Trends in C-Reactive Protein Use in Early-onset Sepsis Evaluations and Associated Antibiotic Use.

OBJECTIVE: To determine the prevalence of C-reactive protein (CRP) use in early-onset sepsis (EOS) evaluations in neonatal intensive care units (NICUs) across the US over time and to determine the association between CRP use and antibiotic use. STUDY DESIGN: A retrospective cohort study of NICUs contributing data to Premier Healthcare Database from 2009 through 2021. EOS evaluation was defined as a blood culture charge ≤ 3 days after birth. CRP use for each NICU was calculated as the proportion of infants with a CRP test obtained ≤ 3 days after birth among those undergoing an EOS evaluation and categorized as, low (<25%); medium-low (25 to < 50%), medium-high (50 to < 75%), and high (≥75%). Outcomes included antibiotic use and mortality ≤ 7 days after birth. RESULTS: Among 572 NICUs, CRP use varied widely and was associated with time. The proportion of NICUs with high CRP use decreased from 2009 to 2021 (24.7% vs 17.4%, P < .001), and those with low CRP use increased (47.9% vs 64.8%, P < .001). Compared with low-use NICUs, high-use NICUs more frequently continued antibiotics > 3 days (10% vs 25%, P < .001). This association persisted in multivariable-adjusted regression analyses (adjusted risk ratio 1.95, 95%CI 1.54, 2.48). Risk of mortality was not different in high-use NICUs (adjusted risk difference -0.02%, 95%CI -0.04%, 0.0008%). CONCLUSIONS: CRP use in EOS evaluations varied widely across NICUs. High CRP use was associated with prolonged antibiotic therapy but not mortality ≤ 7 days after birth. Reducing routine CRP use in EOS evaluations may be a target for neonatal antibiotic stewardship efforts.

Plasma Chemerin Is Induced in Critically Ill Patients with Gram-Positive Infections.

Chemerin is a chemoattractant protein abundantly expressed in hepatocytes. Chemerin exerts pro- and anti-inflammatory effects and acts as a pro-resolving protein. Chemerin levels are low in patients with liver cirrhosis and are increased in sepsis. The aim of this study was to identify associations between plasma chemerin levels and underlying diseases as well as causes of severe illness. The cohort included 32 patients with liver cirrhosis who had low systemic chemerin, and who were not considered for further evaluation. Plasma chemerin levels were similar between the 27 patients with systemic inflammatory response syndrome (SIRS), the 34 patients with sepsis and the 63 patients with septic shock. Chemerin in plasma correlated with C-reactive protein and leukocyte count but not with procalcitonin, a clinical marker of bacterial infection. Plasma chemerin did not differ among patients with and without ventilation and patients with and without dialysis. Vasopressor therapy was not associated with altered plasma chemerin levels. Infection with severe acute respiratory syndrome coronavirus 2 had no effect on plasma chemerin levels. Baseline levels of plasma chemerin could not discriminate between survivors and non-survivors. Notably, Gram-positive infection was associated with higher chemerin levels. In summary, the current study suggests that plasma chemerin might serve as an early biomarker for the diagnosis of Gram-positive infections in patients with sepsis.

Marked Elevation in Serum Procalcitonin Levels Do Not Correlate With Severity of Disease or Mortality in Hospitalized Patients: A Retrospective Study.

BACKGROUND: Bacteremia and sepsis are significant contributors to the morbidity, mortality, and economic burden of health care systems worldwide. Procalcitonin has been identified as a potentially useful marker of disease and severity in sepsis. However, the assumption that greater procalcitonin levels correlate with greater burden of disease has not been adequately studied. METHODS: A retrospective chart review of adult patients admitted to an urban teaching hospital with suspected sepsis was undertaken to test the association of elevated procalcitonin (>30 ng/mL) with other markers of sepsis (lactic acid, white blood cell count, percent bands), severity of disease (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation-II [APACHE II] scores), and mortality. RESULTS: In total, 168 patients were identified over 18 months (42% ward, 11% Stepdown, 44% medical intensive care unit [MICU], 2% surgical intensive care unit (STICU), 1% gynecology [GYN]). The Spearman correlation analysis showed that serum procalcitonin level did not correlate with SOFA (P = .238) or APACHE II (P = .918) scores on admission, and did not correlate with survival (Kruskal-Wallis test, P = .937). However, higher serum procalcitonin levels were associated with patients who had positive blood cultures (Kruskal-Wallis test, P = .0016 for Gram-positive and P = .0007 for Gram-negative bacteria). Lactic acid levels on admission strongly correlated with SOFA APACHE II (the Spearman correlation, P < .0001 for both) and mortality (P = .0001 for both). CONCLUSIONS: Higher serum procalcitonin levels above 30 ng/mL failed to correlate with indicators of sepsis, severity of disease (SOFA and APACHE II scores), and mortality but were associated with positive blood cultures. Lactic acid levels did show correlation to both severity of disease and mortality. Serum procalcitonin levels >30 ng/mL do not appear to correlate with the severity of disease in a sample of patients with markedly elevated initial procalcitonin levels.

[Relevance of clinical and serum parameters on severe urinary sepsis after renal obstruction.] / Importancia de los parámetros clínicos y analíticos de la sepsis grave en la uropatía obstructiva.

INTRODUCTION: Urosepsis is an underdiagnosed entity with high morbidity and mortality and significant associated costs. The delay in diagnosis leads to an increased risk of multiorgan failure and death. Although its prognosis is better than that of other sepsis, the mortality rate is 20 - 40%. OBJECTIVE: Describe the obstructive uropathy cases (OU) that are complicated by severe sepsis (SS) and identify early biomarkers of SS. MATERIAL AND METHODS: Observational and prospective study of 65 patients with urgent high OU. All patients were evaluated at three different times (0, 24 and 48 hours). An SS predictor model has been constructed and a multivariate risk analysis has been carried out. RESULTS: 64.61% (n=42) developed SS (NSS: n=13). The only statistically significant variables in the 3 moments evaluated and that obtained a good area under the curve [AUROC (>0.70)] were the elevation of neutrophils, procalcitonin, and decrease of bicarbonate. At the time of patient admission, the variable that best predicted SS was the elevation of procalcitonin (AUROC:0.919). SS risk factors (p<0.005) were the history of cancer immunosuppression, and/or urinary tract surgeries, complete UO and high blood values of lactate, potassium and decrease of bicarbonate. The potassium-lactate combination on admission predicted SS with a probability function of 0.805. CONCLUSIONS: There is an analytical profile maintained over the time characteristic of SS that allows anearly identification of patients with OU subsidiary of been complicated with SS.

INTRODUCCIÓN: La Sepsis urinaria obstructiva (SUO) es una entidad infradiagnosticada con una elevada morbimortalidad e importantes costes asociados. El retraso en su diagnóstico condiciona un mayor riesgo de fracaso multiorgánico y fallecimiento. Aunque su pronóstico es mejor que el de otros focos de sepsis, su mortalidad es del 20 - 40%. OBJETIVO: Describir los cuadros de uropatía obstructiva (UO) que se complican con sepsis grave (SG) e identificarlos biomarcadores diagnósticos de SG en la UOde forma precoz.MATERIAL Y MÉTODOS: Estudio observacional y prospectivo de 72 pacientes con UO alta ingresados de manera urgente en el Servicio de Urología del Hospital Clínico Universitario de Valladolid. Todos los pacientes del estudio fueron evaluados en tres momentos diferentes (0, 24 y 48 horas). Se ha creado un modelo predictor de SG y se ha realizado un análisis multivariante de riesgo. RESULTADOS: El 64,61% de los pacientes (n=42) desarrolló SG (NSG: n=13). Las únicas variables estadísticamente significativas en los tres momentos evaluados y que obtenían una buena área bajo la curva [AUROC (>0,70)] fueron la elevación de neutrófilos y procalcitonina y la disminución de bicarbonato. En el momento del ingreso la variable que mejor predecía SG fue la elevación de procalcitonina (AUROC: 0,919). Los factores de riesgo de SG (p<0,05) fueron los antecedentes de cáncer, la inmunosupresión y/o cirugías de vías urinarias, la UO completa y los valores elevados en sangre de lactato y potasio y la disminución del bicarbonato en la gasometría venosa. La combinación potasio-lactato al ingreso predecía SG con una función de probabilidad de 0,805. CONCLUSIONES: Existe un perfil analítico, mantenido en el tiempo, característico de SG que permite la identificación precoz de los pacientes con UO subsidiarios de complicarse con SG.

GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype.

Macrophages are critical for regulation of inflammatory response during endotoxemia and septic shock. However, the mediators underlying their regulatory function remain obscure. Growth differentiation factor 3 (GDF3), a member of transforming growth factor beta (TGF-ß) superfamily, has been implicated in inflammatory response. Nonetheless, the role of GDF3 in macrophage-regulated endotoxemia/sepsis is unknown. Here, we show that serum GDF3 levels in septic patients are elevated and strongly correlate with severity of sepsis and 28-day mortality. Interestingly, macrophages treated with recombinant GDF3 protein (rGDF3) exhibit greatly reduced production of pro-inflammatory cytokines, comparing to controls upon endotoxin challenge. Moreover, acute administration of rGDF3 to endotoxin-treated mice suppresses macrophage infiltration to the heart, attenuates systemic and cardiac inflammation with less pro-inflammatory macrophages (M1) and more anti-inflammatory macrophages (M2), as well as prolongs mouse survival. Mechanistically, GDF3 is able to activate Smad2/Smad3 phosphorylation, and consequently inhibits the expression of nod-like receptor protein-3 (NLRP3) in macrophages. Accordingly, blockade of Smad2/Smad3 phosphorylation with SB431542 significantly offsets rGDF3-mediated anti-inflammatory effects. Taken together, this study uncovers that GDF3, as a novel sepsis-associated factor, may have a dual role in the pathophysiology of sepsis. Acute administration of rGDF3 into endotoxic shock mice could increase survival outcome and improve cardiac function through anti-inflammatory response by suppression of M1 macrophage phenotype. However, constitutive high levels of GDF3 in human sepsis patients are associated with lethality, suggesting that GDF3 may promote macrophage polarization toward M2 phenotype which could lead to immunosuppression.

Nanoparticle-Enhanced Plasmonic Biosensor for Digital Biomarker Detection in a Microarray.

Nanoplasmonic devices have become a paradigm for biomolecular detection enabled by enhanced light-matter interactions in the fields from biological and pharmaceutical research to medical diagnostics and global health. In this work, we present a bright-field imaging plasmonic biosensor that allows visualization of single subwavelength gold nanoparticles (NPs) on large-area gold nanohole arrays (Au-NHAs). The sensor generates image heatmaps that reveal the locations of single NPs as high-contrast spikes, enabling the detection of individual NP-labeled molecules. We implemented the proposed method in a sandwich immunoassay for the detection of biotinylated bovine serum albumin (bBSA) and human C-reactive protein (CRP), a clinical biomarker of acute inflammatory diseases. Our method can detect 10 pg/mL of bBSA and 27 pg/mL CRP in 2 h, which is at least 4 orders of magnitude lower than the clinically relevant concentrations. Our sensitive and rapid detection approach paired with the robust large-area plasmonic sensor chips, which are fabricated using scalable and low-cost manufacturing, provides a powerful platform for multiplexed biomarker detection in various settings.

Incidence of elevated procalcitonin and presepsin levels after severe trauma: a pilot cohort study.

Procalcitonin (PCT) and presepsin (PSEP) are useful biomarkers for diagnosing sepsis; however, elevated PCT and PSEP levels may be observed in conditions other than sepsis. We hypothesised that PCT and PSEP levels could increase after severe traumatic injuries. Trauma patients with an Injury Severity Score of ≥16 from October 2013 to September 2015 were enrolled in our study. We examined PCT and PSEP levels and their positive rates on days 0 and 1. PCT and PSEP levels on days 0 and 1 were compared. Risk factors for increasing sepsis biomarker levels were identified by multivariate logistic regression analyses. In this study, 75 patients were included. PCT levels on days 0 and 1 were 0.1±0.4 and 1.8±6.3 ng/ml, respectively (P=0.02). PSEP levels on days 0 and 1 were 221±261 and 222±207 pg/ml, respectively (P=0.98). As per multivariate logistic regression analyses, packed red blood cell (PRBC) transfusion was the only independent risk factor for higher PCT levels on day 1 (P=0.04). Using PCT to diagnose sepsis in trauma patients on day 1 requires caution. PRBC transfusion was found to be a risk factor for increasing PCT levels. On the other hand, PSEP levels were not affected by trauma during the early phases.

Soluble Urokinase Plasminogen Activator Receptor: A New Biomarker in the Pediatric Intensive Care Unit.

OBJECTIVE: To evaluate the value of soluble urokinase plasminogen activator receptor (suPAR) in diagnosing sepsis and predicting mortality in critically ill children. METHODS: In a prospective cohort study, 69 critically ill children admitted into the pediatric intensive care unit (PICU) were randomly enrolled in addition to 15 healthy children as a control group. Clinical examination was performed, including calculation of the Pediatric Risk of Mortality (PRISM) and Pediatric Index of Mortality2 (PIM2). suPAR was measured in patients at admission as well as in the controls. Patients were followed up for 30 d. RESULTS: suPAR level was significantly higher among the total patient cohort compared to controls (p < 0.0001). suPAR was also significantly higher among patients with sepsis compared to both controls (p < 0.0001) and patients without sepsis (p < 0.0001). Furthermore, suPAR level was significantly elevated in non-survivors compared to survivors (p 0.008). Receiver operating characteristic curve (ROC curve) analysis revealed an area under the curve (AUC) of 0.80 for suPAR for diagnosis of sepsis while C-reactive protein (CRP) had an AUC of 0.82. Regarding the prognosis, suPAR had an AUC of 0.69 for prediction of mortality, whereas the AUC for PRISM, PIM2, and CRP were 0.82, 0.81, and 0.77 respectively. CONCLUSIONS: suPAR has both a diagnostic and a prognostic value for critically ill children. However, it does not seem to be superior to the classic laboratory markers and clinical scoring systems.

suPAR remains uninfluenced by surgery in septic patients with bloodstream infection.

Surgical trauma induces activation of the immune system and may cause an increase of inflammatory biomarkers tested postoperatively in septic patients treated for bloodstream infection. The aim of this study was to determine the impact of surgical interventions on the novel sepsis biomarker soluble urokinase plasminogen activator receptor (suPAR) and to compare results with those of routine laboratory parameters CRP, PCT, and IL-6 in patients with culture-proven bloodstream infection. Forty-six adult patients with positive blood culture undergoing minor or major surgical intervention were investigated, 12 blood culture positive patients served as control group. Blood was collected 24 hours before and after surgical intervention for determination of the sepsis biomarkers suPAR, CRP, PCT, and IL-6. Within the surgical study cohort, a non-significant increase of suPAR, CRP, and PCT was observed postoperatively (p 0.642; p 0.773; p 0.087). In contrast, a slight decrease of IL-6 (p 0.599) was observed. A significant correlation was calculated for the pre- and postoperative difference of CRP (p 0.028) and PCT (p 0.008) and type of surgical intervention received: after minor surgical intervention only PCT decreased significantly (p<0.001), while after major surgical interventions no significant differences were observed for all biomarkers evaluated. In the control group, a significant decrease of CRP (p 0.005) and PCT (p 0.005) was observed. In patients treated adequately for bloodstream infections, postoperative suPAR levels remained uninfluenced of the surgical trauma and might therefore be a reliable parameter for postoperative infectious monitoring. After minor surgical intervention, PCT seems to be the most reliable parameter.