Diagnosis of overt disseminated intravascular coagulation in critically Ill adults by Sonoclot coagulation analysis.

Disseminated intravascular coagulation (DIC) diagnosis is hampered by the limited availability of reliable clinical or laboratory tests. Currently available tests are time consuming and expensive. We investigated whether coagulation and platelet function analyses using the Sonoclot system were suitable for overt DIC diagnosis in critically ill adults. This was an observational diagnostic study performed in 498 patients presenting with an underlying disorder associated with DIC. Overt DIC patients were identified according to an International Society on Thrombosis and Hemostasis (ISTH) score of >5. Coagulation and platelet parameters were analyzed using the Sonoclot system, and compared with ISTH as the gold standard. Receiver operating characteristic curves and area under the curves were used to evaluate the value of the Sonoclot parameters. There were no differences for age or gender between the groups. Significant correlations were observed between activated clotting time (ACT) and ISTH score (r = 0.7; P < 0.001), clot rate (CR) and ISTH score (r = 0.5; P < 0.001), platelet function (PF) and ISTH score (r = -0.6; P < 0.001), and PF and platelet count (r = 0.5; P < 0.001). An ACT cut-off value of 213.5 s alone or combined with CR presented good sensitivity (76.7 and 86.8 %, respectively) and specificity (96.2 and 93.3 %, respectively). Sonoclot analysis can be performed using a point-of-care device that effectively discriminates low and high ISTH scores, and that effectively predicts coagulation dysfunction in patients with overt DIC.

Ten-year retrospective analysis of multiple trauma complicated by pulmonary contusion.

BACKGROUND: This study reports a 10-year retrospective analysis of multiple trauma complicated by pulmonary contusion. The purpose of this study is to ascertain the risk factors for mortality due to trauma in patients with pulmonary contusion, the impact of various treatment options for prognosis, and the risk factors for concurrent Acute Respiratory Distress Syndrome (ARDS). METHODS: We retrospectively analyzed 252 trauma patients with lung contusion admitted to the General Hospital of Guangzhou Command from January 2000 to June 2011 by using the statistical processing system SPSS 17.0 for Windows. RESULTS: We included 252 patients in our study, including 214 males and 38 females. The average age was 37.1 ± 14.9 years. There were 110 cases admitted to the ICU, of which 26 cases with ARDS. Nine of the 252 patients died. We compared those who survived with those who died by gender and age, the difference was not statistically significant (P = 0.199, P = 0.200). Separate univariate analysis of those who died and those who survived found that shock on admission (P = 0.000), coagulation disorders (P = 0.000), gastrointestinal bleeding (P = 0.02), the need for emergency surgery on admission (P = 0.000), pre-hospital intubation (P = 0.000), blood transfusion within 24 hours (P = 0.006), the use of mechanical ventilation (P = 0.000), and concurrent ARDS (P = 0.000) are poor prognosis risk factors. Further logistic analysis, including the admission GCS score (OR = 0.708, 95% CI 0.516-0.971, P = 0.032), ISS score (OR 1.135, 95% CI 1.006-1.280, P = 0.039), and concurrent ARDS (OR = 15.814, 95% CI 1.819-137.480, P = 0.012), identified the GCS score, ISS score and concurrent ARDS as independent risk factors of poor prognosis. Shock (OR = 9.121, 95% CI 0.857-97.060, P = 0.067) was also related to poor prognosis. Patients with injury factors such as road accident, falling injury, blunt injury and crush injury, et al.(P = 0.039), infection (P = 0.005), shock (P = 0.004), coagulation disorders (P = 0.006), emergency surgery (P = 0.01), pre-hospital intubation (P = 0.000), chest tube insertion (P = 0.004), blood transfusion (P = 0.000), usage of hormones (P = 0.002), phlegm (P = 0.000), ventilation (P = 0.000) were at a significantly increased risk for ARDS complications. CONCLUSIONS: Those patients with multiple trauma and pulmonary contusion admitted to the hospital with shock, coagulopathy, a need for emergency surgery, pre-hospital intubation, and a need for mechanical ventilation could have a significantly increased risk of mortality and ARDS incidence. A risk for poor prognosis was associated with gastrointestinal bleeding. A high ISS score, high APACHE2, and low GCS score were independent risk factors for poor prognosis. If patients developed an infection or were given drainage, hormones, and phlegm treatment, they were at higher risk of ARDS. Pre-hospital intubation and drainage were independent risk factors for ARDS. In patients with ARDS, the ICU stay, total length of stay, and hospital costs might increase significantly. A GCS score < 5.5, APACHE 2 score > 16.5, and ISS score > 20.5 could be considered indicators of poor prognosis for patients with multiple trauma and lung contusion.

Serum procalcitonin predicting mortality in exertional heatstroke.

BACKGROUND: The aim of this study was to test if Procalcitonin PCT value at the time of admission is a predictor of mortality and/or a diagnostic marker of concomitant infection in exertional heatstroke. METHODS: 68 patients with exertional heatstroke admitted to the multidisciplinary intensive care unit were studied. Serum PCT was detected by means of a specific and ultrasensitive immunoluminometric assay within 2 h of admission. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was evaluated within 24 h of admission. RESULTS: There was no significant difference in PCT levels between concomitant infection and non-infection patients (p=0.712). Elevated PCT level in exertional heatstroke patients was associated with a more critical pathological state. PCT values in patients with multiple organ dysfunction syndrome (MODS) were significantly higher than those without MODS (p=0.007.). PCT values were also positively correlated with APACHE II scores (r=0.588, p=0.016). PCT values in non-survivors were higher than in survivors at univariate regression analysis (p=0.017). After adjusting for confounders, PCT concentration also remained an independent determinant of mortality (OR 2.98; 95% CI 1.02 to 4.41; p=0.039). Receiver operating characteristic curve for PCT concentration was located above the reference line, which shows an association with mortality. The area under the curve for PCT concentration (0.705; 95% CI 0.547 to 0.862) was statistical significantly (p=0.019). As a predictor of mortality, PCT value was inferior to APACHE II score. CONCLUSIONS: PCT value at the time of admission is an independent predictor of mortality, but maybe not a good indicator of concomitant infection in exertional heatstroke.

Early elevated HMGB1 level predicting the outcome in exertional heatstroke.

BACKGROUND: Heatstroke is generally considered as a syndrome of hyperthermia associated with systemic inflammation leading to multiorgan dysfunction. High mobility group box-1 protein (HMGB1) has recently been identified as a late mediator of systemic inflammation inducing multiorgan dysfunction. Elevation of plasma HMGB1 in heatstroke has been observed in animals, but there is no data available about its changes in heatstroke patients. The objectives of this study are to observe the time course of plasma HMGB1 changes and assess its prognostic value in patients with exertional heatstroke. METHODS: Blood samples were taken from the patients with exertional heatstroke. Plasma HMGB1 level was detected by the enzyme-linked immunosorbent assay. C-reactive protein level was measured using a fully automated IMMAGE Immunochemistry System. Secreted HMGB1 in the culture supernatant of peripheral blood monocyte was assessed by immunoblotting. Acute Physiology and Chronic Health Evaluation II score was evaluated within 24 hours of admission. RESULTS: HMGB1 released into circulation at early stage, with peak levels occurring within 6 hours to 13 hours postheatstroke. Plasma HMGB1 levels remained markedly elevated in the following 6 days postheatstroke when compared with healthy volunteers (p<0.005). Positive correlation (r=0.798, p<0.001) was found between Acute Physiology and Chronic Health Evaluation II score and HMGB1 level at admission. HMGB1 levels at admission between survivors and nonsurvivors were significantly different (p<0.001). Receiver operating curve analysis showed that at a level of 47 ng/mL, HMGB1 level at admission indicated lethality with 77.4% sensitivity and 84.2% specificity. CONCLUSIONS: HMGB1 level at admission is an indicator of the severity of illness and a useful mortality predictor in exertional heatstroke.

Pathological changes in the lung and brain of mice during heat stress and cooling treatment.

BACKGROUND: Heatstroke often leads to multiple organ dysfunction syndrome (MODS) with a death rate of 40% or a neurological morbidity of 30%. These high rates in patients with heatstroke are largely due to the progression of heat stress to MODS, resulting in no specific treatment available. This study aimed to develop a mouse model of heat stress and determine the pathological changes in the lung and brain during heat stress and cooling treatment. METHODS: A mouse model of heat stress was established in a pre-warmed incubator set at 35.5 ± 0.5°C and with a relative humidity of 60% ± 5%. Rectal temperature was monitored, and at a temperature of 39 °C, 40 °C, 41 °C, or 42 °C, the mice were sacrificed. The remaining animals were removed from the incubator and cooled at an ambient temperature of 25 ± 0.5 °C and a humidity of 35% ± 5% for 12 or 24 hours at a temperature of 41 °C or for 6 hours at a temperature of 42 °C. The control mice were sham-heated at a temperature of 25 ± 0.5 °C and a humidity of 35% ± 5%. The lungs and brains of all animals were isolated. Hematoxylin and eosin staining and light microscopy were performed to detect pathological changes. RESULTS: All mice demonstrated a uniform response to heat stress. A low degree of heat stress induced marked pathological changes of the lungs. With the rise of the temperature to 42°C, progressively greater damage to the lungs with further congestion of the lung matrix, asystematic hemorrhage of alveolar space, abscission of alveolar epithelial cells, and disappearance of pulmonary alveolus tissue structure were detected. However, absorption of congestion and hemorrhage as well as recovery of pulmonary alveolus tissue structure was observed following cooling treatment at an ambient temperature. With a low degree of heat stress, the brain only showed moderate edema. Neuronal denaturation and necrosis were detected at a temperature of 42°C. Interestingly, the lesions in the brain were further aggravated at 42 °C regardless of cooling treatment, but recovery was observed after cooling treatment at 41 °C. CONCLUSIONS: The pathological changes of the lungs and brain of mice showed distinctive lesions following heat stress and cooling treatment, and they were correlated with the time and duration of cooling treatment. The results of this study are helpful for further study of the mechanisms linking heatstroke.

[Combined effect of high mobile group box-1 protein and lipopolysaccharide on release of cytokines from human HepG2 cells].

OBJECTIVE: To study the effects of high mobile group box-1 protein (HMGB1) and lipopolysaccharide (LPS) singly or in combination on release of cytokines from human liver carcinoma cell line (HepG2). METHODS: HepG2 cells were cultured, and purified HMGB1 protein was prepared by chromatography on Ni(2+)-NTA Sepharose column under natural conditions with recombinant expression plasmid pET14b-HMGB1. Different concentrations of HMGB1 (0, 0.01, 0.1, 1, 10 mg/L) and LPS (0, 0.1, 1, 10, 100 mg/L) were added into the cultured cells for 24 hours, respectively. Then the supernatant were collected to detect the levels of granulocyte/macrophage colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, IL-8, IL-10, and IL-12 by using LiquiChip system. Lastly, HepG2 cells were co-stimulated with 10 mg/L LPS and 1 mg/L HMGB1 for 24 hours. The supernatant were collected to determine the levels of above ten of cytokines . RESULTS: The expression and release of IL-6 and IL-8 increased from HepG2 cells after being stimulated by LPS in a dose-dependent manner, but there were no changes in other eight kinds of cytokines (P<0.05 or P<0.01). Low concentration of HMGB1 could up-regulate the expression of IL-6 and IL-8 in HepG2 cells (both P<0.01). But the extent of induction decreased with higher concentration of HMGB1. Similar to LPS, there was no effect of HMGB1 on the expression of other eight kinds of cytokines from cultured HepG2 cells. Furthermore, high concentration of HMGB1 could obviously inhibit the upregulation of IL-6 and IL-8 by high concentration of LPS when the HepG2 cells were co-stimulated with LPS and HMGB1 (both P<0.01). CONCLUSION: HepG2 cells could only express and release a few kinds of cytokines when the cells were stimulated with pro-inflammatory agents, such as LPS or HMGB1. Two kinds of cytokines, IL-6 and IL-8 could be up-regulated by LPS and low concentration of HMGB1, and HMGB1 acted as an inhibitor of LPS to down-regulate the expression and release of IL-6 and IL-8 from HepG2 cells.

[Clinical effects of ulinastatin and thymosin alpha1 on immune-modulation in septic patients].

OBJECTIVE: To analyze clinical effect of immuno-modulatory therapy with ulinastatin and thymosin alpha1 on patients with sepsis. METHODS: Two hundred and forty-two septic patients admitted to Guangzhou General Hospital of Guangzhou Military Command intensive care unit (ICU) during 2004.10-2008.6 were included, and they were randomly divided into treatment group (128 cases) and control group (114 cases). The patients in control group were given regular conventional treatment according to Surviving Sepsis Campaign (SSC) in 2004, including early fluid resuscitation, antibiotic therapy, mechanical ventilation (MV) and blood purification. The treatment group received conventional treatment plus immuno-modulation therapy including ulinastatin (first 200 kU injection intravenous twice a day for 4 days and 100 kU for another 6 days) and thymosin alpha1 (1.6 mg subcutaneous twice a day for 4 days, followed by 1.6 mg per day subcutaneous for another 6 days). The total treatment course was 10 days. General demographics were observed, and acute physiology and chronic health evaluation II (APACHE II) scores were recorded. Serum interleukin-6 (IL-6), IL-10 levels of peripheral blood were detected by enzyme linked immunosorbent assay (ELISA). Peripheral blood CD14(+) monocyte human leucocyte antigen DR (HLA-DR) expression, and ratio of helper T lymphocyte 1 (Th1) cytokines interferon-gamma (CD4(+)IFN-gammaww(+)), and Th2 cytokines (CD4(+) IL-4(+)) were assessed with flow cytometer. Duration of infection and MV, length of ICU stay, rate of development of multiple organ dysfunction syndrome (MODS) and mortality rate on 28 days were observed as end-point. RESULTS: Before treatment, there was no difference in all biomarkers between two groups (all P>0.05). After treatment, peripheral blood CD14ww+ monocyte HLA-DR expression and the ratio of CD4(+)IFN-gamma (+)/CD4(+) IL-4(+) increased significantly in the treatment group (both P<0.05), with serum IL-6, IL-10 levels and APACHE II scores all reduced remarkably (all P<0.05). The values showed significant differences compared with those of control group (all P<0.05). The MODS development rate in the treatment group was much lower than that of control group (21% vs. 47%, P<0.05), and the length of use of MV was significantly reduced [(6.08+/-2.46) days vs. (8.23+/-3.47) days, P<0.05]. There was no difference in the infection duration and length of ICU stay (both P>0.05). The mortality rate on 28 days in the treatment group was much lower than that in control group (20% vs. 33%, P<0.05). CONCLUSION: The immuno-modulation therapy of ulinastatin and thymosin alpha1 can remarkably improve the duration of MV and the development rate of MODS and mortality rate on 28 days in the patients with sepsis, probably due to its effect in ameliorating the immuno-imbalance state of the patients. However, the duration of infection and length of ICU stay are not effected.

Serum procalcitonin at the time of admission to the ICU as a predictor of short-term mortality.

OBJECTIVE: This purpose of this study was to determine if serum procalcitonin (PCT) concentration at the time of admission to the ICU is a predictor of all-cause short-term mortality. DESIGN AND METHODS: This prospective cross-sectional study was conducted over a 16-month period with 86 consecutive critically ill patients. The semi-quantitative PCT-Q test was performed and APACHE II scores and C-reactive protein (CRP) concentrations were determined within 24 h of admission. RESULTS: PCT-Q test value was a better predictor of all-cause short-term mortality than CRP value or APACHE II score. PCT > or = 10 ng/mL was highly and independently correlated with mortality. Use of PCT-Q > or = 10 ng/mL was superior to use of APACHE II > or = 25 or CRP > or = 10 mg/dL as a predictor of poor outcome. CONCLUSIONS: A PCT-Q value > or = 10 ng/mL obtained at the time of admission to the ICU is a strong predictor of short-term mortality.

[Clinical value of the model for end-stage liver disease score in predicting the prognosis of liver transplantation in patients with end-stage liver disease].

OBJECTIVE: To assess the value of the model for end-stage liver disease (MELD) in predicting the early-stage outcome of liver transplantation in patients with end-stage liver disease. METHODS: The MELD scores of 87 liver transplantation recipients with end-stage liver disease were calculated, and their early-stage complications and mortality were analyzed. RESULTS: The incidence of severe complications was 20.7%; in these recipients, with the 28-day and 3-month survival rates of 89.7%; and 88.5%;, respectively. The mean MELD scores showed significant differences between the complication-free group and survival group (14.6 vs 12.9, P<0.05), and also between the complication group and death group (21.6 vs 29.4, P<0.05). Compared to patients with MELD no greater than 15, patients with MELD between 16 and 24 showed significantly increased complication rate but had comparable survival rate (P>0.05); but in patients with MELD no less than 25, the survival rate was significantly decreased with also increased complication rate. CONCLUSIONS: A higher MELD score before liver transplantation is associated with greater likeliness of early-stage complication rate and mortality. High MELD score (over 25) can be a useful index in predicting severe complications and death in patients undergoing liver transplantation.

[Clinical value of monitoring CD14+ monocyte human leukocyte antigen (locus) DR levels in the early stage of sepsis].

OBJECTIVE: To explore the relationship of monitoring CD14(+) monocyte human leucocyte antigen (locus) DR (HLA-DR) and the outcome in the early stage of sepsis. METHODS: Thirty-six definitely diagnosed septic patients in intensive care unit (ICU) were included. CD14(+) monocyte HLA-DR levels were detected by flow cytometer on the first day of the study, and acute physiology and chronic health evaluation II (APACHE II) scores were evaluated. Their clinical values in predicting the outcome of the disease were assessed through correlation analysis. RESULTS: Among 36 sepsis patients CD14(+) monocyte HLA-DR level<30% was found in 6 patients (16.67%). The average APACHE II score was 24.17+/-4.45 (r=0.212, P=0.687), all of them die, CD14(+) monocyte HLA-DR level <40% was 27.78% (10/36), the scores of APACHE II score was 23.50+/-4.30 (r=-0.0251, P=0.484), and the mortality rate was 80% (8/10). CONCLUSION: CD14(+) monocyte HLA-DR level <30% is an immunosuppressive index. In predicting the outcome of sepsis, it might be better than APACHE II scores. Immunosuppression is primarily found in the early stage of sepsis, suggesting that the classical compensatory anti-inflammatory response syndrome (CARS) hypothesis needs to be revised and improved.

[Management of thyroid disease-induced tracheostenosis].

OBJECTIVE: To investigate the special clinical characteristics of thyroid disease-induced tracheostenosis and elaborate on its clinical management. METHODS: A retrospective analysis of 10 cases of thyroid disease-induced tracheostenosis was performed by reviewing the clinical record of their misdiagnoses and diagnostic approaches with fiberoptic bronchoscopy and/or cervical CT, thyroid scanning and pathological examination. The management included resection of the thyroid gland and airway reconstruction. RESULTS: Of the 10 patients, 3 were misdiagnosed to have bronchial asthma and 2 had a misdiagnosis of acute heart failure. Compression-induced tracheostenosis of grade II or III was identified by fiberoptic bronchoscopy or cervical CT, and the diagnosis of thyroid gland disease was established after pathological examination. Severe dyspnea was relieved in all patients after thyroid gland resection and airway reconstruction. Expandable metal stent placement was the most effective therapy for tracheostenosis induced by nodular goiter. Patients with tracheostomy cannula placement were at high risk of severe infection. CONCLUSIONS: Thyroid disease-induced tracheostenosis is likely to be misdiagnosed, which is not difficult to prevent with constant awareness of the possibility. Severe dyspnea in these patients can be relieved effectively after thyroid gland resection and airway reconstruction, and the prognosis depends on the type of the thyroid disease, degree of the tracheostenosis and management approaches.