Micromotor-based dual aptassay for early cost-effective diagnosis of neonatal sepsis.

Given the long-life expectancy of the newborn, research aimed at improving sepsis diagnosis and management in this population has been recognized as cost-effective, which at early stages continues to be a tremendous challenge. Despite there is not an ideal-specific biomarker, the simultaneous detection of biomarkers with different behavior during an infection such as procalcitonin (PCT) as high specificity biomarker with one of the earliest biomarkers in sepsis as interleukin-6 (IL-6) increases diagnostic performance. This is not only due to their high positive predictive value but also, since it can also help the clinician to rule out infection and thus avoid the use of antibiotics, due to their high negative predictive value. To this end, we explore a cutting-edge micromotor (MM)-based OFF-ON dual aptassay for simultaneous determination of both biomarkers in 15 min using just 2 µL of sample from low-birth-weight neonates with gestational age less than 32 weeks and birthweight below 1000 g with clinical suspicion of late-onset sepsis. The approach reached the high sensitivities demanded in the clinical scenario (LODPCT = 0.003 ng/mL, LODIL6 = 0.15 pg/mL) with excellent correlation performance (r > 0.9990, p < 0.05) of the MM-based approach with the Hospital method for both biomarkers during the analysis of diagnosed samples and reliability (Er < 6% for PCT, and Er < 4% for IL-6). The proposed approach also encompasses distinctive technical attributes in a clinical scenario since its minimal sample volume requirements and expeditious results compatible with few easy-to-obtain drops of heel stick blood samples from newborns admitted to the neonatal intensive care unit. This would enable the monitoring of both sepsis biomarkers within the initial hours after the manifestation of symptoms in high-risk neonates as a valuable tool in facilitating prompt and well-informed decisions about the initiation of antibiotic therapy.These results revealed the asset behind micromotor technology for multiplexing analysis in diagnosing neonatal sepsis, opening new avenues in low sample volume-based diagnostics.

Delta-Procalcitonin and Vitamin D Can Predict Mortality of Internal Medicine Patients with Microbiological Identified Sepsis.

Background: The management of septic patients hospitalized in Internal Medicine wards represents a challenge due to their complexity and heterogeneity, and a high mortality rate. Among the available prognostic tools, procalcitonin (PCT) is considered a marker of bacterial infection. Furthermore, an association between vitamin D deficiency and poor sepsis-related outcomes has been described. Objectives: To evaluate the prognostic accuracy of two consecutive PCT determinations (Delta-PCT) and of vitamin D levels in predicting mortality in a population of patients with microbiological identified sepsis admitted to Internal Medicine wards. Methods: This is a sub-analysis of a previous prospective study. A total of 80 patients had at least two available consecutive PCT determinations, while 63 had also vitamin D. Delta-PCT was defined as a reduction of PCT > 50% after 48 h, >75% after 72 h, and >85% after 96 h. Mortality rate at 28- and 90-days were considered as main outcome. Results: Mortality rate was 18.7% at 28-days and 30.0% at 90-days. Baseline PCT levels did not differ between survived and deceased patients (28-days: p = 0.525; 90-days: p = 0.088). A significantly higher proportion of survived patients showed Delta-PCT (28-days: p = 0.002; 90-days: p < 0.001). Delta-PCT was associated with a lower 28-days (p = 0.007; OR = 0.12, 95%CI 0.02-0.46) and 90-days mortality (p = 0.001; OR = 0.17, 95%CI 0.06-0.48). A significantly higher proportion of deceased patients showed severe vitamin D deficiency (28-days: p = 0.047; 90-days: p = 0.049). Severe vitamin D deficiency was associated with a higher 28-days (p = 0.058; OR = 3.95, 95%CI 1.04-19.43) and 90-days mortality (p = 0.054; OR = 2.94, 95%CI 1.00-9.23). Conclusions: Delta-PCT and vitamin D represent two useful tests for predicting prognosis of septic patients admitted to Internal Medicine wards.

[Sepsis biomarkers dynamics as an indicator of intensive care effectiveness]. / Dinamika biomarkerov sepsisa kak pokazatel' éffektivnosti intensivnoi terapii.

AIM: To evaluate dynamics of presepsin, procalcitonin and C-reactive protein in survived and dead patients with sepsis. MATERIAL AND METHODS: There were 41 patients with diagnosis of 'sepsis' ('Sepsis-3' concept) who were divided into 2 groups: survived patients with sepsis (21 people) - group 1, dead patients with sepsis (20 people) - group 2. All patients underwent generally accepted intensive therapy for sepsis. Besides conventional laboratory and instrumental examination, dynamics of presepsin, procalcitonin and C-reactive protein was assessed. RESULTS: Mean level of presepsin was 1718.00 and 3266.50 pg/ml in groups 1 and group 2, respectively. Half of the values was within (Me (25; 75) 1021.00-3231.00 pg/ml and 1618.50-7469.00 pg/ml in both groups, respectively. Mean level of procalcitonin was 0.995 and 4.465 ng/ml, respectively. Median (25; 75) was 0.49-4.44 ng/ml and 1,625-19.30 ng/ml, respectively. Mean level of C-reactive protein was 95.5 and 215.0 mg/L, respectively, median (25; 75) - 64.00-155.00 mg/L and 155.00-264.00 mg/L, respectively. Significant differences were determined for all variables (p-value 0.000008, 0.000242, 0.0000001 for presepsin, procalcitonin and C-reactive protein, respectively). CONCLUSION: The levels of C-reactive protein, procalcitonin and presepsin were significantly different in patients with sepsis followed by favorable and unfavorable clinical outcome. Unfavorable outcome was associated with increased levels of all biomarkers. Comprehensive assessment of all biological markers of sepsis is useful to assess an effectiveness of intensive therapy and to predict clinical outcome.

Vasopressin in Septic Shock; Assessment of Sepsis Biomarkers: A Randomized, Controlled Trial.

BACKGROUND AND AIMS: Vasopressin (VP) in sepsis apart from vasoconstrictive effect may have some immunomodulatory effects. The aim of this study was to evaluate the effect of VP on different aspect of sepsis by measuring of sepsis biomarkers. MATERIALS AND METHODS: In this trial, a total number of 42 septic shock patients were included. The first group received norepinephrine (NE) infusion to reach the target mean arterial pressure (MAP) of ≥ 65 mm Hg and the second group received arginine vasopressin (AVP) infusion in addition to NE. Serum lactate, C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, pentraxin 3 (PTX3), angiopoietin 1 and 2 (Ang 1 and 2) levels were assessed. RESULTS: Level of IL-6 and IL-10 decreased, but there was no significant difference between the two groups after 48 h. CRP and PTX3 levels were not also significantly different between groups. Although Angs were not statistically different, there was a trend toward higher Ang-1 in and lower Ang 2 in AVP group after 24 and 48 h. In addition, lactate level did not differ between NE and AVP groups. There was no interaction between VP and hydrocortisone use on IL-6, IL-10, and PTX3, but a significant statistical interaction on Ang 1 and Ang 2 were observed. CONCLUSIONS: Although analysis of sepsis biomarkers showed no significant difference between two groups, no immunomodulatory effect for VP alone, subgroup analysis of hydrocortisone used in this study showed that the combination of glucocorticoids and AVP had a significant effect on Angs level which eventually causes less endothelial permeability and higher MAP in this group of patients.

Biomarkers in sepsis-looking for the Holy Grail or chasing a mirage!

Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection. It is a complex syndrome and is characterized by physiologic, pathologic and biochemical abnormalities in response to an infection. Diagnosis of sepsis is based on history, physical examination and other investigations (including biomarkers) which may help to increase the certainty of diagnosis. Biomarkers have been evaluated in the past for many diseases and have been evaluated for sepsis as well. Biomarkers may find a possible role in diagnosis, prognostication, therapeutic monitoring and anti-microbial stewardship in sepsis. Since the pathophysiology of sepsis is quite complex and is incompletely understood, a single biomarker that may be robust enough to provide all information has not been found as of yet. However, many biomarkers have been studied and some of them have applications at the bedside and guide clinical decision-making. We evaluated the PubMed database to search for sepsis biomarkers for diagnosis, prognosis and possible role in antibiotic escalation and de-escalation. Clinical trials, meta-analyses, systematic reviews and randomized controlled trials were included. Commonly studied biomarkers such as procalcitonin, Soluble urokinase-type plasminogen activator (Supar), presepsin, soluble triggering receptor expressed on myeloid cells 1, interleukin 6, C-reactive protein, etc., have been described for their possible applications as biomarkers in septic patients. The sepsis biomarkers are still an area of active research with newer evidence adding to the knowledge base continuously. For patients presenting with sepsis, early diagnosis and prompt resuscitation and early administration of anti-microbials (preferably within 1 h) and source control are desired goals. Biomarkers may help us in the diagnosis, prognosis and therapeutic monitoring of septic patients. The marker redefining our view on sepsis is yet a mirage that clinicians and researchers continue to chase.

Point-of-care diagnostics for sepsis using clinical biomarkers and microfluidic technology.

Sepsis is a life-threatening immune response which is caused by a wide variety of sources and is a leading cause of mortality globally. Rapid diagnosis and appropriate antibiotic treatment are critical for successful patient outcomes; however, current molecular diagnostic techniques are time-consuming, costly and require trained personnel. Additionally, there is a lack of rapid point-of-care (POC) devices available for sepsis detection despite the urgent requirements in emergency departments and low-resource areas. Recent advances have been made toward developing a POC test for early sepsis detection that will be more rapid and accurate compared to conventional techniques. Within this context, this review discusses the use of current and novel biomarkers for early sepsis diagnosis using microfluidics devices for POC testing.

Use of Biomarkers to Improve 28-Day Mortality Stratification in Patients with Sepsis and SOFA ≤ 6.

Early diagnosis and appropriate treatments are crucial to reducing mortality risk in septic patients. Low SOFA scores and current biomarkers may not adequately discern patients that could develop severe organ dysfunction or have an elevated mortality risk. The aim of this prospective observational study was to evaluate the predictive value of the biomarkers mid-regional pro-adrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate for 28-day mortality in patients with sepsis, and patients with a SOFA score ≤6. 284 were included, with a 28-day all-cause mortality of 8.45% (n = 24). Non-survivors were older (p = 0.003), required mechanical ventilation (p = 0.04), were ventilated for longer (p = 0.02), and had higher APACHE II (p = 0.015) and SOFA (p = 0.027) scores. Lactate showed the highest predictive ability for all-cause 28-day mortality, with an area under the receiver-operating characteristic curve (AUROC) of 0.67 (0.55-0.79). The AUROC for all-cause 28-day mortality in patients with community-acquired infection was 0.69 (0.57-0.84) for SOFA and 0.70 (0.58-0.82) for MR-proADM. A 2.1 nmol/L cut-off point for this biomarker in this subgroup of patients discerned, with 100% sensibility, survivors from non-survivors at 28 days. In patients with community-acquired sepsis and initial SOFA score ≤ 6, MR-proADM could help identify patients at risk of 28-day mortality.

Detection of Inflammatory Biomarkers Among Patients with Sepsis of Gram-Negative Bacteria: A Cross-Sectional Study.

Background: Sepsis is a highly mixed ailment that affects patients with numerous conditions of infectious sources and can lead to multi-organ failure with dysregulated host immune response. Objective: To determine inflammatory biomarkers in patients with sepsis caused by Gram-negative bacteria and compare their role in the early detection of sepsis. Methods: This cross-sectional study was conducted on patients with sepsis admitted to the intensive care unit at different hospitals in Sulaimaniyah, Iraq, from May to December 2021. Patients (n=147) were enrolled in this study according to the primary diagnosis of sepsis by Sequential Organ Failure Assessment scores. Blood samples were taken from patients to investigate white blood cells, inflammatory biomarkers (pentraxin-3, procalcitonin, adrenomedullin, lipopolysaccharide binding protein, interleukin-17A, lactate dehydrogenase, and C-creative protein), blood culture, antibiotic susceptibility test, and coagulation biomarkers (Prothrombin time, activated partial thromboplastin time, and international normalized ratio). Then, isolated Gram-negative bacteria were tested for extended-spectrum ß-lactamase enzymes production by screening and combined disc tests. Results: A total of 51.7% samples were blood culture positive for different Gram-negative bacteria, and P. aeruginosa (51.95%) was a more isolated bacterium. Both males and females were affected by sepsis in a ratio of 1.23:1 with different age groups. Extended-spectrum ß-lactamase was estimated to be 77.2% by antibiotic profile, and the rate decreased using two double-disc synergy tests. This was confirmed by combined disc test at a rate of 41.35%. The most prevalent biomarkers were procalcitonin (88.16%), adrenomedullin (84.21%), pentraxin-3 (22.37%), and lipopolysaccharide binding protein (11.84%). Conclusion: Sepsis is a life-threatening condition that can be diagnosed early by several blood biomarkers such as procalcitonin, adrenomedullin, and pentraxin-3 combined with a standard blood culture technique to improve the patient outcome.

Gene filtering strategies for machine learning guided biomarker discovery using neonatal sepsis RNA-seq data.

Machine learning (ML) algorithms are powerful tools that are increasingly being used for sepsis biomarker discovery in RNA-Seq data. RNA-Seq datasets contain multiple sources and types of noise (operator, technical and non-systematic) that may bias ML classification. Normalisation and independent gene filtering approaches described in RNA-Seq workflows account for some of this variability and are typically only targeted at differential expression analysis rather than ML applications. Pre-processing normalisation steps significantly reduce the number of variables in the data and thereby increase the power of statistical testing, but can potentially discard valuable and insightful classification features. A systematic assessment of applying transcript level filtering on the robustness and stability of ML based RNA-seq classification remains to be fully explored. In this report we examine the impact of filtering out low count transcripts and those with influential outliers read counts on downstream ML analysis for sepsis biomarker discovery using elastic net regularised logistic regression, L1-reguarlised support vector machines and random forests. We demonstrate that applying a systematic objective strategy for removal of uninformative and potentially biasing biomarkers representing up to 60% of transcripts in different sample size datasets, including two illustrative neonatal sepsis cohorts, leads to substantial improvements in classification performance, higher stability of the resulting gene signatures, and better agreement with previously reported sepsis biomarkers. We also demonstrate that the performance uplift from gene filtering depends on the ML classifier chosen, with L1-regularlised support vector machines showing the greatest performance improvements with our experimental data.

A combined ratio change of inflammatory biomarkers at 72 h could predict the severity and prognosis of sepsis from pulmonary infections.

PURPOSE: To determine the association of a combined ratio change of inflammatory biomarkers at 72 h after admission on sepsis severity and prognosis from pulmonary infections. METHODS: Data on adult patients diagnosed with sepsis, or septic shock were retrospectively analyzed. Patients were divided into two groups, according to their outcome of hospitalization. Blood specimens were obtained on admission (T0) and 72 h (T72) after therapy. Acute Physiology And Chronic Health Evaluation Score (APACHEII) and Sequential Organ Failure Assessment Score (SOFA) were statistically analyzed on admission. Survivors discharged from hospital were classified into different subgroups according to the change in biomarkers at T72, and compared for different clinical prognosis. RESULTS: Our study showed that IL-6, IL-8, IL-10 and TNF-a could predict the severity of sepsis at T0, since they showed a positive correlation with APACHEII or SOFA score. Another important finding was that survivors discharged from hospital whose ratio change with IL-10, i.e: IL-10/IL-6, IL-10/IL-8, IL-10/TNF-a ≤ 0 exhibited significantly greater 9-month overall survival. We also observed that patients with increased IL-6 after 72 h showed similar improved survival. CONCLUSION: Our findings suggested that a combined ratio change of inflammatory biomarkers was an effective predictor for sepsis severity and prognosis.

An evaluation into the use of procalcitonin levels as a biomarker of bacterial sepsis to aid the management of intrapartum pyrexia and chorioamnionitis.

BACKGROUND: Procalcitonin is an established biomarker for bacterial sepsis in the nonpregnant population with better diagnostic and prognostic value for bacterial infections. OBJECTIVE: This study aimed to evaluate whether procalcitonin levels could be used in the diagnosis and management of intrapartum sepsis in women and their neonates suspected of intrapartum bacterial sepsis. STUDY DESIGN: A prospective observational cohort study was conducted at the University Hospitals of Bristol and Weston NHS Foundation Trust. Overall, 117 women and their neonates managed for suspected intrapartum sepsis from June 2020 to October 2020 were included. Procalcitonin levels were measured in addition to routine biomarkers white cell count and C-reactive protein in women and their neonates during the initial septic screen and follow-up blood samples. The placentas underwent detailed histopathology. Maternal and neonatal parameters were used to categorize cases into "high-suspicion bacterial sepsis," "equivocal bacterial sepsis," and "low-suspicion bacterial sepsis." The Kruskal-Wallis test was used to compare categories with biomarker values and placental histology scores. RESULTS: Procalcitonin level was increased in 6 women in the initial septic screen sample, compared with 100 women with an increased C-reactive protein level. There was a significant difference in maternal postnatal procalcitonin results between "high-suspicion bacterial sepsis" and "low-suspicion bacterial sepsis" categories (P=.004). Moreover, 71.2% of placentas showed varying degrees of chorioamnionitis. CONCLUSION: In our cohort of women, 94.6% had normal procalcitonin levels while in labor at the time of the septic screen, consistent with the low number of confirmed bacteremia. The result provided a basis that procalcitonin may complement clinical judgment and interpretation of already used prognostic and diagnostic tests, improving patient care in the management of intrapartum sepsis.

Emerging Biosensing Technologies towards Early Sepsis Diagnosis and Management.

Sepsis is defined as a systemic inflammatory dysfunction strictly associated with infectious diseases, which represents an important health issue whose incidence is continuously increasing worldwide. Nowadays, sepsis is considered as one of the main causes of death that mainly affects critically ill patients in clinical settings, with a higher prevalence in low-income countries. Currently, sepsis management still represents an important challenge, since the use of traditional techniques for the diagnosis does not provide a rapid response, which is crucial for an effective infection management. Biosensing systems represent a valid alternative due to their characteristics such as low cost, portability, low response time, ease of use and suitability for point of care/need applications. This review provides an overview of the infectious agents associated with the development of sepsis and the host biomarkers suitable for diagnosis and prognosis. Special focus is given to the new emerging biosensing technologies using electrochemical and optical transduction techniques for sepsis diagnosis and management.

The value of sepsis biomarkers and their kinetics in the prognosis of septic shock due to bacterial infections.

INTRODUCTION: In this study, we aim to explore the value of procalcitonin (PCT), C-reactive protein (CRP), and serum cholinesterase (SChE) activity kinetics as useful predictors of mortality in patients with septic shock admitted to the intensive care unit (ICU). MATERIAL AND METHODS: We conducted a prospective single-blinded study in the ICU of a university hospital during a period of 1 year. Were included all patients 18 years of age or older, with confirmed septic shock. For all included patients, blood samples of septic biomarkers (PCT, SChE activity, and CRP) were obtained. Serum was collected at the day of ICU admission (day 0), the day of septic shock (day 1), then 3 and 5 days after the septic shock development. RESULTS: During the study period, 60 patients were included. The mean age (± SD) was 47.7 ± 19 years. There were 46 male (74%) and 14 female (26%) patients. Mean SAPSII on ICU admission was 40.7 ± 16 (median: 37), and mean SOFA score on ICU admission was 16 ± 4 (median: 7). During their ICU stay, out of the 60 included patients, 37 patients died (61%). The comparison between the 2 groups (deaths and survivors) showed that the factors associated with poor outcome were age, SOFA score on ICU admission, and the need for invasive mechanical ventilation. The day of septic shock, there was no difference in the mean concentrations in those of plasma SChE activity or in the PCT and CRP plasma between survivors and non-survivors. However, the comparison of mean plasma SChE activity, and PCT and CRP plasma concentrations (on day 3 and day 5) between survivors and non-survivors, showed a significant difference between the 2 groups. CONCLUSIONS: Our study suggests that, in a group of critically ill patients with severe septic shock, a rise or no change in procalcitonin and/or CRP level, and/or a decrease or no change in SChE activity should warn the clinician about the insufficiency and/or inadequacy of the therapy. However, a fall in procalcitonin and/or CRP levels, and/or a rise in SChE activity were associated with a favourable prognosis. Based on our study and some other data detailed above, we recommend that an estimation of SChE acti-vity, procalcitonin, and CRP on the day of septic shock, followed by estimation within the next 72-120 h, could help the prognostic assessment of critically ill patients with septic shock. Further studies are needed to define the critical values related to mortality.

Detection of Infection and Sepsis in Burns.

Background: Infection is the most frequent complication after severe burns and has a propensity to progress into sepsis then septic shock and multiple organ dysfunction syndrome (MODS). Improving outcomes in acute burn care depends on early detection of infection to allow prompt interventions. Diagnosis of sepsis in severe burns is uniquely challenging because otherwise-typical clinical signs are masked by the hypermetabolic state and systemic inflammation induced by the burn itself. For this reason, burns have historically been excluded from high-impact studies on the diagnosis and treatment of sepsis. Methods: This article provides a comprehensive three-fold review of current findings and guidelines pertinent to the early detection of infection and sepsis in severe burns. Results: First, evidence-based detection of the most common infections encountered in the burn intensive care unit is reviewed. Second, we analyze the evolution of the diagnostic criteria for sepsis and the evidence regarding their utility in severe burns. Last, we examine the development of biomarkers, from procalcitonin to molecular genomics, for the detection of sepsis. Conclusions: Although gold standard methods of early detection of sepsis in burn patients have yet to be identified, improved understanding and appropriate application of the available diagnostic criteria and assays are paramount to providing effective care of patients with severe burns.

Chronic Critical Illness Patients Fail to Respond to Current Evidence-Based Intensive Care Nutrition Secondarily to Persistent Inflammation, Immunosuppression, and Catabolic Syndrome.

BACKGROUND: Sepsis-induced multiple-organ failure (MOF) has plagued surgical intensive care units (ICUs) for decades. Early nutrition (principally enteral) improves hospital outcomes of high-risk ICU patients. The purpose of this study is to document how the growing epidemic of chronic critical illness (CCI) patients responds to adequate evidence-based ICU nutrition. METHODS: This retrospective post hoc subgroup analysis of an ongoing sepsis database identified 56 CCI patients who received early, adequate nutrition per an established surgical ICU protocol compared with 112 matched rapid-recovery (RAP) patients. RESULTS: The matched CCI and RAP groups had similar baseline characteristics. Serial biomarkers showed that CCI patients remained persistently inflamed with ongoing stress metabolism and that despite receiving evidence-based protocol nutrition, they had persistent catabolism and immunosuppression with more secondary infections. More CCI patients were discharged to poor nonhome destinations (ie, skilled nursing facilities, long-term acute care, hospice) (81% vs 29%, P < 0.05). At 12-month follow-up, CCI patients had worse functional status by Zubrod score (3.17 vs 1.62, P < 0.001) and Short Physical Battery Testing (4.78 vs 8.59, P < 0.02), worse health-related quality of life by EQ-5D-3L descriptive measures (9.07 vs 7.45, P < 0.003), and lower survival (67% vs 92%, P < 0.05). CONCLUSIONS: Despite early, adequate, evidence-based ICU nutrition, septic surgical ICU patients who develop CCI exhibit persistent inflammation, immunosuppression, and catabolism with unacceptable long-term morbidity and mortality. Although current evidence-based ICU nutrition may improve short-term ICU outcomes, novel adjuncts are needed to improve long-term outcomes for CCI patients.

Toward Early Diagnosis of Late-Onset Sepsis in Preterm Neonates: Dual Magnetoimmunosensor for Simultaneous Procalcitonin and C-Reactive Protein Determination in Diagnosed Clinical Samples.

Early diagnosis of sepsis, combining blood cultures and inflammation biomarkers, continues to be a challenge, especially in very low birth weight (VLBW) infants because of limited availability of blood samples. Traditional diagnostic procedures are cumbersome, not fast enough, and require relatively large volumes of sample. Empiric use of antibiotics, before diagnostic confirmation, is required to decrease mortality, leading to potential antibiotic resistance and side effects in VLBW infants. To solve such a serious problem, a dual magnetoimmunosensor is proposed for simultaneous assessment of two of the most important sepsis biomarkers: procalcitonin (PCT for early phase) and C-reactive protein (CRP for late phase). This "sample-to-result" approach exhibited excellent sensitivity, selectivity, precision, and stability using low sample volumes (<30 µL) and under 20 min of total assay. The analytical usefulness of the approach was demonstrated by analyzing clinically relevant samples of preterm neonates with suspicion of sepsis.

Vascular Endothelium in Neonatal Sepsis: Basic Mechanisms and Translational Opportunities.

Neonatal sepsis remains a major health issue worldwide, especially for low-birth weight and premature infants, with a high risk of death and devastating sequelae. Apart from antibiotics and supportive care, there is an unmet need for adjunctive treatments to improve the outcomes of neonatal sepsis. Strong and long-standing research on adult patients has shown that vascular endothelium is a key player in the pathophysiology of sepsis and sepsis-associated organ failure, through a direct interaction with pathogens, leukocytes, platelets, and the effect of soluble circulating mediators, in part produced by endothelial cells themselves. Despite abundant evidence that the neonatal immune response to sepsis is distinct from that of adults, comparable knowledge on neonatal vascular endothelium is much more limited. Neonatal endothelial cells express lower amounts of adhesion molecules compared to adult ones, and present a reduced capacity to neutralize reactive oxygen species. Conversely, available evidence on biomarkers of endothelial damage in neonates is not as robust as in adult patients, and endothelium-targeted therapeutic opportunities for neonatal sepsis are almost unexplored. Here, we summarize current knowledge on the structure of neonatal vascular endothelium, its interactions with neonatal immune system and possible endothelium-targeted diagnostic and therapeutic tools for neonatal sepsis. Furthermore, we outline areas of basic and translational research worthy of further study, to shed light on the role of vascular endothelium in the context of neonatal sepsis.

Risk stratification and prognostic evaluation of endothelial cell-specific molecule1, von Willebrand factor, and a disintegrin-like and metalloprotease with thrombospondin type 1 motif for sepsis in the emergency department: An observational study.

This study evaluated endothelial cell-specific molecule1 (endocan), von Willebrand factor (vWF), and A disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS-13), alone or in combination, in the risk stratification and prognosis prediction of patients with sepsis. Clinical data of 301 patients were prospectively analyzed, and divided into systemic inflammatory reaction syndrome, sepsis, severe sepsis, and septic shock groups. A total of 40 healthy individuals were studied as the control group. Endocan, vWF, ADAMTS-13, vWF/ADAMTS-13, and procalcitonin levels were measured, and Acute Physiology and Chronic Health Evaluation (APACHE II) score, Mortality in Emergency Department Sepsis (MEDS) score as well as Sequential Organ Failure Assessment (SOFA) score were calculated. The all-cause death or survival of each patient was recorded during the 28-day follow-up. The endocan, vWF, and vWF/ADAMTS-13 levels significantly increased in patients and were positively correlated with disease severity. On the first day of admission, MEDS score, ADAMTS-13, and vWF/AMAMTS-13 ratio were independent predictors for 28-day mortality from sepsis. Moreover, the combination of vWF/ADAMTS-13 ratio with MEDS score improved the accuracy in predicting the 28-day mortality from sepsis. On day 5, endocan, vWF, ADAMTS-13, and vWF/ADAMTS-13 ratio were independent predictors for the 28-day mortality from sepsis, while the combined use of endocan and vWF/ADAMTS-13 ratio improved the prognostic value of individual indicators. Endocan, vWF, ADAMTS-13, and vWF/ADAMTS-13 ratio are valuable in the risk stratification and prognostic evaluation of sepsis as novel biomarkers.

Pediatric Sepsis Update: How Are Children Different?

BACKGROUND: Although there are some commonalities between pediatric and adult sepsis, there are important differences in pathophysiology, clinical presentation, and therapeutic approaches. The recognition and diagnosis of sepsis is a significant challenge in pediatric patients as vital sign aberrations and examination findings are often subtle as compared to those observed in adults. Gaps in knowledge that have been studied in depth in adult sepsis are still being investigated in pediatric patients such as best practices in ventilation, invasive monitoring, and resuscitation. DISCUSSION: In this review, we address key differences in the etiology, presentation, resuscitation, and outcomes of sepsis in children compared with adults.

Decreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis.

PURPOSE: We sought to determine whether an early high-density lipoprotein cholesterol (HDL-C) measurement at emergency department (ED) admission is prognostic of multiorgan dysfunction syndrome (MODS) and death in a suspected sepsis cohort. MATERIALS AND METHODS: Two hundred patients with clinically suspected sepsis were recruited at admission to our tertiary care hospital's ED. Lipids were measured at the time of first ED blood draw. Clinical data were collected via chart review. Primary outcomes of interest were development of MODS and 28-day mortality. Secondary outcomes included need for critical care, single-organ failures, days alive and free of vasopressor and ventilator support, and 90-day mortality. RESULTS: High-density lipoprotein cholesterol was greatly decreased in patients who developed MODS and/or died and remained stable over the first week of admission. Receiver operator characteristic analysis demonstrated that HDL-C had superior predictive ability compared with all routine clinical markers for both development of MODS and 28-day mortality, and identified an HDL-C cutoff of 25.1 mg/dL below which patients were at significantly greater risk for development of all adverse outcomes. CONCLUSIONS: Plasma HDL-C level was characterized by early decrease and high stability, and was the best prognostic marker for adverse outcomes in a suspected sepsis cohort.