Abstract Background There is conflicting evidence on association between quick sequential organ failure assessment (qSOFA) and sepsis mortality in ICU patients. The primary aim of this study was to determine the association between qSOFA and 28-day mortality in ICU patients admitted for sepsis. Association of qSOFA with early (3-day), medium (28-day), late (90-day) mortality was assessed in low and lower middle income (LLMIC), upper middle income (UMIC) and high income (HIC) countries/regions. Methods This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study. Results Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC ( p < 0.001) and UMIC ( p < 0.001) and not HIC ( p = 0.220) countries/regions. Similarly, higher 90-day mortality was associated with increased qSOFA in LLMIC ( p < 0.001) and UMIC ( p < 0.001) only. In contrast, higher 3-day mortality with increasing qSOFA score was observed across all income countries/regions ( p < 0.001). Multivariate analysis showed that qSOFA remained associated with 28-day mortality (adjusted RR 1.09 (1.00–1.18), p = 0.038) even after adjustments for covariates including APACHE II, SOFA, income country/region and administration of antibiotics within 3 h. Conclusions qSOFA was independently associated with 28-day mortality in ICU patients admitted for sepsis. In LLMIC and UMIC countries/regions, qSOFA was associated with early to late mortality but only early mortality in HIC countries/regions. Graphical Abstract
it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed.The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge.Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing.All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community.At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians.Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews.Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view.By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation.
Abstract Objective To establish a time-to-surgery threshold for elderly aneurysmal subarachnoid hemorrhage patients before the risk of mortality increases. Methods A cohort study using data with consecutive patients 70 years and older(N=743). Risk-adjusted restricted cubic splines modeled the mortality according to wait-time. The inflection point (in hours) when mortality began to increase was used to define early-time, middle-time and late-time surgery. To evaluate the robustness of this definition, outcomes among propensity-score matched non-middle surgical and middle-time surgical patients were compared using percent absolute risk differences. Results There were a total of 535 patients who met inclusion. Their mean age was 74.3 (4.38) years. Cox models with restricted cubic spline showed a statistically significant U shaped association for onset-to-surgery time with two year all cause mortality. 66 patients (12.3%) received middle-time surgery and 469 patients (87.7%) received early-time or late-time surgery. There were 60 (91%) patients in the middle-time surgery group matched to those in the non-middle-time group. Of the 60 matched patients who received surgery after less than 49 hours or more than 68 hours, 23 patients (38.3%) died within 24 months vs 14 patients (23.3%) of 60 who received surgery within 49 to 68 hours, for an absolute risk difference of 15% (95% CI, -2.68% to 31.50%). Conclusions In this study, onset-to-treatment time showed a U shaped association with 24 months all cause mortality. Early surgery was superior to delayed surgery in reducing death rate. Elderly patients with poor tolerance to ultra-early surgery in whom operation was probably postponed.
Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.
To explore the mechanism of complement 5a (C5a) in the pathogenesis of sepsis.SPF male C57BL/6J mice were selected and divided into sham operation group (Sham group), cecal ligation and puncture (CLP) group and CLP+anti-C5A monoclonal antibody intervention group (CLP+anti-C5a group) according to random number table with 20 mice in each group. A CLP model was reproduced to induce sepsis, and those in the Sham group only underwent laparotomy without ligation and perforation. In the CLP+anti-C5a group, 0.15 mg of anti-C5a monoclonal antibody was injected intraperitoneally immediately after CLP, and in the Sham group and CLP group were given equal amount of normal saline. The cumulative survival rate was analyzed by Kaplan-Meier method. Serum levels of tumor necrosis factor-α (TNF-α), interleukins (IL-12, IL-4), and interferon-γ (IFN-γ) were measured 24, 48 and 72 hours after operation by enzyme linked immunosorbent assay (ELISA). Immunohistochemical staining was used to observe the expression of C5a receptor (C5aR) in lung and kidney tissues 48 hours after operation. The proportions of dendritic cell (DC), regulatory T cell (Treg) and helper T cell 17 (Th17) in splenic mononuclear cells 48 hours after operation were analyzed by flow cytometry.The 7-day cumulative survival rate of mice in the CLP group was significantly lower than that in the Sham group (30.00% vs. 100.00%; Log-Rank test: χ2 = 47.470, P < 0.001), and the peripheral blood inflammatory mediators TNF-α, IL-12 and IL-4 were increased 24 hours after operation, followed by a significant decreasing at 48 hours, and then gradually increased at 72 hours. IFN-γ gradually increased 24 hours after operation and lasted for 72 hours. Immunohistochemistry showed that a large number of C5aR was expressed in pulmonary and renal endothelial cells 48 hours after operation in the CLP group. Compared with the Sham group, the proportion of DC [(1.80±0.30)% vs. (6.90±1.20)%, P < 0.05] and Treg [(0.38±0.02)% vs. (4.00±0.50)%, P < 0.05] in splenic mononuclear cells was down-regulated in the CLP group, the proportion of Th17 was up-regulated [(0.83±0.08)% vs. (0.32±0.03)%, P < 0.05], and disorder of immune function was found. After anti-C5A monoclonal antibody intervention, the 7-day cumulative survival rate increased significantly compared with the CLP group (54.54% vs. 30.00%; Log-Rank test: χ2 = 28.090, P < 0.001); TNF-α, IL-12 and IFN-γ were further increased, while IL-4 was significantly decreased; the expression of C5aR in lung and kidney tissues were significantly decreased, and the expression of mature DC cells [(5.10±1.20)% vs. (1.80±0.30)%, P < 0.05] and Treg [(2.58±0.05)% vs. (0.38±0.02)%, P < 0.05] in spleen were significantly increased compared with the CLP group, and Th17 was significantly decreased [(0.54±0.05)% vs. (0.83±0.08)%, P < 0.05].It is preliminarily concluded that anti-C5A monoclonal antibody may improve the prognosis of sepsis by improving the polarization of mature DC and T cells in the spleen, and C5a plays an important role in the immune regulation of sepsis cells.
Sepsis is a life-threatening syndrome with a high incidence and a weighty economic burden. The cytokines storm in the early stage and the state of immunosuppression in the late stage contribute to the mortality of sepsis. Immune checkpoints expressed on lymphocytes and APCs, including CD28, CTLA-4, CD80, CD86, PD-1 and PD-L1, CD40 and CD40L, OX40 and OX40L, 4-1BB and 4-1BBL, BTLA, TIM family, play significant roles in the pathogenesis of sepsis through regulating the immune disorder. The specific therapies targeting immune checkpoints exhibit great potentials in the animal and preclinical studies, and further clinical trials are planning to implement. Here, we review the current literature on the roles played by immune checkpoints in the pathogenesis and treatment of sepsis. We hope to provide further insights into this novel immunomodulatory strategy.
Objective
To investigate the effect of Xuebijing injection on lipopolysaccharide (LPS)-mediated the procoagulant activity of tissue factor (TF) in abdominal aortic endothelial cells from rats.
Methods
Abdominal aortic endothelial cells from rats were randomLy(random number) divided into the control group, LPS group (500 ng/mL), Xuebijing group (1, 5, 25 μL/mL), and LPS+Xuebijing group (1, 5, 25 μL/mL), respectively. Cell proliferation was measured by CCK8 and lactate dehydrogenase (LDH) level in supernatants was determined at 24, 48, and 72 h; Expressions of inositol-requiring enzyme-1α (IRE1α), unspliced-box binding protein-1 (uXBP-1), spliced-box binding protein 1 sXBP-1), and protein disulfide isomerase (PDI) were determined by Western blotting at 72 h. Procoagulant activity of TF was measured as the ability of monolayer to support activation of factor with the addition of a and Ca2+ by chromogenic substrate method.
Results
Compared with the control group, the cell proliferation was decreased and LDH level was increased in the LPS group (P<0.05), and there were markedly up-regulated in the expression of IRE1α, uXBP1, sXBP1, and PDI (P<0.05). Compared with the control group, treatment with Xuebijing injection could promote cell proliferation and reduce the release of LDH (P<0.05 or P<0.01), which were gradually enhanced along with the observational intervals. Compared with the LPS group, the LPS+Xuebijing group showed obviously higher cell proliferation and lower release of LDH (P<0.05 or P<0.01), expressions of IRE1α,uXBP1, sXBP1, and PDI were significantly reduced (P<0.01); meanwhile, FⅩa activity was decreased in the LPS+Xuebijing group, and 5 μL/mL Xuebijing was the optimal dose in down-regulation of FⅩa.
Conclusions
These results suggest that treatment with Xuebijing injection can markedly down-regulate the expression of PDI by inhibiting the IRE1α-XBP1 signaling pathway to suppress the procoagulant activity of TF in abdominal aortic endothelial cells from rats
Key words:
Inositol-requiring enzyme 1α; disulfide isomerase; factorⅩa; Tissue factor
Xuebijing (XBJ) injection, a concoction of several Chinese herbs, has been widely used as an immunomodulator for the treatment of severe sepsis in China. However, the precise mechanisms responsible for its efficacy have not been fully elucidated. In our study, we determined the flow cytometry markers (F4/80, CD11c, and CD206), the levels of secreted cytokines (TNF-α, IL-6, and IL-10), and the expression of specific proteins of M2 (Ym1, Fizz1, and Arg1) to assess macrophage polarization. Treatment with XBJ lowered M1 associated cytokine levels and increased the level of M2 associated cytokine level. The percentage of M2 phenotype cells of XBJ group was much higher than that of the control group. Expressions of phosphorylated Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6) were markedly enhanced after the administration of XBJ; on the other hand, the M2 associated cytokines and proteins were decreased following treatment with JAK1 or STAT6 inhibitor. In addition, the treatment of XBJ significantly improved the survival rate of septic mice. These studies demonstrate that XBJ can markedly promote M2 polarization and improve the survival rate of septic mice, thereby contributing to therapeutic effect in the treatment of septic complications.
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