Decrease in Histidine-Rich Glycoprotein as a Novel Biomarker to Predict Sepsis Among Systemic Inflammatory Response Syndrome.

Histidine-Rich Glycoprotein As a Prognostic Biomarker for Sepsis: A Multicenter Prospective Observational Cohort Study

Few sepsis biomarkers accurately predict severity and mortality. Previously, we had reported that first-day histidine-rich glycoprotein (HRG) levels were significantly lower in patients with sepsis and were associated with mortality. Since the time trends of HRG are unknown, this study focused on the time course of HRG in patients with sepsis and evaluated the differences between survivors and non-survivors. A multicenter prospective observational study was conducted involving 200 patients with sepsis in 16 Japanese hospitals. Blood samples were collected on days 1, 3, 5, and 7, and 28-day mortality was used for survival analysis. Plasma HRG levels were determined using a modified quantitative sandwich enzyme-linked immunosorbent assay. First-day HRG levels in non-survivors were significantly lower than those in survivors (mean, 15.7 [95% confidence interval (CI), 13.4-18.1] vs 20.7 [19.5-21.9] μg/mL; P = 0.006). Although there was no time × survivors/non-survivors interaction in the time courses of HRG (P = 0.34), the main effect of generalized linear mixed models was significant (P < 0.001). In a univariate Cox proportional hazards model with each variable as a time-dependent covariate, higher HRG levels were significantly associated with a lower risk of mortality (hazard ratio, 0.85 [95% CI, 0.78-0.92]; P < 0.001). Furthermore, presepsin levels (P = 0.02) and Sequential Organ Function Assessment scores (P < 0.001) were significantly associated with mortality. Harrell's C-index values for the 28-day mortality effect of HRG, presepsin, procalcitonin, and C-reactive protein were 0.72, 0.70, 0.63, and 0.59, respectively. HRG levels in non-survivors were consistently lower than those in survivors during the first seven days of sepsis. Repeatedly measured HRG levels were significantly associated with mortality. Furthermore, the predictive power of HRG for mortality may be superior to that of other singular biomarkers, including presepsin, procalcitonin, and C-reactive protein.

Our aim was to determine the risk factors of postoperative systemic inflammatory response syndrome (SIRS) in patients with transcatheter aortic valve replacement (TAVR), identify those with ahigh risk of SIRS, and help reduce SIRS occurrence. Aretrospective cohort study was conducted to collect the clinical data of patients who underwent TAVR from January 2014 to December 2019 atatertiary hospital in Zhejiang Province. The study included 156 men and 94women. Patients were divided into SIRS and non-SIRS groups. The pre-, intra-, and postoperative indices of the two groups were recorded. The data of the two groups were compared, and univariate analysis was performed. All statistically significant factors were assessed using binary logistic regression analysis to clarify the risk factors of SIRS after TAVR. Overall, 30 patients developed SIRS after TAVR, with an incidence rate of 12%, an odds ratio (OR) of 0.571, and a95% confidence interval (CI) of 0.469-0.694 (p = 0.000). There was asignificant correlation between SIRS and glucose (OR: 0.823, 95%CI: 0.678-1.000, p = 0.049), albumin (OR: 0.938, 95%CI: 0.881-0.998, p = 0.044), brain natriuretic peptide (OR: 1.000, 95%CI: 1.000-1.000, p = 0.010), sex (OR: 0.412, 95%CI: 0.190-0.892, p = 0.025), and history of hypertension (OR: 0.375, 95%CI: 0.169-0.819, p = 0.014). Multivariate regression analysis demonstrated that age (OR: 1.190, 95%CI: 1.073-1.319, p = 0.001) and body mass index (BMI; OR: 0.559, 95%CI: 0.447-0.698, p = 0.000) were independent risk factors for postoperative SIRS in patients with TAVR. The incidence of SIRS after TAVR was 12%. There was asignificant correlation between SIRS and albumin, glucose, and hypertension. The independent risk factors for SIRS after TAVR were age and BMI.

Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3+ T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3+ T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3+ T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3+CD29+ T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.

Role of Myeloperoxidase as Predictor of Systemic Inflammatory Response Syndrome in Patients With ST-Segment Elevation Myocardial Infarction After Primary Percutaneous Coronary Intervention

Background Although recently challenged, systemic inflammatory response syndrome (SIRS) criteria are still commonly used in daily practice to define sepsis. However, several factors in liver cirrhosis may negatively impact its prognostic ability. Goals. To investigate the factors associated with the presence of SIRS, the characteristics of SIRS related to infection, and its prognostic value among patients hospitalized for acute decompensation of cirrhosis. Study. In this cohort study from two tertiary hospitals, 543 patients were followed up, up to 90 days. Data collection, including the prognostic models, was within 48 hours of admission. Results SIRS was present in 42.7% of the sample and was independently associated with upper gastrointestinal bleeding (UGB), ACLF, infection, and negatively related to beta-blockers. SIRS was associated with mortality in univariate analysis, but not in multiple Cox regression analysis. The Kaplan–Meier survival probability of patients without SIRS was 73.0% and for those with SIRS was 64.7%. The presence of SIRS was not significantly associated with mortality when considering patients with or without infection, separately. Infection in SIRS patients was independently associated with Child-Pugh C and inversely related to UGB. Among subjects with SIRS, mortality was independently related to the presence of infection, ACLF, and Child-Pugh C. Conclusions SIRS was common in hospitalized patients with cirrhosis and was of no prognostic value, even in the presence of infection.

Clinical value of alkaline phosphatase on the surface membrane of neutrophils for prediction of bacteremia in patients with systemic inflammatory response syndrome

Objective To investigate the changes of serum inflammatory factors and blood glucose in patients with systemic inflammatory response syndrome (SIRS) . Methods Seventy eight SIRS patients were divided into survival subgroup (n =37) and fatal subgroup ( n = 41), 35 non-SIRS patients were designated as control group. Thirty eight out 76 patients whose blood glucose was higher than 6. 1 mmol/L were randomly selected for intensive insulin therapy. Serum IL-6, IL-10, IL-13, TNF-α and blood glucose were measured; HLA-DR expression on monocytes was detected. Results Serum IL-6, TNF-αand blood glucose levels were (80±8) vs. (42±7)×10~3μg/L, (52±20) vs. (17±6) ×10~3μg/L and (11.9±1.1)vs.(6.5±1.5)mmoL/L in SIRS vs.non-SIRS group respectively(all P＜0.05);those were(108±21)vs.(66±22)×10~3μg/L,(28±8)vs.(16±9)×10~3μg/L,(14.4±2.1)vs.(7.0±1.0)mmol/L in fatal vs.survival group,respectively(all P＜0.05).The changes of IL-10,IL-13 and HLA-DR expression intensity of monocyte showed a reverse trend.The intensive insulin therapy reversed the above tendency and reduced the fatality rate.Conclusions Blood glucose levels are corrected with serum cytokines in SIRS patients and reflex the immune status and disease prognosis.Intensive insulin therapy can improve the prognosis of SIRS patients. Key words: Systemic inflammatory response syndrome; Cytokines; Blood glucose

To determine whether heme oxygenase-1 messenger RNA expression in peripheral blood mononuclear cells is induced in pediatric cancer patients with the systemic inflammatory response syndrome (SIRS) and whether this expression correlates with the heme oxygenase-1 products, bilirubin and carboxyhemoglobin. Prospective, controlled study. A tertiary care pediatric oncology hospital. Fourteen patients admitted to the intensive care unit with a diagnosis of SIRS by American College of Chest Physicians/Society for Critical Care Medicine consensus criteria and 17 control patients (off therapy, no acute illness). Blood for bilirubin, carboxyhemoglobin, and heme oxygenase-1 messenger RNA expression was collected at study entry. SIRS patients continued to have samples collected every 12 hrs for 1 wk or until intensive care unit discharge. Heme oxygenase-1, bilirubin, and carboxyhemoglobin levels of SIRS patients were compared with controls, and correlation between heme oxygenase-1 and products was assessed. Within 48 hrs of study entry, maximum heme oxygenase-1 expression for all SIRS patients compared with controls was 5.5 +/- 1.0 vs. 1.1 +/- 0.1 (p < .0006). Maximum expression was > or =2.3-fold in 13 of 14 SIRS patients. Maximum heme oxygenase-1 expression also differed from minimum (5.5 +/- 1.0 vs. 1.6 +/- 0.3, p < .003). Maximum bilirubin and carboxyhemoglobin levels within 48 hrs of study entry differed between SIRS patients and controls (3.0 +/- 0.8 vs. 0.3 +/- 0.1, p = .006; and 1.2 +/- 0.2 vs. 0.6 +/- 0.1, p = .001, respectively). Bilirubin, but not carboxyhemoglobin, correlated with heme oxygenase-1 expression (p = .0013). Heme oxygenase-1 messenger RNA, bilirubin, and carboxyhemoglobin levels were increased within 48 hrs of admission in pediatric cancer patients with SIRS. Heme oxygenase-1 expression correlated with serum bilirubin levels. The increase in heme oxygenase-1 expression may add to the understanding of the increase in serum bilirubin observed in patients with SIRS/sepsis. These findings support a role for heme oxygenase-1 in the physiologic response to inflammatory stress.

We sought to determine whether leukocytes from intensive care unit (ICU) patients have altered ERK and p38 kinase activation and specifically if septic patients manifest changes of endotoxin (lipopolysaccharide [LPS]) tolerance. In vitro pretreatment of monocytes (Mono) with LPS induces LPS tolerance with impaired cytokine release and inhibition of ERK and p38 activation after LPS rechallenge. We hypothesized that macrophage dysregulation, similar to that seen with in vitro LPS tolerance, occurs in critically ill patients with severe sepsis. Heparinized whole blood from 16 surgical ICU patients and 16 healthy controls was incubated for 15 minutes +/- 10 ng/mL LPS at 37 degrees C. Mono and neutrophil (polymorphonuclear leukocytes [PMN]) diphospho (active) ERK and p38 kinase activation were determined using flow cytometry with monoclonal antibodies. Results are expressed as mean +/- SEM of basal and percentage change (delta %) in positive cells (delta = LPS stimulated - basal). Chi2 test was used for statistics. Basal ERK was seen in Mono from all groups, but delta % positive only increased in healthy subjects and systemic inflammatory response syndrome (SIRS) patients. No basal Mono or PMN p38 was seen in healthy controls, but LPS significantly activated p38 in both cell types. Mono from patients with sepsis, but not SIRS, had impaired ERK activation. Both PMN and Mono from patients with SIRS had low basal but high LPS-stimulated p38, whereas p38 activation was impaired in patients with sepsis. Alterations in mitogen activated protein kinases (MAPK) activation are seen in ICU patients. Leukocytes of septic patients, but not those with SIRS, showed characteristics of LPS tolerance. Assessment of leukocyte MAPK activation may identify and differentiate patients with sepsis from those with SIRS.

BLOOD-TYPE AND AGE AFFECT HUMAN PLASMA LEVELS OF HISTIDINE-RICH GLYCOPROTEIN IN A LARGE POPULATION

Objective To investigate the distribution and resistance in patients with systemic inflammatory response syndrome (SIRS) induced by bacterial infection in the hospital respiratory ward.Methods A total of 632 SIRS patients were retrospectively analyzed from October 2006 to October 2007.Results 376 cases of SIRS (59.49%) were induced by infection,while 256 cases of SIRS (40.51%) were induced by non-infectional factors. The etiology of SIRS was identified in 76 patients (20.21%). Gram-positive coccus and gram-negative bacilli accounted for 68.42% (52/76) and 31.58% (24/76) respectively.Three main pathogenic bacteria were Staphylococcus aureus [23.68% (18/76)], Pseudomonas aeruginosa [19.73%(15/76)] and Acinetobacter baumanii [15.78% (12/76)]. Conclusions Main pathogenic bacteria of SIRS patients are Staphylococcus aureus and Pseudomonas aeruginosa. Key words: Systemic inflammatory response syndrome; Infection; Bacterium; Drug resistance

Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD's therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.

Objective To investigate the effects of continuous veno-venous hemofiltration (CVVH) on albumin metabolism of patients with systemic inflammatory response syndrome (SIRS).Methods The clinical data of 28 patients who were admitted to the Nanjing General Hospital of Nanjing Military Command from December 2010 to Decemer 2011 were retrospectively analyzed.All the patients were divided into the control group (8 patients),the low-volume CVVH group (2 000 ml/h,10 patients),and the high-volume CVVH group (4 000 mL/h,10 patients).Two stable isotopes,[1-13C] phenylalanine and d5-phenylalanine,were simultaneously intravenously infused into all the patients.The peak areas were calculated for segments with the mass to charge ratios of 192,194,197,218,219 by the selected ion mode of the gas chromatography mass spectrometry.The fractional synthesis rate (FSR) and the fractional breakdown rate (FBR) of albumin were calculated by the mathematical model.All data were analyzed using the one-way analysis of variance,LSD test or Dunnett's T3 test.Results The FSRs of albumin were 5.8％±0.9％,5.7％ ± 1.1％ and 5.7％ ± 1.0％ in the control group,the low-volume CVVH group and the high-volume CVVH group before treatment,with no significant difference between the 3 groups (F =0.04,P＞0.05).The FSRs of albumin were 5.9％±0.8％,7.3％±0.9％ and 7.8％± 1.1％ in the control group,the low-volume CVVH group and the high-volume CVVH group after treatment,with significant difference between the 3 groups (F =9.15,P ＜0.05).The FSRs of albumin of the low-volume CVVH group and the highvolume CVVH group were significantly higher than that of the control group (t =3.40,3.96,P ＜ 0.05),while no significant difference was detected between the low-volume CVVH group and the high-volume CVVH group in the FSR of albumin (t =1.02,P ＞ 0.05).The FBRs of albumin were 7.0％ ± 1.2％,6.5％ ± 0.9％ and 7.2％ ±1.2％ in the control group,the low-volume CVVH group and the high-volume CVVH group before treatment,with no significant difference between the 3 groups (F =0.88,P ＞ 0.05).The FBRs of albumin were 6.9％ ± 1.1％,6.2％±0.9％ and 7.4％± 1.0％ in the control group,the low-volume CVVH group and the high-volume CVVH group after treatment.There was no significant difference in the FBR of albumin after treatment between the 3 groups (F =2.82,P ＞ 0.05).Conclusions Simultaneous infusion of multiple isotopes for the detection of FSR and FBR of albumin is effective and feasible to detect the albumin metabolism.CVVH regulates the albumin metabolism in SIRS patients,and it can increase FSR of albumin in SIRS patients,while the FBR of albumin cannot be decreased by CVVH. Key words: Systemic inflammatory response syndrome; Stable isotope; Albumin; Continuous veno-venous hemofiltration

Systemic inflammatory response syndrome is a major determinant of late cardiovascular outcome in Takotsubo syndrome