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Introduction: The present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarker of endothelial dysfunction in sepsis or septic shock from articles published in PubMed between 2010 and March 2022., Materials and Methods: A systematic review of studies studying sFLT-1 monitoring in intensive care units in adults with sepsis or septic shock vs. controls for sepsis diagnosis and prognosis has been carried out (PROSPERO CRD42023412929 Registry)., Results: The endothelial dysfunction of sepsis is one of the keys to the development of the disease. VEGF binds to sFLT-1 acting as a competitive inhibitor of VEGF signalling in endothelial cells and thus neutralizes its pro-inflammatory effects. Endothelial dysfunction is reflected in increased sFLT-1 levels. High values of sFLT-1 were used for the differential diagnosis of sepsis versus other inflammatory pathologies, septic shock versus other types of shock, were elevated over time, estimation of disease prognosis, correlation with sepsis severity, organ dysfunction, and mortality prediction., Conclusions: It is evident that sepsis is based on endothelial dysfunction. sFLT-1 is one of the main biomarkers of microvascular alteration and is a predictive diagnostic and prognostic biomarker., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Background: Pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae can vary in severity, and several risk factors for the development of organ dysfunction in PLA have been implicated. However, few studies to date have explored the most common risk factors for clinical severity., Methods: We conducted a study on patients with PLA caused by Klebsiella pneumoniae between February 2013 and December 2022.Using logistic regression analysis, we sought to identify factors associated with positive blood culture, septic shock, and intensive care unit (ICU) admission., Results: After included 200 patients, we found that an elevated procalcitonin (PCT) level (p = 0.03), higher glucose level (p = 0.03), and lower total cholesterol (TC) level (p = 0.01) were associated with a higher likelihood of positive blood bacteriological culture. Additionally, an increased PCT level (p = 0.02) and lower TC level (p < 0.01) were associated with an elevated risk of septic shock. Furthermore, a higher PCT level (p < 0.01) was associated with a higher probability of ICU admission., Conclusion: In patients with PLA caused by Klebsiella pneumoniae, the PCT, glucose, and TC levels were found to be associated with positive blood culture, septic shock, and ICU admission., (© 2024. The Author(s).)

Introduction: Dysregulated host response to infection causes life-threatening organ dysfunction. Excessive inflammation and abnormal blood coagulation can lead to disseminated intravascular coagulation (DIC) and multiple-organ failure in the late sepsis stages. Platelet function impairment in sepsis contributes to bleeding, secondary infection, and tissue injury. Platelet transfusion is considered in patients with sepsis with DIC and bleeding; however, its benefits are limited and of low quality. Fibrinogen plays a crucial role in platelet function, and establishing a fibrin network binds to activated integrin αIIbβ3 and promotes outside-in signaling that amplifies platelet functions. However, the role of fibrinogen in sepsis-induced platelet dysfunction remains unclear., Materials and Methods: We evaluated the effects of fibrinogen on platelet hyporeactivity during septic shock in adult male Wistar rats using lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP) surgery. Changes in the hemodynamic, biochemical, and coagulation parameters were examined. Platelet activation and aggregation were measured using whole-blood assay, 96-well plate-based aggregometry, and light-transmission aggregometry. Additionally, platelet adhesion, spreading, and fibrin clot retraction were evaluated., Results: Rats with LPS- and CLP-induced sepsis displayed considerable decreases in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and clot retraction. The aggregation of platelets obtained from rats with sepsis was markedly augmented by fibrinogen supplementation. Additionally, fibrinogen administration improved platelet adhesion, spreading, and clot retraction in rats with sepsis., Conclusions: Fibrinogen supplementation could serve as a potential therapeutic intervention for alleviating platelet hyporeactivity in patients with sepsis and bleeding., Competing Interests: Declaration of competing interest All authors declared that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract: Background: Histidine-rich glycoprotein (HRG), a potential prognostic factor in sepsis, lacks clarity regarding its relevance in septic-induced shock, disseminated intravascular coagulation (DIC), and acute respiratory distress syndrome (ARDS) pathogenesis. This study investigated the association between HRG concentrations and these critical conditions. Methods: Blood samples were collected from 53 critically ill patients on days 1, 3, 5, and 7 after ICU admission at the Kyushu University Hospital. Daily clinical and laboratory data were recorded, and patient survival was assessed 28 days after ICU admission. Results: Serum HRG concentrations were significantly reduced on days 3, 5, and 7 in patients with septic shock and DIC but not in those with ARDS. While initial HRG levels on day one were not correlated with survival, nonsurvivors displayed decreased HRG levels, notably on days 3, 5, and 7 post-ICU admissions. The HRG levels remained stable in survivors. A progressive decrease was associated with higher mortality rates, particularly on days 5 and 7. On day 5, an HRG level with a cutoff of 25.5 μg/mL showed a sensitivity of 0.77 and a specificity of 0.75, indicating significantly lower survival rates (log-rank test, P < 0.05). Conclusion: HRG presents a potential intervention for critically ill sepsis patients, providing a novel strategy to enhance outcomes. Further research is needed to explore the therapeutic potential of HRG in sepsis management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Abstract: Objective: The goal of this study is to investigate the clinical value of vasopressor inflection points in the evaluation of short-term prognosis among individuals afflicted with septic shock. Methods: A retrospective analysis was conducted on a cohort comprising 56 patients diagnosed with septic shock and receiving treatment at the department of critical care medicine of the hospital between January 2021 and March 2023. These patients were divided into two groups based on the prognostic outcome: a survival group consisting of 34 patients and a death group consisting of 22 patients. The determination of vasopressor inflection time and procalcitonin (PCT) inflection time of each patient was undertaken with the initiation of vasopressor therapy serving as the reference point. The vasopressor inflection point was defined as the time when the dosage of vasopressors commenced decreasing, while the PCT inflection point denoted the time when PCT levels began to decline. The incidence of patients reaching the vasopressor and PCT inflection points on the 2nd, 3rd, and 4th days following the initiation of vasopressor therapy was tabulated for both groups. The comparison of inflection points between the two groups at each time point was conducted using Fisher's exact test. Furthermore, logistic regression analysis was employed for univariate prognostic assessment. The diagnostic performance of vasopressor and PCT inflection point was assessed using the four-table method. The discrepancy and consistency between the two methods were evaluated through paired chi-squared test and Kappa consistency test. Results: The vasopressor inflection point demonstrates promising utility in the assessment of short-term prognosis among patients with septic shock, exhibiting sensitivities of 76.4%, 88.2%, and 100%, specificities of 90.9%, 90.9%, and 86.4%, positive predictive values of 92.9%, 93.8%, and 91.9%, and negative predictive values of 71.4% on the 2nd, 3rd, and 4th day, respectively. Correspondingly, the Youden indices were calculated as 0.673, 0.791, and 0.864 on these respective days. Notably, all metrics at comparable intervals surpassed those of the PCT inflection point. Conclusion : The vasopressor inflection point presents as a robust prognostic tool for the short-term outcomes in patients with septic shock and exhibits superiority over PCT in prognostic assessment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48-1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17-1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18-0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation., (© 2024. The Author(s).)

Background: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction., Methods and Results: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped., Conclusions: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Abstract: Background: The association between neutrophil extracellular traps (NETs) and the requirement for vasopressor and inotropic support in vasoplegic shock is unclear. This study aimed to investigate the dynamics of plasma levels of NETs and cell-free DNA (cfDNA) up to 48 h after the admission to the intensive care unit (ICU) for management of vasoplegic shock of infectious (SEPSIS) or noninfectious (following cardiac surgery, CARDIAC) origin. Methods: This is a prospective, observational study of NETs and cfDNA plasma levels at 0H (admission) and then at 12H, 24H, and 48H in SEPSIS and CARDIAC patients. The vasopressor inotropic score (VIS), the Sequential Organ Failure Assessment (SOFA) score, and time spent with invasive ventilation, in ICU and in hospital, were recorded. Associations between NETs/cfDNA and VIS and SOFA were analyzed by Spearman's correlation (rho), and between NETs/cfDNA and ventilation/ICU/hospitalization times by generalized linear regression. Results: Both NETs and cfDNA remained elevated over 48 h in SEPSIS (n = 46) and CARDIAC (n = 30) patients, with time-weighted average concentrations greatest in SEPSIS (NETs median difference 0.06 [0.02-0.11], P = 0.005; cfDNA median difference 0.48 [0.20-1.02], P < 0.001). The VIS correlated to NETs (rho = 0.3-0.60 in SEPSIS, P < 0.01, rho = 0.36-0.57 in CARDIAC, P ≤ 0.01) and cfDNA (rho = 0.40-0.56 in SEPSIS, P < 0.01, rho = 0.38-0.47 in CARDIAC, P < 0.05). NETs correlated with SOFA. Neither NETs nor cfDNA were independently associated with ventilator/ICU/hospitalization times. Conclusion: Plasma levels of NETs and cfDNA correlated with the dose of vasopressors and inotropes administered over 48 h in patients with vasoplegic shock from sepsis or following cardiac surgery. NETs levels also correlated with organ dysfunction. These findings suggest that similar mechanisms involving release of NETs are involved in the pathophysiology of vasoplegic shock irrespective of an infectious or noninfectious etiology., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background and Objective: Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF)., Methods: Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cl eff ) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days., Results: HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (β = - 8.90 (95% CI - 12.9 to - 4.87), p < 0.001) and tazobactam (β = - 8.29 (95% CI - 13.5 to - 3.08), p = 0.002) and Cl eff for each antibiotic (meropenem β = - 10,206 (95% CI - 14,787 to - 5787), p = 0.001); tazobactam (β = - 4551 (95% CI - 7781 to - 1322), p = 0.012); piperacillin (β = - 3913 (95% CI - 6388 to - 1437), p = 0.002), even if the carryover effect influenced the Cl eff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (β = - 38.1 (95% CI - 47.9 to - 28.3), p < 0.001) and tazobactam (β = - 4.45 (95% CI - 6.17 to - 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type., Conclusion: MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Abstract: Purpose: This study aimed to develop and validate a model for prediction of septic shock in neonates with sepsis. Materials and methods: This retrospective study included early-onset septic neonates in the Renmin Hospital of Wuhan University between January 2017 and June 2021. The neonates were divided into the training set and the validation set in a ratio of 7:3 and further categorized into septic shock group and none-shock group according to presence or absence of shock symptoms. Results: A total of 406 septic neonates were enrolled, including 217 in septic shock group. Sex (odds ratio [OR] = 0.092, 95% confidence interval [CI]: 0.012 to 0.683, P = 0.020), C-reactive protein at 6 h (OR = 8.475, 95% CI: 3.154 to 22.774, P < 0.001), serum amyloid A at 6 h (OR = 1.179, 95% CI: 1.094 to 1.269, P < 0.01), white blood cells at 6 h (OR = 0.173, 95% CI: 0.092 to 0.326, P < 0.001), platelets at 6 h (OR = 0.985, 95% CI: 0.975 to 0.995, P < 0.001), and Ca 2+ at 6 h (OR = 1.44 × 10 11 , 95% CI: 2.70 × 10 6 to 7.70 × 10 15 , P < 0.001) were identified as independent risk factors for septic shock and were further included in the nomogram. The areas under the receiver operator characteristic curve were 0.873 and 0.920 in training and validation sets, respectively. Conclusions: A predictive model for early diagnosis of septic shock in neonates was developed and initially validated in this study, allowing for timely intervention., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers., Methods: Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis., Results: A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p < 0.05) observed for all parameters. When compared to SOFA score and traditional markers of CRP, PCT, IL-6 and IL-8, the combined indexes of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB demonstrated significantly improved diagnostic performance for sepsis and septic shock (AUC 0.911 and 0.902 respectively, p < 0.001)., Conclusions: The combined measurements of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB can augment the diagnostic capacity of HBP for sepsis, and offer reliable early supplementary indicators to traditional biomarkers for assessing disease severity in patients with infection., (© 2024. The Author(s).)

Background: Microvascular dysfunction plays a central role in organ dysfunction during septic shock. Endothelial glycocalyx (eGC) damage could contribute to impaired microcirculation. The aim was to assess whether several eGC-damaged biomarkers are associated with microvascular dysfunction in resuscitated septic shock patients., Methods: This cross-sectional study included resuscitated septic shock patients (N = 31), and a group of healthy individuals (N = 20). The eGC damage biomarkers measured were syndecan-1 (SDC-1), soluble CD44 (CD44s), hyaluronic acid (HYAL) in blood sample; sulfated glycosaminoglycans (GAGs) in urine sample; and thrombomodulin (TBML) in blood sample as biomarker of endothelial cell damage. Microcirculation was assessed through sublingual videocapillaroscopy using the GlycoCheck™, which estimated the perfused vascular density (PVD); the perfused boundary region (PBR), an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). We defined a low MVHS (<50th percentile in septic patients) as a surrogate for more impaired microvascular function., Results: The SDC-1, CD44s, TBML and GAGs levels were correlated with impaired microvascular parameters (PVD of vessels with diameter < 10 μm, MVHS and flow-adjusted PBR); p < 0.05 for all comparisons, except for GAGs and flow-adjusted PBR. The SDC-1 [78 ng/mL (interquartile range (IQR) 45-336) vs. 48 ng/mL (IQR 9-85); p = 0.052], CD44s [796ρg/mL (IQR 512-1995) vs. 526ρg/mL (IQR 287-750); p = 0.036], TBML [734ρg/mL (IQR 237-2396) vs. 95ρg/mL (IQR 63-475); p = 0.012] and GAGs levels [0.42 ρg/mg (IQR 0.04-1.40) vs. 0.07 ρg/mg (IQR 0.02-0.20); p = 0.024]; were higher in septic patients with more impaired sublingual microvascular function (low MVHS vs. high MVHS)., Conclusion: SDC-1, CD44s, TBML and GAGs levels were associated with impaired microvascular function in resuscitated septic shock patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Background : This study aimed to evaluate the effect of polymyxin B hemoperfusion (PMX-HP) in patients with peritonitis-induced septic shock who still required high-dose vasopressors after surgical source control. Methods : This retrospective study included adult patients admitted to the surgical intensive care unit (ICU) at Seoul National University Hospital between July 2014 and February 2021 who underwent major abdominal surgery to control the source of sepsis. Patients were divided into two groups based on whether PMX-HP was applied after surgery or not. The primary and secondary endpoints were the vasopressor reduction effect, and in-ICU mortality, respectively. Propensity score matching was performed to compare the vasopressor reduction effect. Results : A total of 338 patients met the inclusion criteria, of which 23 patients underwent PMX-HP postoperatively, whereas 315 patients did not during the study period. Serum norepinephrine concentration decreased over time regardless of whether PMX-HP was applied. However, it decreased more rapidly in the PMX-HP(+) group than in the PMX-HP(-) group. There were no significant differences in demographics including age, sex, body mass index, and most underlying comorbidities between the two groups. Risk factors for in-ICU mortality were identified by comparing patient characteristics and perioperative factors between the two groups using multivariate analysis. Conclusion : For patients with peritonitis-induced septic shock, PMX-HP rapidly reduces the requirement of vasopressors immediately after surgery but does not reduce in-ICU mortality. This effect could potentially accelerate recovery from shock, reduce sequelae from vasopressors, and ultimately improve quality of life after discharge., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 10 9 /L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p  = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p  = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p  = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 10 9 /L had a higher 28-day mortality rate (63.6% vs. 45%, p  = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; p  = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia ( p value from the log-rank test, p  = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.

Background: Lactate is a commonly used biomarker for sepsis, although it has limitations in certain cases, suggesting the need for novel biomarkers. We evaluated the diagnostic accuracy of plasma renin concentration and renin activity for mortality and kidney outcomes in patients with sepsis with hypoperfusion or hypotension., Methods: This was a multicenter, prospective, observational study of 117 patients with septic shock treated at three tertiary emergency departments between September 2021 and October 2022. The accuracy of renin activity, renin, and lactate concentrations in predicting 28-day mortality, acute kidney injury (AKI), and renal replacement requirement was assessed using the area under the ROC curve (AUC) analysis., Results: The AUCs of initial renin activity, renin, and lactate concentrations for predicting 28-day mortality were 0.66 (95% confidence interval [CI], 0.55-0.77), 0.63 (95% CI, 0.52-0.75), and 0.65 (95% CI, 0.53-0.77), respectively, and those at 24 hrs were 0.74 (95% CI, 0.62-0.86), 0.70 (95% CI, 0.56-0.83), and 0.67 (95% CI, 0.54-0.79). Renin concentrations and renin activity outperformed initial lactate concentrations in predicting AKI within 14 days. The AUCs of renin and lactate concentrations were 0.71 (95% CI, 0.61-0.80) and 0.57 (95% CI, 0.46-0.67), respectively ( P =0.030). The AUC of renin activity (0.70; 95% CI, 0.60-0.80) was also higher than that of lactate concentration ( P =0.044)., Conclusions: Renin concentration and renin activity show comparable performance to lactate concentration in predicting 28-day mortality in patients with septic shock but superior performance in predicting AKI.

Objective: Our aim was to analyse the relation between serial values of the indocyanine green plasma disappearance rate (ICG-PDR) with hospital mortality in the first 48 hours of ICU admission in patients with septic shock., Methods: A prospective observational study was carried out over 12 months of patients admitted to the ICU with septic shock. Each patient underwent noninvasive determination of ICG-PDR at 24 and 48 hours with the LiMON® module. Follow-up was performed until hospital discharge or exitus., Results: 63 patients. Age 61.1±12.3 years. 60.3% men. SOFA score on admission 8.7±3.3, APACHE II score was 27.9±10.7 points. A total of 44.4% of patients died. The ICG-PDR values in the first 24 hours of ICU admission were lower in nonsurvivors: 10.5 (5.7-13.0)%/min vs. 15.9 (11.4-28.0)%/min, p <0.001. Furthermore, in nonsurvivors, there was no improvement in ICG-PDR between 24 h and 48 h, while in survivors, there was an increase of 25%: 15.9 (11.4-28.0)%/min and 20.9 (18.0-27.0)%/min, p=0.020. The silhouette measure of ICG-PDR cohesion and separation for the clusters analysed (nonsurvivors and survivors) was satisfactory (0.6). ICG-PDR<11.7%/min was related to in-hospital mortality, ICG-PDR> 18%/min to survival, and the interval between 11.7% and 18%/min covered a range of uncertainty. In the two-stage cluster, ICG-PDR, SOFA and APACHE II present satisfactory predictive scores 24 hours after patient admission., Conclusions: ICG-PDR in our setting is a useful clinical prognostic tool and could optimise the decision tree in patients with septic shock., (©The Author 2024. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Septic shock is the most serious complication of sepsis, with more secure and efficient biomarkers urgently needed. Systemic immune-inflammation index (SII) and serum procalcitonin (PCT) show involvement in predicting septic shock prognosis., Objective: Herein, we explored the clinical value of the SII-PCT combination in the short-term prognosis of septic shock patients., Methods: Totally 200 septic shock patients were analyzed retrospectively and allocated into the survival and death groups upon 28-day in-hospital outcomes. Correlations of SII, PCT, acute physiology and chronic health evaluation II (APACHE II)/sepsis-related organ failure assessment (SOFA) scores, C-reactive protein (CRP), and serum creatinine (Scr) were analyzed using Spearman. The influencing factors of SII and serum PCT for short-term poor prognosis were analyzed using logistic multivariate regression model. The auxiliary predictive value of SII, PCT, and their combination for short-term adverse septic shock prognosis was evaluated by the receiver operating characteristic curve. Differences in the area under the curve (AUC) were compared using MedCalc., Results: The death group had higher APACHE II/SOFA scores, LYM, CRP, Scr, SII, and PCT levels than the survival group. SII and PCT were positively correlated with APACHE II and SOFA scores, LYM, CRP, and Scr, and were independent risk factors influencing the adverse septic shock prognosis. The AUC of the SII-PCT combination in predicting short-term adverse septic shock prognosis was 0.893 (0.841-0.932), with 76.12% sensitivity and 87.97% specificity, with the combination showing a higher AUC than SII/PCT alone., Conclusions: The SII-PCT combination helps predict the adverse prognosis of septic shock patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: We investigated the association between the administration of phosphodiesterase 3 inhibitors (PDE3i) and lactate kinetics, resolution of organ failure, ICU and hospital length of stay (LOS) and hospital mortality in a retrospective cohort of patients with septic shock and persistently elevated lactate concentrations., Material and Methods: Patients with septic shock and two arterial lactate concentrations ≥4 mmol/L with at least 4 h between measurements were eligible. Clinical data of the first four days of admission were collected in an online database. For each patient, the area between the actual lactate concentrations and 2.2 mmol/L (AUC lact2.2 ), was calculated for three days., Results: Data on 229 patients from 10 hospitals were collected, of whom 123 received PDE3i (54%). First, a linear multivariate model was developed to predict AUC lact2.2 (R 2  = 0.57). Adding PDE3i as a cofactor did not affect R 2 . Second, 60 patients receiving PDE3i at any time between days 0 and 2 were compared to 60 propensity matched no-PDE3i patients. Third, 30 patients who received PDE3i from ICU admission to day 3 were compared to 30 propensity-matched no-PDE3i patients. These analyses showed no differences in AUC lact2.2 , SOFA scores, ICU or hospital LOS or hospital mortality between treatment groups., Conclusions: No association was found between the administration of PDE3i and lactate kinetics, resolution of organ failure, ICU or hospital LOS or hospital mortality., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum norepinephrine (NE) dosage (MND) and mortality in neonates with septic shock. This retrospective cohort study included neonates with evidence of septic shock and those who received NE infusion. The study included 123 neonates, with 106 in the survival group and 17 in the death group. The death group exhibited significantly lower birth weight (p = 0.022), 1-min Apgar score (p = 0.005), serum albumin (p < 0.001), and base excess (BE) (p = 0.001) levels, but higher lactate (LAC) levels (p = 0.009) compared to the survival group. MND demonstrated an ROC area under the curve of 0.775 (95% CI 0.63-0.92, p < 0.001) for predicting mortality, with an optimal threshold of 0.3 µg/(kg·min), a sensitivity of 82.4%, and a specificity of 75.5%. Multivariate logistic regression indicated that an MND > 0.3 µg/(kg·min) (OR, 12.08, 95% CI 2.28-64.01) was associated with a significantly higher mortality risk. Spearman rank correlation showed a positive correlation between MND and LAC (r = 0.252, p = 0.005), vasoactive-inotropic score (VIS) (r = 0.836, p < 0.001), and a negative correlation with BE (r = - 0.311, p = 0.001). MND > 0.3 µg/(kg min) is a useful predictive marker of mortality in neonatal septic shock., (© 2024. The Author(s).)

Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury., (© 2024. The Author(s).)

Background: There are numerous methods available for predicting sepsis following Percutaneous Nephrolithotomy. This study aims to compare the predictive value of Quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SISR), National Early Warning Score (NEWS), interleukin-6 (IL-6), and procalcitonin (PCT) for septicemia., Methods: Patients who underwent percutaneous nephrolithotomy were included in the study and divided into a control group and a septic shock group. The effectiveness of qSOFA, SIRS, NEWS, Interleukin-6, and Procalcitonin was assessed, with Receiver Operating Characteristic curves and Area Under the Curve used to compare the predictive accuracy of these four indicators., Results: Among the 401 patients, 16 cases (3.99%) developed septic shock. Females, elderly individuals, and patients with positive urine culture and positive nitrite in urine were found to be more susceptible to septic shock. PCT, IL-6, SIRS, NEWS, qSOFA, and surgical time were identified as independent risk factors for septic shock. The cutoff values are as follows: qSOFA score > 0.50, SIRS score > 2.50, NEWS score > 2.50, and IL-6 > 264.00 pg/ml. Among the 29 patients identified by IL-6 as having sepsis, 16 were confirmed to have developed sepsis. The qSOFA identified 63 septicemia cases, with 16 confirmed to have developed septicemia; NEWS identified 122 septicemia cases, of which 14 cases actually developed septicemia; SIRS identified 128 septicemia patients, with 16 confirmed to have developed septicemia. In terms of predictive ability, IL-6 (AUC 0.993, 95% CI 0.985 ~ 1) demonstrated a higher predictive accuracy compared to qSOFA (AUC 0.952, 95% CI 0.928 ~ 0.977), NEWS (AUC 0.824, 95% CI 0.720 ~ 0.929) and SIRS (AUC 0.928, 95% CI 0.888 ~ 0.969)., Conclusions: IL-6 has higher accuracy in predicting septic shock after PCNL compared to qSOFA, SIRS, and NEWS., (© 2024. The Author(s).)

Objective: To construct a nomogram model for predicting the 28-day mortality of patients with septic shock in the emergency medicine department and to validate the predictive efficacy., Methods: Based on the database of the emergency medicine department of Chu Hsien-I Memorial Hospital of Tianjin Medical University, Tianjin Medical University General Hospital and the Second Hospital of Tianjin Medical University, the data of 913 patients with septic shock admitted to the emergency medicine department from January 2017 to October 2020 were collected, including baseline demographic information and clinical characteristics, laboratory indices, and the main endpoints (28-day mortality). The patients were divided into a training set and a validation set based on simple random sampling. All significant variables from the one-way binary Logistic regression analysis of the training set were included in the multivariate Logistic regression analysis to analyze the risk factors for 28-day mortality in patients with septic shock and to construct a column-line graphical model. The predictive efficacy of the nomogram model was assessed using calibration curves and receiver operator characteristic curve (ROC curve)., Results: A total of 860 patients with septic shock meeting the criteria were finally enrolled, including 472 in the training set and 388 in the validation set. The 28-day mortalities were 52.5% (248/472) and 54.1% (210/388) for the training and validation sets, respectively. In the training set, age, respiratory rate (RR), the levels of C-reactive protein (CRP), D-dimer, white blood cell count (WBC), neutrophil count (NEU), neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), mean platelet volume (MPV), and platelet count (PLT) in the death group were significantly higher than those in the survival group, and the levels of base remaining (BE), lymphocyte count (LYM), hemoglobin (Hb) and the proportion of chronic obstructive pulmonary diseases (COPD) were significantly lower than those in the survival group (all P < 0.05). Multifactorial Logistic regression analysis showed that NLR [odds ratio (OR) = 0.023 0, 95% confidence interval (95%CI) was -0.204 4 to 0.113 0], MPV (OR = 0.179 8, 95%CI was -0.877 6 to 0.172 7), Hb (OR = 0.007 8, 95%CI was 0.010 3 to 0.040 8), procalcitonin (PCT; OR = 1.957 0, 95%CI was 1.243 0 to 3.081 0), and D-dimer (OR = 0.000 1, 95%CI was -0.000 4 to 0.000 1) were independent predictors of 28-day mortality in patients with septic shock in the emergency department (all P < 0.05). A column-line graph model was established based on the above variables, and the ROC curves showed that the area under the ROC curve (AUC) of the nomogram model in the training set and validation set for predicting the 28-day mortality of patients with septic shock was 0.907 (95%CI was 0.864 to 0.940) and 0.822 (95%CI was 0.781 to 0.863), respectively. The calibration curves showed good agreement between the predicted and observed results for both the training and validation sets., Conclusions: The nomogram model constructed based on NLR, MPV, Hb, PCT and D-dimer has significant clinical value in predicting the 28-day mortality of patients with septic shock in the emergency medicine department.

Objectives: Identification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. We sought to the determine reproducibility of the data-driven "persistent hypoxemia, encephalopathy, and shock" (PHES) phenotype and determine its association with inflammatory and endothelial biomarkers, as well as biomarker-based pediatric risk strata., Design: We retrained and validated a random forest classifier using organ dysfunction subscores in the 2012-2018 electronic health record (EHR) dataset used to derive the PHES phenotype. We used this classifier to assign phenotype membership in a test set consisting of prospectively (2003-2023) enrolled pediatric septic shock patients. We compared profiles of the PERSEVERE family of biomarkers among those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk strata., Setting: Twenty-five PICUs across the United States., Patients: EHR data from 15,246 critically ill patients with sepsis-associated MODS split into derivation and validation sets and 1,270 pediatric septic shock patients in the test set of whom 615 had complete biomarker data., Interventions: None., Measurements and Main Results: The area under the receiver operator characteristic curve of the modified classifier to predict PHES phenotype membership was 0.91 (95% CI, 0.90-0.92) in the EHR validation set. In the test set, PHES phenotype membership was associated with both increased adjusted odds of complicated course (adjusted odds ratio [aOR] 4.1; 95% CI, 3.2-5.4) and 28-day mortality (aOR of 4.8; 95% CI, 3.11-7.25) after controlling for age, severity of illness, and immunocompromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and were more likely to be stratified as high risk based on PERSEVERE biomarkers predictive of death and persistent MODS., Conclusions: The PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlapped with higher risk strata based on prospectively validated biomarker approaches., Competing Interests: This work was supported by grant R21HD096402 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (Dr. Sanchez-Pinto). Drs. Atreya and Sanchez-Pinto received funding from R21GM151703. Cincinnati Children’s Hospital Medical Center (CCHMC) and the estate of the late Dr. Hector Wong hold patents for the pediatric sepsis biomarker risk model (PERSEVERE) for risk stratification of pediatric sepsis patients and gene expression-based adaptive endotypes. Dr. Atreya received funding from the National Institute of Child Health and Human Development (NICHD) (R21HD096402) and the National Institute of General Medical Sciences, he disclosed he holds patents for the pediatric sepsis biomarker risk model (PERSEVERE) for risk stratification of pediatric sepsis patients and gene expression-based adaptive endotypes. Drs. Atreya, Bennett, Faustino, Lufti, and Sanchez-Pinto received support for article research from the National Institutes of Health (NIH). Dr. Bennett’s institution received funding from the NICHD, the National Center for Advancing Translational Sciences, and the National Heart, Lung, and Blood Institute. Drs. Faustino and Sanchez-Pinto’s institutions received funding from the NIH. Dr. Cvijanovich’s institution received funding from CCHMC, Boston Children’s Hospital, the Centers for Disease Control, and Nationwide Children’s Hospital. Dr. Thomas received funding from Bayer AG. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Sepsis and septic shock are global healthcare problems associated with mortality rates of up to 40% despite optimal standard-of-care therapy and constitute the primary cause of death in intensive care units worldwide. Circulating biomarkers of septic shock severity may represent a clinically relevant approach to individualize those patients at risk for worse outcomes early in the course of the disease, which may facilitate early and more precise interventions to improve the clinical course. However, currently used septic shock biomarkers, including lactate, may be non-specific and have variable impact on prognosis and/or disease management. Activation of the renin-angiotensin-aldosterone system (RAAS) is likely an early event in septic shock, and studies suggest that an elevated level of renin, the early and committed step in the RAAS cascade, is a better predictor of worse outcomes in septic shock, including mortality, than the current standard-of-care measure of lactate. Despite a robust increase in renin, other elements of the RAAS, including endogenous levels of Ang II, may fail to sufficiently increase to maintain blood pressure, tissue perfusion, and protective immune responses in septic shock patients. We review the current clinical literature regarding the dysfunction of the RAAS in septic shock and potential therapeutic approaches to improve clinical outcomes., Competing Interests: Declaration of Competing Interest AKK is an advisory board member for Innoviva and Viatris Pharmaceuticals, distributors for Angiotensin II in the United States and the European Union. Other authors declare no competing financial interests in the work described., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock., Methods: The current prospective study was conducted in the PICU of University Children's Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0-Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome., Results: A total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were < 10% and ≥ 4 mmol/L, respectively. Patients with higher Lac H6 levels and lower lactate clearance rates had significantly higher PICU mortality based on Kaplan-Meier survival curve analysis., Conclusions: This study highlights the significance of lactate level trends over time for the prediction of mortality in the PICU in patients with severe sepsis or septic shock. Elevated lactate levels and decreased lactate clearance six hours after hospitalisation are associated with a higher mortality rate., (© 2024. The Author(s).)

Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level is primarily used as a biomarker for left ventricular (LV) dysfunction. It is influenced by various conditions, such as myocardial strain and situations affecting the clearance of NT-proBNP, including sepsis and shock. In this study, we investigated the appropriateness of NT-proBNP as a prognostic factor for septic shock. Patients with septic shock who visited the emergency department of the Ewha Womans' University Mokdong Hospital between January 1, 2018, and December 31, 2020, were classified into the survival group (those who survived in the hospital and were discharged) and the death group (those who died in the hospital). The effectiveness of NT-proBNP, lactate, and blood urea nitrogen as predictive factors of in-hospital mortality was evaluated using the area under the receiver operating characteristic (AUROC) curve. The AUROC curve was 0.678 and 0.648 for lactate and NT-proBNP, respectively, with lactate showing the highest value. However, there was no significant difference between lactate and NT-proBNP levels in the comparison of their AUROC curve (p = 0.6278). NT-proBNP could be a useful predictor of in-hospital mortality in patients with septic shock who present to the emergency department., (© 2024. The Author(s).)

Intensive Care Unit-acquired weakness (ICU-AW) is a common complication that significantly impedes patient recovery. In the study, we investigated the correlation between early serum myoglobin levels in patients with septic shock due to pneumonia, and the incidence of ICU-AW, duration of mechanical ventilation, and prognosis. Patients were classified based on the development of ICU-AW within the first 10 days of ICU admission. We measured serum myoglobin levels upon ICU entry, and analyzed demographic data, APACHE II scores, use of mechanical ventilation, and clinical outcomes, including mortality and duration of mechanical ventilation. The results indicated significantly elevated serum myoglobin levels in the ICU-AW group, correlated with prolonged mechanical ventilation and increased mortality. ROC analysis revealed myoglobin as a promising biomarker for predicting ICU-AW, with an area under the curve of 0.843 (95% CI: 0.819~0.867), demonstrating a sensitivity of 76.00% and specificity of 82.30%. These findings underscored serum myoglobin as a predictive biomarker for early ICU-AW in septic shock patients, highlighting its potential to guide clinical decision-making.

Background: Sepsis is a disease characterized by infection-induced multiorgan dysfunction, which can progress to septic shock if not promptly treated. Early identification of sepsis is crucial for its treatment. However, there are currently limited specific biomarkers for sepsis or septic shock. This study aims to identify potential biomarkers for sepsis and septic shock., Methods: We analyzed single-cell transcriptomic data of peripheral blood mononuclear cells (PBMCs) from healthy individuals, sepsis and septic shock patients, identified differences in gene expression and cell-cell communication between different cell types during disease progression. Moreover, our analyses were further validated with flow cytometry and bulk RNA-seq data., Results: Our study elucidates the alterations in cellular proportions and cell-cell communication among healthy controls, sepsis, and septic shock patients. We identified a specific augmentation in the Resistin signaling within sepsis monocytes, mediated via RETN-CAP1 ligand-receptor pairs. Additionally, we observed enhanced IL16 signaling within monocytes from septic shock patients, mediated through IL16-CD4 ligand-receptor pairs. Subsequently, we confirmed our findings by validating the increase in CAP-1 + monocytes in sepsis and IL16 + monocytes in septic shock in mouse models. And a significant upregulation of CAP-1 and IL16 was also observed in the bulk RNA-seq data from patients with sepsis and septic shock. Furthermore, we identified four distinct clusters of CD14 + monocytes, highlighting the heterogeneity of monocytes in the progress of sepsis., Conclusions: In summary, our work demonstrates changes in cell-cell communication of healthy controls, sepsis and septic shock, confirming that the molecules CAP-1 and IL16 on monocytes may serve as potential diagnostic markers for sepsis and septic shock, respectively. These findings provide new insights for early diagnosis and stratified treatment of the disease., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Acute kidney injury (AKI) is a common and severe complication in patients treated at an Intensive Care Unit (ICU). The pathogenesis of AKI has been reported to involve hypoperfusion, diminished oxygenation, systemic inflammation, and damage by increased intracellular iron concentration. Hepcidin, a regulator of iron metabolism, has been shown to be associated with sepsis and septic shock, conditions that can result in AKI. Heparin binding protein (HBP) has been reported to be associated with sepsis and AKI. The aim of the present study was to compare serum hepcidin and heparin binding protein (HBP) levels in relation to AKI in patients admitted to the ICU., Methods: One hundred and forty patients with community acquired illness admitted to the ICU within 24 hours after first arrival to the hospital were included in the study. Eighty five of these patients were diagnosed with sepsis and 55 with other severe non-septic conditions. Logistic and linear regression models were created to evaluate possible correlations between circulating hepcidin and heparin-binding protein (HBP), stage 2-3 AKI, peak serum creatinine levels, and the need for renal replacement therapy (RRT)., Results: During the 7-day study period, 52% of the 85 sepsis and 33% of the 55 non-sepsis patients had been diagnosed with AKI stage 2-3 already at inclusion. The need for RRT was 20% and 15%, respectively, in the groups. Hepcidin levels at admission were significantly higher in the sepsis group compared to the non-sepsis group but these levels did not significantly correlate to the development of stage 2-3 AKI in the sepsis group (p = 0.189) nor in the non-sepsis group (p = 0.910). No significant correlation between hepcidin and peak creatinine levels, nor with the need for RRT was observed. Stage 2-3 AKI correlated, as expected, significantly with HBP levels at admission in both groups (Odds Ratio 1.008 (CI 1.003-1.014, p = 0.005), the need for RRT, as well as with peak creatinine in septic patients., Conclusion: Initial serum hepcidin, and HBP levels in patients admitted to the ICU are biomarkers for septic shock but in contrast to HBP, hepcidin does not portend progression of disease into AKI or a later need for RRT. Since hepcidin is a key regulator of iron metabolism our present data do not support a decisive role of initial iron levels in the progression of septic shock into AKI., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Hansa Medical (Lund, Sweden) has filed patent applications on HBP as a diagnostic marker. Heiko Herwald is listed as inventor. All other authors have no conflicts of interest to declare., (Copyright: © 2024 Olinder et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective: The diagnosis of infection, to diagnose septic shock, has been qualified by leukocyte counts and protein biomarkers. Septic shock mortality is persistently high (20%-50%), and rising in the long term. The definition of sepsis does not include leukocyte count, and lymphopenia has been associated with its mortality in the short term. Immunosuppression and increased mortality in the long term due to sepsis have not been demonstrated. The aim is to relate the occurrence of lymphopenia and its lack of recovery during septic shock with mortality at 2 years., Patients and Methods: Cohort of 332 elderly patients diagnosed with septic shock. Mortality at 28 days and 2 years was analysed according to leukocyte, neutrophil, and lymphocyte counts, and the ability to recover from lymphopenia (LRec)., Results: A total of 74.1% of patients showed lymphopenia, and 73.5% did not improve during ICU stay. Mortality was 31.0% and 50.3% at 28 days and 2 years, respectively. Lymphopenia was a predictor of early mortality (OR 2.96) and LRec of late mortality (OR 3.98). Long-term mortality was associated with LRec (HR 1.69)., Conclusions: In elderly patients with septic shock, 28-day mortality is associated with lymphopenia and neutrophilia, and LRec with 2-year mortality; this may represent 2 distinct phenotypes of behaviour after septic shock., (Copyright © 2024 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Despite advancements in antibiotic therapy and resuscitation protocols, sepsis and septic shock remain major contributors to morbidity and mortality in children. We aimed to investigate the utility of soluble urokinase plasminogen activator receptor (suPAR) for the early detection of septic shock and to evaluate its accuracy in predicting mortality., Methods: A prospective study was conducted in a tertiary pediatric emergency department (ED), enrolling patients diagnosed with the sepsis, severe sepsis, or septic shock. In addition to assessing infection biomarkers such as C-reactive protein and procalcitonin, suPAR levels were quantified upon admission using enzyme-linked immunosorbent assay. The primary outcome measure was 30-day mortality., Results: Overall 72 patients and 80 healthy children included. Plasma suPAR levels demonstrated a statistically significant elevation in the sepsis, severe sepsis, and septic shock groups compared with the control group (p < 0.001 for all). The septic shock group exhibited the highest suPAR levels upon admission, surpassing both the sepsis and severe sepsis groups (p = 0.009 and 0.042). ROC analysis underscored the promising potential of suPAR with an AUC of 0.832 for septic shock. Analysis of mortality prediction revealed significantly higher suPAR levels in nonsurvivors than survivors (9.7 ng/mL vs. 4.2 ng/mL; p < 0.001). Employing plasma suPAR levels to discriminate between mortality and survival, a threshold of ≥7.0 ng/mL demonstrated a sensitivity of 90.9% and specificity of 71.0%., Conclusion: Plasma suPAR levels have the potential as a biomarker for predicting mortality in children with septic shock. In pediatric septic shock, the presence of plasma suPAR ≥7 ng/mL along with an underlying disease significantly increases the risk of mortality., (© 2024 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Purpose: The aim of this study was to examine the effects of intravenous (IV) fluid restriction on time to resolution of hyperlactatemia in septic shock. Hyperlactatemia in sepsis is associated with worse outcome. Sepsis guidelines suggest targeting lactate clearance to guide fluid therapy despite the complexity of hyperlactatemia and the potential harm of fluid overload., Methods: We conducted a post hoc analysis of serial plasma lactate concentrations in a sub-cohort of 777 patients from the international multicenter clinical CLASSIC trial (restriction of intravenous fluids in intensive care unit (ICU) patients with septic shock). Adult ICU patients with septic shock had been randomized to restrictive (n = 385) or standard (n = 392) intravenous fluid therapy. The primary outcome, time to resolution of hyperlactatemia, was analyzed with a competing-risks regression model. Death and discharge were competing outcomes, and administrative censoring was imposed 72 h after randomization if hyperlactatemia persisted. The regression analysis was adjusted for the same stratification variables and covariates as in the original CLASSIC trial analysis., Results: The hazard ratios (HRs) for the cumulative probability of resolution of hyperlactatemia, in the restrictive vs the standard group, in the unadjusted analysis, with time split, were 0.94 (confidence interval (CI) 0.78-1.14) at day 1 and 1.21 (0.89-1.65) at day 2-3. The adjusted analyses were consistent with the unadjusted results., Conclusion: In this post hoc retrospective analysis of a multicenter randomized controlled trial (RCT), a restrictive intravenous fluid strategy did not seem to affect the time to resolution of hyperlactatemia in adult ICU patients with septic shock., (© 2024. The Author(s).)

Introduction: In septic patients the damage of the endothelial barrier is decisive leading to circulatory septic shock with disseminated vascular coagulation, edema and multiorgan failure. Hemadsorption therapy leads to rapid resolution of clinical symptoms. We propose that the isolation of proteins adsorbed to hemadsorption devices contributes to the identification of mediators responsible for endothelial barrier dysfunction., Material and Methods: Plasma materials enriched to hemadsorption filters (CytoSorb ® ) after therapy of patients in septic shock were fractionated and functionally characterized for their effect on cell integrity, viability, proliferation and ROS formation by human endothelial cells. Fractions were further studied for their contents of oxidized nucleic acids as well as peptides and proteins by mass spectrometry., Results: Individual fractions exhibited a strong effect on endothelial cell viability, the endothelial layer morphology, and ROS formation. Fractions with high amounts of DNA and oxidized DNA correlated with ROS formation in the target endothelium. In addition, defined proteins such as defensins (HNP-1), SAA1, CXCL7, and the peptide bikunin were linked to the strongest additive effects in endothelial damage., Conclusion: Our results indicate that hemadsorption is efficient to transiently remove strong endothelial damage mediators from the blood of patients with septic shock, which explains a rapid clinical improvement of inflammation and endothelial function. The current work indicates that a combination of stressors leads to the most detrimental effects. Oxidized ssDNA, likely derived from mitochondria, SAA1, the chemokine CXCL7 and the human neutrophil peptide alpha-defensin 1 (HNP-1) were unique for their significant negative effect on endothelial cell viability. However, the strongest damage effect occurred, when, bikunin - cleaved off from alpha-1-microglobulin was present in high relative amounts (>65%) of protein contents in the most active fraction. Thus, a relevant combination of stressors appears to be removed by hemadsorption therapy which results in fulminant and rapid, though only transient, clinical restitution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kasper, Rodriguez-Alfonso, Ständker, Wiese and Schneider.)

Introduction: Comparison of the marker kinetics procalcitonin, presepsin, and endotoxin during extracorporeal hemoperfusion with polymyxin-B adsorbing cartridge (PMX-HA) has never been described in abdominal sepsis. We aimed to compare the trend of three biomarkers in septic post-surgical abdominal patients in intensive care unit (ICU) treated with PMX-HA and their prognostic value., Methods: Ninety abdominal post-surgical patients were enrolled into different groups according to the evidence of postoperative sepsis or not. Non-septic patients admitted in the surgical ward were included in C group (control group). ICU septic shock patients with endotoxin levels &lt;0.6 EAA receiving conventional therapy were addressed in S group and those with endotoxin levels ≥0.6 EAA receiving treatment with PMX-HA, besides conventional therapy, were included in SPB group. Presepsin, procalcitonin, endotoxin and other clinical data were recorded at 24 h (T0), 72 h (T1) and 7 days (T2) after surgery. Clinical follow-up was performed on day 30., Results: SPB group showed reduced levels of the three biomarkers on T2 versus T0 (p &lt; 0.001); presepsin, procalcitonin and endotoxin levels decreased, respectively, by 25%, 11%, and 2% on T1 versus T0, and 40%, 41%, and 26% on T2 versus T0. All patients in C group, 73% of patients in SPB group versus 37% of patients in S group survived at follow-up. Moreover, procalcitonin had the highest predictive value for mortality at 30 days, followed by presepsin., Conclusion: The present study showed the reliability of presepsin in monitoring PMX-HA treatment in septic shock patients. Procalcitonin showed better predicting power for the mortality riSsk., (© 2024 S. Karger AG, Basel.)

Introduction: Toll-like receptors play crucial roles in the sepsis-induced systemic inflammatory response. Septic shock mortality correlates with overexpression of neutrophilic TLR2 and TLR9, while the role of TLR4 overexpression remains a debate. In addition, TLRs are involved in the pathogenesis of viral infections such as COVID-19, where the single-stranded RNA of SARS-CoV-2 is recognized by TLR7 and TLR8, and the spike protein activates TLR4., Methods: In this study, we conducted a comprehensive analysis of TLRs 1-10 expressions in white blood cells from 71 patients with bacterial and viral infections. Patients were divided into 4 groups based on disease type and severity (sepsis, septic shock, moderate, and severe COVID-19) and compared to 7 healthy volunteers., Results: We observed a significant reduction in the expression of TLR4 and its co-receptor CD14 in septic shock neutrophils compared to the control group (p &lt; 0.001). Severe COVID-19 patients exhibited a significant increase in TLR3 and TLR7 levels in neutrophils compared to controls (p &lt; 0.05). Septic shock patients also showed a similar increase in TLR7 in neutrophils along with elevated intermediate monocytes (CD14+CD16+) compared to the control group (p &lt; 0.005 and p &lt; 0.001, respectively). However, TLR expression remained unchanged in lymphocytes., Conclusion: This study provides further insights into the mechanisms of TLR activation in various infectious conditions. Additional analysis is needed to assess their correlation with patient outcome and to evaluate the impact of TLR-pathway modulation during septic shock and severe COVID-19., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background/aim: Extracorporeal blood purification (EBP) therapies have shown promise as potential rescue treatments for patients with septic shock. However, precise evidence regarding their effectiveness is lacking. This case-control study aimed to evaluate the 28-day survival benefit of a resin cartridge-based EBP therapy compared to conventional therapies in patients with septic shock., Materials and Methods: The study sample was collected retrospectively from the medical records of patients admitted to the intensive care unit (ICU) between 2015 and 2020. The study included patients with septic shock aged ≥18 years who had ICU stays >96 h and excluded those lost to follow-up by 28 days or readmitted. First, 28-day survival was compared between EBP patients and 1:1 matched conventionally treated controls. Second, the EBP patients were evaluated for clinical and laboratory improvements within 72 h of EBP therapy., Results: Of 3742 patients, 391 were included in this study, of whom 129 received EBP therapy and had a 28-day survival rate of 44%, compared to 262 matched controls who received conventional therapy alone and had a survival rate of 33% (p = 0.001, log-rank = 0.05, number needed to treat = 8, and odds ratio = 1.7). After receiving EBP therapy for 72 h, improvements were observed in the Sequential Organ Failure Assessment scores (p < 0.05), shock indices (p < 0.05), partial pressure of oxygen in the arterial blood to the fraction of inspiratory oxygen concentration ratios (p < 0.001), vasopressor requirements (p < 0.001), pH (p < 0.05), lactate levels (p < 0.001), and C-reactive protein levels (p < 0.05)., Conclusion: The findings suggest that administering resin cartridge-based EBP therapy to patients with septic shock may improve their survival compared to conventional therapies., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest., (© TÜBİTAK.)

Background: Ferritin, an acute phase reactant, and the ferritin index (FI = observed ferritin level/upper limit of normal level for age and sex) may be prognostic biomarkers in septic shock and cardiac surgery patients., Objective: The purpose of this exploratory study is to assess the outcome associations of ferritin and FI levels in septic shock compared to post-cardiac surgery patients., Design: This was a prospective, double-centre, observational study., Setting: The study setting involved two adult intensive care units (ICUs) in Victoria, Australia., Participants: Sixty-one septic shock and 30 post-cardiac surgery patients participated in this study., Main Outcome Measures: We measured ferritin and FI on ICU admission (T1) and 24 h later (T2) to assess its correlation with mortality, illness severity, and hospital length of stay (LOS)., Results: The baseline characteristics of patients in the septic shock group and cardiac surgery group were similar apart from illness severity scores (APACHE III and modified SOFA score). Septic shock patients had more physiological derangements as well as greater use and higher doses of norepinephrine at both T1 and T2. Septic shock patients had significantly higher median ferritin levels (372 μg/L versus 198 μg/L; p < 0.001 at T1, 457 μg/L versus 264 μg/L; p = 0.001 at T2) than post-cardiac surgery patients. Ferritin levels, however, did not have a linear correlation with illness severity or hospital mortality. Instead, there was an association between high ferritin levels at T2 and longer ICU (p = 0.017) and hospital LOS (p = 0.013). Females with septic shock had significantly higher FI (p < 0.001 at T1, p = 0.004 at T2) than males., Conclusion: In septic shock patients, ferritin levels and FI were twice the level compared to post-cardiac surgery patients. Both had no association with mortality, but levels above the median at 24 h were associated with longer ICU and hospital LOS., (Copyright © 2022 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers., Methods: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations., Results: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS., Conclusion: Serum cytokine profiles may be useful for differentiating between KD and its mimickers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Coronavirus disease 2019 (COVID-19) infection is characterized by a dysregulated inflammatory response, which may result in severe hemodynamic instability and septic shock. The Seraph-100® Microbind® Affinity Blood Filter is a commercially available extracorporeal pathogen absorbent device with the ability to bind pathogens and cytokines present within the blood. Our study aimed to evaluate the efficacy of the Seraph-100® for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and septic shock., Materials and Methods: A retrospective review was performed to evaluate the use of the Seraph-100® blood filter at a Single Center tertiary-care facility at Brooke Army Medical Center from 2020 to 2021. Nine patients (11 treatments) were completed with the Seraph-100® blood filter in patients with SARS-CoV-2 infection and septic shock. The Seraph-100® blood filter was used in combination with continuous renal replacement therapy and slow low-efficiency dialysis or directly in parallel with the extracorporeal membrane oxygenation circuit., Results: Within this cohort, there was a statistically significant improvement in the following clinical parameters comparing values to before and after treatment with the Seraph-100® blood filter: Mean arterial pressure (mmHg) (64.2 ± 2.36 vs. 76.2 ± 2.68; P < .001), heart rate (beats per minute) (128 ± 6.6 vs. 100.3 ± 6.07; P < .001), administered fraction of oxygen (%) (74.4 ± 10.58 vs. 60.3 ± 10.35; P < .001), serum lactate (mmol/L) (6.14 ± 1.25 vs. 2.8 ± 1.14; P = .0095), and pH (7.29 ± 0.03 vs. 7.39 ± 0.04; P = .0203). There were statistically significant improvements in vasopressor requirements: norepinephrine (mcg/min) (36.3 ± 4.74 vs. 8.3 ± 3.92; P < .001), vasopressin (units/min) (0.04 ± 0.004 vs. 0.02 ± 0.003; P < .001), dobutamine (mcg/kg/min) (2.3 ± 1.00 vs. 0.2 ± 0.75; P = .006) and angiotensin II (ng/kg/min) (34.5 ± 6.4 vs. 3.3 ± 5.26; P < .001)., Conclusions: The use of the Seraph-100® blood filter was associated with statistically and clinically significant improvements in hemodynamic parameters and decreased vasopressor requirements in patients with septic shock and SARS-CoV-2 infection., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (DIO3) is present in immune cells, but there is no description of its presence in patients with sepsis. Here, we aimed to determine the prognostic impact of thyroid hormones levels (TH), measured on ICU admission, on mortality and evolution to chronic critical illness (CCI) and the presence of DIO3 in white cells. We used a prospective cohort study with a follow-up for 28 days or deceased. Low T3 levels at admission were present in 86.5% of the patients. DIO3 was induced by 55% of blood immune cells. The cutoff value of 60 pg/mL for T3 displayed a sensitivity of 81% and specificity of 64% for predicting death, with an odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 for mortality and 0.75 for evolution to CCI, thus displaying better performance than commonly used prognostic scores. The high expression of DIO3 in white cells provides a novel mechanism to explain the reduction in T3 levels in sepsis patients. Further, low T3 levels independently predict progression to CCI and mortality within 28 days for sepsis and septic shock patients.

Granzyme B could be released from cytotoxic T lymphocytes producing apoptosis activation. The objective of our study was to determine whether an association between septic patient mortality and blood granzyme B concentrations exist. We recruited septic patients admitted in 3 Intensive Care Units. We recorded mortality at 30 days and we determined serum granzyme B concentrations at moment of sepsis diagnosis. We found higher rate of history of diabetes mellitus (P = 0.02), serum granzyme B concentrations (P < 0.001), age (P = 0.001), serum lactic acid levels (P = 0.001) and sepsis-related organ failure assessment (P < 0.001) exhibited non-surviving patients (n = 67) than surviving ones (n = 110). We found in multiple logistic regression analysis an association of serum granzyme B concentrations with mortality (odds ratio = 1.223; 95% confidence interval = 1.104-1.355; P < 0.001) controlling for diabetes mellitus, sepsis-related organ failure assessment, lactic acid and age. That we know, our study is the first reporting the existence of an association of high serum granzyme B concentrations with high septic patients mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate the predictive value of D-dimer for deep venous thrombosis (DVT) of lower extremity in adult burn patients. Methods: A retrospective case series study was conducted. The clinical data of 3 861 adult burn patients who met the inclusion criteria and were admitted to the Department of Burns of Zhengzhou First People's Hospital from January 1, 2015 to December 31, 2019 were collected. The patients were divided into DVT group ( n =77) and non-DVT group ( n =3 784) according to whether DVT of lower extremity occurred during hospitalization or not. Data of patients in the two groups were collected and compared, including the gender, age, total burn area, D-dimer level, with lower limb burn and inhalation injury or not on admission, with sepsis/septic shock, femoral vein indwelling central venous catheter (CVC), history of surgery, and infusion of concentrated red blood cells or not during hospitalization. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. The indicators with statistically significant differences between the two groups were analyzed with multivariate logistic regression analysis to screen the independent risk factors for DVT of lower extremity in 3 861 adult burn patients. The receiver operating characteristic (ROC) curve of the independent risk factors predicting DVT of lower extremity in 3 861 adult burn patients were drawn, and the area under the curve (AUC), the optimal threshold value, and the sensitivity and specificity under the optimal threshold value were calculated. The quality of the AUC was compared by Delong test, and the sensitivity and specificity under the optimal threshold value were compared using chi-square test. Results: There were no statistically significant differences in gender, occurrence of sepsis/septic shock or history of surgery during hospitalization between patients in the two groups ( P >0.05), while there were statistically significant differences in age, total burn area, D-dimer level, lower limb burn and inhalation injury on admission, and femoral vein indwelling CVC and infusion of concentrated red blood cells during hospitalization between patients in the two groups ( t =-8.17, with Z values of -5.04 and -10.83, respectively, χ 2 values of 21.83, 5.37, 7.75, and 4.52, respectively, P <0.05 or P <0.01). Multivariate logistic regression analysis showed that age, total burn area, and D-dimer level were the independent risk factors for DVT of lower extremity in 3 861 adult burn patients (with odds ratios of 1.05, 1.02, and 1.14, respectively, 95% confidence intervals of 1.04-1.06, 1.00-1.03, and 1.10-1.20, respectively, P <0.05 or P <0.01). The AUCs of ROC of age, total burn area, and D-dimer level for predicting DVT of lower extremity in 3 861 adult burn patients were 0.74, 0.67, and 0.86, respectively (with 95% confidence intervals of 0.68-0.80, 0.60-0.74, and 0.83-0.89, respectively, P values<0.01), the optimal threshold values were 50.5 years old, 10.5% total body surface area, and 1.845 mg/L, respectively, the sensitivity under the optimal threshold values were 71.4%, 70.1%, and 87.0%, respectively, and the specificity under the optimal threshold values were 66.8%, 67.2%, and 72.9%, respectively. The AUC quality and sensitivity and specificity under the optimal threshold value of D-dimer level were significantly better than those of age ( z =3.29, with χ 2 values of 284.91 and 34.25, respectively, P <0.01) and total burn area ( z =4.98, with χ 2 values of 326.79 and 29.88, respectively, P <0.01), while the AUC quality and sensitivity and specificity under the optimal threshold values were similar between age and total burn area ( P >0.05). Conclusions: D-dimer level is an independent risk factor for DVT of lower extremity in adult burn patients, its AUC quality and sensitivity and specificity under the optimal threshold value are better than those of age and total burn area, and it has good predictive value for DVT of lower extremity in adult burn patients.

Introduction: In septic shock, mitochondrial dysfunction, and hypoperfusion are the main triggers of multi-organ failure. Little is known about the crosstalk between mitochondrial dysfunction and hemodynamic alterations, especially in the post-resuscitation phase. Here, we assess whether hypoperfusion and lactate levels are associated with oxygen consumption linked to mitochondrial bioenergetic activity in lymphocytes of patients admitted with septic shock., Patients and Methods: Prospective cohort study in patients with septic shock defined as the requirement of vasopressors to maintain a mean arterial pressure 65 mm Hg after initial fluid administration. Basal mitochondrial and Complex I respiration was measured to evaluate mitochondrial activity. Both variables and capillary refill time were compared with arterial lactate post-fluid resuscitation. We also compared mitochondrial activity measurements between patients with and without hypoperfusion status., Results: A total of 90 patients were included in analysis. The median arterial lactate at the time of septic shock diagnosis was 2.0 mmol/Dl (IQR 1.3-3.0). Baseline respiration at the time of septic shock diagnosis was correlated with lactate (Spearman -0.388, 95% CI -0.4893 to -0.1021; P = 0.003), as well as Complex I respiration (Spearman -0.403, 95% CI -0.567 to -0.208; P < 0.001). Patients with hypoperfusion status had no difference in basal respiration when compared with patients who did not have hypoperfusion status (P = 0.22) nor in Complex I respiration (P = 0.09)., Conclusion: Changes in lymphocytic mitochondrial metabolism are associated with post-resuscitation arterial lactate in septic shock; however, they are not associated with the presence of a hypoperfusional status. In this scenario, it is therefore suggested that systemic perfusion and mitochondrial metabolism have different courses., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Objective: Sepsis is a host response with life-threatening organ dysfunction caused by an infection. Although the overall mortality rate has increased from 30% to 37% by the surviving sepsis campaign, it is still not acceptable. Early identification, accurate stratification and appropriate intervention can improve the prognosis. In this study we assessed the risk stratification and prognostic value of serum neutrophil gelatinase-associated lipocalin (sNGAL) as a biomarker in sepsis patients., Methods: A total of 112 sepsis patients (38 patients with sepsis, 41 patients with severe sepsis, 33 patients with septic shock) and 25 healthy controls were enrolled in this study. Serum samples of all patients were collected and frozen before testing. Basic patient information was collected, including age, gender, primary infection, complications, and so on. Results of serum calcitonin, lactic acid, and SOFA score were followed up for 28 days., Results: Levels of serum procalcitonin (PCT), serum lactate, Sequential Organ Failure Assessment (SOFA) score and sNGAL of sepsis patients were significantly higher (p<0.05) than those of controls. The sNGAL level in sepsis patients who were alive on the 28th day of follow-up was significantly lower (p<0.05) than that of sepsis patients who had died before the 28th day of follow-up. Multiple logistic regression analysis showed that sNGAL-0h and lactates were independent risk factors of death due to sepsis within 28 days. At cut-off value of 250 ng/mL, the sensitivity and specificity sNGAL-0h predicting the 28-day mortality in septic patients were 0.838 and 0.827, respectively. The sNGAL level in sepsis patients with acute kidney injury (AKI) was significantly higher (p<0.05) than in sepsis patients without AKI., Conclusion: Serum NGAL may contribute to the assessment of the severity of sepsis. Serum NGAL and lactate can be independent risk factors for 28-day mortality in sepsis patients. Serum NGAL has potential of predicting septic-AKI.

Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 μg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 μg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 μg/L, p < 0.001; one week after: 374.9 ± 95.3 vs. 261.6 ± 91.9 μg/L, p < 0.001), and in nonsurvivors than survivors (sepsis onset: 427.2 ± 96.7 vs. 306.9 ± 92.1 μg/L, p < 0.001; one week after: 414.1 ± 94.5 vs. 264.2 ± 79.9 μg/L, p < 0.001). Moreover, patients with septic shock and nonsurvivors, presented a significantly lower absolute and relative decrease in chemerin one week after sepsis onset compared to baseline ( p < 0.001). Based on ROC curve analyses, the diagnostic performance of chemerin (AUC 0.78, 95% CI 0.69-0.87) was similar to C-reactive protein (CRP) (AUC 0.78, 95% CI 0.68-0.87) in discriminating sepsis severity. However, increased chemerin at sepsis onset and one week later was an independent predictor of 28-day mortality (sepsis onset: HR 3.58, 95% CI 1.48-8.65, p = 0.005; one week after: HR 10.01, 95% CI 4.32-23.20, p < 0.001). Finally, serum chemerin exhibited significant correlations with the severity scores, white blood cells, lactate, CRP and procalcitonin, as well as with biomarkers of glucose homeostasis, but not with cytokines and soluble urokinase-type plasminogen activator receptor (suPAR). Circulating chemerin is increased early in sepsis and its kinetics may have diagnostic and prognostic value in critically ill patients. Further studies are needed to shed light on the role of chemerin in sepsis.

Purpose: To explore the clinical value of serum calcium (Ca) in elderly patients with sepsis., Materials and Methods: The clinical data and laboratory data of elderly patients with sepsis (n = 165) and elderly population for physical examination (n = 67) in a tertiary hospital from January 2020 to November 2020 were collected. We analyzed serum Ca levels in sepsis and septic shock firstly, and then continued to investigate them in the survival group and the death group. Meanwhile, we also assessed the correlation between serum Ca and PCT., Results: The serum Ca levels of the elderly patients with sepsis were lower than that of the control group (median 1.98 vs 2.31 mmol/L, P < 0.001), and the more severe the sepsis, the lower the serum Ca levels. Sepsis patients with decreased serum Ca had higher shock rate and mortality. There was a negative correlation between serum Ca and PCT (r = -0.2957, P < 0.001)., Conclusion: Serum Ca has a certain value for the early recognition of elderly patients with sepsis and the judgment of the severity of the disease., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Disseminated intravascular coagulation (DIC) is a life-threatening complication of septic shock; however, risk factors for its development after admission are unknown. Thromboelastography (TEG) can reflect coagulation disturbances in early non-overt DIC that are not detected by standard coagulation tests. This study investigated the risk factors including TEG findings as early predictors for DIC development after admission in septic shock patients with non-overt DIC., Methods: This retrospective observation study included 295 consecutive septic shock patients with non-overt DIC at admission between January 2016 and December 2019. DIC was defined as an International Society on Thrombosis and Hemostasis (ISTH) score ≥ 5. The primary outcome was non-overt DIC at admission that met the ISTH DIC criteria within 3 days after admission., Results: Of the 295 patients with non-overt DIC, 89 (30.2%) developed DIC after admission. The DIC group showed a higher ISTH score and 28-day mortality rate than the non-DIC group (2 vs. 3, P < 0.001; 13.6% vs. 27.0%, P = 0.008, respectively). The DIC rate increased with the ISTH score (7.7%, 13.3%, 15.8%, 36.5%, and 61.4% for scores of 0, 1, 2, 3, and 4, respectively). Among TEG values, the maximum amplitude (MA) was higher in the non-DIC group (P < 0.001). On multivariate analysis, an MA < 64 mm was independently associated with DIC development (odds ratio, 2.311; 95% confidence interval, 1.298-4.115)., Conclusions: DIC more often developed among those with admission ISTH scores ≥ 3 and was associated with higher mortality rates. An MA < 64 mm was independently associated with DIC development in septic shock patients., Competing Interests: The authors report no funding and conflicts of interest., (Copyright © 2021 by the Shock Society.)

Introduction: We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock., Methods: This was a post-hoc analysis of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial, a multicenter, double-blind, randomized controlled trial. Patients were randomized to either a treatment group (intravenous vitamin C and thiamine for 48 h) or a control group. Interleukin (IL)-6, IL-10, angiopoietin-II (AP2), and S100β were assessed at baseline and at 72 h. The primary outcomes were the biomarker levels at 72 h, and the secondary outcome was reduction rate., Results: Forty-five patients were assigned to the treatment group and 52 were assigned to the control group. Baseline biomarker levels and at 72 h were not significantly different between the treatment and the placebo groups. The reduction rates were not significantly different between the two groups. These outcome variables showed fair diagnostic accuracy for predicting 28-day mortality according to the area under the receiver operating characteristic curve., Conclusion: Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β., Trial Registration: NCT, ClinicalTrials.gov NCT03756220, ATESS. Registered 28 November 2018, https://clinicaltrials.gov/ct2/show/NCT03756220., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)