[Clinical features and risk factors for secondary hemophagocytic lymphohistiocytosis in elderly patients with severe SARS-CoV-2 infection: a multicenter retrospective cohort study].

OBJECTIVE: To explore the incidence of secondary hemophagocytic lymphohistiocytosis (sHLH) in elderly patients with severe SARS-CoV-2 infection, and to analyze and summarize its clinical features and risk factors for early identification of high-risk groups. METHODS: A retrospective cohort study was conducted. From January to May 2020, No. 960 Hospital of People's Liberation Army, the Second Hospital Affiliated to Cheeloo College of Medicine of Shandong Province, the First Rehabilitation Hospital of Shandong Province, the Public Health Clinical Center Affiliated to Shandong University, and Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine received 248 patients over 60 years old who were diagnosed with severe SARS-CoV-2 infection during their assistance to Hubei or support for diagnosis and treatment of SARS-CoV-2 infection in Shandong Province. The clinical data of patients were collected. According to the hemophagocytic lymphohistiocytosis diagnosis scoring (HScore) criteria, the patients were divided into sHLH group (HScore > 169) and non-sHLH group (HScore < 98). The demographic data, clinical features, laboratory results, the proportion of organ failure and 60-day mortality of patients were collected and compared between the two groups. The risk factors of sHLH and 60-day death were evaluated through binary multivariate Logistic regression analysis in elderly patients with severe SARS-CoV-2 infection. The receiver operator characteristic curve (ROC curve) was plotted to analyze the diagnostic value of indicators only or combined for sHLH. RESULTS: Among 248 elderly patients with severe SARS-CoV-2 infection, 82 patients with incomplete data and untraceable clinical outcomes, and 35 patients with HScore of 98-169 were excluded. Finally, 131 patients were enrolled in the final follow-up and statistics, including 25 patients in the sHLH group and 106 patients in the non-sHLH group. Compared with the non-sHLH group, plasma albumin (ALB), hemoglobin (Hb), lymphocyte count (LYM), platelet count (PLT), fibrinogen (Fib) and prealbumin (PAB) in the sHLH group were significantly reduced, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), D-dimer, ferritin (Fer), lactate dehydrogenase (LDH), procalcitonin (PCT), cardiac troponin I (cTnI), triglycerides (TG), interleukin-6 (IL-6), total bilirubin (TBil) were significantly higher. The fever and fatigue in the sHLH group were more severe than those in the non-sHLH group, and the patients in the sHLH group had higher rates of shock, acute kidney injury, liver dysfunction, and cardiac injury than the non-sHLH group. The 60-day mortality of patient in the sHLH group was significantly higher than that in the non-sHLH group [84.0% (21/25) vs. 40.6% (43/106), P < 0.01]. Binary multivariate Logistic regression analysis showed that high Fer [odds ratio (OR) = 0.997, 95% confidence interval (95%CI) was 0.996-0.998], D-dimer (OR = 0.960, 95%CI was 0.944-0.977), LDH (OR = 0.998, 95%CI was 0.997-0.999) and TG (OR = 0.706, 95%CI was 0.579-0.860) were independent risk factors for sHLH in elderly patients with severe SARS-CoV-2 infection (all P < 0.01), while elevated Fer (OR = 1.001, 95%CI was 1.001-1.002), LDH (OR = 1.004, 95%CI was 1.002-1.005) and D-dimer (OR = 1.036, 95%CI was 1.018-1.055) were independent risk factors for 60-day death of patients (all P < 0.01). The death risk of the sHLH patients was 7.692 times higher than that of the non-sHLH patients (OR = 7.692, 95%CI was 2.466-23.987, P = 0.000). ROC curve analysis showed that a three-composite-index composed of LDH, D-dimer and TG had good diagnostic value for sHLH in elderly patients with severe SARS-CoV-2 infection [area under the ROC curve (AUC) = 0.920, 95%CI was 0.866-0.973, P = 0.000]. CONCLUSIONS: Elderly patients with severe SARS-CoV-2 infection complicated by sHLH tend to be critically ill and have refractory status and worse prognosis. High Fer, LDH, D-dimer and TG are independent risk factors for sHLH, and are highly suggestive of poor outcome. The comprehensive index composed of LDH, D-dimer and TG has good diagnostic value, and can be used as an early screening tool for sHLH in elderly patients with severe SARS-CoV-2 infection.

Association between Mean Arterial Pressure during the First 24 Hours and Clinical Outcome in Critically Ill Stroke Patients: An Analysis of the MIMIC-III Database.

Abnormal blood pressure is common in critically ill stroke patients. However, the association between mean arterial pressure (MAP) and mortality of critically ill stroke patients remains unclear. We extracted eligible acute stroke patients from the MIMIC-III database. The patients were divided into three groups: a low MAP group (MAP ≤ 70 mmHg), a normal MAP group (70 mmHg < MAP ≤ 90 mmHg), and a high MAP group (MAP > 90 mmHg). The Cox proportional hazards model and restricted cubic splines were used to assess the association between MAP and mortality. Sensitivity analyses were conducted to investigate whether MAP had different effects on mortality in different subpopulations. A total of 2885 stroke patients were included in this study. The crude 7-day and 28-day mortality was significantly higher in the low MAP group than that in the normal MAP group. By contrast, patients in the high MAP group did not have higher crude 7-day and 28-day mortality than those in the normal MAP group. After multiple adjustments using the Cox regression model, patients with low MAP were consistently associated with higher 7-day and 28-day mortality than those with normal MAP in the following subgroups: age > 60 years, male, those with or without hypertension, those without diabetes, and those without CHD (p < 0.05), but patients with high MAP were not necessarily associated with higher 7-day and 28-day mortality after adjustments (most p > 0.05). Using the restricted cubic splines, an approximately L-shaped relationship was established between MAP and the 7-day and 28-day mortality in acute stroke patients. The findings were robust to multiple sensitivity analyses in stroke patients. In critically ill stroke patients, a low MAP significantly increased the 7-day and 28-day mortality, while a high MAP did not, suggesting that a low MAP is more harmful than a high MAP in critically ill stroke patients.

Corticosteroid treatment in severe patients with SARS-CoV-2 and chronic HBV co-infection: a retrospective multicenter study.

BACKGROUND: The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients. METHODS: This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score. RESULTS: The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors. CONCLUSIONS: In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality.

Study on the Mechanism of Capillary Leakage Caused by Hypoxia-Inducible Factor-1α through Inducing High Expression of Matrix Metalloproteinase-9.

PURPOSES: This study mainly explored the mechanism of capillary leakage caused by hypoxia-inducible factor-1α through inducing high expression of matrix metalloproteinase-9. Method. We established a monolayer endothelial cell model by culturing human umbilical vein endothelial cells (HUVEC) in vitro, used tumor necrosis factor (TNFα) and HIF-1α inhibitor 2-methoxyestradiol (2ME2) to act on HUVEC, and at the same time constructed siRNA-transfected HUVEC to interfere with the expression of HIF-1α. The permeability of monolayer endothelial cells was measured by transwell chamber method, the concentration of MMP-9 in the supernatant was measured by ELISA method, the expression of key molecules related to permeability (HIF- 1α, MMP-9, claudin-5, and ZO-1) was measured by RT-PCR and Western blot method, and the localization and expression of claudin-5 and ZO-1 were measured by immunofluorescence method. We searched for 7 HIF-1α hypoxia response elements within 4000 bp before the transcription start site in the MMP-9 promoter region, constructed the MMP-9 promoter-luciferase reporter gene recombinant plasmid, transfected and stimulated HUVEC with TNFα, and detected the effect of 7 hypoxia response element plasmids on the transcription activity of MMP-9 promoter. RESULTS: Under the action of TNFα, the permeability of monolayer endothelial cells increased, and the concentration of MMP-9 in the cell supernatant increased. 2ME2 and HIF-1α-siRNA transfection can improve the above situation (P < 0.05). 2ME2 and HIF-1α-siRNA transfection can inhibit the high expression of HIF-1α and MMP-9 caused by TNFα, thereby increasing the expression of claudin-5 and ZO-1 (P < 0.05). 2ME2 and HIF-1α-siRNA transfection can reduce the inhibition of TNFα on the expression of cell membrane protein claudin-5 and tight junction protein ZO-1. Element 1, element 5, and element 7 are the sites where HIF-1α interacts with MMP-9 at the transcription level. CONCLUSION: This study shows that HIF-1α can increase the permeability of monolayer epithelial cells by inducing the high expression of MMP-9, leading to capillary leakage. Its target is at the -3798 bp, -1878 bp, and -1489 bp points of the transcription initiation site in the MMP-9 promoter region.

Tumor Necrosis Factor-α-Induced Protein 8-like 2 Downregulation Reduces CD4⁺ T Lymphocyte Apoptosis in Mice with Thermal Injury.

BACKGROUND Cellular immunity plays a crucial role in sepsis, and lymphocyte apoptosis is a key factor in immune homeostasis. Tumor necrosis factor-alpha (TNF-alpha)-induced protein 8-like 2 (TIPE2) is suggested to play a critical role in maintaining immune homeostasis. This study investigated the role of TIPE2 in CD4⁺ T lymphocyte apoptosis based on a mouse model of thermal injury. MATERIAL AND METHODS BALB/c male mice were randomized into 6 groups: sham, burn, burn with siTIPE2, burn with siTIPE2 control, burn with TIPE2, and burn with TIPE2 control groups. Splenic CD4⁺ T lymphocytes were collected by use of a magnetic cell sorting system. RESULTS We found that TIPE2 downregulation reduced the CD4⁺ T lymphocytes apoptosis in the burn with siTIPE2 group, and the protein expression of P-smad2/P-Smad3 were remarkably downregulated. In the burn with siTIPE2 group, Bcl-2 expression was increased compared with that in the sham group (P<0.05), and Bim expression was reduced (P<0.05). In the burn with TIPE2 group, the mitochondrial membrane potential was markedly reduced (P<0.01), while cytochrome C expression was clearly higher than that in the other groups (P<0.01). Activities of caspase-3, -8, and -9 were notably higher in the burn with TIPE2 group relative to those for other groups (P<0.05). CONCLUSIONS Downregulation of TIPE2 in vivo can reduce the apoptosis of CD4⁺ T lymphocytes following thermal damage, and activate the TGFß downstream signaling of Smad2/Smad3, upregulating Bim, and downregulating Bcl-2.

Diagnostic accuracy of interferon-gamma in pericardial effusions for tuberculous pericarditis: a meta-analysis.

BACKGROUND: Several studies have investigated the diagnostic accuracy of tests of pericardial effusion interferon-gamma for tuberculous pericarditis in patients with pericardial effusion, but the results have varied. The aim of this study was to investigate the diagnostic accuracy of interferon-gamma for tuberculous pericarditis using meta-analysis. METHODS: The PubMed and EMBASE databases were searched to identify studies investigating the diagnostic accuracy of tests for interferon-gamma in pericardial effusion for tuberculous pericarditis. The quality of eligible studies was assessed by the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), and the sensitivities and specificities of interferon-gamma across eligible studies were pooled by a bivariate model. RESULTS: A total of four studies encompassing 488 subjects were included. The pooled sensitivity, specificity, positive and negative likelihood ratios (NLRs) were 0.97 [95% confidence interval (CI): 0.87-0.99], 0.99 (95% CI: 0.74-1.00), 187 (95% CI: 3-12,542) and 0.03 (95% CI: 0.01-0.14), respectively. CONCLUSION: Testing for interferon-gamma in cases of pericardial effusion is adequate for identifying or ruling out tuberculous pericarditis.

Rhubarb Monomers Protect Intestinal Mucosal Barrier in Sepsis via Junction Proteins.

BACKGROUND: Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins. METHODS: Healthy male Sprague-Dawley rats (weighing 230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured. RESULTS: Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001),and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P< 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P< 0.001), D (0.029 ± 0.003, P< 0.001), E (0.026 ± 0.003, P< 0.001), F (0.027 ± 0.003, P< 0.001), G (0.030 ± 0.005, P< 0.001), and H (0.026 ± 0.002, P< 0.001) were significantly lower than that in Group B. ZO-1, occludin and claudin-5 transcription, translation, and expression in Group B were significantly lower than that in Group A (P < 0.001), but they were significantly higher in Groups C, D, E, F, G, and H than those in Group B (P < 0.05). CONCLUSION: Rhubarb monomer treatment ameliorated mucosal damage in sepsis via enhanced transcription, translation, and expression of junction proteins.

Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits.

Seawater instillation-induced acute lung injury involves oxidative stress and apoptosis. Although hydrogen gas inhalation is reportedly protective in multiple types of lung injury, the effect of hydrogen gas inhalation on seawater instillation-induced acute lung injury remains unknown. This study investigated the effect of hydrogen gas on seawater instillation-induced acute lung injury and explored the mechanisms involved. Rabbits were randomly assigned to control, hydrogen (2 % hydrogen gas inhalation), seawater (3 mL/kg seawater instillation), and seawater + hydrogen (3 mL/kg seawater instillation + 2 % hydrogen gas inhalation) groups. Arterial partial oxygen pressure and lung wet/dry weight ratio were detected. Protein content in bronchoalveolar lavage fluid (BALF) and serum as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels were determined. Hematoxylin-eosin staining was used to monitor changes in lung specimens, and malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were assayed. In addition, NF-E2-related factor (Nrf) 2 and heme oxygenase (HO)-1 mRNA and protein expression were measured, and apoptosis was assessed by measuring caspase-3 expression and using terminal deoxy-nucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. Hydrogen gas inhalation markedly improved lung endothelial permeability and decreased both MDA content and MPO activity in lung tissue; these changes were associated with decreases in TNF-α, IL-1ß, and IL-6 in BALF. Hydrogen gas also alleviated histopathological changes and cell apoptosis. Moreover, Nrf2 and HO-1 expressions were significantly activated and caspase-3 expression was inhibited. These results demonstrate that hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury in rabbits and that the protective effects observed may be related to the activation of the Nrf2 pathway.

Rhubarb Antagonizes Matrix Metalloproteinase-9-induced Vascular Endothelial Permeability.

BACKGROUND: Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability. METHODS: Rhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR), carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers. RESULTS: A total of 21 rhubarb monomers were extracted and identified. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer (emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-ß-D-glucose, daucosterol linoleate, and rhein) or a combination of all five monomers (1 µmol/L for each monomer). Mechanistically, the five-monomer mixture at 1 µmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE-cadherin into the culture medium, which was significantly inhibited by the five-monomer mixture. CONCLUSIONS: The rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-ß-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations.

Comparative Study of Plasma Endotoxin with Procalcitonin Levels in Diagnosis of Bacteremia in Intensive Care Unit Patients.

BACKGROUND: Both procalcitonin (PCT) and plasma endotoxin levels cannot be solely used for a definite diagnosis of bacteremia or sepsis, and there has been few study comparing the values of the two biomarkers for the diagnosis of bacteremia. The aim of this study was to identify bacteria causing bacteremia and evaluate the role of the two biomarkers in the diagnosis of bacteremia in Intensive Care Unit (ICU). METHODS: The medical records of 420 patients in ICU were retrospectively reviewed. Patients (n = 241) who met the inclusion criteria were subjected to blood culture (BC) for the analysis of the endotoxin or PCT levels. The exclusion criteria included the presence of infection with human immunodeficiency virus and/or AIDS, neutropenia without sepsis, pregnancy, treatment with immunosuppressive therapies, or blood diseases such as hematological tumors. Patients' BC episodes were divided into BC negative, Gram-negative (GN) bacteria, Gram-positive bacteria, and fungi groups. The PCT and plasma endotoxin levels were compared in the different groups. RESULTS: A total of 241 patients with 505 episodes of BC were analyzed. The GN bacteria group showed higher levels of PCT and endotoxin than the BC negative, Gram-positive bacteria, and fungi groups. GN bacteremia was more prevalent than Gram-positive bacteremia. The GN bacteremia caused by non-Enterobacteriaceae infection presented higher endotoxin level than that by Enterobacteriaceae, but no significant difference in PCT levels was observed between the two groups. The plasma endotoxin significantly differed among different groups and was bacterial species dependent. CONCLUSIONS: Plasma endotoxin was more related to GN than to Gram-positive bacteremia, and that endotoxin level was species dependent, but PCT level remained relatively more stable within the GN bacteria caused bacteremia. Both GN and positive bacteria caused bacteremia in the ICU patients in different regions of China. And PCT is a more valuable biomarker than endotoxin in the diagnosis of bacteremia.

Use of Platelet Indices for Determining Illness Severity and Predicting Prognosis in Critically Ill Patients.

BACKGROUND: Decreased platelet (PLT) count is one of the independent risk factors for mortality in intensive care unit (ICU) patients. This study was to investigate the relationship between PLT indices and illness severity and their performances in predicting hospital mortality. METHODS: Adult patients who admitted to ICU of Changzheng Hospital from January 2011 to September 2012 and met inclusion criteria were included in this study. Univariate analysis was used to identify potential independent risk factors for mortality. Multiple logistic regression analysis was used to calculate adjusted odds ratio for mortality in patients with normal or abnormal PLT indices. The relationship between PLT indices and illness severity were assessed by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores or sequential organ failure assessment (SOFA) scores in patients with normal and abnormal PLT indices. The performances of PLT indices in predicting mortality were assessed by receiver operating curves and diagnostic parameters. The survival curves between patients with normal and abnormal PLT indices were compared using Kaplan-Meier method. RESULTS: From January 2011 to September 2012, 261 of 361 patients (204 survivors and 57 nonsurvivors) met the inclusion criteria. After adjustment for clinical variables, PLT count <100 × 10 12 /L (P = 0.011), plateletcrit (PCT) <0.108 (P = 0.002), mean platelet volume (MPV) >11.3 fL (P = 0.023) and platelet distribution width (PDW) percentage >17% (P = 0.009) were identified as independent risk factors for mortality. The APACHE II and SOFA scores were 14.0 (9.0-20.0) and 7.0 (5.0-10.5) in the "low PLT" tertile, 13.0 (8.0-16.0) and 7.0 (4.0-11.0) in the "low PCT" tertile, 14.0 (9.3-19.0) and 7.0 (4.0-9.8) in the "high MPV" tertile, 14.0 (10.5-20.0) and 7.0 (5.0-11.0) in the "high PDW" tertile, all of which were higher than those in patients with normal indices. Patients with decreased PLT and PCT values (all P < 0.001), or increased MPV and PDW values (P = 0.007 and 0.003, respectively) had shortened length of survival than those with normal PLT indices. CONCLUSIONS: Patients with abnormally low PLT count, high MPV value, and high PDW value were associated with more severe illness and had higher risk of death as compared to patients with normal PLT indices.

Effect of rhubarb pre-treatment on intestinal microcirculation in septic rats.

The intestine plays a vital role in the pathophysiology of sepsis development. The objective of the present study was to explore the effects of rhubarb on intestinal microcirculation in septic rats. We used moorFLPI laser speckle imaging to detect the blood flow of the intestinal mucosa and wall. Using an ELISA, we assayed the concentration of lactate (L) and pyruvic acid (P) in the intestinal tissue to calculate the ratio of lactate to pyruvic acid (L/P ratio). To observe the intestinal mucosal capillaries, gelatin and ink were perfused into the intestine and subsequently stained with hematoxylin and eosin (HE) to measure the ratio of the vessel area. We then used immunohistochemistry to measure CD31 expression. Using an MTT assay, the effect of the rhubarb extract on the proliferation of human umbilical vein endothelial cells (HUVECs) was analyzed. The blood flow in the intestinal wall and mucosa of the control, sham and rhubarb-treated groups was significantly higher, while the sepsis group had relatively low blood flow. The L/P ratio in the intestinal tissue was larger in the sepsis group than in the other three groups. The microvascular area (MVA) in the sepsis group was smaller than in the control group, sham group or rhubarb group. Positive expression for CD31 was observed in the cytoplasm of vascular endothelial cells. The intestinal mucosal capillaries were reduced in septic rats as compared to the other three groups. HUVEC proliferation was enhanced by the rhubarb extract monomers at 1 µmol/L, but suppressed at higher concentrations of 10 to 100 µmol/L. These results suggest that pre-treatment with rhubarb prior to sepsis induction promotes the expansion of the intestinal mucosal capillaries, protects intestinal mucosal capillary endothelial cells and increases the number of functional intestinal capillaries.

Comparison of Charlson's weighted index of comorbidities with the chronic health score for the prediction of mortality in septic patients.

BACKGROUND: Comorbidity is one of the most important determinants of short-term and long-term outcomes in septic patients. Charlson's weighted index of comorbidities (WIC) and the chronic health score (CHS), which is a component of the acute physiology and chronic health evaluation (APACHE) II, are two frequently-used measures of comorbidity. In this study, we assess the performance of WIC and CHS in predicting the hospital mortality of intensive care unit (ICU) patients with sepsis. METHODS: A total of 338 adult patients with sepsis were admitted to a multisystem ICU between October 2010 and August 2012. Clinical data were collected, including age, gender, underlying diseases, key predisposing causes, severity-of-sepsis, and hospital mortality. The APACHE II, CHS, acute physiology score (APS), sequential organ failure assessment (SOFA) and WIC scores were assessed within the first 24 hours of admission. Univariate and multiple Logistic regression analyses were used to compare the performance of WIC and CHS. The area under the receiver operating characteristic curve (AUC) was used to predict hospital mortality over classes of risk. RESULTS: Of all the enrolled patients, 224 patients survived and 114 patients died. The surviving patients had significantly lower WIC, CHS, APACHE II, and SOFA scores than the non-surviving patients (P < 0.05). Combining WIC or CHS with other administrative data showed that the hospital mortality was significantly associated with age, severe sepsis, key predisposing causes such as pneumonia, a history of underlying diseases such as hypertension and congestive cardiac failure, and WIC, CHS and APS scores (P < 0.05). The AUC for the hospital mortality were 0.564 (95% confidence interval (CI) 0.496-0.631) of CHS, 0.663 (95% CI 0.599-0.727) of WIC, 0.770 (95% CI 0.718-0.822) of APACHE II, 0.856 (95% CI 0.815-0.897) of the CHS combined with other administrative data, and 0.857 (95% CI 0.817-0.897) of the WIC combined with other administrative data. The diagnostic value of WIC was better than that of CHS (P = 0.0015). CONCLUSIONS: The WIC and CHS scores might be independent determinants for hospital mortality among ICU patients with sepsis. WIC might be an even better predictor of the mortality of septic patients with comorbidities than CHS.

[Combination of Weighted index of comorbidities and sepsis-related organ failure assessment score in death risk evaluation of septic patients].

OBJECTIVE: To predict the risk of 28- day mortality on septic patients in intensive care unit (ICU) with the combination of the Weighted index of comorbidities (WIC) and sepsis-related organ failure assessment (SOFA) score. METHODS: The clinical data of adult sever sepsis/ septic shock patients in Department of Emergency Medicine of Chagzeng Hospital and Department of Clinical Care Medicine of Jinan Military General Hospital from October 2011 to February 2013 were analyzed retrospectively. The etiological factor, past history, having sever sepsis or not were recorded. Age score, WIC score, acute physiology and chronic health evaluation II (APACHE II) score and SOFA score were calculated at or 24 hours after admission. The logistic regression was used and the receiver operating characteristic curve (ROC curve) was drawn to calculate the patients' outcome. RESULTS: In 310 enrolled patients, 223 (71.9%) patients survived and 87 (28.1%) died. Univariate analysis showed the P values of the age score, WIC score, APACHE II score and SOFA score. chronic cardiac insufficiency, type 2 diabetes, cerebrovascular disease, tumor, multiple injury, pulmonary infection and having severe sepsis or not were all less tha 0.2. The above 11 variables were put into the multivariate logistic regression equation 1, of which predicted probability was reserved. It revealed that 5 variables were independently associated with 28-day prognosis, of which influence power in descending order were SOFA score [odds ratio (OR)=1.308, 95 % confidence interval (95% CI): 1.158-1.478, P=0.000], having sever sepsis or not (OR=0.206, 95% Cl:0.100-0.424, P=0.000), APACHE II score (OR=1.090, 95% CI:1.021-1.164, P=0.010) WIC score (OR=1.441, 95% CI:1.067-1.947, P=0.017) age score (OR=1.228, 95% CI:1.027-1.468, P=0.024), the Wals were 18.554, 18.369, 6.725, 5.662, 5.067, respectively. The 3 variables, age score, WIC score and SOFA score, were brought into the multivariate logistic regression equation 2, of which predicted probability was reserved too. It revealed that age score (OR=1.330, 95 % CI: 1.145-1.546, P=0.000), WIC score (OR=1.496, 95% CI: 1.145-1.546, P=000) and SOFA score (OR=1.429, 95% CI: 1.303-1.567, P=0.000), were independently associated with the septic patients' 28-day prognosis. There was no significant difference in the area under receiver operating characteristics curve (AUC) between the SOFA score and APACHE II score (0.784 vs. 0.780, Z=0.014, P=0.989). However, compared with APACHE II score, the AUC of equation 1 (0.888) and 2 (0.851) were much more (Z=4.333, P= 0.000; Z= 2.669, P= 0.008). CONCLUSION: The sensitivity of 28-day prognosis 28-day prognosis by WIC score was improved greatly with the combination of SOFA score and age score.

[Prognostic value of arterial lactate content combined with base excess in patients with sepsis: a retrospective study].

OBJECTIVE: To study the prognostic value of arterial lactate combined with base excess (BE) in sepsis patients. METHODS: Clinical data of patients admitted to intensive care unit (ICU) from July 2009 to December 2012 were retrospectively analyzed. Patients were divided into survivor group and non-survivor group, and the arterial blood lactate and BE concentrations were compared between groups. The receiver operating characteristic curve (ROC curve) was drawn and area under the ROC curve (AUC) was calculated to analyze the function of arterial lactate, BE and their combination in judging the prognosis of sepsis. The best cut-off values of arterial lactate and BE for sepsis prognosis were searched. RESULTS: One hundred and eighteen patients were enrolled with 75 in survivor group and 43 in non-survivor group. There were significant differences in arterial lactate [1.20(0.90) mmol/L, 2.30(1.90) mmol/L] and BE (0.44 ± 5.13 mmol/L, -4.35 ± 4.86 mmol/L) between two groups (both P=0.000). The AUC for mortality prediction was 0.805, 0.755 and 0.822 for arterial blood lactate, BE, and their combination respectively. Using arterial lactate higher than 1.7 mmol/L and BE lower than -3 mmol/L as cut-off values, a better sensitivity (79.1% and 69.8%) and positive predictive value (3.955 and 2.493) can be obtained. CONCLUSION: Combination of arterial lactate and BE can be a better indicator of prognosis in sepsis patients.

[The use of Charlson weighted index of comorbidities scoring system to evaluate the impact of original diseases for prognosis in intensive care unit patients].

OBJECTIVE: To investigate the efficiency of original diseases by the Charlson weighted index of comorbidities (WIC) in predicting 28-day mortality in patients with critical illnesses in intensive care unit (ICU). METHODS: A single-center retrospective analysis of clinical data of 406 patients admitted between January 2009 and October 2011 to Shanghai Changzheng Hospital was conducted. The patients were divided into non-survivor group (n=104) and survivor group (n=302) according to 28-day outcome. The data were recorded, and the WIC and the acute physiology and chronic health evaluation II (APACHEII) score were calculated. Logistic regression analysis was used to determine the independent predictors for 28-day mortality. RESULTS: Compared with survivors, the average age, WIC and APACHEII scores, severe sepsis, pneumonia, and multiple injuries were higher in non-survivors. The univariate analysis showed that age, the WIC score, APACHEII score, pneumonia, multiple injuries and severe sepsis were related with patients' 28-day prognosis. The multivariate logistic regression revealed that 28-day prognosis depended significantly on WIC score [odds ratio (OR)=1.538, 95% confidence interval (95%CI) 1.265 - 1.869, P=0.000], APACHEII score (OR=1.193, 95%CI 1.137 - 1.252, P=0.000), pneumonia (OR=0.546, 95%CI 0.304 - 0.982, P=0.043), and severe sepsis (OR=0.178, 95%CI 0.098 - 0.323, P=0.000). The area under the receiver operating characteristics curve (ROC curve) in predicting mortality was 0.657 (0.592 - 0.722) for the WIC score, 0.790 (0.739 - 0.841) for APACHEII score and 0.821 (0.772 - 0.869) for their combination. CONCLUSION: The WIC scoring system can be a good evaluation method for 28-day prognosis in ICU patients.

[Value of a model based on PIRO conception in predicting the prognosis in critical patients].

OBJECTIVE: To investigate the values of factors based on PIRO conception in predicting the prognosis of critical patients. METHODS: The clinical data of critical patients admitted to Hainan Branch of PLA General Hospital from December 2011 to August 2013 were retrospectively analyzed. The patients were randomly divided into non-survivors and survivors groups according to 28-day outcome. Predisposition (P), injury (I), response (R) and organ dysfunction induced by injury (O) were compared between two groups. The indexes with statistical significance (P<0.2) by univariate analysis were included in multivariate logistic regression analysis, and the receiver operating characteristic curve (ROC curve) was plotted to evaluate the values of factors based on PIRO conception in predicting the prognosis of critical patients. RESULTS: One hundred and eighty-seven critical patients were enrolled, and among them 75 (40.1%) patients died. Univariate analysis showed that the age, underlying disease scores, history of cardiovascular disease, diabetes mellitus, and cerebrovascular disease, positive blood culture, whether or not complicated with acute respiratory distress syndrome (ARDS) or severe sepsis/septic shock, procalcitonin (PCT), acute physiology and chronic health evaluation II (APACHE II), acute pathophysiology score (APS) and sequential organ failure assessment (SOFA) were found to be the factors related with the prognosis (all P<0.2). Multivariate logistic regression analysis showed that the underlying disease scores [odds ratio (OR)=1.874, 95% confidence interval (95%CI) 1.138-3.084, P=0.014], whether patients occurrence of severe sepsis/septic shock (OR=0.167, 95%CI 0.064-0.435, P=0.000) and SOFA scores (OR=1.498, 95%CI 1.283-1.750, P=0.000) were independent factors for predicting 28-day mortality. The new model combined with above factors had more prognostic value in predicting the mortality than a single variable. The area under ROC curve (AUC) for PIRO model based on indexes with statistical significance by univariate analysis was 0.877 (0.821-0.934), P=0.000. AUC for PIRO model based on underlying disease scores, severe sepsis/septic shock, SOFA scores was 0.871 (0.814-0.928), P=0.000. AUC for SOFA was 0.762 (0.687-0.837), P=0.000. AUC for APS was 0.726 (0.647-0.805), P=0.000. AUC for underlying disease scores was 0.678 (0.593-0.763), P=0.000. AUC for PCT was 0.636 (0.548-0.724), P=0.004. AUC for age was 0.618 (0.532-0.705), P=0.013]. CONCLUSIONS: The multivariate regression analysis based on PIRO system may help to predict 28 days mortality in critical patients.