Early Stage Of Sepsis Research Articles

Analysis of the Value of the Blood Urea Nitrogen to Albumin Ratio as a Predictor of Mortality in Patients with Sepsis.

PurposeAt present, simple, accurate, and efficient prognostic tools for the evaluation of cases with early-stage sepsis in the emergency department (ED) are lacking. An increased blood urea nitrogen to albumin ratio (BAR) has previously been shown to be a valuable biomarker with predictive utility in several diseases. The relationship between BAR and sepsis patient outcomes, however, is not well-understood. This exploration was thus developed for the exploration of the link between BAR values and the short-term prognosis of cases with sepsis.MethodsThis was a retrospective cohort research of sepsis cases admitted to the West China Hospital of Sichuan University ED from July 2015 to June 2016. Laboratory data were collected upon ED admission, and 7-day all-cause mortality was the primary study endpoint. Relationships between BAR values and APACE II and SOFA scores were generated assessed with correlation coefficient heatmaps. Independent risk factors were identified through multivariate analyses, with the curves of receiver operating characteristic (ROC) being employed to gauge the value of BAR as a predictor of the risk of mortality in sepsis cases.ResultsIn sum, 801 patients participated in the present investigation. BAR values were strongly correlated with APACHE II and SOFA scores. In a multivariate logistic regression assessment, BAR was identified as an independent predictor of mortality among patients with sepsis (HR=1.032, 95% CI: 1.010–1.055, P=0.004). BAR exhibited an AUC of 0.741 (95% CI: 0.688–0.793, P<0.001) when used to predict patient mortality risk, with 5.27 being the optimal BAR cut-off.ConclusionWe found that BAR can be used as a reliable biomarker to predict mortality in patients with sepsis.

Speckle-tracking echocardiography for detecting myocardial dysfunction in sepsis and septic shock patients: A single emergency department study.

Septic cardiomyopathy (SCM) occurs in the early stage of sepsis and septic shock, which has implications for treatment strategies and prognosis. Additionally, myocardial involvement in the early stages of sepsis is difficult to identify. Here, we assess subclinical myocardial function using laboratory tests and speckle-tracking echocardiography (STE). Emergency department patients diagnosed with sepsis or septic shock were included for analysis. Those with other causes of acute or pre-existing cardiac dysfunction were excluded. Transthoracic echocardiography (TTE), including conventional echocardiography and STE, were performed for all patients three hours after initial resuscitation. Samples for laboratory tests were taken around the time of TTE. Left ventricular functions of 60 patients were analyzed, including 21 septic shock patients and 39 sepsis patients. There was no significant difference in global longitudinal strain (GLS), global circumferential strain (GCS), or global radical strain (GRS) between patients with sepsis and septic shock (all with P>0.05). However, GLS and GCS were significantly less negative in patients with abnormal troponin levels or in patients with abnormal left ventricular ejection fraction (LVEF) values (all with P<0.05). There were also moderate correlations between GLS and levels of cTnI (r=0.40, P=0.002) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r=0.44, P=0.001) in sepsis and septic shock patients. Myocardial dysfunction, e.g., lower LVEF or less negative GLS in patients with sepsis or septic shock, is more affected by myocardial injury. GLS could be incorporated into mainstream clinical practice as a supplementary LVEF parameter, especially for those with elevated troponin levels.

Non-invasive Early Prediction of Septic Acute Kidney Injury by Doppler-Based Renal Resistive Indexes Combined With Echocardiographic Parameters: An Experimental Study

Non-invasive early prediction of septic acute kidney injury (S-AKI) is still urgent and challenging. Increased Doppler-based renal resistive index (RRI) has been shown to be associated with S-AKI, but its clinical use is limited, which may be explained by the complex effects of systemic circulation. Echocardiogram allows non-invasive assessment of systemic circulation, which may provide an effective supplement to RRI. To find the value of RRI combined with echocardiographic parameters in the non-invasive early prediction of S-AKI, we designed this experiment with repeated measurements of ultrasonographic parameters in the early stage of sepsis (3, 6, 12, and 24 h) in cecum ligation and puncture (CLP) rats (divided into AKI and non-AKI groups at 24 h based on serum creatinine), with sham-operated group serving as controls. Our results found that RRI alone could not effectively predict S-AKI, but when combined with echocardiographic parameters (heart rate, left ventricular end-diastolic internal diameter, and left ventricular end-systolic internal diameter), the predictive value was significantly improved, especially in the early stage of sepsis (3 h, AUC: 0.948, 95% CI 0.839–0.992, P < 0.001), and far earlier than the conventional renal function indicators (serum creatinine and blood urea nitrogen), which only significantly elevated at 24 h. Our method showed novel advances and potential in the early detection of S-AKI.

De-escalation antibiotic therapy alleviates organ injury through modulation of NETs formation during sepsis

Empiric broad-spectrum antimicrobials therapy is suggested to be started immediately for sepsis patients. Empiric antimicrobial therapy should be narrowed once pathogen identification and sensitivities are established. However, the detailed mechanisms of de-escalation strategy are still unclear. Here we hypothesized neutrophil extracellular traps (NETs) played an essential role and de-escalation strategy might alleviate organs injury through regulation of NETs formation in sepsis. We evaluated the effect of imipenem and ceftriaxone on NETs formation in vitro and examined the role of reactive oxygen species (ROS). Next, we designed de-escalation and escalation strategy in cecum ligation and puncture (CLP) models. Organ injury, inflammatory cytokines, NETs levels were compared and evaluated. In CLP models, de-escalation therapy resulted in an increased serum MPO-DNA level during the early stage and decreased MPO-DNA level during late stage, which exerted the reverse effects in escalation therapy. Inflammatory response and organ injury exacerbated when eliminated NETs with DNAse I during the early stage of sepsis (p < 0.01). Histopathological analysis showed decreased injury in lung, liver, and intestine in de-escalation therapy compared with escalation therapy (p < 0.01). De-escalation therapy results in the highest 6-day survival rate compared with the control group (p < 0.01), however, no significant difference was found between de-escalation and escalation group (p = 0.051). The in vitro study showed that the imipenem could promote, while the ceftriaxone could inhibit the formation of NETs in PMA-activated PMNs through a ROS-dependent manner. We firstly demonstrate that de-escalation, not escalation, therapy reduces organ injury, decreases inflammatory response by promoting NETs formation in the early stage, and inhibiting NETs formation in the late stage of sepsis.

An analysis of urine and serum amino acids in critically ill patients upon admission by means of targeted LC\u2013MS/MS: a preliminary study

Sepsis, defined as a dysregulated host response to infection, causes the interruption of homeostasis resulting in metabolic changes. An examination of patient metabolites, such as amino acids, during the early stage of sepsis may facilitate diagnosing and assessing the severity of the sepsis. The aim of this study was to compare patterns of urine and serum amino acids relative to sepsis, septic shock and survival. Urine and serum samples were obtained from healthy volunteers (n = 15) once or patients (n = 15) within 24 h of a diagnosis of sepsis or septic shock. Concentrations of 25 amino acids were measured in urine and serum samples with liquid chromatography-electrospray mass spectrometry. On admission in the whole cohort, AAA, ABA, mHis, APA, Gly-Pro and tPro concentrations were significantly lower in the serum than in the urine and Arg, Gly, His, hPro, Leu, Ile, Lys, Orn, Phe, Sarc, Thr, Tyr, Asn and Gln were significantly higher in the serum than in the urine. The urine Gly-Pro concentration was significantly higher in septic shock than in sepsis. The serum Cit concentration was significantly lower in septic shock than in sepsis. The urine ABA, mHis and Gly-Pro, and serum Arg, hPro and Orn concentrations were over two-fold higher in the septic group compared to the control group. Urine and serum amino acids measured in septic patients on admission to the ICU may shed light on a patient’s metabolic condition during sepsis or septic shock.

COMPARISON OF SIRS CRITERIA, QSOFA SCORE, AND A COMBINATION OF BOTH FOR THE DIAGNOSIS OF SEPSIS AND PREDICTION OF MORTALITY IN HOSPITALIZED ADULT PATIENTS WITH COVID-19

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Sepsis is common in critically ill COVID-19 patients and is associated with high mortality. However, the diagnosis of sepsis and the prediction of mortality are challenging in COVID-19 patients, especially in the early stage of sepsis. Research about the performance of SIRS criteria and qSOFA score in patients with COVID sepsis is limited. Therefore, this study aimed to compare the performance of SIRS, qSOFA, and a combination of both in hospitalized COVID-19 adult patients regarding the diagnosis of sepsis and the prediction of in-hospital mortality. METHODS: Retrospective data analysis included 341 patients who were hospitalized with laboratory-confirmed COVID-19 infection during April 2020 and January 2021 (the peaks of the first and second waves in New York state) at a 242-bed university-affiliated community-based hospital. Data from the initial patient encounter at the emergency room was collected by reviewing the electronic health records. SIRS criteria, qSOFA score, and a combination of both (SIRS+qSOFA) were analyzed by the MATLAB software. SIRS+qSOFA includes 5 parameters: tachypnea (respiratory rate ≥ 22), tachycardia (heart rate >90/min), fever or hypothermia (temperature >38°C (100.4°F) or 12000/mm³, 10% bands), altered mentation, and hypotension (systolic blood pressure ≤100 mmHg). The area under the receiver operating characteristic curves (AUC) was calculated to evaluate the performance of SIRS, qSOFA, and SIRS+qSOFA. RESULTS: In 341 COVID-19 patients, 128 patients were diagnosed with sepsis (37.5%), which included 77 expired patients (60.2%);213 patients were not diagnosed with sepsis (62.5%), which included 50 expired patients (23.5%). The AUCs for the diagnosis of sepsis with SIRS, qSOFA, and SIRS+qSOFA were 0.739, 0.731, and 0.793, respectively. The AUCs for the prediction of mortality with SIRS, qSOFA, and SIRS+qSOFA were 0.593, 0.665, and 0.646, respectively. For diagnosing sepsis, the sensitivity of SIRS (≥ 2), qSOFA (≥ 2), and SIRS+qSOFA (≥ 3) were 82.0%, 48.4%, and 68.8%, respectively;the specificity of SIRS (≥ 2), qSOFA (≥ 2), and SIRS+qSOFA (≥ 3) were 54.9%, 85.4%, and 76.5%, respectively. For predicting mortality, the sensitivity of SIRS (≥ 2), qSOFA (≥ 2), and SIRS+qSOFA (≥ 3) were 68.5%, 42.5%, and 55.9%, respectively;the specificity of SIRS (≥ 2), qSOFA (≥ 2), and SIRS+qSOFA (≥ 3) were 46.7%, 81.8%, and 68.7%, respectively. CONCLUSIONS: For diagnosing sepsis in COVID-19 patients, the performance of SIRS+qSOFA with 5 parameters (AUC=0.793) is better than either SIRS (AUC=0.739) or qSOFA (AUC=0.731). For predicting mortality, the performance of qSOFA (AUC=0.665) is superior to either SIRS (AUC=0.593) or SIRS+qSOFA (AUC=0.646). CLINICAL IMPLICATIONS: This study will facilitate the diagnosis of sepsis and the prediction of mortality in the hospitalized COVID-19 adult patients. DISCLOSURES: No relevant relationships by Shraddha Acharya, source=Web Response No relevant relationships by Inigo Atienza, source=Web Response No relevant relationships by Stephen Jesmajian, source=Web Response No relevant relationships by Jeffrey Lederman, source=Web Response No relevant relationships by Liyun Liu, source=Web Response No relevant relationships by Junfeng Xue, source=Web Response

The expression of STEAP4 in peripheral blood predicts the outcome of septic patients.

BackgroundSepsis is a systemic disease characterized by extensive inflammatory responses and impaired organ function, which are characteristics that make it easily missed and complex to treat. A large number of laboratory and clinical studies on the diagnosis and treatment of sepsis have been continuously carried out, confirming the importance of mitochondrial function during the development of sepsis. STEAP4 is an important metalloreductase in mitochondria, which is involved in the biogenesis and respiratory chain of mitochondria. The role of STEAP4 in inflammation remains controversial. Research in this field may contribute to the development of new diagnostic and treatment options for sepsis.MethodsThe expression of STEAP4 was measured in the peripheral blood of patients with severe sepsis and compared with healthy controls. Cell and mouse inflammatory models were established to detect the expression of STEAP4 and other inflammatory cytokines.Results(I) The expression of STEAP4 in the peripheral blood of patients with severe sepsis is higher than that of healthy volunteers (P<0.01), which is related to the SOFA score and transaminase. (II) STEAP4 has a certain predictive effect on the outcome of patients [area under curve (AUC) =0.696, P<0.05, 95% CI: 0.528 to 0.833]. (III) Inflammation led to increased expression of STEAP4 gene in RAW264.7 cells and mouse liver tissue.ConclusionsThe expression of STEAP4 is elevated in the early stage of sepsis and the degree of its elevation can be used to predict the clinical outcome of sepsis patients.

Fecal Microbiota Transplantation Protects the Intestinal Mucosal Barrier by Reconstructing the Gut Microbiota in a Murine Model of Sepsis.

The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies have shown that the gut flora was significantly altered in critically ill patients. This study aimed to observe what kind of GM dysbiosis is in the early stage of sepsis and whether the application of fecal microbiota transplantation (FMT) can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. The study investigated the effect of FMT on gut microbiota, mucosal barrier function, inflammatory response, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). It is found that FMT can not only reduce morbidity and mortality and restore the abundance and diversity of the gut flora in septic mice, but can also improve the intestinal barrier function by reducing epithelial cell apoptosis, improving the composition of the mucus layer, upregulating the expression of tight junction proteins, and reducing intestinal permeability and the inflammatory response. After FMT, Lachnospiraceae contributed the most to intestinal protection through enhancement of the L-lysine fermentation pathway. FMT offers a microbe-mediated survival advantage in a murine model of sepsis. Therefore, an improved understanding of the connection between microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.

Human Chorionic Gonadotropin and Related Peptides: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis.

Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory disorders, including COVID-19. The clinical onset of sepsis is often marked by the explosive release into the extracellular fluids of a multiplicity of host-derived cytokines and other pro-inflammatory hormone-like messengers from endogenous sources (“cytokine storm”). In patients with sepsis, therapies to counter the pro-inflammatory torrent, even when administered early, typically fall short. The major focus of our proposed essay is to promote pre-clinical studies with hCG (human chorionic gonadotropin) as a potential anti-inflammatory therapy for sepsis.

Protective effects of Nrf2 against sepsis-induced hepatic injury

AimThis study was designed to investigate the changes of liver injury and Nrf2 signaling pathway in the process of sepsis. We also aimed to examine the role of Nrf2 in resisting oxidative stress and relieving inflammation in sepsis-induced hepatic injury. Main methodsBy operating cecal ligation and puncture (CLP) on Nrf2−/− mice and wild type mice, a sepsis-induced hepatic injury model was established. We compared and contrasted the wild type mice with the Nrf2−/− mice during sepsis-induced hepatic injury, and evaluated the liver damage by biochemical analyses and staining hematoxylin-eosin (HE). Western blot or real-time PCR was performed to detect Nrf2 and its regulated genes NQO-1, GCLM and HO-1. Additionally, we detected the expressions and secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), IL-1β and anti-inflammatory cytokines IL-10. We assessed the oxidative stress through the levels of MDA and NO. Key findingsThe results showed that Nrf2 expressions at mRNA and protein levels were increased 1 day after CLP, namely the early stage of sepsis. Compared with wild type mice after CLP, Nrf2−/− mice showed more severe liver injury, accompanied by higher expression of inflammatory cytokines and oxidative stress. Notably, Nrf2-regulated genes GCLM and NQO-1, were strongly downregulated in Nrf2−/− mice. SignificanceNrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress to alleviate sepsis-induced hepatic injury, mainly through regulating GCLM and NQO-1 in the early stage after CLP.

Clinical importance of screening differential gene set of monocytes based on single-cell sequencing and digital polymerase chain reaction technology for early diagnosis of sepsis

To verify the specific differentiated subsets of monocytes in sepsis, and to screen and construct the differential gene set of monocytes used for early diagnosis of sepsis. Patients with sepsis admitted to Guangdong Provincial People's Hospital from June 2020 to March 2021 were enrolled, and peripheral blood mononuclear cells (PBMC) were extracted. Single-cell sequencing technology and pseudo-time analysis were used to verify the differential subsets of monocytes. Bioinformatics methods were used to analyze the expression of genes in differential subsets of monocytes and screen out differential genes for the preliminary construction of a candidate differential gene set. The digital polymerase chain reaction (PCR) technology was used to verify the candidate differential genes in PBMC of sepsis patients and sepsis human myeloid leukemia mononuclear cells (THP-1) models, and the Venn diagram was used to construct the final differential gene set of monocytes. Gene Expression Omnibus (GEO) database was used to validate the differential gene set of monocytes. (1) The results of cell annotation and pseudo-time analysis showed that the differentiation of NEAT1+CD163+ monocyte occurred in the early stage of sepsis was significantly different from other subsets, which validated that NEAT1+CD163+ monocyte was the characteristic subset in the pathological process of sepsis. (2) Twenty-two differential genes related to sepsis were screened out from the gene expression of NEAT1+CD163+ monocyte. After further verification by digital PCR, basic leucine zipper ATF-like transcription factor (BATF), JUNB proto-oncogene, carcinoembryonic antigen-related cell adhesion molecule 4 (CEACAM4), chromosome 9 open reading frame 95 (C9orf95), G protein subunit alpha 15 (GNA15), complement C3a receptor 1 (C3AR1), transforming growth factor beta 1 (TGFB1) and mitochondrial carrier homolog 1 (MTCH1) were screened out to construct the final differential gene set of monocytes. (3) The external validation results showed that C9orf95 gene had no data in GSE154918 and GSE133822 from GEO, it was excluded during validation. In GSE154918, the expressions of BATF, JUNB, CEACAM4, GNA15, C3AR1, TGFB1, and MTCH1 in the sepsis group were significantly higher than those in the healthy control group (log2expression level: BATF was 12.78±0.08 vs. 11.39±0.35, JUNB was 16.88±0.07 vs. 16.04±0.03, CEACAM4 was 14.73±0.08 vs. 13.77±0.05, GNA15 was 13.16±0.06 vs. 12.30±0.04, C3AR1 was 14.62±0.13 vs. 12.87±0.05, TGFB1 was 16.95±0.05 vs. 16.57±0.36, MTCH1 was 14.80±0.02 vs. 14.61±0.15, all P < 0.05). In GSE133822, the expressions of BATF, CEACAM4, GNA15, and C3AR1 in the sepsis group were significantly higher than those in the health control group (log2expression level: BATF was 8.66±0.16 vs. 7.92±0.14, CEACAM4 was 9.20±0.16 vs. 8.36±0.20, GNA15 was 10.66±0.18 vs. 10.13±0.16, C3AR1 was 11.49±0.27 vs. 10.48±0.16, all P < 0.05), while the expressions of JUNB, TGFB1, and MTCH1 were not statistically different between two groups. The results of gene set variation analysis (GSVA) showed that the enrichment scores of monocytes differential gene set of sepsis group were significantly higher than those of the healthy control group in both GSE154918 (0.38±0.04 vs. -0.44±0.02) and GSE133822 (0.56±0.02 vs. 0.20±0.05, both P < 0.01). Receiver operator characteristic curve (ROC curve) analysis showed that the differential gene set of monocytes had a reliable diagnostic value for early sepsis with the area under ROC curve (AUC) of 0.993 [95% confidence interval (95%CI) was 0.980-1.000] in GSE154918 and 0.944 (95%CI was 0.873-1.000) in GSE133822. A differential gene set of monocytes (BATF, JUNB, CEACAM4, GNA15, C3AR1, TGFB1, and MTCH1) screened out by single-cell sequencing and digital PCR technology has a reliable diagnostic value for the early sepsis, and may provide a new idea for the early diagnosis of sepsis.

Clinical value of neutrophil/lymphocyte ratio in early prediction of the incidence of organ dysfunction and 28-day mortality in patients with sepsis

To evaluate the clinical value of neutrophil/lymphocyte ratio (NLR) in early prediction of the incidence of sepsis-induced organ dysfunction and 28-day mortality. A retrospective study was conducted in 815 adult patients with sepsis admitted to the department of critical care medicine of the First Affiliated Hospital of China Medical University from January 2017 to December 2019. The clinical data including age, gender and complication were collected, and the peripheral blood routine indexes at 24, 48 and 72 hours after the diagnosis of sepsis were collected, and the NLR was calculated. The primary endpoint of the study was the incidences of sepsis related acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) and acute liver failure (ALF); the secondary endpoint was the 28-day in-hospital mortality in septic patients with organ dysfunction. Univariate and multivariate Logistic regression were used to analyze the risk factors of organ dysfunction and 28-day mortality in patients with sepsis, the receiver operating characteristic curve (ROC curve) was drawn and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of NLR for organ dysfunction and 28-day mortality in patients with sepsis. A total of 714 patients with sepsis were enrolled for final statistical analysis. There was no significant difference in NLR at 24, 48 and 72 hours in patients with or without organ dysfunction (such as AKI, ARDS, DIC and ALF). Logistic regression analysis showed that there was no significant difference in NLR at 24 hours with 28-day in-hospital mortality [odds ratio (OR) = 1.006, 95% confidence interval (95%CI) was 0.994-1.019, P = 0.323]. However, NLR at 48 hours and 72 hours had a significant difference with 28-day mortality (48 hours: OR = 1.026, 95%CI was 1.013-1.040, P = 0.000; 72 hours: OR = 1.021, 95%CI was 1.005-1.037, P = 0.010), which suggested that NLR at 48 hours and 72 hours after diagnosis were independent risks factor for 28-day mortality in patients with sepsis. ROC curve showed that the AUC of NLR at 48 hours was 0.598, 95%CI was 0.540-0.658, P = 0.02; when the cut-off value was 10.1, the sensitivity and specificity for predicting 28-day mortality was 75.2% and 58.0%, respectively; the AUC of NLR at 72 hours was 0.595, 95%CI was 0.536-0.655, P = 0.03; when the cut-off value was 9.24, the sensitivity and specificity for predicting 28-day mortality was 75.3% and 59.9%, respectively. NLR cannot predict the occurrence of AKI, ARDS, DIC and ALF in sepsis in early stage. NLR has a certain clinical value in predicting 28-day mortality in patients with sepsis, but its predictive efficiency is low.

Xuebijing injection in septic rats mitigates kidney injury, reduces cortical microcirculatory disorders, and suppresses activation of local inflammation

Ethnopharmacological relevanceXuebijing injections originate from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It is composed of five Chinese herbal extracts; Carthami flos, Paeoniae radix rubra, Chuanxiong rhizoma, Salviae miltiorrhizae, and Angelicae Sinensis radix. The China Food and Drug Administration approved Xuebijing injections as a TCM preparation for the adjuvant treatment of sepsis. Aim of the studyThis study aims to determine the effects of Xuebijing injections as an adjuvant to antibiotics for the treatment of renal microcirculatory dysfunction and renal inflammation in rats with sepsis. Materials and methodsThe rats received a sham operation (Sham), sham operation followed by Xuebijign injection (Sxbj), cecal ligation and puncture (CLP), or CLP followed by Xuebijing injection (Cxbj). Renal microvascular perfusion in the cortex and oxygenation were assessed at different times after sepsis induction. Renal levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and high mobility group box (HMGB)-1 were measured. Urinary TIMP-2 × IGFBP-7 and neutrophil gelatinase-associated lipocalin (NGAL) were measured as kidney biomarkers, and serum creatinine (SCr) was used to assess kidney injury. Tissue samples were stained for histologic evaluation. ResultsThe induction of sepsis increased local inflammation and decreased renal microvascular perfusion and oxygenation. Compared with the CLP group, the Cxbj group displayed improvements in microvascular perfusion and oxygenation (p < 0.05). The CLP group had significant increases in renal inflammatory biomarkers (IL-1β, IL-6, TNF-α, and HMGB-1; p < 0.05) and Xuebijing injection reduced the levels of these markers. The levels of urinary TIMP-2 × IGFBP-7, NAGL, and SCr were lower in the Cxbj group than in the CLP group (p < 0.05), and the CLP group had a higher Paller score than the Cxbj group (p < 0.05). However, the CLP and Cxbj groups had no significant difference in mortality. ConclusionsThis study into the early stages of sepsis in a rat model indicated that as an adjuvant therapy to antibiotics, Xuebijing injection improved renal perfusion and oxygenation, suppressed renal inflammation, and ameliorated kidney dysfunction. However, Xuebijing injection had no impact on mortality.

Effect of protein C activator from Agkistrodon acutus venom on early adaptive immune response of septic rats

To investigate the effect of protein C activator (PCA) from Agkistrodon acutus venom (AAV) in modulating early adaptive immune response of septic rats. Rat models of sepsis were established by intraperitoneal injection of lipopolysaccharide (LPS; 10 mg/kg) in 36 SD rats, which were divided into 6 groups (n=6) for sample collection at 4, 6, 8, 12, 16 and 24 h after LPS injection, with 6 rats injected with saline as the control group. Another 36 rats were divided into two groups, and 30 min after LPS injection, the rats were treated with SEW2871 (a sphingosine-1-phosphate receptor 1 agonist; 0.5 mg/kg) or PCA group (0.1 mg/kg), and each group was divided into 3 groups (n=6) for sample collection at 6, 12 and 24 h after LPS injection. Plasma IL-4, S1P, IL-12 and IFN-γ levels of the rats were detected using ELISA, and the expressions of S1PR1 and CD103 in the mesenteric lymph nodes were detected with immunofluorescence assay. The plasma levels of S1P, IL-12, IL-4 and IFN-γ (P < 0.05) and the expressions of S1PR1 and CD103 in the mesenteric lymph nodes (P < 0.05) all increased significantly in the rats 24 h after LPS injection; IFN-γ/IL-4 ratio increased progressively within 6 h after LPS injection and then subsided gradually. Compared with those in the corresponding sepsis model subgroups, the levels of S1P, IL-12 and IFN-γ increased while IL- 4 level decreased significantly (P < 0.05), and the expression of S1PR1 and CD103 were reduced significantly (P < 0.05) in SEW2871-treated rats; both the plasma level of IL-4 and the expression of S1PR1 in the mesenteric lymph nodes increased significantly in PCA-treated rats (P < 0.05). PCA can regulate the balance of inflammation and immune response in the early stage of sepsis in rats possibly through the S1P-S1PR1 pathway.

Progress in the pathogenesis of cholestasis during the early stage of sepsis

The effects of sepsis on the liver include hypoxic hepatitis caused by ischemia and shock, liver cell damage caused by excessive inflammation, and cholestasis caused by changes in bile metabolism. Among them, cholestasis is a common complication in patients with sepsis. Cholestasis and jaundice in patients with sepsis are associated with an increased risk of infection, leading to an increased mortality rate. So far, the exact mechanism of sepsis with cholestasis is still unclear, so this article briefly reviews the mechanism of cholestasis during the early stage of sepsis.

Hyperphosphatemia rather than hypophosphatemia indicates a poor prognosis in patients with sepsis

BackgroundSepsis is the leading cause of hospitalization and death in the intensive care unit. It is vital to identify high-risk patients with poor prognosis in the early stages of sepsis. We aimed to investigate the prognostic value of serum phosphorus levels for sepsis. MethodsThe data of 4767 patients with sepsis were collected from the Multiparameter Intelligent Monitoring in Intensive Care III database. The Locally Weighted Scatterplot Smoothing technique and Kaplan–Meier analysis were used to test the crude relationship between serum phosphorus levels and mortality or overall survival. The multivariable logistic regression was used to further analyze the relationship between serum phosphorus levels and in-hospital mortality. The subgroup analysis was performed according to renal failure, use of vasopressin and the Sequential Organ Failure Assessment (SOFA) score. ResultsOnly hyperphosphatemia significantly correlated with in-hospital mortality [odds ratio (OR) 1.48; 95% confidence interval (CI) 1.19–1.85], while the correlation between hypophosphatemia and in-hospital mortality was not significant (OR 0.91; 95% CI 0.70–1.19). The interactions between serum phosphorus and renal failure, use of vasopressin or the SOFA score were not significant. ConclusionsHyperphosphatemia rather than hypophosphatemia indicates a poor prognosis in patients with sepsis.

MicroRNA-155: Regulation of Immune Cells in Sepsis.

MicroRNAs are small noncoding RNAs which regulate gene expression at the posttranscriptional level. miR-155 is encoded by the miR-155 host gene (miR155HG), also known as the noncoding B cell integration cluster (BIC). MicroRNAs are widely expressed in various hematopoietic cells and are involved in regulating the immune system. In this review, we summarized how miR-155 modulates specific immune cells and the regulatory role of miR-155 in sepsis. miR-155 is expressed by different populations of innate and adaptive immune cells and is involved in the regulation of development, proliferation, and function in these cells. Sepsis is associated with uncontrollable inflammatory responses, accompanied by unacceptably high mortality. Due to the inadequacy of diagnostic markers as well as treatment strategies, treating sepsis can be a huge challenge. So far, a large number of experiments have shown that the expression of miR-155 is increased at an early stage of sepsis and that this increase is positively correlated with disease progression and severity. In addition, by blocking the proinflammatory effects of miR-155, it can effectively improve sepsis-related organ injury, providing novel insights to identify potential biomarkers and therapeutic targets for sepsis. However, since most of the current research is limited to animal experiments, further clinical research is required to determine the function of miR-155 and its mechanism related to sepsis.

Detection of Blood Cell Surface Biomarkers in Septic Mice.

Sepsis arises when an infection induces a dysregulated immune response, resulting in organ damage. New methods are urgently needed to diagnose patients in the early stages of sepsis, and identify patients with a poor disease prognosis. One promising approach is to identify the rapid changes in cell surface antigens (biomarkers) that occur during sepsis, as a consequence of leukocyte mobilization and activation. This chapter describes the method for staining whole blood with fluorescently conjugated antibodies that detect cell surface biomarkers, and performing flow cytometry analysis to quantify biomarker-positive cells. Our protocol is designed to detect blood cell surface biomarkers in septic mice, but could also be applied to study potential biomarkers in blood obtained from human patients with sepsis and other medical conditions.

Koenzim Q10 (ubikvinon) i bolesti mozga - veza sa okom i telom

Coenzyme Q10 (CoQ10; ubiquinone) is a vitamin-like substance that is involved in the respiratory chain in the mitochondria. Ubiquinone is synthesized in all tissues, but with age, the content decreases, as well as in some pathological conditions and with the use of statins. Ubiquinone is necessary for the growth and maintenance of cells in the human body, and with age, food intake is desirable, because endogenous synthesis is no longer sufficient. CoQ10 participates in oxidative phosphorylation and adenosine triphosphate (ATP) production and is a potent antioxidant. Primary CoQ10 deficiencies manifest as multisystem disease, encephalomyopathy, cerebellar ataxia, myopathy, and nephrotic syndrome. In the case of CoQ10 deficiency, reactive oxygen species occur first, and in the case of severe deficiency, the loss of ATP. CoQ10 deficiency also causes apoptosis which is found in the brain and retina of the elderly. CoQ10 deficiency contributes to heart muscle dysfunction in chronic heart failure. The effects of CoQ10 deficiency are inflammation and oxidative stress. An inverse relationship between serum CoQ10 and the risk of developing dementia has been shown. CoQ10 administration resulted in a reduction in depression in patients with metabolic syndrome as well as an improvement in concentration in schizophrenia and schizoaffective disorder. CoQ10 deficiency may be associated with the occurrence of static myopathy. In people with primary CoQ10 deficiencies, there is retinopathy, and in acquired macular degeneration and glaucoma, CoQ10 levels are reduced. High doses of CoQ10 help survive chronic heart failure and coronary heart disease. Beneficial effects of CoQ10 on the treatment of obesity, oxidative stress, metabolic syndrome, type II diabetes mellitus and non-alcoholic fatty liver have been shown. Fatigue applications are controversial. There has been some positive effect of CoQ10 in breast cancer. Studies indicate that the use of CoQ10 has beneficial effects in the early stages of sepsis. For therapeutic purposes, CoQ10 is administered in doses of 30-3000 mg. Doses of 22 mg daily to 400 mg/day are considered safe. Side effects are mostly mild and rare.

Heparin-Binding Protein Enhances NF-κB Pathway-Mediated Inflammatory Gene Transcription in M1 Macrophages via Lactate.

In early-stage sepsis, glucose metabolism is increased primarily through glycolysis in the inflammatory response of M1 macrophages. Heparin-binding protein (HBP) has been linked to sepsis, which can promote macrophage activation and inflammatory factor release. However, the mechanism by which glucose metabolism regulates the inflammatory response is unclear. We show that HBP contributes to sepsis by modulating the inflammatory response via lactate-dependent glycolysis in macrophages. Peritoneal macrophages from BALB/c mouse were treated with lipopolysaccharide (LPS). The expression of M1-related proinflammatory genes was investigated by PCR array. IL-1β, iNOS, TNF-α, and IL-6 mRNA expression was determined by qRT-PCR. Intracellular lactate levels were measured using lactate assays. Nuclear factor-kappaB (NF-κB) activity was determined by electrophoretic mobility shift assays (EMSAs). TNF-α levels were measured by qRT-PCR. HBP enhanced inflammatory gene expression in mouse peritoneal macrophages and intracellular lactate accumulation and significantly increased LPS-stimulated NF-κB transcriptional activity and TNF-α expression through lactate. Lactate was essential for the HBP-induced increase in LPS-stimulated TNF-α expression. The critical role of lactate in HBP-induced NF-κB signaling was confirmed, as α-CHCA-mediated (MCT) suppression significantly inhibited NF-κB activity and TNF-α expression. HBP plays an important role in the initial inflammatory reaction, presumably by activating M1 macrophages, increasing lactate levels, and regulating proinflammatory factor release via NF-κB pathway activation.