Septic Mortality Research Articles

Abstract 4132120: Down syndrome-trisomy-mediated gene, Dscr-1, protects against lifestyle-related vascular diseases

Epidemiological studies indicate that individuals with Down syndrome (DS) have an increased risk of leukemia and neuronal diseases but a significantly reduced incidence of most solid tumors and advanced vascular dysfunction. This suggests that one or a combination of trisomy genes on human chromosome 21 (HSA21) or murine chromosome 16 ( Mmu16 ) may be responsible for protecting against vasculopathy. Our previous research has shown that the Down syndrome critical region (Dscr)-1 gene, located on HSA21 or Mmu16 , encodes a feedback modulator of calcineurin-NFAT signaling in endothelial cells (ECs). Null mutation or overexpression of Dscr-1 has been found to increase or prevent septic mortality, angiogenesis, liver steatosis, and susceptibility of tumor metastasizing to the lung, respectively, demonstrating its significant role in these processes. In a unique approach, we crossed DS model mice with ApoE -null mice and fed them a high-fat diet (HFD) for 12 weeks to survey the effects of DS-related genes on atherosclerosis. The results were striking, with HFD-mediated increased LDL and triglyceride levels in ApoE -null mice significantly reduced in the combined DS plus ApoE -null mice. This innovative method allowed us to observe a remarkable (~35%) reduction in ApoE-null mediated atheroma formation in the DS model. This finding was also replicated in EC-specific DSCR-1 transgenic (DSCR-1 ECTg ) mice. Furthermore, to test the effect of HSA21, we have collected DS patient-derived trisomy and disomy iPS cells and executed them for the chromatin conformation capture analysis and the in vitro ECs differentiation experiments. DS-derived trisomy iPS cells already changed the whole chromatin structure, typically within the X chromosome. Moreover, the trisomy iPS-derived ECs revealed less proliferation compared to the disomy. RNA-seqs indicated trisomy iPS derived ECs dramatically (21-fold) increased DSCR-1 , but some HSA21 genes, Alzheimer’s related App and Bace2 , e.g., were inversely reduced the expression. Our comprehensive studies not only shed new light on the mechanisms of atherosclerosis in vascular pathology but also offer potential therapeutic strategies. The discovery of the Dscr-1 gene on the DS chromosome, which could be a powerful tool in combating lifestyle-related vascular diseases, underscores the significance of our research.

Drainage and irrigation on demand may decrease severe septic complications and mortality in pancreatic resections.

The necessity of routine drain placement in pancreatic resections is controversial. Some randomized controlled trials have shown that the omission of drainage is safe for some patients, whereas reintervention rates and mortality rates are substantial for others. The present study aimed to assess fistula-associated outcomes in the setting of routine drain placement and drain irrigation on demand. Between 01/2017 and 12/2022, perioperative and outcome data from patients who underwent consecutive pancreatoduodenectomies (PD, n = 253) or distal pancreatectomies (DP, n = 72) were prospectively collected in the electronic StuDoQ database and analysed. All patients underwent intraoperative drain placement. Drains were removed starting at postoperative day 2 in PD or at day 5 in DP after testing for amylase concentration. In case of high amylase levels or macroscopically suspicious pancreatic fistulas, drain irrigation was started. Nondrained fluid collections underwent percutaneous radiologic or transluminal endoscopic evacuation. Clinically relevant pancreatic fistulas were detected in 53 of 325 patients (POPF grade B 16.3%, grade C 1.2%). 43.3% of those had drain irrigation. Additional interventional or endoscopic drainage was necessary in 14 and 5 patients, respectively (overall 5.8%), and were observed in 4.0% of patients with PD and in 12.5% with DP (p = 0.009). Delayed fistula-associated postpancreatectomy haemorrhage (PPH) was present in 1.2% (4/325) of patients. The fistula- and delayed PPH-associated reoperation rate was 1.5% (5/325). The 30-day and in-hospital mortality rates were both 1.5% (5/325), and the rate of fistula-associated mortality was 0.6% (2/325). The overall 90-day mortality rate was 4.5%. In pancreatectomies, a standardized drainage protocol including on-demand drain irrigation results in very low fistula-associated morbidity and mortality and an infrequent need for interventional or surgical reintervention as compared to previously published drainage studies.

Comparison of Hypervirulent and Non-Hypervirulent Carbapenem-Resistant Acinetobacter baumannii Isolated from Bloodstream Infections: Mortality, Potential Virulence Factors, and Combination Therapy In Vitro.

Hypervirulent carbapenem-resistant Acinetobacter baumannii (hv-CRAB) has emerged in bloodstream infections (BSI). Cases of BSI caused by hv-CRAB (hv-CRAB-BSI) had posed a significant threat to hospitalized patients. In this study, 31 CRAB strains isolated from Chinese BSI patients were analyzed, of which 24 were identified as hv-CRAB-BSI and 7 as non-hv-CRAB-BSI, using the Galleria mellonella infection model. Patients with hv-CRAB-BSI had higher rates of septic shock (79.2% vs. 14.3%, p = 0.004) and mortality (66.7% vs. 14.3%, p = 0.028). All strains were resistant to most antibiotics but sensitive to colistin. Hv-CRAB-BSI showed lower resistance to minocycline than non-hv-CRAB-BSI (54.2% vs. 100%, p = 0.03). Whole-genome sequencing revealed that the detection rates of immune modulation genes ptk and epsA in hv-CRAB-BSI were significantly higher than in non-hv-CRAB-BSI (91.7% vs. 28.6%, p = 0.002). Additionally, all ST457 hv-CRAB-BSI lacked abaR, and all ST1486 non-hv-CRAB-BSI lacked adeG. The checkerboard dilution method assessed the efficacies of various antibiotic combinations, revealing that although synergism was rarely observed, the combination of colistin and minocycline showed the best efficacy for treating CRAB-BSI, regardless of whether the infections were hv-CRAB-BSI or non-hv-CRAB-BSI. These findings highlight the importance of analyzing molecular characteristics and exploring effective treatment strategies for hv-CRAB-BSI.

Simultaneous removal of endotoxins, inflammatory mediators and uremic toxins in ICU patients with septic shock: a retrospective cohort study

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.

Infectious Foci, Comorbidities and Its Influence on the Outcomes of Septic Critically Ill Patients.

Sepsis is among the most frequent diagnoses on admission to the intensive care unit (ICU). A systemic inflammatory response, activated by uncontrolled infection, fosters hypoperfusion and multiorgan failure and often leads to septic shock and mortality. These infections arise from a specific anatomic source, and how the infection foci influence the outcomes is unknown. All patients admitted to the ICU of Hospital de Vila Franca de Xira, between 1 January 2017 and 31 June 2023, were screened for sepsis and categorized according to their infection foci. During the study period, 1296 patients (32.2%) had sepsis on admission. Their mean age was 67.5 ± 15.3 and 58.1% were male; 73.0% had community-acquired infections. The lung was the main focus of infection. Septic shock was present in 37.9% of the patients and was associated with hospital mortality. Severe imbalances were noted in its incidence, and there was lower mortality in lung infections. The hospital-acquired infections had a slightly higher mortality but, after adjustment, this difference was non-significant. Patients with secondary bacteremia had a worse prognosis (one-year adjusted hazard ratio of 1.36, 95% confidence interval 1.06-1.74, p = 0.015), especially those with an isolated non-fermenting Gram-negative infection. Lung, skin, and skin structure infections and peritonitis had a worse prognosis, whilst urinary, biliary tract, and other intra-abdominal infections had a better one-year outcome.

Cerebral Endothelial CXCR2 Promotes Neutrophil Transmigration into Central Nervous System in LPS-Induced Septic Encephalopathy.

Septic encephalopathy (SE) represents a severe inflammatory syndrome linked to elevated septic mortality rates, lacking specific therapeutic interventions, and often resulting in enduring neurological sequelae. The present investigation endeavors to elucidate the involvement of C-X-C Motif Chemokine Receptor 2 (CXCR2) in the pathogenesis of SE and to explore the potential of CXCR2 modulation as a therapeutic avenue for SE. Employing a murine SE model induced by lipopolysaccharide (LPS) administration, CXCR2 knockout mice and the CXCR2 inhibitor SB225002 were utilized to assess neutrophil recruitment, endothelial integrity, and transendothelial migration. Our findings substantiate that either CXCR2 deficiency or its inhibition curtails neutrophil recruitment without impacting their adhesion to cerebral endothelial cells. This phenomenon is contingent upon endothelial CXCR2 expression rather than CXCR2's presence on neutrophils. Furthermore, the CXCR2 blockade preserves the integrity of tight junction protein ZO-1 and mitigates F-actin stress fiber formation in cerebral endothelial cells following septic challenge. Mechanistically, CXCL1-mediated CXCR2 activation triggers cerebral endothelial actin contraction via Rho signaling, thereby facilitating neutrophil transmigration in SE. These observations advocate for the potential therapeutic efficacy of CXCR2 inhibition in managing SE.

Isaridin E Protects against Sepsis by Inhibiting Von Willebrand Factor-Induced Endothelial Hyperpermeability and Platelet-Endothelium Interaction.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

Preoperative examination of inflammatory biomarkers in relation to the prognosis of postoperative complications after heart transplantation

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Semmelweis University Heart transplantation (HTX) is the definitive therapy for end-stage heart failure. Although complications have drastically decreased with modern immunosuppressive therapy, surgical and anesthetic techniques, significant complications such as graft failure, acute rejection or infection must still be expected. The purpose of the study is to examine cytokine pathways linked to inflammation from direct preoperative serum samples, which can serve as prognostic factors in relation to septic events and mortality in the early postoperative period. The study was conducted using the blood samples of 102 patients who underwent HTX. Blood samples were taken from the patients immediately before HTX. The amounts of a total of 32 cytokines and related proteins were determined using LEGENDplex assays. After that, we correlated the biomarker amounts determined in the serum samples with the end points we indicated. In patients undergoing HTX who developed septic events during postoperative intensive care, the preoperative MMP2 serum concentration was significantly higher compared to other patients undergoing HTX (n=23, p=0.04). Independent predictors of mortality in the intensive care unit (n=5) were preoperative MRP8/14 (AUC=0.8), NGAL (AUC=0.75), IGFBP-4 (AUC=0.73), cystatin C (AUC=0.7) and the MMP2 (AUC=0.74) serum concentrations. Patients transplanted from left ventricular mechanical circulatory support (LVAD) (n=11) were examined as a separate group, where early postoperative mortality was significantly higher (n=4, p=0.02), the independent predictor of which was the concentration of IGFBP-4 (p=0.04 , AUC=0.73). Based on our results, it can be said that the differences in the preoperative concentration of certain inflammatory biomarkers that can be measured in the serum show correlations with the postoperative septic events and mortality of patients undergoing HTX.

Early vs. late lead extraction in CIED infections: evaluating the interplay of infection type, timing, and comorbidities

Abstract Background Cardiovascular Implantable Electronic Devices (CIEDs) may be associated with peri- and post-procedural complications like device-related infection, one of the most serious challenge of CIEDs therapy associated with significant morbidity, mortality, and financial healthcare burden. Despite a routine use of antibiotics, recent studies reported an increase in CIEDs infections, with or without systemic involvement, that often require surgical interventions like transvenous lead extraction. Purpose This study evaluates the outcomes of transvenous lead extraction in patients with infected CIEDs, focusing on the impact of early versus delayed extraction timing on patient outcomes. Methods A retrospective analysis of 165 patients who underwent transvenous lead extraction for CIED infections between 2019 and 2022 was conducted. Patients were categorized into systemic (n=64) or local (n=101) infection groups and further into early (within 7 days from admission, n=102) or delayed (after 7 days, n=63) extraction groups. Post-procedural outcomes, including septic shock, complications, and mortality rates were described. Results The majority of patients were male (75%) with a median age of 73 (IQR 64-80) years. In the early extraction group, the 1-year mortality rate was significantly lower at 6.4%, compared to 25% in the delayed group. Patients with systemic infections had higher 1-month and 1-year mortality rates compared to those with local infections. The success rates of complete device removal were similar across groups. However, the delayed extraction group exhibited higher rates of comorbidities like anemia, chronic kidney disease, and elevated C-reactive protein levels, which were prevalent in 70% of these patients, compared to 45% in the early extraction group. Conclusions Timely management of CIED infections is crucial for improving patient outcomes. Early extraction within 7 days from hospital admission is associated with significantly lower mortality, regardless of local or systemic infection. Patients undergoing delayed extraction often present with greater comorbidity, which may contribute to their higher mortality rates. This underscores the importance of considering patient comorbidities and prompt intervention in managing CIED infections.

High-Intensity Blue Light (450-460 nm) Phototherapy for Pseudomonas aeruginosa-Infected Wounds.

Background: Nosocomial wound infection with Pseudomonas aeruginosa (PA) is a serious complication often responsible for septic mortality of burn patients. High-intensity antimicrobial blue light (aBL) treatment may represent an alternative therapy for PA infections. Methods: Antibacterial effects of an light-emitting diode (LED) array (450-460 nm; 300 mW/cm2; 15/30 min; 270/540J/cm2) against PA were determined by suspension assay, biofilm assay, and a human skin wound model and compared with 15-min topically applied 3% citric acid (CA) and wound irrigation solution (Prontosan®; PRT). Results: The aBL reduced the bacterial number (2.51-3.56 log10 CFU/mL), whereas PRT or CA treatment achieved a 4.64 or 6.60 log10 CFU/mL reduction in suspension assays. The aBL reduced biofilm formation by 60%-66%. PRT or CA treatment showed reductions by 25% or 13%. In this study, aBL reduced bacterial number in biofilms (1.30-1.64 log10 CFU), but to a lower extent than PRT (2.41 log10 CFU) or CA (2.48 log10 CFU). In the wound skin model, aBL (2.21-2.33 log10 CFU) showed a bacterial reduction of the same magnitude as PRT (2.26 log10 CFU) and CA (2.30 log10 CFU). Conclusions: The aBL showed a significant antibacterial efficacy against PA and biofilm formation in a short time. However, a clinical application of aBL in wound therapy requires effective active skin cooling and eye protection, which in turn may limit clinical implementation.

Diastolic/systolic blood pressure ratio for predicting febrile children with sepsis and progress to septic shock in the emergency department

ObjectiveGiven the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality.MethodsWe conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed.ResultsOverall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively.ConclusionsThe D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

High-Intensity Blue Light (450-460 nm) Phototherapy for Pseudomonas aeruginosa-Infected Wounds.

Background: Nosocomial wound infection with Pseudomonas aeruginosa (PA) is a serious complication often responsible for the septic mortality of burn patients. Objective: High-intensity antimicrobial blue light (aBL) treatment may represent an alternative therapy for PA infections and will be investigated in this study. Methods: Antibacterial effects of a light-emitting diode array (450-460 nm; 300 mW/cm2; 15/30 min; 270/540 J/cm2) against PA were determined by suspension assay, biofilm assay, and a human skin wound model and compared with 15-min topically applied 3% citric acid (CA) and wound irrigation solution (Prontosan®; PRT). Results: aBL reduced the bacterial number [2.51-3.56 log10 colony-forming unit (CFU)/mL], whereas PRT or CA treatment achieved a 4.64 or 6.60 log10 CFU/mL reduction in suspension assays. aBL reduced biofilm formation by 60-66%. PRT or CA treatment showed reductions by 25% or 13%. Here, aBL reduced bacterial number in biofilms (1.30-1.64 log10 CFU), but to a lower extend than PRT (2.41 log10 CFU) or CA (2.48 log10 CFU). In the wound skin model, aBL (2.21-2.33 log10 CFU) showed a bacterial reduction of the same magnitude as PRT (2.26 log10 CFU) and CA (2.30 log10 CFU). Conclusions: aBL showed a significant antibacterial efficacy against PA and biofilm formation in a short time. However, a clinical application of aBL in wound therapy requires effective active skin cooling and eye protection, which in turn may limit clinical implementation.

Listeria monocytogenes Infections in Hematopoietic Cell Transplantation Recipients: Clinical Manifestations and Risk Factors. A Multinational Retrospective Case-Control Study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls. The 41 listeriosis episodes (all due to Listeria monocytogenes [LM]) occurred in 30 allogeneic (allo)-HCT recipients and 11 autologous (auto)-HCT recipients at a median of 6.2 months (interquartile range [IQR], 1.6 to 19.3 months) post-HCT. The estimated incidence was 49.8/100,000 allo-HCT recipients and 13.7/100,000 auto-HCT recipients. The most common manifestations in our cohort were fever (n = 39; 95%), headache (n = 9; 22%), diarrhea, and impaired consciousness (n = 8 each; 20%). Four patients (10%) presented with septic shock, and 19 of 38 (50%) were severely lymphocytopenic. Thirty-seven patients (90%) had LM bacteremia. Eleven patients (27%) had neurolisteriosis, of whom 4 presented with nonspecific signs and 5 had normal brain imaging findings. Cerebrospinal fluid analysis revealed high protein and pleocytosis (mainly neutrophilic). Three-month mortality was 17% overall (n = 7), including 27% (n = 3 of 11) in patients with neurolisteriosis and 13% (n = 4 of 30) in those without neurolisteriosis. In the multivariate analysis comparing cases with 74 controls, non-first HCT (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.10 to 30.82; P = .038); and lymphocytopenia <500 cells/mm3 (OR, 7.54; 95% CI, 1.50 to 37.83; P = .014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. HCT recipients are at increased risk for listeriosis compared to the general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with nonspecific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with an increased risk of listeriosis, and cotrimoxazole was not protective.

Influence of lymphopenia on long-term mortality in septic shock, a retrospective observational study

Background and objectiveThe 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 methodsCohort 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). ResultsA 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). ConclusionsIn 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.

Novel therapeutic role of Ganoderma Polysaccharides in a septic mouse model - The key role of macrophages

Ganoderma lucidum polysaccharides (G. PS) have been recognized for their immune-modulating properties. In this study, we investigated the impact of G. PS in a sepsis mouse model, exploring its effects on survival, inflammatory cytokines, Treg cell differentiation, bacterial load, organ dysfunction, and related pathways. We also probed the role of macrophages through chlorphosphon-liposome pretreatment. Using the cecal ligation and puncture (CLP) model, we categorized mice into normal, PBS, and G. PS injection groups. G. PS significantly enhanced septic mouse survival, regulated inflammatory cytokines (TNF-α, IL-17A, IL-6, IL-10), and promoted CD4+Foxp3+ Treg cell differentiation in spleens. Additionally, G. PS reduced bacterial load, mitigated organ damage, and suppressed the NF-κB pathway. In vitro, G. PS facilitated CD4+ T cell differentiation into Treg cells via the p-STAT5 pathway. Chlorphosphon-liposome pretreatment heightened septic mortality, bacterial load, biochemical markers, and organ damage, emphasizing macrophages' involvement. G. PS demonstrated significant protective effects in septic mice by modulating inflammatory responses, enhancing Treg cell differentiation, diminishing bacterial load, and inhibiting inflammatory pathways. These findings illuminate the therapeutic potential of G. PS in sepsis treatment.

The prehospital NEW score to assess septic shock in-hospital, 30-day and 90-day mortality

BackgroundThe early identification of sepsis presenting a high risk of deterioration is a daily challenge to optimise patient pathway. This is all the most crucial in the prehospital setting to optimize triage and admission into the appropriate unit: emergency department (ED) or intensive care unit (ICU). We report the association between the prehospital National Early Warning Score 2 (NEWS-2) and in-hospital, 30 and 90-day mortality of SS patients cared for in the pre-hospital setting by a mobile ICU (MICU).MethodsSeptic shock (SS) patients cared for by a MICU between 2016, April 6th and 2021 December 31st were included in this retrospective cohort study. The NEWS-2 is based on 6 physiological variables (blood pressure, heart rate, respiratory rate, temperature, oxygen saturation prior oxygen supplementation, and level of consciousness) and ranges from 0 to 20. The Inverse Probability Treatment Weighting (IPTW) propensity method was applied to assess the association with in-hospital, 30 and 90-day mortality. A NEWS-2 ≥ 7 threshold was chosen for increased clinical deterioration risk definition and usefulness in clinical practice based on previous reports.ResultsData from 530 SS patients requiring MICU intervention in the pre-hospital setting were analysed. The mean age was 69 ± 15 years and presumed origin of sepsis was pulmonary (43%), digestive (25%) or urinary (17%) infection. In-hospital mortality rate was 33%, 30 and 90-day mortality were respectively 31% and 35%. A prehospital NEWS-2 ≥ 7 is associated with an increase in-hospital, 30 and 90-day mortality with respective RRa = 2.34 [1.39–3.95], 2.08 [1.33–3.25] and 2.22 [1.38–3.59]. Calibration statistic values for in-hospital mortality, 30-day and 90-day mortality were 0.54; 0.55 and 0.53 respectively.ConclusionA prehospital NEWS-2 ≥ 7 is associated with an increase in in-hospital, 30 and 90-day mortality of septic shock patients cared for by a MICU in the prehospital setting. Prospective studies are needed to confirm the usefulness of NEWS-2 to improve the prehospital triage and orientation to the adequate facility of sepsis.

Bisphosphoglycerate mutase predicts myocardial dysfunction and adverse outcome in sepsis: an observational cohort study

BackgroundSepsis not only causes inflammation, but also damages the heart and increases the risk of death. The glycolytic pathway plays a crucial role in the pathogenesis of sepsis-induced cardiac injury. This study aims to investigate the value of bisphosphoglycerate mutase (BPGM), an intermediate in the glycolytic pathway, in evaluating cardiac injury in septic patients and predicting poor prognosis in sepsis.MethodsThis prospective study included 85 patients with sepsis. Serum BPGM was measured at the time of enrollment, and the patients were divided into a BPGM-positive group (n = 35) and a BPGM-negative group (n = 50) according to their serum BPGM levels. Baseline clinical and echocardiographic parameters, and clinical outcomes were analyzed and compared between the two groups. Kaplan–Meier analysis was used to compare the 28-day survival rate between BPGM-negative and BPGM-positive patients. Multivariate logistic regression analysis was conducted to explore the independent risk factors for 28-day mortality in septic patients. The predictive value of serum BPGM for sepsis-induced myocardial injury and poor prognosis in sepsis was evaluated using receiver operating characteristic (ROC)curve analysis.ResultThe serum level of BPGM was significantly higher in patients who died within 28 days compared to survivors (p < 0.001). Kaplan–Meier analysis showed that serum BPGM-positive sepsis patients had a significantly shorter 28-day survival time (p < 0.001). Multivariate logistic regression analysis showed that serum BPGM (OR = 9.853, 95%CI 1.844–52.655, p = 0.007) and left ventricular ejection fraction-simpson(LVEF-S) (OR = 0.032, 95% CI 0.002–0.43, p = 0.009) were independent risk factors for 28-day mortality in sepsis patients. Furthermore, BPGM levels was negatively correlated with LVEF-S (p = 0.005) and positively correlated with the myocardial performance (Tei) index (p < 0.001) in sepsis patients. ROC curve analysis showed that serum BPGM was a good predictor of septic myocardial injury and 28-day mortality in sepsis patients.ConclusionThe level of BPGM in the serum of sepsis patients can serve as a monitoring indicator for myocardial injury, with its high level indicating the occurrence of secondary myocardial injury events and adverse outcomes in sepsis patients.

Characteristics of acute kidney injury and mortality in patients with sepsis and septic shock

Background and Objective: Acute kidney injury (AKI) is a life-threatening disease and a global health burden, with an increasing incidence in both developed and developing countries. 40 - 50% of AKI cases are caused by sepsis and septic shock. Mortality increases respectively with disease severity. Therefore, we conduct this research with the objective of determining the incidence of sepsis-associated and septic shock-associated AKI and mortality in these patients. Methods: This cross sectional study was conducted on 65 patients with sepsis or septic shock in the Department of ICU - Hue Central Hospital - Vietnam, from February 2022 to March 2023. Results: Of the 65 patients admitted with sepsis and septic shock, 38 (58.5%) developed AKI, the rates of KDIGO stage 1, 2, 3 were 44.7%, 38.8%, and 18.5%, respectively. The rate of patients receiving RRT was 39.5%. The rate of patients with positive blood cultures was 12.6%. The average SOFA score, APACHE II score at admission were respectively 7.63 ± 5.8; 19.18 ± 9.2. The average serum levels of lactate and PCT in patients with sepsis and septic shock were respectively 3.9 ± 3.23 mmol/l; 33.13 ± 38.49 ng/ml. The average ICU length of stay was 9.03 ± 5.23 days, the rate of requiring mechanical ventilation was 36.9%, in-28-day mortality was 32.3%. Mortality was statistically significantly higher in the AKI groups compared to non-AKI group (p &lt; 0.05). Conclusion: Patients with sepsis and septic shock have high rates of AKI and mortality, increased length of hospital stay. Key words: acute kidney injury, sepsis, septic shock.

Investigation of thiol/disulfide homeostasis changes and their relationship with prognosis in sepsis patients

Aim: Sepsis is the most common life-threatening syndrome. Oxidative stress is one of the mechanisms involved in the pathogenesis of sepsis. Thiols are antioxidant buffers. Changes in thiol parameters refer to changes in oxidative balance. In this study, we aimed to investigate thiol homeostasis changes in sepsis patients.&#x0D; &#x0D; Methods: We included 99 patients (53 patients diagnosed with sepsis in the Intensive Care Unit and 46 controls). Sepsis patients were divided into two groups based on their diagnosis, follow-up, and disease severity: sepsis and septic shock. Total thiol and native thiol levels were analyzed in the patients and controls. Disulfide levels were calculated. The thiol parameters were compared between the patient and control groups, sepsis and septic shock, mortality, and survivor groups.&#x0D; &#x0D; Results: In sepsis patients, the disulfide/native thiol and disulfide/total thiol rates were significantly higher (p

Presepsin as a predictor of septic shock and mortality in patients with urinary tract infection according to the Sepsis-3 definitions

The objective of this study was to investigate whether presepsin can serve as a useful biomarker for predicting septic shock and mortality rates in patients with urinary tract infections (UTI) as defined by the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). This single-center and prospective observational study was carried out between December 2019 and December 2022 and included 171 UTI patients divided into two groups: a non-septic shock group (n = 121) and a septic shock group (n = 50). The primary outcome of this study was the development of septic shock; the secondary outcome was 30-day hospital mortality. Receiver operating characteristic (ROC) curves and multivariate regression analyses were performed to investigate the predictive value of presepsin levels for septic shock and the Cox proportional hazards model was used to determine the risk factors for 30-day hospital mortality in UTI patients. Septic shock patients had significantly higher serum levels of presepsin when compared to the non-septic shock group (p &lt; 0.001). In multivariate logistic regression analysis, presepsin demonstrated its independent role as a risk factor for septic shock (odds ratio (OR): 1.002; 95% confidence interval (CI): 1.001–1.002; p &lt; 0.001). The multivariate Cox proportional hazards model indicated that presepsin represents a significant predictor of 30-day hospital mortality in septic shock patients (hazard ratio (HR): 1.0005; 95% CI: 1.0001–1.001; p &lt; 0.05). The ROC curve for diagnosing septic shock had an area under the curve (AUC) of 0.739 with a cutoff value of 447 pg/mL for presepsin. For the prediction of 30-day hospital mortality in patients with UTI, an optimal presepsin cutoff of 709 pg/mL was determined; ROC curve analysis yielded an AUC of 0.744. When applying the Sepsis-3 criteria, presepsin levels represented a significant independent risk factor for septic shock and 30-day hospital mortality in UTI patients.