Presepsin As a Biomarker for Evaluating Prognosis and Early Innate Immune Response of Out-of-Hospital Cardiac Arrest Patients After Return of Spontaneous Circulation.

OBJECTIVES: After return of spontaneous circulation, patients who experienced out-of-hospital cardiac arrest present an impaired innate immune response that resembles sepsis. Presepsin, a new biomarker for sepsis, has not been studied in out-of-hospital cardiac arrest patients. This study explored the role of presepsin in evaluating the prognosis and early innate immune alteration of out-of-hospital cardiac arrest patients after return of spontaneous circulation by observing presepsin levels, CD14, and human leukocyte antigen-DR expression on monocytes. DESIGN: Retrospective analysis. SETTING: The emergency department of an urban university tertiary hospital. PARTICIPANTS: One hundred sixty-five out-of-hospital cardiac arrest patients with return of spontaneous circulation more than 12 hours, and 100 healthy individuals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma presepsin and procalcitonin levels were tested after resuscitation (day 0) and on days 1 and 3 after return of spontaneous circulation. Presepsin levels were higher in out-of-hospital cardiac arrest patients than in healthy individuals. In the first 3 days, presepsin and procalcitonin levels were persistently lower in 28-day survivors and patients with favorable neurologic outcome patients than in 28-day nonsurvivors and patients with unfavorable neurologic outcome. On days 0, 1, and 3, different cut-off values of presepsin showed prognostic value for 28-day mortality and favorable neurologic outcomes similar to procalcitonin. CD14 and human leukocyte antigen-DR expression on monocytes were analyzed by flow cytometry. Compared with controls, CD14 expression in out-of-hospital cardiac arrest patients increased on day 1 and began to decrease on day 3, whereas human leukocyte antigen-DR+ monocyte percentages decreased on days 1 and 3. Presepsin and procalcitonin had a low positive correlation with CD14 expression and a strong negative correlation with human leukocyte antigen-DR+ monocyte percentages on day 1. CONCLUSIONS: Plasma presepsin concentrations are independent prognostic factors for out-of-hospital cardiac arrest patients after return of spontaneous circulation and are correlated with abnormal CD14 and human leukocyte antigen-DR expression on monocytes. Monitoring presepsin levels may be helpful for evaluating the prognosis and impaired innate immune response in the early period after return of spontaneous circulation.

Patients with out-of-hospital cardiac arrest show decreased human leucocyte antigen-DR expression on monocytes and B and T lymphocytes after return of spontaneous circulation.

Immune disorders are an important feature of patients with out-of-hospital cardiac arrest (OHCA) after return of spontaneous circulation (ROSC). However, the precise immune alterations in patients with OHCA that occur immediately after ROSC are unclear. In this study, we investigated human leucocyte antigen-DR (HLA-DR) expression on circulatory monocytes and B and T lymphocytes. Sixty-eight consecutive patients with OHCA with ROSC >12 hours were enrolled. Clinical data and 28-day survival were recorded. Peripheral blood samples after ROSC days 1 and 3 were analysed to evaluate HLA-DR expression. Fifty healthy individuals were enrolled as controls. Compared with levels in healthy individuals, HLA-DR expression on monocytes and B lymphocytes, but not on T lymphocytes, decreased on days 1 and 3 after ROSC. No significant difference in HLA-DR expression was detected between survivors and non-survivors on day 1. For 41 patients with expression data for days 1 and 3, HLA-DR expression on monocytes and B lymphocytes in non-survivors was lower than that in survivors on day 3. In non-survivors, the mean fluorescence intensities of HLA-DR on B lymphocytes and percentages of HLA-DR+ T lymphocytes were lower on day 3 than on day 1. On days 1 and 3, there were significant correlations between HLA-DR expression on monocytes and B lymphocytes and clinical indicators, such as time to ROSC, adrenaline dose, acute physiology, chronic health evaluation II and the sequential organ failure assessment. The decreases in HLA-DR expression on circulatory monocytes and B and T lymphocytes after ROSC may be involved in the observed immunosuppression in patients with OHCA.

Efficacy of vasopressin-epinephrine compared to epinephrine alone for out of hospital cardiac arrest patients: A systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to conduct a meta-analysis to evaluate the efficacy of vasopressin-epinephrine compared to epinephrine alone in patients who suffered out-of-hospital cardiac arrest (OHCA). METHODS: Relevant studies up to February 2017 were identified by searching in PubMed, EMBASE, the Cochrane Library, Wanfang for randomized controlled trials(RCTs) assigning adults with cardiac arrest to treatment with vasopressin-epinephrine (VEgroup) vs adrenaline (epinephrine) alone (E group). The outcome point was return of spontaneous circulation (ROSC) for patients suffering from OHCA. Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored. RESULTS: Individual patient data were obtained from 5047 participants who experienced OHCA in nine studies. Odds ratios (ORs) were calculated using a random-effects model and results suggested that vasopressin-epinephrine was associated with higher rate of ROSC (OR=1.67, 95% CI=1.13-2.49, P<0.00001, and total I2=83%). Subgroup showed that vasopressin-epinephrine has a significant association with improvements in ROSC for patients from Asia (OR=3.30, 95% CI=1.30-7.88); but for patients from other regions, there was no difference between vasopressin-epinephrine and epinephrine alone (OR=1.07, 95% CI=0.72-1.61). CONCLUSION: According to the pooled results of the subgroup, combination of vasopressin and adrenaline can improve ROSC of OHCA from Asia, but patients from other regions who suffered from OHCA cannot benefit from combination of vasopressin and epinephrine.

Evaluating the value of dynamic procalcitonin and presepsin measurements for patients with severe sepsis.

OBJECTIVE: This study comparatively evaluated the value of dynamic procalcitonin (PCT) and presepsin measurements in assessing therapeutic efficacy and prognosis for patients with severe sepsis. METHODS: Patients with severe sepsis (n=109) were enrolled and divided into survival and non-survival groups based on 90-day survival. PCT and presepsin levels were evaluated on days 1, 3, 5, 7, and 12. Sequential organ failure assessment (SOFA) was calculated. RESULTS: PCT from day 5 onward was weakly to moderately positively correlated with SOFA, whereas presepsin from day 3 onward was positively correlated. From day 5 onward, the clearance ratio (CR) of PCT was weakly to moderately negatively correlated with SOFA, while the CR of presepsin was strongly negatively correlated as early as day 3. PCT levels had no statistical difference between survival and non-survival groups. Within 12days, PCT levels in both survival and non-survival groups decreased synchronously. Comparatively, presepsin levels in the survival group decreased persistently, while they rose gradually in the non-survival group. CRs of PCT in the survival group were higher than those in the non-survival group on days 3, 5, 7, and 12. However, CRs of PCT rose synchronously in both groups. Comparatively, CRs of presepsin in the survival group rose persistently, while they decreased gradually in the non-survival group. CONCLUSIONS: Dynamic monitoring of presepsin and PCT demonstrated that both presepsin and CR of presepsin are continuous and better markers than are PCT and CR of PCT for evaluating the therapeutic efficacy and prognosis of patients with severe sepsis.

Prognostic Value of Dynamic Monitoring of Cellular Immunity and HMGB1 in Severe Sepsis: Delayed Chronic Inflammation may be the Leading Cause of Death in Late Severe Sepsis.

BACKGROUND: Sepsis is a life-threatening response to infection with a high mortality rate. In order to explore the prognostic value of dynamic monitoring of cellular immunity during late severe sepsis, we assessed levels of Tlymphocyte subsets, the human leukocyte antigen D-related (HLA-DR), and the high mobility group box-1 (HMGB1) protein. METHODS: Study participants included 247 consecutive severe sepsis patients who were admitted to Beijing ChaoYang Hospital's Emergency Intensive Care Unit. Patients were divided into survivors and non-survivors based on 90-day survival rates, and clinical data were collected. T-lymphocyte subsets on days 1 and 7, HLA-DR on days 1 and 12, and HMGB1 on days 1, 3, 5, 7, and 12 were analyzed. RESULTS: Counts of CD3+, CD3+CD4+, and CD3+CD8+ T cells on day 1 in non-survivors were lower than those in survivors. By day 7, counts of all three types of T cells had increased in both survivors and non-survivors, but CD3+ and CD3+CD8+ T cells remained lower in non-survivors than in survivors. There was no significant difference in HLA-DR levels between survivors and non-survivors on day 1, but HLA-DR levels increased in survivors and decreased in non-survivors by day 12. In contrast, over days 1 - 12, HMGB1 levels increased in non-survivors and decreased in survivors. CONCLUSIONS: Patients with severe sepsis present with cellular immune dysfunction and persistent chronic inflammation, both of which may lead to death in the late phase of severe sepsis. Dynamic monitoring of indicators of cellular immunity and HMGB1 is useful for evaluating the immune status, chronic inflammation processes, and prognoses of patients with severe sepsis.

Renal Replacement Therapy as a New Indicator of Voriconazole Clearance in a Population Pharmacokinetic Analysis of Critically Ill Patients.

AIMS: The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of using extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and those of various biological covariates on the voriconazole PK profile. METHODS: Modeling analyses of the PK parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) with a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different stratifications of quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges. RESULTS: A total of 408 critically ill patients with 746 voriconazole concentration-time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CLCR), platelets (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM. CONCLUSIONS: We found that qCRP, CRRT, CLCR, PLT, and PT affected the voriconazole clearance. The most commonly used clinical regimen of 200 mg q12h was sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L), regardless of whether CRRT was performed and the level of qCRP. When the MIC was 0.5 mg/L, 200 mg q12h was insufficient only when the qCRP was <40 mg/L and CRRT was performed. When the MIC was ≥2 mg/L, a dose of 300 mg q12h could not achieve ≥ 90% PTA, necessitating the evaluation of a higher dose.

The effect of nebulized heparin on clinical outcomes in mechanically ventilated patients: a meta-analysis and review of the literature.

OBJECTIVE: To determine the relationship between use of nebulized heparin and clinical outcomes in mechanically ventilated patients. METHODS: The Medline, Embase, Web of Science, Cochrane Library, and PubMed databases were searched for relevant randomized controlled trials (RCTs), published between database inception and May 2022. Primary outcomes were intensive care unit (ICU) length of stay and in-hospital mortality; secondary outcomes included duration of mechanical ventilation, ventilator-free days (VFDs) in 28 days, and length of hospitalization. The study protocol was registered on PROSPERO (registration No: CRD42022345533). RESULTS: A total of eight RCTs (651 patients) were included. Nebulized heparin was associated with reduced ICU length of stay (six studies; mean difference [MD] -1.10, 95% confidence interval [CI] -1.87, -0.33, I2 = 76%), reduced duration of mechanical ventilation (two studies; MD -2.63, 95% CI -3.68, -1.58, I2 = 92%) and increased VFDs in 28 days (two studies; MD 4.22, 95% CI 1.10, 7.35, I2 = 18%), without increased incidence of adverse events, such as bleeding; but was not associated with a reduction in length of hospitalization (three studies; MD -1.00, 95% CI -2.90, -0.90, I2 = 0%) or in-hospital mortality (five studies; odds ratio 1.10, 95% CI 0.69, 1.77, I2 = 0%). CONCLUSION: Nebulized heparin reduces ICU length of stay and duration of mechanical ventilation in mechanically ventilated patients, but has no effect on length of hospitalization or mortality.

Severe pulmonary co-infection with varicella-zoster virus, Pneumocystis jirovecii and Cytomegalovirus: a case report.

Pneumocystis jirovecii, Cytomegalovirus and varicella-zoster virus are all opportunistically infective pathogens, but pulmonary co-infection with these pathogens is rare. Herein, this case report describes a patient with autoimmune haemolytic anaemia treated with methylprednisolone and cyclosporine that presented with rapidly progressive severe respiratory failure. Analysis of microbial nucleic acid sequences in both blood and sputum using next-generation sequencing revealed pulmonary co-infection with Pneumocystis jirovecii, varicella-zoster virus, and possibly Cytomegalovirus. After timely targeted and supportive treatments, the patient recovered. This case report highlights the imaging features of co-infection with these pathogens, the importance of next-generation sequencing for early diagnosis in immunosuppressed patients, and the effects of corticosteroid therapy.

Alveolar epithelial glycocalyx shedding aggravates the epithelial barrier and disrupts epithelial tight junctions in acute respiratory distress syndrome.

The main pathophysiological mechanism of acute respiratory distress syndrome (ARDS) invovles the increase in alveolar barrier permeability that is primarily caused by epithelial glycocalyx and tight junction (TJ) protein destruction. This study was performed to explore the effects of the alveolar epithelial glycocalyx on the epithelial barrier, specifically on TJ proteins, in ARDS. We used C57BL/6 mice and human lung epithelial cell models of lipopolysaccharide (LPS)-induced ARDS. Changes in alveolar permeability were evaluated via pulmonary histopathology analysis and by measuring the wet/dry weight ratio of the lungs. Degradation of heparan sulfate (HS), an important component of the epithelial glycocalyx, and alterations in levels of the epithelial TJ proteins (occludin, zonula occludens 1, and claudin 4) were assessed via ELISA, immunofluorescence analysis, and western blotting analysis. Real-time quantitative polymerase chain reaction was used to detect the mRNA of the TJ protein. Changes in glycocalyx and TJ ultrastructures in alveolar epithelial cells were evaluated through electron microscopy. In vivo and in vitro, LPS increased the alveolar permeability and led to HS degradation and TJ damage. After LPS stimulation, the expression of the HS-degrading enzyme heparanase (HPA) in the alveolar epithelial cells was increased. The HPA inhibitor N-desulfated/re-N-acetylated heparin alleviated LPS-induced HS degradation and reduced TJ damage. In vitro, recombinant HPA reduced the expression of the TJ protein zonula occludens-1 (ZO-1) and inhibited its mRNA expression in the alveolar epithelial cells. Taken together, our results demonstrate that shedding of the alveolar epithelial glycocalyx aggravates the epithelial barrier and damages epithelial TJ proteins in ARDS, with the underlying mechanism involving the effect of HPA on ZO-1.

Programmed Cell Death-1/Programmed Death-Ligand 1 Blockade Improves Survival of Animals with Sepsis: A Systematic Review and Meta-Analysis.

OBJECT: To investigate effects of programmed cell death-1 (PD-1) related blockade in sepsis animals. METHODS: Two reviewers independently searched electronic databases including PubMed, EMBASE, and the Cochrane Library up to February 2017. Strict literature retrieval and data extraction were performed to extract relevant data. Data analysis was conducted using RevMan 5.3 software and Stata version 12.0. And relative risks (RRs) for survival rate were calculated. A fixed-effect model was selected to pool and a forest plot was used to display RRs. RESULTS: Four studies involving 394 animals were finally included. Nine control groups are used to pool. A fixed-effect model was applied to estimate a pooled RR of 2.19 (95% CI: 1.74-2.76), indicating that PD-1 related blockade increased survival rate in sepsis animals. CONCLUSION: We concluded that PD-1 related blockade can improve survival of animals with sepsis. But robust standardized clinical experiments for sepsis patients are highly desirable.

Prognostic value of gasping for short and long outcomes during out-of-hospital cardiac arrest: an updated systematic review and meta-analysis.

OBJECTIVE: We systematically reviewed the literature to investigate whether gasping could predict short and long outcomes in patients with out of hospital cardiac arrest (OHCA). METHODS: PubMed, Embase, and Cochrane Library were searched for observational studies regarding the prognostic effect of gasping on short and long outcomes in adults with OHCA. The primary outcome was return of spontaneous circulation (ROSC). The secondary outcomes were favorable neurological outcome at discharge or at 30 days after cardiac arrest;long term (≥6 months) survival; initial shockable rhythm.The Mantel-Haenszel method with random-effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Five studies (six cohorts) were included in the final analysis. In the pooled analysis, gasping was not only associated with a significant increase in ROSC (RR, 1.87; 95% CI, 1.64-2.13; I2 = 70%), but also a high likelihood of favorable neurological outcomes (RR, 3.79; 95% CI, 1.86-7.73), long-term survival (RR, 3.46; 95% CI, 1.70-7.07), and initial shockable rhythm (RR, 2.25; 95% CI, 2.05-2.48). CONCLUSIONS: Current evidence indicates that gasping can predict short and long outcomes in patients with OHCA.In addition, gasping is associated with a high likelihood of initial shockable rhythm,which may contribute to positive outcomes.

Predictors of survival and favorable neurological outcome in patients treated with targeted temperature management after cardiac arrest: A systematic review and meta-analysis.

This study was aimed at a serial evaluation of the prognostic values of initial shockable rhythm, bystander cardiopulmonary resuscitation (CPR) and gender for neurological outcome and survival in adults treated with targeted temperature management (TTM) following cardiac arrest (CA). PubMed, Embase and the Cochrane Library were searched for eligible studies. Pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate prognostic values using RevMan 5.3. The outcomes were favorable neurological outcome (defined as cerebral performance category of 1 and 2) and survival. Seventeen studies were subjected to the meta-analysis. Favorable neurological outcome was associated with significantly higher odds of an initial shockable rhythm (OR: 7.63, 95%CI: 6.51-8.96), bystander CPR (OR: 1.44, 95%CI: 1.14-1.82), male (OR: 1.39, 95%CI: 1.20-1.61). Survival was associated with higher odds of an initial shockable rhythm (OR: 4.88, 95%CI: 3.18-4.79), higher odds of bystander CPR (OR: 1.71, 95%CI: 1.05-2.77). No significant association was found between survival and male. In adult patients treated with TTM, initial shockable rhythm, bystander CPR and male sex were associated with a higher likelihood of favorable neurological outcome. Initial shockable rhythm and bystander CPR were associated with a higher likelihood of survival. These factors could help in identifying patients who are eligible for TTM.

Early Changes in Circulatory T Helper Type 1, 2, and 17 Cells of Patients with Out-of-Hospital Cardiac Arrest after Successful Cardiopulmonary Resuscitation.

BACKGROUND: Immune disorder is an important feature of patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC). We investigated the expression of circulatory T helper type (Th) 1, Th2, and Th17 cells to explore the early immune alteration in OHCA patients after ROSC. METHODS: During July-September 2016 and March-September 2017, 65 consecutive OHCA patients with ROSC >12 h and 30 healthy individuals were enrolled in this study. Clinical and 28-day survival data were collected. Peripheral blood samples were analyzed to evaluate the expression of Th1/Th2/Th17 cells by flow cytometry from OHCA patients after ROSC on days 1 and 3 and from healthy individuals. RESULTS: Compared with healthy individuals, T lymphocyte counts and Th1 cell counts decreased on days 1 and 3 after ROSC (1464 [1198, 2152] vs. 779 [481, 1140] vs. 581 [324, 1118]/µl, χ2 = 30.342, P < 0.001; 154 [90, 246] vs. 39 [19, 78] vs. 24 [12, 53]/µl, χ2 = 42.880, P < 0.001), and Th2 and Th17 cell counts decreased on day 3 (17.0 [10.8, 24.0] vs. 9.0 [3.0, 15.5]/µl, Z = -3.228, P = 0.001; 4.7 [2.7, 9.1] vs. 2.7 [1.0, 6.5]/µl, Z = -2.294, P = 0.022). No change in CD4+/CD3+ lymphocyte ratio was seen on day 1 or day 3 (57.9 [49.4, 63.0] vs. 55.4 [46.5, 66.5] vs. 55.4 [50.2, 67.0]%, χ2 = 0.171, P = 0.918). Th1/CD4+ lymphocyte ratio decreased on days 1 and 3 (19.0 [14.0, 24.9] vs. 9.3 [4.6, 13.9] vs. 9.5 [4.9, 13.6]%, χ2 = 25.754, P < 0.001), and Th2/CD4+ lymphocyte ratio increased on day 1 and decreased on day 3 (1.9 [1.2, 2.5] vs. 2.5 [1.6, 4.0] vs. 1.9 [1.6, 3.8]%, χ2 = 6.913, P = 0.032). Th1/Th2 cell ratio also decreased on both days (9.4 [7.3, 13.5] vs. 3.1 [1.9, 5.6] vs. 4.2 [2.8, 5.9], χ2 = 44.262, P < 0.001). Despite an upward trend in the median of Th17/CD4+ lymphocyte ratio in OHCA patients, there was no significant difference compared with healthy individuals (0.9 [0.4, 1.2] vs. 0.7 [0.4, 1.2] vs. 0.6 [0.3, 1.0]%, χ2 = 2.620, P = 0.270). The dynamic expression of Th1/Th2/Th17 cells on days 1 and 3 were simultaneously analyzed in 28/53 OHCA patients who survived >3 days; patients were divided into survivors (n = 10) and nonsurvivors (n = 18) based on 28-day survival. No significant differences in Th1/Th2/Th17 cell counts, ratios in CD4+ lymphocytes, and Th1/Th2 cell ratio were seen between survivors and nonsurvivors on both days (all P > 0.05). There was no difference over time in both survivors and nonsurvivors (all P > 0.05). CONCLUSION: Downregulated T lymphocyte counts, including Th1/Th2/Th17 subsets and Th1/Th2 cell ratio imbalance, occur in the early period after ROSC, that may be involved in immune dysfunction in OHCA patients.

Presepsin as a novel diagnostic biomarker for differentiating active pulmonary tuberculosis from bacterial community acquired pneumonia.

BACKGROUND: The expression of presepsin in active pulmonary tuberculosis (APTB) is unknown. We observed the expression of presepsin in APTB, and to evaluate the value for discriminating between APTB and bacterial community acquired pneumonia (BCAP). METHODS: Consecutive APTB patients who were accurately diagnosed by sputum culture and BCAP patients were enrolled from August 2013 to July 2015. Clinical data were collected, and plasma presepsin concentrations were tested. Receiver operating characteristic (ROC) curves were performed for diagnostic analysis. RESULTS: In all, 133 healthy individuals, 103 APTB and 202 BCAP patients were enrolled. Presepsin concentrations in APTB group (218.0 [146.0, 368.0] pg/ml) were higher than those in the healthy control group (128.0 [101.5, 176.5] pg/ml, P<0.001), and lower than the concentrations measured in the BCAP group (532.0 [364.0, 852.3] pg/ml, P<0.001). Simple APTB and miliary tuberculosis patients showed no significant differences in presepsin concentrations. Compared with both Gram-positive and negative bacteria, Mycobacterium tuberculosis caused a limited increase of presepsin. With the cut-off value set at 401pg/ml, presepsin demonstrated high positive predictive value, allowing initial discriminating between APTB and BCAP. Presepsin combined with CURB-65 score could significantly improve the discrimination ability. CONCLUSIONS: Presepsin concentrations in APTB patients were slightly increased, and may be helpful for initial discrimination between APTB and BCAP.

Overexpression of programmed cell death-1 and human leucocyte antigen-DR on circulatory regulatory T cells in out-of-hospital cardiac arrest patients in the early period after return of spontaneous circulation.

AIM: Whether regulatory T cells (Tregs) are involved in immune disorders of out-of-hospital cardiac arrest (OHCA) patients after return of spontaneous circulation (ROSC) is still unknown. We aimed to observe the expression of circulatory Tregs in OHCA patients and investigate programmed cell death-1 (PD-1) and human leucocyte antigen-DR (HLA-DR) on Tregs to evaluate the induction and activity of Tregs. METHODS: Sixty-seven consecutive OHCA patients who recovered from spontaneous circulation over 12 h were enrolled. Clinical and 28-day outcome data were collected. Peripheral blood samples collected on days 1 and 3 after ROSC were analysed to evaluate PD-1 and HLA-DR expression on Tregs. Fifty healthy individuals were enrolled as healthy controls. RESULTS: Compared with those in healthy individuals, circulatory Treg counts significantly decreased without changes of Treg/cluster-of-differentiation (CD)4+ lymphocyte ratios on day 1 after ROSC, and the percentage of PD-1+ Tregs and HLA-DR+ Tregs significantly rose. On day 3, Treg/CD4+ lymphocyte ratios rose with persistently low Treg counts, and the expression of PD-1 and HLA-DR on Tregs was not different from that on day 1. On day 1, both circulatory Treg counts and Treg/CD4+ lymphocyte ratios in non-survivors were lower than those in survivors, and Treg/CD4+ lymphocyte ratios increased in non-survivors on day 3. No significant difference of PD-1 and HLA-DR expression on Tregs was found between survivors and non-survivors on day 1. CONCLUSIONS: After ROSC, despite decreased circulatory Treg counts, a relative increase of Treg percentage and enhanced activity of Tregs are involved in early immune regulation of OHCA patients.

Association Between Angiopoietin-2 and Enterovirus 71 Induced Pulmonary Edema.

OBJECTIVE: To characterize pulmonary edema (PE) fluid induced by enterovirus 71 (EV71) infection, elucidate the relationship between angiopoietin-2 (Ang-2) and PE, and explore the pathogenesis of PE. METHODS: Clinical data were collected from critical infants with EV71 infection. The infants were grouped into PE, non-PE, and control groups. The control group included infants in the preoperative period of elective inguinal hernia surgery. Biochemical changes in PE fluid were evaluated, and Ang-2 levels in serum and PE fluid were measured. Human pulmonary microvascular endothelial cells (HPMECs) were incubated with serum from the control and PE groups and human recombinant Ang-2 or serum from the PE group and human recombinant Ang-1, and changes in the intercellular junctions were recorded via immunofluorescence. RESULTS: Of the 161 infants with critical EV71 infection admitted to the hospital, 39 had PE. PE fluid was collected from 18 of these infants. The PE fluid-to-serum (P/S) ratio of total protein was 0.9 ± 0.2, and all P/S ratios of albumin were 1.0 ± 0.3. The Ang-2 level was higher in the non-PE group (333.2 ± 79.7 pg/ml) than in the control group (199.9 ± 26.7 pg/ml), although without statistical significance (P = 0.115). The Ang-2 level in the PE group (2819.2 ± 908.7 pg/ml) was higher than those in both the non-PE and the control groups (both, P < 0.001). Serum samples from the PE group had damaged cell junctions of confluent HPMEC monolayers that were reversed by Ang-1. CONCLUSIONS: The PE fluid of infants with EV71-induced PE was protein-rich, and elevated Ang-2 expression was associated with PE. The mechanism through which PE develops may be related to Ang-2-induced cell junction damage.

A rare case of primary pulmonary diffuse large B cell lymphoma with CD5 positive expression.

Primary pulmonary diffuse large B-cell lymphoma (PPDLBCL) is extremely rare. Its clinical symptoms and signs are nonspe cific, and imaging features also have not yet been well-defined. Further description is important for the diagnosis and treatment of PPDLBCL. Herein, we reported a case of a patient who suffered from bilateral chest pain and dyspnea. Computed tomography (CT) of chest demonstrated bilateral lung mass, consolidations and reverse halo sign, while consolidations and reverse halo sign are uncommon according to previous reports. Tissue samples were taken by CT guided needle biopsy. The histological samples showed PPDLBCL. This case was special in view of positive expression of CD5. After the case was treated by cyclophosphamide pirarubicin vindesine dexamethasone (CHOP) chemotherapy for six courses, her clinical symptoms were partially alleviated, while CT showed progression disease. This case report highlights different imaging features and characteristics of molecular biology, and reviews study progress of PPDLBCL.

Low molecular weight heparin may prevent acute lung injury induced by sepsis in rats.

The purpose of this study was to assess the protective effect of low molecular weight heparin (LMWH) on acute lung injury (ALI) in rats induced by sepsis. Rat ALI model was reproduced by cecal ligation and puncture (CLP). All rats were randomly divided into three groups (n=50): control group (A), ALI group (B), and LMWH-treated group (C). Group A received a sham operation and the other groups underwent CLP operation. Groups A and B accepted intraperitoneal injection (i.p.) of normal saline (NS) at a dose of 2.0 ml kg(-1) and ceftriaxone (30 mg kg(-1)), group C was intraperitoneally injected with additional LMWH (150 U kg(-1)) except saline and ceftriaxone. Blood was collected and lung tissue was harvested at the designated time points for analysis. The lung specimens were harvested for morphological studies, immunohistochemistry examination. Lung tissue edema was evaluated by tissue water content. The levels of lung tissue myeloperoxidase (MPO) were determined. Meanwhile, the nuclear factor-kappa B (NF-κB) activation, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) levels, high mobility group box 1 (HMGB1) and intercellular adhesion molecule-1 (ICAM-1) protein levels in the lung were studied. There was a significant difference in each index between groups A and B (P<0.05). Treatment with LMWH significantly decreased the expression of TNF-α, IL-1ß, HMGB1 and ICAM-1 in the lungs of ALI rats. Similarly, treatment with LMWH dramatically diminished sepsis-induced neutrophil sequestration and markedly reduced the enhanced lung permeability. In the present study, LMWH administration inhibited the nuclear translocation of NF-κB in the lungs. These data suggest that LMWH attenuates inflammation and ameliorates lung pathology in CLP-induced sepsis in a rat model.

[The significance of lactic acid in early diagnosis and goal-directed therapy of septic shock patients].

OBJECTIVE: To investigate the application of lactic acid in early diagnosis and goal-directed therapy of septic shock, and to provide reference for the early clinical diagnosis and treatment of septic shock. METHODS: A prospective observational study was conducted, in which patients satisfied with the criteria of septic shock diagnosis were enrolled. The patients were randomly divided into two groups. The lactic group was defined using blood lactic acid concentration < 2 mmol/L as treatment guide target. Control group was defined according to the traditional diagnostic criteria of shock which systolic blood pressure was less than 90 mmHg (1 mmHg= 0.133 kPa) or systolic blood pressure value fell > 40 mmHg baseline or oliguria ( < 0.5 ml. kg-1.h-1) et al traditional septic shock diagnosis criteria and bundle treatment was performed. Organ dysfunction index, the sequential organ failure score (SOFA), acute physiology and chronic health evaluation score II ( APACHE II) score, the time of mechanical ventilation, the time of stay in the intensive care unit ( ICU), and the 7-and 28-day mortality were recorded. RESULTS: There were 26 and 31 septic shock patients in lactic group and control group respectively. Organ dysfunction index had been improved in different degrees after treatment compared with that before treatment. Creatinine ( Cr) at 48 hours after treatment in lactic group was significantly lower than that in control group (µmol/L: 94.48 ± 6.68 vs. 107.44 ± 10.35, P < 0.05), and there was no statistical difference in other indexes. The SOFA score of lactic group at 24 hours and 48 hours after treatment was lower than that of control group (9.27 ± 4.62 vs. 9.79 ± 3.80, t=2.103, P=0.040; 8.54 ± 5.53 vs. 9.70 ± 4.30, t=2.302, P=0.023). APACHE II score of two group after treatment were lower than that before treatment, and lactic group decreased more obviously compared with control group ( 14.25 ± 5.29 vs. 20.00 ± 9.74, t=2.298, P=0.026; 13.60 ± 6.18 vs 18.15 ± 6.62, t=2.653, P=0.011). The time of stay in the ICU and the time of mechanical ventilation of lactic group were shorter that those of control group, but there was no statistical difference [ICU time (days): 8.95 ± 5.19 vs. 9.45 ± 6.18, t=0.605, P=0.652; mechanical ventilation time (hours): 101.15 ± 11.50 vs. 110.63 ±13.26, t= 0.631, P=0.564]. There was no statistical difference regarding 7-day mortality of lactic group was lower than that of control group [15.38% (4/26) vs. 16.13% ( 5/31), Χ2=0.000, P=1.000]. The 28-day mortality of lactic group was lower than that of control group [26.92 % (7/26) vs. 54.84% (17/31). Χ2=4.520, P=0.033]. CONCLUSION: By blood lactic acid monitoring, inadequacy of organization perfusion i.e. septic shock can be found in the early stage, thus early intervention can be performed and improve resuscitation result and reduce the mortality of septic shock patients. Blood lactic acid ≥ 4 mmol/L can be used as one of the criteria for the diagnosis of septic shock, and 6-hour blood lactic acid < 2 mmol/L as a goal to guide shock treatment with obvious prognosis improvement.