Sepsis Research Articles

Translating PK-PD principles into improved methodology for clinical trials which compare intermittent with prolonged infusion of beta-lactam antibiotics.

Based on the fact that beta-lactam antibiotics demonstrate time-dependent killing, different dosing strategies have been implemented to increase the time that free (f) (unbound) antibiotic concentrations remain above the Minimal Inhibitory Concentration (MIC), including prolonged and continuous infusion. Multiple studies have been performed that compared continuous with traditional intermittent infusion to improve outcomes in patients with severe sepsis and/or septic shock. These studies have yielded inconsistent results for patients as measured by clinical response to treatment and mortality due to heterogeneity of included patients, pathogens, dosing strategies and the absence of Therapeutic Drug Monitoring (TDM). The MERCY and BLING III studies failed to show a difference in mortality between patients randomized to receive continuous and intermittent infusion of beta-lactam antibiotics. A deeper understanding of pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms that occur in critically ill patients should guide us in dose optimization and improvement in methodology for future clinical trials.

Recent Discovery of Diverse Prophages Located in Genomes of Vibrio spp. and Their Implications for Bacterial Pathogenicity, Environmental Fitness, Genome Evolution, Food Safety, and Public Health

Bacteria in the genus Vibrio, including at least 152 species, thrive in marine and estuarine environments and are frequently detected in aquatic products worldwide. Of these, 12 species have been implicated in human infectious diseases, such as the life-threatening pandemic cholera, acute gastroenteritis, and severe sepsis. Nevertheless, molecular mechanisms of their pathogenesis are not fully uncovered yet. Prophages are found prevalent in Vibrio spp. genomes, carrying a number of genes with various functions. In this review, we deciphered the evolutionary relationship between prophages and Vibrio species and highlighted the impact of prophages on the bacterial pathogenicity, environmental fitness, and genome evolution, based on 149 newly discovered intact prophages located in the genomes of 82 Vibrio spp., which we searched and collected from Web of Science Core Collection in the most recent 5 years. The effects of prophages on resistance to superinfection, strain competition, and their regulation were also discussed. This review underscored crucial roles of prophages in shaping Vibrio spp. genomes and their implications for food safety and public health.

Crimean–Congo Hemorrhagic Fever Mimicking HELLP Syndrome in a Pregnant Woman and Her Infant in Kosovo: A Case Report

Crimean–Congo hemorrhagic fever (CCHF) is fatal in 10 to 40% of cases. It is caused by CCHF virus (CCHFV). Symptoms include fever, headache, myalgia, and often hemorrhage and other complications. This report shows that CCHF may resemble HELLP syndrome (hemolysis, elevated liver enzymes, low platelets). We report CCHF in a pregnant mother with fever and suspected HELLP syndrome, who survived, and her infant (week 36), who died six days after C-section. The high CCHF viral load and bacterial sepsis may have jointly contributed to the death of the infant. CCHF should be considered as a differential diagnosis of HELLP syndrome in regions where this viral disease is endemic.

Health-Related Quality of Life Among Patients Who Have Survived an Episode of Sepsis in the United States: A Systematic Review.

Sepsis is a serious condition that may lead to death or profoundly affect the well-being of those who survive. The aim of this systematic review was to identify and summarize evidence on the impact of all-cause sepsis on health-related quality of life (HRQoL), physical, cognitive, and psychological outcomes among sepsis survivors in the USA. Studies assessing HRQoL, physical, cognitive, and psychological outcomes in patients who survived an episode of sepsis and published from January 1, 2010, to September 30, 2023, were systematically identified through EMBASE, MEDLINE, and MEDLINE In-Process databases, as well as through gray literature. Of 2885 records identified, 7 studies (7 publications; N = 180,592 participants) met the eligibility criteria for inclusion in this review. Studies examined the effects of sepsis on the following outcomes of interest: HRQoL (4 studies), physical functioning (5 studies), cognitive status (3 studies), and psychological well-being (3 studies). After 12months, sepsis survivors who developed chronic critical illness (N = 63) had significantly poorer HRQoL as measured by EuroQoL 5-dimensional (EQ-5D) questionnaire mean utility index score and Short Form 36-item (SF-36) physical and mental summary scores compared with patients who rapidly recovered (N = 110). Among patients admitted to a skilled nursing facility post-sepsis (N = 66,540), 34% and 72.5% had severe or very severe cognitive impairment and dependence to perform activities of daily living, respectively. Significant increase in moderate-to-severe cognitive impairment among severe sepsis survivors (N = 623) before and after sepsis was reported (median 0.9 [IQR: 0.4, 1.4]years; 6.1% and 16.7%, respectively [P < 0.001]). Substantial depression and anxiety symptoms were frequently observed post-sepsis, but with limited evidence for increased burden as assessed by specific psychological measures. These findings underscore the profound negative impacts of sepsis on patients' HRQoL, ability to perform activities of daily living, and cognitive abilities.

Plasma EphA2 level is a superior biomarker to Del-1 for sepsis diagnosis and prognosis

BackgroundSepsis, characterized by a dysregulated host response to infection, often leads to organ dysfunction, and vascular endothelial dysfunction plays a central role. The erythropoietin-producing hepatocellular carcinoma (Eph)A2 receptor is associated with increased vascular permeability; however, the developmental endothelial locus-1 (Del-1), has contrasting effects on endothelial function. Hence, we examined their potential as biomarkers of sepsis.MethodsIn total, 117 participants, including 20 healthy controls, 21 patients with systemic inflammatory response syndrome (SIRS), and 76 patients with sepsis, were enrolled in this study. Sepsis severity was assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Sequential Organ Failure Assessment (SOFA) scores.ResultsThe Median plasma EphA2 levels increased progressively from healthy controls to SIRS and sepsis cases (154.29, 293.52, and 554.24 pg/mL; all p &amp;lt; 0.05). The median plasma Del-1 levels were highest in healthy controls, lowest in SIRS, and intermediate level in sepsis (101.27, 16.88, and 36.9 pg/mL; all p &amp;lt; 0.001). The levels of both biomarkers were higher in 28-day non-survivors than in survivors, in patients with sepsis (EphA2:898.09 vs. 475.88 pg/mL, p &amp;lt; 0.001; Del-1:46.09 vs. 32.68 pg/mL, p = 0.193); however, only EphA2 was statistically significant. The area under the curve for the EphA2 was 0.74 in the receiver operating characteristic curve analysis for predicting 28-day mortality, whereas APACHE II, SOFA, and Del-1 showed values of 0.762, 0.614, and 0.595, respectively. Kaplan–Meier analysis using these cutoffs revealed that survival was significantly higher in the group with both low EphA2 and Del-1 levels compared to the group with high levels of both markers (p &amp;lt; 0.001).ConclusionPlasma EphA2 levels consistently increased with sepsis severity, suggesting its biomarker value for sepsis diagnosis and prognosis. In contrast, plasma Del-1 response was variable, indicating its limited prognostic utility.

Closure of ventricular septal defect in children with trisomy 18: perioperative events and long-term survival.

This retrospective study aimed to investigate the feasibility of surgical closure of ventricular septal defect in children with trisomy 18 by assessing perioperative events and long-term survival. From April 2008 to March 2024, 41 consecutive patients were referred to us for ventricular septal defect surgery. The defect was closed in 35 patients at the end (median age, 16 months; median body weight, 5.7 kg), 31 out of 37 patients after the preceding pulmonary artery banding according to our staged surgery policy, and 4 patients without the banding. Sixty-five significant non-cardiac lesions existed concurrently and 14 patients underwent tracheostomy before closure. The investigation was conducted by checking medical records and contacting the primary physician. Four patients died during the inter-stage after banding to closure (10.8%). Two of them were awaiting closure. Concomitant surgeries, 15 right ventricular muscle resections, or 1 arch repair, were performed along with closure. Arrhythmia was the most common adverse event (51.4%). Three patients required extracorporeal membrane oxygenation support. Transient but severe hepatic injury occurred in 11 patients (31.4%). There were 2 hospital death (5.7%) due to severe respiratory insufficiency or fulminant sepsis. Five patients died after discharge, 3 pneumonia and 2 sudden death, resulting in a 5-year estimated survival of 79.5%. Three hepatoblastoma and 1 hepatoangioma developed, but complete remission was achieved in all patients. Although further studies are mandatory, surgical closure of ventricular septal defect may be an effective treatment option even for children with trisomy 18.

Hyaluronic acid-silybin conjugate for the preparation of multifunctional, biomimetic, vancomycin-loaded self-assembled polymersomes against bacterial sepsis.

Sepsis, a life-threatening disruption, remains a significant global healthcare challenge that urgently needs novel strategies to improve management. This study aimed to develop multifunctional vancomycin-loaded polymersomes (VCM-HA-SIL-Ps) using a novel hyaluronic acid-silybin (HA-SIL) conjugate to target the TLR inflammatory pathway and enhance VCM's efficacy against bacterial sepsis. HA-SIL was synthesized and characterized by FT-IR, UV-Vis spectroscopy, and 1H NMR. The biomimetic properties of HA-SIL were confirmed via in silico (-73.35kcal/mol) and in vitro (dissociation constant=2.872μM) binding affinity studies against TLR2. VCM-HA-SIL-Ps exhibited appropriate physicochemical properties, biocompatibility, and stability. VCM-HA-SIL-Ps sustained VCM release for 48h, achieving 73.38% cumulative release. In vitro antibacterial studies showed that VCM-HA-SIL-Ps had superior minimum inhibitory concentration against sensitive and resistant Staphylococcus aureus and faster bacterial killing, compared to free VCM. Additionally, VCM-HA-SIL-Ps demonstrated excellent DPPH radicals scavenging and effective anti-inflammatory activity on bacterial toxin-stimulated cells. Finally, in a mouse model of MRSA-induced sepsis, VCM-HA-SIL-Ps achieved 100% bacterial eradication, significantly reduced pro-inflammatory markers (IL-6, TNF-α, IL-1β by 2.9-, 1.8-, and 5-fold, respectively), and minimized organ damage. Collectively, these findings demonstrate the potential of HA-SIL as a novel multifunctional adjuvant for effective antibiotic delivery against bacterial sepsis.

P0915 Real-life experience with Upadacitinib in Crohn’s disease (UPARECOL-CD Induction): A Colombian cohort

Abstract Background In Latin America, clinical experience with Upadacitinib for CD in terms of effectiveness and safety is limited. In Colombia, CD is an orphan disease and in many cases is highly refractory to conventional treatments. The objective of this study is to describe the real-life experience in Colombian patients with CD treated with Upadacitinib. Methods Descriptive observational study, patients with CD treated with Upadacitinib in induction phase (45 mg orally once a day for 12 weeks) in different reference centers nationwide. The therapeutic response was evaluated in endoscopic and/or imaging, paraclinical and clinical terms (CDAI). Additionally, the frequency of adverse events (AE), steroid use and extraintestinal manifestations (EIM) were measured. Results 10 patients, 5/10 (50%) female, mean age 43.15 years (SD; 22.7 range 14.2-21.3). Mean age at diagnosis of CD 37.7 (SD 23.15) years (range 6.9-67.5). Mean time between disease onset and start of Upadacitinib 3.33 (SD 8.17) years (range 0.1-15.9). Most patients had moderate to severe CD; 7/10 (70%) patients with ileocolonic disease and 3 (30%) with ileal disease. 5 patients with stricturing disease and 3 patients with active penetrating disease. All patients had previously failed tumor necrosis factor inhibitors, 8/10 (80%) had failed integrin alpha4 beta7 inhibitors (Vedolizumab). Six patients had EIM. Six patients had a history of surgery for CD. Additionally, 4/10 (40%) patients were using a steroid before starting Upadacitinib and 6/10 (60%) patients were using an immunomodulator. During the induction phase, 7/10 (70%) achieved clinical response, 2/10 (20%) clinical remission, and 5/10 (50%) paraclinical remission. 4/6 (66.6%) patients achieved improvement in imaging findings. All patients with EIM showed improvement of EIM. 2/5 (40%) patients showed improvement of perianal disease. Only one patient required surgery for CD. 3/4 (75%) were able to discontinue corticosteroid and 1/4 (25%) achieved steroid dose reduction. One patient required discontinuation of Upadacitinib, due to lack of response and severe sepsis. One patient reported acne after induction. No other AEs were reported. Conclusion Upadacitinib is an effective option for patients with CD with inflammatory, stenosing and penetrating phenotypes refractory to multiple treatments, suggesting a reduced requirement for surgical procedures. Long-term real-life studies are needed to determine whether there is persistence of response in maintenance.

LncRNA FENDRR/ miR-424-5p serves as a diagnostic biomarker for sepsis and its predictive value for clinical outcomes.

This study intends to investigate the relationship between FENDRR and miR-424-5p and their clinical significance in sepsis, aiming to provide new diagnostic markers and prognostic markers for sepsis. 136 patients with sepsis and 132 healthy volunteers were included as study subjects. The expression levels of FENDRR and miR-424-5p were detected by qPCR. ROC was applied to evaluate the diagnostic value of FENDRR and miR-424-5p. COX analyzed the independent risk factors for the occurrence of death in sepsis patients. Dual luciferase reporter assay detected the binding of FENDRR and miR-424-5p. The miR-424-5p target genes were predicted and enriched for GO function and KEGG pathway. FENDRR was up-regulated and miR-424-5p was down-regulated in patients with sepsis. FENDRR can target and bind to miR-424-5p. Both FENDRR and miR-424-5p showed significant diagnostic potential in sepsis and their combination significantly improved the diagnostic efficiency. FENDRR/miR-424-5p were significantly correlated with WBC, CRP, APACH II, and SOFA of sepsis patients. FENDRR and miR-424-5p were independent risk factors for mortality in sepsis patients. Sepsis patients with high FENDRR levels or low miR-424-5p levels had higher mortality. GO and KEGG enrichment analyses revealed that the targets of miR-424-5p were predominantly associated with cell functions and inflammatory signaling pathways. Upregulated FENDRR and downregulated miR-424-5p expression can serve as biomarkers of sepsis with predictive value on the onset and prognostic outcome. FENDRR and miR-424-5p were correlated with the severity of sepsis and FENDRR can play a function in the sepsis progression via targeting miR-424-5p.

Fluid Resuscitation and Initial Management in Patients Presenting with Sepsis in the General Ward.

The optimal management of hospital-presenting sepsis remains poorly understood. We investigated the initial management in patients presenting with sepsis in the general ward, the association between fluid resuscitation and clinical outcomes, and the factors affecting fluid resuscitation. A retrospective study was conducted on patients who presented with sepsis-induced hypotension in the general ward. Patients were divided into Less 30 (fluid resuscitation less than 30 mL/kg) and More 30 (fluid resuscitation 30 mL/kg or more) groups. Multivariable logistic regression analysis was performed. The median resuscitation fluid volume was 500 mL (9.2 mL/kg) and 2000 mL (35.9 mL/kg) in the Less 30 (n = 79) and More 30 (n = 11) groups, respectively. The intensive care unit (ICU) mortality was similar between the two groups (43.0% vs. 45.5%). Twenty-two patients received continuous renal replacement therapy (CRRT) in the Less 30 group, whereas none received it in the More 30 group (27.8% vs. 0%). Fluid resuscitation ≥30 mL/kg was not associated with ICU mortality. Low body weight and systolic blood pressure were associated with fluid resuscitation ≥30 mL/kg. Most hospital-presenting sepsis patients received less than 30 mL/kg of fluid, and fluid resuscitation was not associated with ICU mortality.

Outcome prediction for late-onset sepsis after premature birth.

Our aim was to develop a quantitative model for immediately estimating the risk of death and/or brain injury in late-onset sepsis (LOS) in preterm infants, based on objective and measurable data available at the time sepsis is first suspected (i.e., time of blood culture collection). Retrospective study on neonates ≤36 weeks' gestation with a positive blood and/or cerebrospinal fluid culture after 72 hours from birth. Among 3217 preterm live births, 94 cases were included (median gestational age 26.5 weeks' IQR 25.0;28.0), of whom 26 (27.7%) had poor outcomes (17 death; 9 brain injuries). Infants with poor outcomes showed lower postnatal age (11.5 vs 12.5 days, p < 0.001), lower mean blood pressure (30.5 vs 43 mmHg, p < 0.001) and higher lactate levels (4.4 vs 1.5 mmol/l, p < 0.001). Our multivariable model showed good discrimination and calibration (c statistic=0.8618, Hosmer-Lemeshow p = 0.8532), stratifying the population into 3 groups: low-risk (sensitivity 97%, specificity 52%), middle-risk, and high-risk (sensitivity 77%, specificity 80%). This predictive model performs well as a practical and easy-to-use tool to help clinicians early identify the sickest neonates who may benefit from timely and aggressive support (e.g., central line, haemodynamic assessment) and close monitoring (e.g., 1:1 nursing assignment, frequent reassessments). We lack data to early identify the severity of neonatal late-onset sepsis in preterm infants. Delay in treatment contributes to poor prognosis. We developed a model for early prediction of poor outcomes (mortality and brain injuries). The model utilizes immediately available and measurable data at the time sepsis is first suspected. This can help clinicians in tailoring management based on individual risks.

Systemic inflammatory response index improves prognostic predictive value in intensive care unit patients with sepsis

Sepsis is a severe infectious disease with high mortality. However, the indicators used to evaluate its severity and prognosis are relatively complicated. The systemic inflammatory response index (SIRI), a new inflammatory indicator, has shown good predictive value in chronic infection, stroke, and cancer. The purpose of this study was to investigate the connection between sepsis and SIRI and evaluate its predictive usefulness. A total of 401 patients with sepsis were included in this study. Multiple linear regression and logistic regression analyses were performed to evaluate the relationship between SIRI and sepsis. The restricted cubic spline (RCS) method was employed to illustrate the dose-response relationship. The area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the prognostic value of SIRI. Multiple linear regression analysis revealed a significant positive correlation between SIRI and both blood cell count and Sequential Organ Failure Assessment (SOFA) score. Additionally, higher SIRI levels were significantly linked to a higher risk of sepsis worsening, according to logistic regression analysis. The RCS curve demonstrated that the risk of poor prognosis rose with increasing SIRI, particularly when SIRI exceeded 6.1. Furthermore, AUC and DCA results showed that SIRI had superior predictive value compared to traditional indicators. A higher SIRI is linked to a worse prognosis and more severe sepsis. SIRI may serve as a novel prognostic indicator in sepsis, though further clinical studies are necessary to confirm these findings.

Current Concepts in Fluid Resuscitation and Vasopressor Use in Cirrhosis.

Critically ill patients with cirrhosis and liver failure not uncommonly have hypotension due to multifactorial reasons, that include hyperdynamic state with increased cardiac index, low systemic vascular resistance due to portal hypertension, following the use of beta blocker or diuretic therapy, and severe sepsis. These changes are mediated by microvascular alterations in the liver, systemic inflammation, activation of renin angiotensin aldosterone system, and vasodilatation due to endothelial dysfunction. Hemodynamic assessment includes measuring inferior vena cava indices, cardiac output and systemic vascular resistance using point-of-care ultrasound (POCUS), in addition to arterial waveform analysis, or pulmonary artery pressures, and lactate clearance to guide fluid resuscitation. Fluid responsiveness reflects the ability of fluid bolus to increase the cardiac output and is assessed effectively by POCUS, passive leg raise manoeuvre, and dynamic tests such as pulse pressure and stroke volume variation both in spontaneously breathing and mechanically ventilated patients. Albumin has pleotropic benefits through anti-inflammatory properties besides its standard action on oncotic pressure and volume expansion in patients with cirrhosis but has potential for precipitating pulmonary edema. In conclusion, fluid therapy in critically ill patients with liver disease is a complex and dynamic process that requires individualised management protocols to optimise patient outcomes.

P16INK4a Aggravated Sepsis-associated Cardiac Injury by Inhibiting the PI3K/AKT Pathway and Inducing Redox Imbalance.

Severe sepsis can promote myocardial injury and cardiac dysfunction, but role of p16 in sepsis-induced myocardial injury remains undefined. PBMCs were collected from patients. Expression of inflammatory factors and NLRP3 pathway were detected by Western blotting and qPCR in WT and p16KO mice. Then detect cardiomyocyte apoptosis and ROS levels in vitro. Detailed pathways and mechanisms were revealed through quantitative proteomic analysis combined with GSEA and KEGG analysis. p16 was overexpressed in PBMCs of patient. p16 knockout alleviated cardiac dysfunction in LPS-induced mice and inhibited NLRP3 inflammasome pathway in vivo and in vitro. Quantitative proteomic analysis revealed that p16 knockout contributed to the activation of the PI3K/Akt pathway in LPS-induced cardiac injury. p16 knockout promoted activation of the PI3K/Akt pathway and ameliorated NLRP3 pathway inhibition and redox imbalance thus improving cardiac function in LPS-induced cardiomyopathy mice.

Clinical and Microbiological Profile of Melioidosis in a Tertiary Care Hospital in Kerala, India.

Melioidosis is a neglected tropical infection caused by the Gram-negative bacterium Burkholderia pseudomallei, which is found in soil and water across tropical countries. The infection spectrum ranges from mild localized lesions to severe sepsis. The clinical presentation, severity, and outcome are influenced by the route of infection, bacterial load, strain virulence, and specific virulence genes of B. pseudomallei. This case series discusses nine melioidosis cases, highlighting the clinical and diagnostic challenges. It underscores the necessity for a high level of clinical suspicion to ensure a timely diagnosis and the prompt initiation of treatment.

The influence of interleukin-27 on metabolic fitness in a murine neonatal model of bacterial sepsis.

Human neonates are predisposed to an increased risk of mortality from infection due to fundamental differences in the framework of innate and adaptive immune responses relative to those in the adult population. As one key difference in neonates, an increase in the immunosuppressive cytokine, IL-27, is responsible for poor outcomes in a murine neonatal model of bacterial sepsis. In our model, the absence of IL-27 signaling during infection is associated with improved maintenance of body mass, increased bacterial clearance with reduced systemic inflammation, and decreased mortality rates that correlate to preservation of glucose homeostasis and insulin production. To further elucidate the mechanisms associated with IL-27 signaling and metabolic fitness, we analyzed global transcriptomes from spleen, liver, pancreas, and hindlimb muscle during Escherichia coli-induced sepsis in wild-type (WT) and IL-27Rα-deficient (KO) mice. Metabolically important tissues such as the liver, pancreas, and hindlimb muscle exhibit a shift in differential gene expression of pathways involved in oxidative phosphorylation, glycolysis, gluconeogenesis, lipid metabolism, and fatty acid beta oxidation. The hindlimb muscle of KO pups demonstrated a significant reduction in all of these pathways during infection. The KO liver showed a significant down-regulation in gluconeogenesis and glycolytic pathways. Collectively, these findings suggest a negative influence of IL-27 on the metabolic profile during early life infection. This is an important consideration for antagonization of IL-27 as a potential host-directed therapeutic opportunity as our findings point to an overall improvement in infectious disease parameters and metabolic fitness.

Understanding the neurobiological mechanisms of LPS‑induced memory impairment.

In recent years, growing evidence suggests that lipopolysaccharide (LPS), a bacterial endotoxin found in the outer membrane of gram‑negative bacteria, can influence cognitive functions, particularly memory formation and retrieval. However, the underlying mechanisms through which LPS exerts its effects on memory remain incompletely understood. This review used various electronic databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published between 2000 and 2024. Articles were selected based on their focus on LPS‑induced memory impairments, including experimental models, molecular pathways, and neurochemical alterations. LPS administration has been consistently shown to disrupt memory processes in both animals and humans, although the magnitude and duration of memory impairments might vary depending on factors such as dose, timing, and context of LPS exposure. Several potential mechanisms have been proposed to explain LPS‑induced memory deficits, including neuroinflammation, alterations in synaptic plasticity, disruption of neurotransmitter systems, and dysfunction of the blood‑brain barrier. Moreover, LPS has been found to activate immune signaling pathways, such as toll‑like receptors, interleukins, and microglia, which can further contribute to cognitive impairments. Such insights may pave the way for the development of targeted therapeutic interventions aimed at ameliorating memory deficits associated with conditions involving LPS exposure, including bacterial infections, sepsis, and neuroinflammatory disorders.

Advances of immunosensors based on noble metal composite materials for detecting procalcitonin.

Procalcitonin (PCT) is a reliable biomarker for diagnosing and monitoring bacterial infections and sepsis. PCT exhibits good stability both in vivo and in vitro, and its levels drastically increase in response to bacterial infection or inflammatory reactions in the human body, making it a dependable indicator for sepsis diagnosis and monitoring with significant implications for clinical diagnosis and treatment guidance. Currently, immunosensors are widely utilized in PCT detection due to their high sensitivity and low detection limits. Noble metals, because of their excellent electronic conductivity, biocompatibility, and superior physicochemical properties, are extensively combined with other materials to play a pivotal role in the construction of PCT immunosensors. This review summarizes the research progress on PCT antigen immunosensors based on noble metal composite materials, encompassing the classification and principles of immunosensors. Starting from noble metals, which are widely used as electrode materials in sensors, the review categorizes and discusses the carbon materials, metal oxides, metal sulfides, and other composites with noble metals. The reviewalso elaborates on the influence of sensitive materials on the performance of immunosensors. Finally, the review discusses and anticipates the challenges and future opportunities for the research on PCT antigen immunosensors using noble metal-composite nanomaterials, providing new insights and directions for their application in the treatment and clinical management of sepsis and other diseases.

Fever in the Trauma Bay: A Marker for Greater Risk of Adverse Outcomes.

Purpose: Previous work identified a sub-group of trauma patients at risk for bacteremia who presented with signs of infection, including fever. A majority were older adult falls who had early onset bacteremia. Hypothesis: Fever in the trauma bay is associated with a greater risk of adverse outcomes and identifies patients who might benefit from early initiation of interventions for sepsis. Methods: Trauma patients ≥18 years, drawn from a system-wide electronic medical record (EMR) (2017-2020), were included. Fever+ patients (temperature >38°C) were compared with Fever- patients (36°C-38°C). Multi-variable logistic regressions assessed the association of fever status with outcomes. The interaction between fever, age, and outcomes was assessed. Results: A total of 140,647 patients were included from 89 centers. Eight hundred ninety (0.6%) were Fever+ and had worse unadjusted outcomes. After adjustment, Fever+ patients had significantly greater mortality (adjusted odds ratios [aOR], 95% confidence interval: 1.05 [1.04-1.07]), intensive care unit use (1.08 [1.04-1.11]), and ventilator use (1.11 [1.09-1.13]). Fever+ status was associated with a significantly larger aOR of severe sepsis in older versus younger patients (≥65 y: 1.12 [1.11-1.13]; <65 y: 1.04 [1.03-1.05]). Fever+ status was also associated with a significantly larger aOR of bacteremia in older versus younger patients (≥65 y: 1.09 [1.08-1.10]; <65 y: 1.04 [1.03-1.05]). Implications: Although uncommon, fever at presentation is an ominous sign for trauma patients and portends significantly greater risks for bacteremia, sepsis, and mortality. These risks increase with age. These findings suggest older adults who present with fever warrant early aggressive intervention and may sustain injury as a consequence of debility from systemic infection.

The predictive value of the serum creatinine-to-albumin ratio (sCAR) and lactate dehydrogenase-to-albumin ratio (LAR) in sepsis-related persistent severe acute kidney injury

Background/objectivesSepsis-related acute kidney injury (SA-AKI) is a severe condition characterized by high mortality rates. The utility of the sCAR (secrum creatinine/albumin) and LAR (Lactate dehydrogenase/albumin) as diagnostic markers for persistent severe SA-AKI remains unclear.MethodsWe acquired training set data from the MIMIC-IV database and validation set data from the First Affiliated Hospital of Harbin Medical University. Logistic regression analysis was used to identify key predictors of persistent severe SA-AKI, considering factors such as sCAR, LAR, PAR (Platelet/albumin), BAR (BUN/albumin), and LAO (Lactic/albumin). Independent predictors, sCAR and LAR, were combined into a composite Log(sCAR)_Log(LAR) score, denoted as the Log(sCAR)_Log(LAR) score. Possible confounding factors were screened out by univariate logistic regression, and multivariable logistic regression was applied to evaluate the association of Log (sCAR) _Log (LAR) score with persistent severe sepsis and other secondary clinical outcomes. The ROC curve was utilized to obtain the best cutoff value of the Log(sCAR)_Log(LAR) score. The Kaplan–Meier curve was used to evaluate the prognosis predictive ability of the risk model.ResultsLogistic regression analysis indicated that sCAR and LAR independently predicted persistent severe SA-AKI. This led to the creation of Log(sCAR)_Log(LAR) score on the base of logarithms of sCAR and LAR. ROC curve analysis showed that the Log(sCAR)_Log(LAR) score was more effective in predicting persistent severe SA-AKI (AUC = 0.71) than Log(sCAR) (AUC = 0.69), Log(LAR) (AUC = 0.65), SOFA score (AUC = 0.66) and Δ Scr (AUC = 0.70). Multivariate regression identified that the SOFA score, PT, ΔScr, Tbil, chronic liver disease, and Vasopressor use as independent risk factors for persistent severe SA-AKI (P < 0.05). A basic clinical prediction model was created using these variables, and its predictive ability, recognition capability, and clinical utility improved with the inclusion of the Log(sCAR)_Log(LAR) score. The model's predictive ability for secondary outcomes, such as renal replacement therapy (RRT), also improved with the addition of the Log(sCAR)_Log(LAR) score. The sensitivity analysis further corroborated the stability of the Log(sCAR)_Log(LAR) score in predicting persistent severe SA-AKI and secondary outcomes, such as RRT.ConclusionsThe Log(sCAR)_Log(LAR) score effectively predicted persistent severe SA-AKI, potentially aiding intensive care physicians in risk assessment.