.

Aim To investigate in a Chinese population the occurrence of polymorphisms Bcl I, N363S and ER22/23EK in the glucocorticoid receptor and their association with outcome of trauma. Methods In all, 266 healthy volunteers and 95 victims of major trauma were recruited. The presence of glucocorticoid receptor polymorphisms (ER22/23EK, N363S and Bcl I) was sought by restriction fragment length polymorphism analysis. The injured group were monitored as to respiratory, renal, hepatic, cardiovascular, haematological and central nervous functions. The association was determined between polymorphisms and the development of multiple organ dysfunction syndrome and sepsis after trauma. Results Only the Bcl I polymorphism was identified. The frequency of its G allele was 23.5% among volunteers and 26.3% among casualties. There were no significant differences in MOD score or sepsis rate between participants classified according to genotype. Conclusions Only the Bcl I polymorphism of the glucocorticoid receptor gene is common in the Chinese Han population; it may not influence the development of complications following major trauma.

BACKGROUND Interleukin (IL)-4 is a pleiotropic cytokine, severed as an important component of the adaptive immune system, and implicated in the pathophysiology of sepsis. Data from other studies show that the -589T/C polymorphism in IL-4 promoter may alter IL-4 expression and susceptibility of inflammatory or autoimmune diseases. Whether this genetic variation is associated with sepsis susceptibility is unknown. The aim of this study was to search for the association of IL-4 -589T/C with the susceptibility to sepsis. METHODS The polymorphism was genotyped among 308 severe trauma patients using restriction fragment length polymorphism polymerase chain reaction. The IL-4 and interferon-γ levels in the supernatants were determined with enzyme-linked immunosorbent assay. RESULTS The IL-4/-589C allele was shown to be significantly associated with higher plasma IL-4 and lower interferon-γ production after lipopolysaccharide stimulation, indicating its effect on regulating T helper T(H)1/T(H)2 balance. Moreover, homozygosity and heterozygosity for the -589C were associated with an increased susceptibility of sepsis (p = 0.009; OR, 1.69; 95% confidence interval, 1.14-2.51). There was no relationship between the IL-4 -589T/C and multiple organ dysfunction scores in severe trauma patients. CONCLUSIONS These results suggest that the IL-4 -589T/C polymorphism might affect T(H)1/T(H)2 balance and predispose trauma patients to susceptibility sepsis.

To investigate the surgical treatment for patients with multiple injuries in ICU.Clinical data of 163 multiple injury patients admitted to ICU of our hospital from January 2006 to January 2009 were retrospectively studied, including 118 males and 45 females, with the mean age of 36.2 years (range, 5-67 years). The injury regions included head and neck (29 cases), face (32 cases), chest (89 cases), abdomen (77 cases), pelvis and limbs (91 cases) and body surface (83 cases). There were 57 cases combined with shock. ISS values varied from 10 to 54, 18.42 on average. Patients received surgical treatments in ICU within respectively 24 hours (10 cases), 24-48 hours (8 cases), 3-7 days (7 cases) and 8-14 days (23 cases).For the 163 patients, the duration of ICU stay ranged from 2 to 29 days, with the average value of 7.56 days. Among them, 143 were cured (87.73%), 11 died in the hospital (6.75%) due to severe hemorrhagic shock (6 cases), craniocerebral injury (3 cases) and multiple organ failure (2 cases), and 9 died after voluntarily discharging from hospital (5.52%). The total mortality rate was 12.27%.The damage control principle should be followed when multiple injury patients are resuscitated in ICU. Surgical treatment strategies include actively controlling hemorrhage, treating the previously missed injuries and related wounds or surgical complications and performing planned staging operations.

To investigate the possibility that the level of Tie2 mRNA in peripheral blood could reflect the severity of sepsis.Trauma patients in intensive care unit (ICU) were recruited, and they were divided into sepsis group (n=13) and non-sepsis group (n=19). The severity of disease was evaluated with acute physiology and chronic health evaluation II (APACHEII) score on the day of ICU admission. Blood of patients was sampled on day 1, 3, 7 after ICU admission to determination of the white blood cell (WBC) count, contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cr), mRNA levels of Tie2 in blood measured by quantitative real-time polymerase chain reaction (PCR), and the contents of plasma von Willebrand factor (vWF) with enzyme linked immunosorbent assay (ELISA).No significant difference in contents of ALT, AST and plasma vWF was found between sepsis group and non-sepsis group [ALT (U/L): 53.30 (199.58) vs. 80.65 (202.62), AST (U/L): 316.53 (49.90) vs. 66.10 (285.03), vWF: (272.47+/-114.61)% vs. (246.66+/-128.77)%, all P0.05]. The number of WBC [x10(9)/L, 18.26 (21.82) vs. 10.11 (4.72)], the contents of BUN [mmol/L, 20.70 (11.20) vs. 7.70 (5.45)] and Cr [micromol/L: 252.00 (364.55) vs. 68.00(23.20)], and the circulating mRNA levels of Tie2 (1.86+/-0.67 vs. 0.91+/-0.42) in sepsis group were higher than those in the non-sepsis group (all P0.01). The Tie2 mRNA level in peripheral blood of each patient was positively correlated with APACHEII score (r=0.532, P0.01). The linear regression equation was Y=12.66+4.922 X (R2=0.283). Besides, there was a significant correlation between the amount of Tie2 mRNA and plasma levels of vWF (r=0.334, P0.05). The linear regression equation was Y=180.932+57.93 X (R2=0.112).The level of Tie2 mRNA in peripheral blood could reflect the damage of endothelial cell and severity of sepsis.

Objective: Toll-like receptor 4 is an important signaling receptor for lipopolysaccharide in mammals, and the variation of the promoter may affect the activity of toll-like receptor 4 expression. Although 12 single nucleotide polymorphisms have been identified in the toll-like receptor 4 promoter, little is known about the functional significance of these single nucleotide polymorphisms. Design: Genetic functional and association studies. Setting: National Key Laboratory of Trauma and Departments of Traumatic Surgery in two teaching hospitals. Subjects: Three hundred seventy-nine healthy volunteers and 303 patients with major trauma. Interventions: None. Measurements and Main Results: Five single nucleotide polymorphisms identified in the toll-like receptor 4 promoter in the Chinese Han population were selected. Three of them revealed a close relationship with transcription factor binding sites. Among the three single nucleotide polymorphisms, only the T-2242C polymorphism significantly increased transcriptional activities of the toll-like receptor 4 promoter, as shown by reporter gene assay. Results from flow cytometry and ex vivo responsiveness of peripheral blood leukocytes indicated that the T-2242C polymorphism was well-associated with increased expression of toll-like receptor 4 protein and production of tumor necrosis factor-α. The clinical relevance of these single nucleotide polymorphisms was then investigated in 303 patients with major trauma. The peripheral blood leukocytes of trauma patients with the variant C allele revealed greater capacity to produce tumor necrosis factor-α and interleukin-6 on the admission day. Furthermore, the toll-like receptor 4/−2242 polymorphism was significantly associated with higher sepsis morbidity rates and multiple organ dysfunction scores in patients with major trauma. Conclusions: The toll-like receptor 4/−2242 polymorphism is a functional variant and might be used as a relevant risk estimate for organ dysfunction and sepsis in trauma patients.

Introduction An excessive inflammatory response is thought to account for the pathogenesis of sepsis and multiple organ dysfunction syndrome (MODS) after severe trauma. The interleukin-10 (IL-10) is a potent anti-inflammatory cytokine. The objectives of this prospective study were to investigate the distribution of IL-10 promoter polymorphisms in a cohort of 308 Chinese Han patients with major trauma, and to identify associations of IL-10 promoter polymorphisms with IL-10 production and incidence of sepsis and MODS. Methods A total of 308 patients with major trauma were included in this study. The genotypes of polymorphisms -1082, -819 and -592 were determined by polymerase chain reaction-restriction fragment length polymorphism. The IL-10 levels in the supernatants were determined with enzyme-linked immunoabsorbent assay. Results The -1082A and -592A alleles were significantly associated with lower lipopolysaccharide-induced IL-10 production in an allele-dose dependent fashion. There was no significant difference for the -819 polymorphism. Except for the -1082 polymorphism, the -819 and -592 polymorphisms were not significantly associated with sepsis morbidity rate and MOD scores. Conclusions Our results further confirm the functionality of the IL-10 promoter single nucleotide polymorphisms in relation to IL-10 production. They also suggest that individual difference in IL-10 production in trauma patients might be at least in part related to genetic variations in the IL-10 promoter region.

To determine the clinical relevance of 13 reported common single-nucleotide polymorphisms (SNPs) of cytokine genes in patients with major trauma.Thirteen SNPs in nine key cytokine genes were selected for association study in 308 patients with major trauma on the basis of previous functional or association data. An allele-specific oligonucleotide array was developed and used to genotype 308 patients with major trauma. The clinical relevance of the 13 SNPs was assessed by observation of cytokine production and outcome of trauma patients.Results from the allele-specific oligonucleotide array indicated that 8 [interleukin-1beta (IL-1beta)/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and tumor necrosis factor alpha (TNFalpha)/-308] out of the 13 SNPs were associated with respective ex vivo cytokine production by peripheral leukocytes in response to lipopolysaccharide (LPS) stimulation at admission, or risk of development of sepsis or organ dysfunction in major trauma patients. Patients with more than four risk alleles of the eight SNPs had more than 50% sepsis morbidity and more severe organ dysfunction.Polymorphisms of IL-1beta/-1470, IL-1beta/-511, IL-1beta/-31, IL-4/-589, IL-6/-572, IL-8/-251, IL-10/-819, and TNFalpha/-308 are susceptibility loci for the development of sepsis and organ dysfunction in major trauma patients.

To investigate the polymorphisms of myeloid differentiation-2 (MD-2) gene promoters, and to explore whether such polymorphisms are associated with the susceptibility to multiple organ dysfunction syndrome (MODS) and sepsis in Chinese Han population.Using polymerase chain reaction-restriction fragment length polymorphism method, the authors detected the single nucleotide polymorphisms of the promoter region of MD-2 gene at position - 1625C/G in 105 severe trauma patients (42 with sepsis). The organ function was scored.The frequency of CC genotype in MD-2 gene promoter region at position - 1625 was 0.5 (21/42) in septic patients and 0.7 (44/63) in non-septic patients. The frequency of CG genotype was 0.38 (16/42) in septic patients and 0.27 (17/63) in non-septic patients. The frequency of GG genotype was 0.12 (5/42) in septic patients and 0.03 (2/63) in non-septic patients. The MODS scores in trauma patients carrying G allele at position - 1625 were significantly higher than those carrying C allele (P0.001 for dominant effect, and P0.05 for recessive effect). Moreover, trauma patients carrying G allele appeared to have higher risk of sepsis comparing to those carrying C allele (OR 0.477, 95% CI 0.266-0.855, P0.05). Sepsis morbidity was significantly different between subjects with C and G alleles (P0.05 for dominant effect, P0.05 for recessive effect).The polymorphisms of the promoter region of MD-2 gene at position - 1625 C/G is correlated with MODS and sepsis after severe trauma in Chinese Han population. The people with - 1625 G allele in the promoter region of MD-2 gene may be a risk factor of severe complications.

Several polymorphisms in the CD14 promoter have been reported to be associated with various inflammatory diseases. However, conflicting results have been shown in association studies in different populations. This study aimed to investigate the possible functional significance of both the G-1145A and T-159C polymorphisms in the CD14 promoter and their association with organ dysfunction and sepsis in adult trauma patients.Genetic, functional, and association studies.National Key Laboratory of Trauma and Departments of Traumatic Surgery in two teaching hospitals.Three hundred twenty-five healthy volunteers and 105 patients with major trauma.None.Among the five single nucleotide polymorphisms identified within CD14 promoter in a Chinese Han population, two single nucleotide polymorphisms (G-1145A and T-159C) were selected according to bioinformatics analysis. Promoter activity of polymorphisms was determined using the reporter gene assay. Plasma sCD14 and tumor necrosis factor-alpha levels were measured by enzyme-linked immunosorbent assay. Both single nucleotide polymorphisms significantly reduced transcriptional activity of the promoter, and were significantly associated with a decrease of inducible sCD14 and tumor necrosis factor-alpha production in an allele-dose effect. Moreover, trauma patients carrying the -1145 A or -159 C allele appeared to have a decreased risk of multiple organ dysfunction and sepsis. In addition, both polymorphisms had a marked synergistic effect.The CD14/-1145 and -159 polymorphisms are functional variants, which may function in a synergistic fashion, and could be used as biological risk predictors of multiorgan dysfunction and sepsis in trauma patients.

To investigate the functional significance of the reported single nucleotide polymorphisms (SNPs) in the promoter of the myeloid differentiation-2 (MD-2) gene.Functional gene polymorphisms of innate immune receptors have been shown to be critical determinants of the immune inflammatory response. MD-2 is an important signaling enhancer protein in the endotoxin (LPS) receptor complex. Although a total of 156 SNPs have been identified within the whole MD-2 gene, little is known about the functional significance of these SNPs.: The possible biosignificance of 8 reported SNPs was analyzed using on-line software tools. The selected SNPs were then genotyped using a restriction fragment length polymorphism method applied to 711 healthy Chinese volunteers. Their functional effects were assessed by the observation of transcription activity, MD-2 mRNA expression, and leukocyte response to ex vitro LPS stimulation. Moreover, the clinical relevance of these SNPs was investigated in 105 patients with major trauma.Three SNPs (C-1625G, A-1064G, and A-475T) in the MD-2 promoter were selected based on bio-informatic analysis. Both -1625 and -1064 SNPs, rather than -475, were seen in the Chinese population, with frequencies of 19.8% (-1625G) and 34.7% (-1064G). But only the -1625 polymorphism was found to affect MD-2 promoter activity. Moreover, the expression of MD-2 mRNA and the production of TNF-alpha in whole blood leukocytes, in response to LPS stimulation, were significantly increased in subjects with the -1625 G allele. Patients who possessed the -1625 G allele were more likely to experience complications with organ dysfunction and sepsis after major trauma. All these associations were in allele-dose dependent effect.The MD-2/-1625 polymorphism is an important functional variant.

Introduction Variations in genetic background are the leading cause of differential susceptibility to traumatic infection. Heat shock protein 90 (HSP90), a broadly distributed and conserved molecule, regulates inflammation under stressful and traumatic conditions. However, the relationships between HSP90 genetic polymorphisms, post-traumatic inflammatory responses and organ function remain unknown. Methods A total of 286 healthy volunteers and patients with severe trauma took part in a single nucleotide polymorphism (SNP)-based analysis of the HSP90beta gene and a clinical association analysis. HSP90beta and TNF-alpha levels were determined using quantitative PCR and western blot. The transcriptional activity of the HSP90beta promoter was assayed using the Dual-Luciferase Reporter Assay System. Results The minor allele frequencies for the SNP located at −144 bp relative to the HSP90beta transcriptional start site were 28.47% and 28.52% in the normal and trauma populations, respectively; no significant differences were found between these two distributions. However, the results showed that a promoter containing the -144A allele had a higher transcriptional activity than did a promoter containing the wild-type -144C allele. Furthermore, the -144A promoter induced high expression of HSP90beta and low expression of the inflammatory factor TNF-alpha in a lipopolysaccharide-induced inflammatory model. A clinical association analysis showed that the multiple organ dysfunction scores for -144AA genotype carriers were significantly lower than those of -144CC carriers following trauma. No significant correlations were found between the presence of the two alleles and the incidence of sepsis. Conclusions These results indicate that differences in expression caused by the -144 polymorphism in the HSP90beta promoter are associated with cellular inflammatory responses and the severity of organ injury. These findings will aid in risk assessment and early prevention of complications for patients with severe trauma.

Introduction The nucleotide-binding oligomerization domain-like receptor (NLR) family has been recognized as comprising intracellular pattern recognition receptors in which NLRP3 (NLR family, pyrin domain containing 3) plays an important role in the initiation of host immune inflammatory responses. The genetic variants have been recognized to be critical determinants of interindividual differences in both inflammatory responses and clinical outcomes in critical illness. However, little is known about the clinical relevance of NLRP3 gene polymorphisms in critical illness. Methods A total of 718 patients with major blunt trauma were included in this study. Six tag SNPs (tSNPs) were selected from the entire NLRP3 gene through construction of haplotype bins, and they were genotyped using a pyrosequencing method. They were analyzed in relation to sepsis morbidity rate, multiple organ dysfunction (MOD) scores and IL-1β production. Moreover, the functionality of the rs2027432 polymorphism was assessed by the observation of its effect on transcriptional activities. Results Among the six tSNPs genotyped in this study, two of them (rs2027432 and rs12048215) were significantly associated with sepsis morbidity rate and MOD scores. A significant association was also observed between these two polymorphisms and IL-1β production by peripheral leukocytes in response to ex vivo lipopolysaccharide stimulation. However, no combined effects were found between these two polymorphisms. In addition, the rs2027432 polymorphism could significantly enhance the promoter activities of the NLRP3 gene. Conclusions rs2027432 and rs12048215 polymorphisms might be used as relevant risk estimates for the development of sepsis and MOD syndrome in patients with major trauma, in which rs2027432 might be a functional SNP.