There is a current, absence of reliable, blood-sparing, diagnostic tools to measure and trend real-time changes in the levels of inflammation and its effects on the immune cells in the infant.

We deployed the BiophysicaL Immune Profiling for Infants (BLIPI) system in the neonatal intensive care unit to describe immune cell biophysical profiles using 50 microliters of blood per sample from term and preterm infants.

A total of 19 infants (8 term, 11 preterm) were recruited and 24 blood samples were collected in their first month. Based on the profiles of immune cells' size and deformation, there was a clear distinction between term and preterm infants, with 48/50 markers significantly different. A preterm infant with late-onset bacterial sepsis had notable size and deformability differences compared to the rest of the preterm cohort. There was a significant correlation between immune cell biophysical profiles and clinical markers such as C-reactive protein, white blood cell counts, and immature-to-total neutrophil (I:T) ratios, with Pearson correlation coefficients for linear regression models of 0.98, 0.97 and 0.94 respectively.

This study highlights the potential for the biophysical immune cell profiling system to provide an overview of the infant's current immune activation and response.

We present a novel, minimally invasive diagnostic system that leverages the physical properties of immune cells to provide a rapid and direct assessment of the immune status, requiring 20 times less blood volume than standard tests. This study demonstrates the potential of a compact, deployable system that is capable of performing biophysical profiling to assess immune cell activation in term and preterm infants, by revealing distinct differences in cell size and deformation between groups. The system's sensitive, quantitative measures were correlated with routine clinical biomarkers, highlighting its ability to provide a rapid, minimally invasive, real-time monitoring of neonatal immune status.

Interleukin-6 (IL-6) is an early biomarker for sepsis and necrotizing enterocolitis (NEC). We assessed IL-6's ability to differentiate between late-onset sepsis (LOS) and NEC and between medical and surgical NEC.

This retrospective cohort study included infants born preterm (birth weight <1500 g, gestational age <32 weeks) with ≥1 episodes of suspected late-onset sepsis (sLOS) between 2018 and 2023. Plasma IL-6 levels at sLOS onset were analyzed. Infants were grouped into (1) control (no sepsis/NEC), (2) LOS (culture negative/positive sepsis), or (3) NEC (medical/surgical), on the basis of the greatest classification of their observed episodes. IL-6's predictive value (alone and in combination with C-reactive protein) for sLOS outcomes was assessed with receiver operating characteristic analysis, with the area under the curve (AUC) quantifying its discriminative quality.

sLOS was observed in 421 infants (670 episodes); 131 (31%) had no LOS or NEC, 225 (53%) had LOS without NEC, and 65 (15%) had NEC. Median IL-6 values significantly differed between all groups, with highest in infants with NEC. The odds of NEC over LOS increased by a factor of 1.53 (95% CI 1.42-1.65, P < .001) for every doubling of IL-measurements. IL-6 was not associated with the odds of surgical NEC compared with medical NEC. IL-6's ability to distinguish NEC from LOS was moderate (AUC 0.73). IL-6 combined with C-reactive protein (AUC 0.64) showed poor discriminative ability.

Although elevated IL-6 levels are associated with greater odds of having NEC instead of LOS, the moderate predictive value suggests that IL-6 alone may not be sufficient for accurate early diagnosis or differentiation.

To evaluate the predictive value of procalcitonin (PCT) in assessing the therapeutic response of patients with uroseptic shock.

This retrospective case-control study included 220 patients treated for uroseptic shock at Liyang People's Hospital between January 2018 and December 2023. Patients were classified into high-risk (HR) (n = 116) and low-risk (LR) (n = 104) groups based on their Sepsis-related Organ Failure Assessment (SOFA) scores after 14 days of treatment. Demographic, clinical, and laboratory data were collected, and PCT levels were measured using chemiluminescence. Correlation analysis and receiver operating characteristic (ROC) curve analysis were used to assess the predictive value of PCT.

The HR group had significantly higher PCT levels (25.33 ± 5.32 ng/mL) compared to the LR group (18.47 ± 2.88 ng/mL, P < 0.001). Elevated PCT levels were strongly correlated with poor therapeutic response (rho = -0.635, P < 0.001). Other markers, including hypertension (rho = -0.207, P = 0.002), CRP (rho = -0.224, P < 0.001), IL-6 (rho = -0.200, P = 0.003), TNF-α (rho = -0.151, P = 0.025), NEUT% (rho = -0.208, P = 0.002), GGT (rho = -0.160, P = 0.017), and BUN (rho = -0.198, P = 0.003), also showed significant negative correlations with treatment outcome. Conversely, PLT (rho = 0.156, P = 0.021) and the CD4+/CD8+ ratio (rho = 0.242, P < 0.001) were positively correlated with better treatment outcome. ROC analysis revealed an area under the curve (AUC) of 0.867 for PCT, indicating its strong predictive value.

PCT level is a robust predictor of therapeutic response in uroseptic shock patients and may be integrated into clinical protocols for sepsis management.

Sepsis is the overwhelming immunological response to infection, which if not treated can lead to multi-organ failure, shock and death. Specifically, neonatal sepsis results in 225,000 neonatal deaths globally per annum. Moreover, Uganda experiences one of the highest materno-fetal death rates (62,000 p.a.), with neonatal sepsis deaths at approximately 6,500 p.a.. The difficulty in diagnosing neonatal sepsis lies in the non-specific signs and symptoms associated with sepsis and an absence of definitive sepsis-specific biomarkers. However, serum amyloid A (SAA) detection has potential as a superior biomarker for the diagnosis of probable neonatal sepsis. Herein, in ethically-approved studies we have deployed a competitive lateral flow test (NeoSep-SAA (research-use only)) to detect SAA in whole blood at patient bedside in a resource-limited environment. Results are available within 10 minutes and test format is compatible with small blood volumes available from neonates (5 μl). NeoSep-SAA exhibited a high sensitivity and specificity for diagnosis of adult sepsis, and in neonates showed a sensitivity and specificity of 92% (89%, 95%) and 73% (68%, 77%) with PPV and NPV of 78% (75%, 81%) and 90% (86%, 93%), respectively (n = 714 individuals; 95% CI). NeoSep-SAA showed superior sensitivity for neonatal sepsis over C-Reactive Protein detection (sensitivity: 37%), albeit with some sacrifice of specificity. NeoSep-SAA enabled rapid diagnosis, which combined with minimally-invasive blood withdrawal, was less stressful for neonates. Overall, NeoSep-SAA can readily identify infection/inflammation and has the potential to enable rapid and informed clinical decisions to combat sepsis. This approach has potential to improve neonatal sepsis detection and reduce neonatal mortality in line with United Nations Sustainable Development Goal (SDG) 3.2 objectives.

Nosocomial infection (NI) is a serious health concern primarily for premature neonates and for term babies with illnesses requiring continued hospitalisation. Early diagnosis of NI using biomarkers is central to decreased neonatal mortality and morbidity. We aimed to evaluate the predictive value of C-reactive protein (CRP) as a marker of NI.

Sixty-four neonates, suspected of sepsis, admitted to the Department of Paediatrics and Neonatology with a negative workup for sepsis on their first day of admission were investigated for various haematological parameters, blood culture positivity, and CRP levels. The patients were then stratified into culture-positive and culture-negative groups. All the parameters analysed were compared between these 2 groups, and ROC curve analysis was performed to determine the value of CRP in predicting positive blood culture in NI.

NI was seen in a total of 70.31% (n = 45) neonates based on blood culture-positive status. Compared to females, a greater number of male neonates were culture-positive (60% vs 40%). The mean birth-weight of the culture-positive group was significantly lower than the negative group (P = 0.03). The mean CRP levels were elevated in the positive group (98.5 ± 47.8) when compared to the negative group (32.2 ± 24.1; P < .001). Using the ROC curve,a cut-off value (45.05 mg/L) of CRP had sensitivity and specificity of 80.0% and 73.7% respectively in predicting blood culture-positive NI.

Serum CRP is a sensitive marker to diagnose NI in admitted neonates.

CRP levels can aid in the diagnosis of clinical deterioration, and a treating physician can modify the regimen based on elevated CRP levels.

Neonatal sepsis is a global health threat, contributing to high morbidity and mortality rates among newborns. Recognizing the profound impact of neonatal sepsis on long-term health outcomes emphasizes the critical need for timely detection to mitigate its consequences and ensure optimal health for the affected newborns. Currently, various diagnostic approaches have been implemented, but they are limited by their invasiveness, high costs, centralized testing, frequent delays, inaccuracies in results, and the need for sophisticated laboratory equipment.

We introduced a novel, non-invasive, cost-efficient, and easy-to-use technology that can provide rapid results at a point-of-care. The technology utilized a lab-built metal oxide semiconductor-based electronic nose (cNose) combined with volatile organic compound (VOC) biomarkers identified through gas chromatography-mass spectrometry (GC-MS) analysis. The system was evaluated using fecal profiling tests involving a total of 32 samples, including 17 positive and 15 negative sepsis, confirmed by blood culture. To assess the performance in discriminating patients from healthy controls, four machine learning algorithms were implemented.

Based on the cross-validation results, the MLPNN model provided the best results in distinguishing between neonates with positive and negative sepsis, achieving high-performance results of 90.63 % accuracy, 88.24 % sensitivity, and 93.33 % specificity at a 95 % confidence interval. Specific VOCs associated with neonatal sepsis, such as alcohols, acids, and esters, were successfully identified through GC-MS analysis, further validating the diagnostic capability of the cNose device.

The overall observations show the feasibility of using cNose system as a promising tool for real-time and bedside sepsis detection, potentially improving patient outcomes.

Very-low-birth-weight infants (VLBWIs; birth weight < 1500 g) are at an increased risk of complicated influenza infection, which frequently includes pneumonia, encephalitis or even death. Data on influenza immunization and its outcome in VLBWIs are scarce. This study aimed to provide epidemiological data on influenza immunization for German VLBWIs and hypothesized that immunization would protect VLBWIs from infection-mediated neurodevelopmental impairment and preserves lung function at early school age.

In this observational population-based German Neonatal Network (GNN) study, infants born between 2009 and 2015 were invited to partake in a 6-year follow-up investigation including lung function and developmental testing. Uni- and multivariate analyses were performed to evaluate the clinical characteristics and outcomes of influenza-immunized VLBWIs compared to non-immunized VLBWIs.

Influenza immunization was performed in 871 out of the 3358 VLBWIs (26%) with six-year follow-up. Immunized infants were characterized by a low gestational age and higher rates of morbidity, particularly bronchopulmonary dysplasia. Although early immunization showed no safety signals and had protective effects on the long-term risk of bronchitis (OR: 0.2; CI: 0.1-0.6; p = 0.002), most VLBWIs (88.0%) were unimmunized in their first influenza season.

Influenza immunization was not associated with improved lung function (forced expiratory volume in one second and forced vital capacity) or a better neurocognitive outcome (intelligence quotient and strengths and difficulties questionnaire) at early school age. In Germany, only one quarter of 6-year-old VLBWIs were immunized against influenza, particularly those born <28 gestational weeks and/or BPD. Specific influenza immunization guidelines that define evidence-based recommendations are needed for this vulnerable group.

The aim of this study is to investigate the utility of interleukin-6 (IL-6) in the early diagnosis of serious bacterial infections (SBI) in febrile infants and to compare it with C-reactive protein (CRP).

Retrospective study conducted in the paediatric emergency department in Gothenburg, Sweden, on previously healthy, full-term infants aged ≤60 days with fever without a source (FWS) from 2014 to 2017.

We included 536 infants with FWS, of whom IL-6 was analysed in 364 (68%) and CRP was analysed in 494 (92%). Approximately 70% of the infants presented with a fever duration of less than 12 h. The prevalence of SBIs was 14.8% (95% CI,11.3-18.9) in the IL-6 group and 17.8% (95% CI,14.5-21.5) in the CRP group. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of IL-6 ≥50 ng/L were 93%, 66%, 98% and 33%, respectively. For CRP ≥20 mg/L, the sensitivity, specificity, NPV, and PPV were 76%, 89%, 95%, and 55%, respectively. Logistic regression analysis showed that CRP was significantly associated with SBI (p < 0.0001) in the entire population, whereas IL-6 was not.

Interleukin-6 showed high sensitivity and NPV, which might assist in identifying SBIs early in febrile infants. However, IL-6 was not shown to be superior to CRP and further studies are needed to investigate whether IL-6 should be incorporated in clinical management.

Neonatal sepsis remains a significant cause of neonatal morbidity and mortality globally. At present, no clear consensus definition for sepsis in neonates exists, even though a positive blood culture is considered as the gold standard for definitive diagnosis. The accurate and timely diagnosis of sepsis in neonates presents significant difficulties, since "culture negative" or "suspected" sepsis varies widely worldwide. Antibiotic overuse and resistance are emerging problems, but on the other hand, under-recognition of sepsis and delayed antibiotic treatment could have serious or even fatal adverse outcomes in this vulnerable population. In the context of rapid recognition of sepsis and timely initiation of appropriate antibiotic therapy, various sepsis risk assessment tools have been developed, a variety of biomarkers are in clinical use or under research for future use, and new diagnostic techniques are under evaluation. In this review, we summarize the most recent data on neonatal sepsis, the utility of sepsis risk assessment tools for term and preterm infants with sepsis, and current diagnostic and preventive tools.

Excessive antimicrobial exposure is associated with an increase in neonatal mortality, morbidities and adverse neurodevelopment. Canadian Neonatal Network has been promoting judicious antimicrobial use through the Evidence-based Practice for Improving Quality processes. Our objective was to evaluate the antimicrobial consumption among neonates in tertiary neonatal intensive care units (NICU) in Canada in the recent decade.

This is a retrospective cohort study including data from very preterm infants (born at <33 weeks gestational age) admitted to all NICUs in Canada between January 1, 2013, and December 31, 2022. Nationwide antimicrobial utilization rate (AUR) benchmarking started in 2016, and quality improvement initiatives were continued in the subsequent years to promote judicious use of antimicrobials across the network. AUR is defined as the number of days with ≥1 antimicrobial divided by the total patient days (PD). Culture-proven sepsis refers to a neonate with positive culture of pathogens in blood and/or cerebrospinal fluid. The outcomes were evaluated during pre- (2013-2017) and post-intervention periods (2018-2022). Interrupted time-series analysis was used, and comparison of AUR calculated per each 3-month time block and the slope changes were conducted across the pre- and post-intervention periods regarding total patients and subgroups.

A total of 41,253 infants were included, with 22,644 (55%) being male. The AUR was significantly lower among infants from the post- vs. those from the pre-intervention periods (152 vs. 184, p < 0.0001). Among 35,670 infants without culture-proven sepsis or necrotizing enterocolitis ≥ Stage 2, AUR was significantly lower in the post-intervention group vs. the pre-intervention group (110 vs. 136, p < 0.0001). Interrupted time-series showed significant reduction in AUR during both pre- and post-intervention periods among all infants with and without culture proven sepsis or necrotizing enterocolitis ≥ Stage 2 (all p < 0.0001), as well as those born at <29 weeks gestational age.

A comprehensive, network-wide quality improvement initiatives led to a significant and sustained reduction in antimicrobial use among preterm infants born at <33 weeks gestational age with and without culture-proven sepsis or necrotizing enterocolitis ≥ Stage 2.

This study was supported by the Canadian Institutes of Health Research Project Grant 2019 (201903PJT-420294-CA2-CAAA-245530), matched funding from the British Columbia Women's Health Foundation and start-up funding from the Women and Children's Health Research Institute, University of Alberta. The coordinating center in Toronto is funded by the Canadian Institutes of Health Research grant for the Canadian Preterm Birth Network (PBN 150642).

The need of the hour is to incorporate a rapid assay that could efficiently detect neonatal sepsis. We evaluated the diagnostic utility of 16SrRNA broad-range polymerase chain reaction (PCR) in neonatal sepsis.

The demographic and clinical details of 100 neonates clinically suspected to have sepsis were collected adopting pretested clinical proforma, followed by baseline laboratory investigations, including blood culture, complete blood counts, and C-reactive protein (CRP). Around, 0.2-0.3 ml of the EDTA blood was subjected to enrichment followed by DNA isolation using the modified spin column method. Based on the blood culture report, neonates were further divided into the suspected sepsis group (n = 50) and the confirmed sepsis group (n = 50). We performed 16SrRNA broad-range PCR to identify the presence of bacteria, and the results were analyzed statistically using SPSS software.

Neonates in both groups were found to have clinical parameters comparable to each other except for birth weight, length, and head circumference, which was found to be lower in the culture-positive group than in culture-negative group (p < 0.05). The diagnosis of neonatal sepsis by 16SrRNA broad-range PCR compared to blood culture revealed 100% sensitivity, 64% specificity, and 73.5% positive and 100% negative predictive value. The 18 cases detected positive by PCR had clinical and other diagnostic findings consistent with sepsis.

The 16SrRNA broad-range PCR effectively ruled out sepsis in 32 neonates within 8 h of sample collection compared to blood culture, which took 24 h. The method may not replace blood culture but can be used to complement it.

Neonatal sepsis represents a significant cause of morbidity and mortality among infants in healthcare settings. This study explored nurses' experiences in preventing and managing neonatal sepsis in the Tamale metropolis.

An exploratory, descriptive qualitative cross-sectional study design was used, and data was collected using semi-structured interviews. The sample size was determined at the point of data saturation of fifteen participants. Thematic analysis was employed to identify codes, subthemes, and themes within the interview transcripts.

Three major challenges nurses face in preventing and managing neonatal sepsis, including (1) the absence of a protocol for handling newborns upon admission, (2) an excessive workload that made it difficult for staff to follow infection prevention protocols, and (3) inadequate, obsolete and/or lack of equipment that caused devices to be overused. The nurses also identified critical psychological and emotional difficulties they encounter as a result of working within such a stressful environment. Other activities nurses conducted were handwashing before and after every procedure, infection prevention, and separating the babies in the incubator. In managing babies with neonatal sepsis, nurses provided daily treatment, hygiene care, and supported activities of living. The nurses also assert that the availability of resources, appropriate staff, and critical skills are important for preventing and managing neonatal sepsis.

The lack of basic working consumables like gloves, syringes, and needles, inadequate staff, and lack of defined protocol of care were identified as critical challenges that hamper the care provided in neonatal care units. Hospital authorities must focus attention on addressing the critical challenges faced by neonatal care units. Also, measures should be instituted to address the emotional and psychological concerns associated with nursing care. Future research must consider the level of influence of each of the challenges enumerated on nurses' overall health.

Antimicrobial resistance (AMR) is a global problem, which is particularly challenging in developing countries like India. This study attempts to determine the competencies of health care professionals and to update evidence-based policies to address AMR.

A survey-based educational interventional study was conducted using a validated structured survey and knowledge questionnaire under 3 domains through an antimicrobial stewardship program. Pooled data were analyzed using SPSS version 16.0.

Out of 58 participants, 53 (91%) have observed an increasing trend of multidrug-resistant infections over the last 5 years. There is a significant difference between the overall pretest mean scores (8.12 ± 2.10) and posttest mean scores (12.5 ± 1.49) of clinicians' knowledge with a mean difference of 4.38 ± 0.61, 95% CI of 5.003-3.92, t(57) = 16.62, P < .001).

The antimicrobial stewardship program was effective in improving the competencies of clinical physicians to improve antimicrobial prescribing and reduce AMR. Moreover, improving the knowledge and competencies among health care professionals will minimize neonatal morbidity and mortality.

Neonatal sepsis is a serious condition with high rates of morbidity and mortality, caused by the rapid growth of microorganisms that trigger a systemic reaction. Symptoms can range from mild to severe presentations. The causative microorganism is usually transmitted from mothers, especially from the urogenital tract, or can originate from the community or hospital.

Our retrospective study assessed 121 newborns, including both preterm and term infants, divided into three groups within the first 28 days of life: early-onset sepsis (35), late-onset sepsis (39), and a control group (47). Blood samples and cultures were obtained upon admission or at the onset of sepsis (at 24 and 72 hours). The study aimed to evaluate the limitations of commonly used biomarkers and new markers such as lactate dehydrogenase and ferritin in more accurately diagnosing neonatal sepsis.

Our study revealed a significant difference between the initial and final measures of lactate dehydrogenase (LDH) and ferritin in the early-onset sepsis (EOS) and late-onset sepsis (LOS) groups.

Ferritin and LDH may serve as potential markers associated with systemic response and sepsis in cases of both early and late-onset sepsis. Monitoring these biomarkers can aid in the timely detection and management of sepsis, potentially improving patient outcomes.

Neonatal sepsis, a bloodstream infection in the first 28 days of life, is a leading cause of morbidity and mortality among infants in both developing and developed countries. Additionally, sepsis is distinguished in neonates by unique pathophysiological and presentational factors relating to its development in immature neonatal immune systems. This review focuses on the current understanding of the mechanics and implications of neonatal sepsis, providing a comprehensive overview of the epidemiology, aetiology, pathophysiology, major risk factors, signs and symptoms and recent consensus on the diagnosis and management of both early-onset and late-onset neonatal sepsis. It also includes a discussion on novel biomarkers and upcoming treatment strategies for the condition as well as the potential of COVID-19 infection to progress to sepsis in infants.

Systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are comprehensive markers of inflammatory status. However, the correlation between SII and SIRI and the prevalence of cardiovascular disease (CVD) in populations with obesity remains unknown.

This is a cross-sectional study with data obtained from the National Health and Nutrition Examination Survey from 1999 to 2018. SII and SIRI were calculated using the following equations: SII = (platelet count × neutrophil count)/lymphocyte count. SIRI = (neutrophil count × monocyte count)/lymphocyte count. Spearman's rank correlation coefficient was used to assess the relationship between SII and SIRI and baseline variables. Logistic regression models and generalized additive model (GAM) with a spline smoothing function were used to evaluate the association between SIRI and CVD prevalence. Nomogram and receiver operating characteristic curve (ROC) analysis were used to assess the value of the risk prediction model.

A total of 17,261 participants with obesity and SII and SIRI publicly available data were used for this study. Multivariate logistic regression analysis revealed that SIRI, rather than SII, was an independent risk factor for CVD prevalence. For every standard deviation increase in SIRI, there was a 13%, 15%, and 28% increase in the odds ratios of CVD prevalence (OR = 1.13, 95% CI: 1.04-1.22, P = 0.01), coronary heart disease (OR = 1.15, 95% CI: 1.05-1.26, P = 0.002), and congestive heart failure (OR = 1.28, 95% CI: 1.16-1.41, P < 0.001). ROC results demonstrated that SIRI had a certain accuracy in predicting CVD prevalence (AUC = 0.604), especially when combined with other variables used in the nomogram (AUC = 0.828). The smooth curve fitting regression analysis demonstrated a significant linear association between the risk of SIRI and the odds ratio of CVD prevalence (P for nonlinear = 0.275).

SIRI is a relatively stable indicator of inflammation and is independently associated with the prevalence of CVD. It may serve as a novel inflammatory indicator to estimate CVD prevalence in populations with obesity.

Purpose: This study aimed to develop and validate a model for prediction of septic shock in neonates with sepsis. Materials and methods: This retrospective study included early-onset septic neonates in the Renmin Hospital of Wuhan University between January 2017 and June 2021. The neonates were divided into the training set and the validation set in a ratio of 7:3 and further categorized into septic shock group and none-shock group according to presence or absence of shock symptoms. Results: A total of 406 septic neonates were enrolled, including 217 in septic shock group. Sex (odds ratio [OR] = 0.092, 95% confidence interval [CI]: 0.012 to 0.683, P = 0.020), C-reactive protein at 6 h (OR = 8.475, 95% CI: 3.154 to 22.774, P < 0.001), serum amyloid A at 6 h (OR = 1.179, 95% CI: 1.094 to 1.269, P < 0.01), white blood cells at 6 h (OR = 0.173, 95% CI: 0.092 to 0.326, P < 0.001), platelets at 6 h (OR = 0.985, 95% CI: 0.975 to 0.995, P < 0.001), and Ca 2+ at 6 h (OR = 1.44 × 10 11 , 95% CI: 2.70 × 10 6 to 7.70 × 10 15 , P < 0.001) were identified as independent risk factors for septic shock and were further included in the nomogram. The areas under the receiver operator characteristic curve were 0.873 and 0.920 in training and validation sets, respectively. Conclusions: A predictive model for early diagnosis of septic shock in neonates was developed and initially validated in this study, allowing for timely intervention.

Clinical manifestations of neonatal sepsis are often unspecified. Therefore, sepsis biomarkers could be used to support diagnosis while waiting for blood culture results, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). The aim of this study was to evaluate the role of NLR and PLR as diagnostic markers in neonatal sepsis. A cross-sectional study was conducted at Haji Adam Malik General Hospital, Medan, Indonesia, from April to October 2019. This study included neonates aged less than 28 days, diagnosed with suspected sepsis, and had no previous history of antibiotics administration. Patients underwent clinical assessment, laboratory examination, and blood culture. Patients were grouped into sepsis and non-sepsis based on the blood culture results. The median hematological examination and the range of NLR and PLR in both the sepsis and non-sepsis groups were subjected to analysis using the Mann-Whitney U test to assess differences. NLR and PLR optimal cut-off values were determined using a receiver operator curve (ROC) with a confidence interval of 95%. A total of 137 neonates were enrolled, of which 49 were classified as sepsis and 89 as non-sepsis based on blood culture results. The optimal cutoff values for NLR and PLR were 2.75 and 11.73. Using those cutoff values, NLR and PLR could predict neonatal sepsis with sensitivities of 52.1% and 47.9%, specificities of 50.6% and 47.2%, area under the curve (AUC) of 0.46 and 0.47, with p=0.525 and p=0.662, respectively. Further investigation is warranted to refine the NLR and PLR utility and enhance diagnostic accuracy in clinical practices.

Neonatal sepsis remains one of the key challenges of neonatal medicine, and together with preterm birth, causes almost 50% of all deaths globally for children younger than 5 years. Compared with advances achieved for other serious neonatal and early childhood conditions globally, progress in reducing neonatal sepsis has been much slower, especially in low-resource settings that have the highest burden of neonatal sepsis morbidity and mortality. By contrast to sepsis in older patients, there is no universally accepted neonatal sepsis definition. This poses substantial challenges in clinical practice, research, and health-care management, and has direct practical implications, such as diagnostic inconsistency, heterogeneous data collection and surveillance, and inappropriate treatment, health-resource allocation, and education. As the clinical manifestation of neonatal sepsis is frequently non-specific and the current diagnostic standard blood culture has performance limitations, new improved diagnostic techniques are required to guide appropriate and warranted antimicrobial treatment. Although antimicrobial therapy and supportive care continue as principal components of neonatal sepsis therapy, refining basic neonatal care to prevent sepsis through education and quality improvement initiatives remains paramount.

Implementation of biomarkers in sepsis and septic shock in emergency situations, remains highly challenging. This viewpoint arose from a public-private 3-day workshop aiming to facilitate the transition of sepsis biomarkers into clinical practice. The authors consist of international academic researchers and clinician-scientists and industry experts who gathered (i) to identify current obstacles impeding biomarker research in sepsis, (ii) to outline the important milestones of the critical path of biomarker development and (iii) to discuss novel avenues in biomarker discovery and implementation. To define more appropriately the potential place of biomarkers in sepsis, a better understanding of sepsis pathophysiology is mandatory, in particular the sepsis patient's trajectory from the early inflammatory onset to the late persisting immunosuppression phase. This time-varying host response urges to develop time-resolved test to characterize persistence of immunological dysfunctions. Furthermore, age-related difference has to be considered between adult and paediatric septic patients. In this context, numerous barriers to biomarker adoption in practice, such as lack of consensus about diagnostic performances, the absence of strict recommendations for sepsis biomarker development, cost and resources implications, methodological validation challenges or limited awareness and education have been identified. Biomarker-guided interventions for sepsis to identify patients that would benefit more from therapy, such as sTREM-1-guided Nangibotide treatment or Adrenomedullin-guided Enibarcimab treatment, appear promising but require further evaluation. Artificial intelligence also has great potential in the sepsis biomarker discovery field through capability to analyse high volume complex data and identify complex multiparametric patient endotypes or trajectories. To conclude, biomarker development in sepsis requires (i) a comprehensive and multidisciplinary approach employing the most advanced analytical tools, (ii) the creation of a platform that collaboratively merges scientific and commercial needs and (iii) the support of an expedited regulatory approval process.

Background Sepsis poses a critical medical challenge due to its profound systemic inflammatory response, which frequently results in organ dysfunction and high mortality rates, especially in pediatric patients. The condition requires prompt recognition and aggressive management to mitigate its severe outcomes. Methods This prospective study enrolled 248 pediatric patients admitted with sepsis to the pediatric intensive care unit (PICU) at our tertiary care center. Patients were randomly assigned to either the C-reactive protein (CRP) or procalcitonin (PCT) groups, with biomarker levels measured upon admission (hour zero) and again at 72 hours post-admission. Clinical parameters such as the need for ionotropic support, use of steroids, incidence of acute kidney injury (AKI), requirement for invasive ventilation, patient outcomes, and changes in antibiotic management were assessed based on these biomarker levels. Results Procalcitonin-positive sepsis cases demonstrated notable clinical severity compared to their C-reactive protein counterparts, showing significantly lower systolic blood pressure (p = 0.012), heightened need for ionotropic support (p < 0.0001), and more pronounced liver and renal dysfunction as indicated by elevated serum bilirubin (p = 0.001) and creatinine levels (p = 0.0058). The incidence of AKI was also higher in procalcitonin-positive cases. Despite these severe clinical parameters, there were no significant differences in the length of the PICU stay or in patient outcomes concerning discharge and mortality rates. Procalcitonin levels effectively guided antibiotic management, resulting in therapy adjustments in a substantial proportion of cases, with 67 (54%) experiencing downgrades and 33 (27%) requiring upgrades based on procalcitonin levels measured 72 hours post-admission. Conclusion Procalcitonin proves to be a valuable biomarker in assessing the severity and management of sepsis in pediatric patients. It correlates significantly with clinical parameters such as blood pressure, the need for ionotropic support, and markers of organ dysfunction.

This study evaluates the role of D-dimer in identifying neonatal sepsis and their potential value in clinical decision-making due to challenges in early detection.

A case-control study was conducted on 102 neonates at the Children's Clinical Hospital "Louis Turcanu" in Timisoara, Romania, from October 2018 to July 2023. The participants were divided into two groups: those with neonatal sepsis and those without sepsis.

The study found that neonates with sepsis were more likely to be delivered by cesarean section and had higher rates of premature ruptured membranes compared to those without sepsis. The D-dimer biomarker's predictive value for sepsis was assessed using a receiver operating characteristic (ROC) curve, with an area under the curve (AUC) exceeding 0.982 and an optimum cutoff value of 342 ng/mL. An increase in neonatal D-dimer significantly increases the likelihood of sepsis by 2.7% per unit increase. A value above 250 ng/mL indicates a 127-fold increased likelihood of sepsis. The D-dimer's ability to predict mortality in newborns with sepsis is unsatisfactory, with an AUC of 0.528.

D-dimer, a potential biomarker of neonatal sepsis, warrants further clinical investigation to enhance diagnostic sensitivity and specificity, demonstrating its potential in conjunction with other sepsis markers.

To determine the factors associated with the procalcitonin levels in newborns with hypoxic-ischemic encephalopathy (HIE) who received therapeutic hypothermia (TH). The neonates, who had moderate/severe HIE and were treated with TH, were included. The neonates were arranged into 2 groups by procalcitonin (PCT) level after rewarming was completed. The neonates who had a procalcitonin level of < 2.5 ng/ml constituted Group 1 and the ones who had a procalcitonin level of ≥ 2.5 ng/ml constituted Group 2. Univariate and multivariate logistic regression was used to assess the factors related with PCT level. The first group included 123 (87.9%) neonates and the second group included 17 (12.1%) neonates. The median gestational age was 38 (36-39) weeks and the mean birth weight was 3081.7 ± 552.8 grams. In group 2, the rates for severe HIE, cesarean section, antibiotic switch, convulsion, inotrope use and mortality were higher, and duration of hospitalization was longer, whereas Apgar scores were lower (P < .05). The risk of a high procalcitonin level was found to be 6-fold (95% CI 1.9-19.1) higher in severe HIE and 5.2-fold higher (95% CI 1.7-16) in cesarean delivery. In neonates with HIE/TH, high post-rewarming procalcitonin levels were related with severe HIE and cesarean delivery. Some other clinical and laboratory findings, which may reflect worse clinical status, were also associated with high procalcitonin levels.

The moment of birth represents a complex physiological process that is followed by adaptive changes in the vital systems of the newborn. Such reactions have their positive but also negative effects. The aim of this research was to determine the difference in laboratory values of stress indicators in newborn children delivered by cesarean section (CS) with general and spinal anesthesia. We attempted to make a recommendation about the optimal type of anesthesia based on our results.

The study was performed on 150 healthy term newborns delivered by urgent or planned CS. Samples for adrenocorticotropic hormone (ACTH), cortisol, triglycerides, and interleukin-6 (IL-6) were analyzed.

Leukocyte numbers, triglycerides, and blood sugar values were normal for the newborns' age, with statistically significantly lower values of blood sugar and triglycerides in newborns delivered by CS in spinal anesthesia (p < 0.005) compared to general anesthesia. There were no significant differences in ACTH, cortisol, and IL-6 levels between those newborns delivered via CS after spinal or general anesthesia.

In cases where vaginal delivery is not possible, when CS is indicated, the use of well-controlled spinal anesthesia is followed by lower degrees of metabolic, inflammatory, and stress responses and better vitality of the baby upon birth.

Patients with ankylosing spondylitis (AS) frequently suffer from comorbid sleep disorders, exacerbating the burden of the disease and affecting their quality of life.

To investigate the clinical significance of serum inflammatory factors, health index and disease activity scores in patients with AS complicated by sleep disorders.

A total of 106 AS patients with comorbid sleep disorders were included in the study. The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes. The serum levels of inflammatory factors, including C-reactive protein, erythrocyte sedimentation rate, interleukin (IL)-6, tumour necrosis factor-α and IL-1β, were measured. Disease activity scores, such as the Bath AS functional index, Bath AS disease activity index, Bath AS metrology index and AS disease activity score, were assessed. The health index was obtained through the Short Form-36 questionnaire.

The study found significant associations amongst serum inflammatory factors, health index and disease activity scores in AS patients with comorbid sleep disorders. Positive correlations were found between serum inflammatory factors and disease activity scores, indicating the influence of heightened systemic inflammation on disease severity and functional impairment. Conversely, negative correlations were found between disease activity scores and health index parameters, highlighting the effect of disease activity on various aspects of health-related quality of life. Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes, underscoring their potential utility in risk assessment and prognostication.

The findings demonstrate the intricate interplay amongst disease activity, systemic inflammation and patient-reported health outcomes in AS patients complicated by sleep disorders. The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors, health index and disease activity scores as prognostic markers in this patient population.

Neonatal sepsis is associated with significant mortality and morbidity. Low-middle-income countries are disproportionately affected, but late-onset sepsis (LOS) still occurs in up to 20% of infants <28 weeks in high-income countries. Understanding site-specific data is vital to guide management.

A retrospective cohort study was conducted at King Edward Memorial Hospital (KEMH), Perth. Infants admitted between January 2012 and June 2022 were included. Data were extracted from routine electronic databases. Incidence and aetiology of sepsis were determined and the association of sepsis with neonatal outcomes analysed.

During the study period, 23,395 newborns were admitted with a median gestation of 37 weeks and birth weight of 2,800 g. There were 370 sepsis episodes in 350 infants; 102 were early-onset sepsis (EOS) (1.6 per 1,000 live births), predominantly Streptococcus agalactiae (35, 34.3%) and Escherichia coli (27, 26.5%); 268 were LOS (0.9 per 1,000 inpatient days), predominantly coagulase-negative staphylococci (CONS) (156, 57.6%) and E. coli (30, 11.1%). The incidence of LOS declined from 2012 to 2022 (p = 0.002). Infants with EOS had increased brain injury (25.7% vs. 4.1%; p = 0.002) and mortality (18.8% vs. 1.6%; p < 0.001). Those with LOS had increased hospital stay (median 95 vs. 15 days; p < 0.001), mortality (15.3% vs. 1.6%; p = 0.018), necrotising enterocolitis (NEC) (7.4% vs. 0.5%; p < 0.001), and chronic lung disease (CLD) (58.1% vs. 5.9%; p = 0.005). Infants <28 weeks with sepsis were at increased risk of neurodevelopmental impairment compared to those without infection (43.2% vs. 30.9%, p = 0.027).

While we observed a reduction in LOS incidence, sepsis remains associated with higher mortality, and in survivors with longer hospital stay and increased risk of brain injury, NEC, CLD, and neurodevelopmental impairment.

Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) sham, 2) sepsis (cecal ligation and puncture) without subsequent resuscitation, and 3) sepsis with lactated Ringer plus norepinephrine resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output and glomerular filtration rate were measured noninvasively. Mean arterial pressure, total renal blood flow, cortical perfusion, medullary perfusion, and medullary tissue oxygen tension (mtPO 2 ) were determined for 12 h. Cecal ligation and puncture decreased mean arterial pressure and cardiac output by more than 50%, with a proportional increase in renal vascular resistance and a 60-80% reduction in renal blood flow, cortical perfusion, medullary perfusion, and mtPO 2 compared to sham. Cecal ligation and puncture also decreased glomerular filtration rate by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO 2 , changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to cecal ligation and puncture develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury.

Stem cell therapy may prevent late-onset sepsis (LOS) via antimicrobial peptide LL37 secretion and regulatory T cell (Treg) regulation. The early prediction of LOS is still a challenge. This study evaluated whether immunological state of LL37 or Tregs precedes LOS. We firstly analyzed the LL37 level, Treg proportion, and LOS incidence in very preterm infants treated with autologous cord blood mononuclear cells (ACBMNCs) in our previous trial. Then, we constructed a prediction model and built validation cohort. We found ACBMNC intervention reduced the incidence of LOS from 27.3% to 6.9% (p = 0.021). LL37 and Treg abundances were higher in the ACBMNCs group. The nomogram demonstrated that early-life Treg and LL37 characteristics were closely associated with LOS (area under the curve, AUC 0.936), with implications for early prediction and timely clinical management. This composite model was also helpful to evaluate the beneficial effect of ACBMNCs intervention on LOS, thus promoting translational research.

This retrospective cohort study aimed to assess the utility of maternal C-reactive protein (CRP) and leukocyte levels in predicting neonatal sepsis after preterm premature rupture of membranes (pPROM).

We conducted a retrospective cohort study (2009-2021), encompassing preterm infants born ≤29 + 6 weeks of gestation following pPROM. The primary outcome was early-onset neonatal sepsis within the initial 72 h of life.

We analysed data from 706 patients with a median gestational age at pPROM of 25.1 weeks and a median gestational age at birth of 26.4 weeks. Overall survival rate was 86.1%, with 65.7% survival without severe morbidities. These rates were significantly worse in preterm infants with sepsis. Maternal CRP and leukocyte levels correlated significantly with neonatal infection markers and sepsis. However, their predictive values, correlation coefficients, and area under the curve values were generally low. Using maternal CRP ≥2 mg/dL to predict neonatal sepsis yielded a positive predictive value of 18.5%, negative predictive value of 91.5%, AUC of 0.589, 45.5% sensitivity, and 74.5% specificity.

Maternal CRP and leukocyte levels were ineffective as a tool for predicting early-onset neonatal sepsis following early pPROM. Consequently, these biomarkers lack the reliability required for clinical decision-making in this context.

To assess Gram-positive bacterial (GPB) bloodstream infection (BSI) in neonates, covering incidence, morbidity, mortality, antimicrobial resistance patterns and biomarkers in Region Stockholm, Sweden between 2006 and 2016.

A population-based retrospective epidemiological study including infants with GPB-BSI, admitted to the neonatal units at Karolinska University Hospital (KUH). Data were collected from patient records, the Swedish Neonatal Quality Register, the microbiological laboratory at KUH and the Swedish Public Health Agency.

We identified 357 infants with GPB-BSI, representing an incidence of 1.47/1000 live births (LB). Group B streptococcus (GBS) was the most common pathogen causing BSI in full-term infants and early-onset sepsis (EOS) (0.20/1000 LB), while coagulase-negative staphylococci (CoNS) were predominant in infants born very preterm and in late-onset sepsis (LOS) (0.79/1000 LB). There were no fatal GBS BSI cases, but 10.2% developed meningitis. The GPB case fatality rate was 9.5% and the sepsis fatality rate 2.8%. In GPB-BSI, 1/10 did not have an elevated C-reactive protein level. Staphylococcus aureus (S. aureus) BSI increased during the study period, but no methicillin or vancomycin resistant strains were found. The antimicrobial resistance (AMR) rate was highest in CoNS isolates.

GPB-BSI was four times more common than Gram-negative BSI in neonates but resulted in lower mortality rate. GBS was the most common pathogen in full-term infants and in EOS. CoNS was the most common pathogen in LOS and infants born very preterm, and the AMR rate was high in these isolates. The increasing trend of S. aureus BSI indicates a need of further investigation.

This prospective study investigated the association between elevated neutrophil-to-monocyte ratio (NMR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP), procalcitonin, and tumor necrosis factor-alpha (TNF-alpha) and the risk of developing neurological complications in mechanically ventilated neonates. The aim was to evaluate these biomarkers' predictive value for neurological complications. Within a one-year period from January to December 2022, this research encompassed neonates born at ≥35 weeks of gestational age who required mechanical ventilation in the neonatal intensive care unit (NICU) from the first day of life. Biomarkers were measured within the first 24 h and at 72 h. Sensitivity, specificity, and area under the curve (AUC) values were calculated for each biomarker to establish the best cutoff values for predicting neurological complications. The final analysis included a total of 85 newborns, of which 26 developed neurological complications and 59 without such complications. Among the studied biomarkers, TNF-alpha at >12.8 pg/mL in the first 24 h demonstrated the highest predictive value for neurological complications, with a sensitivity of 82%, specificity of 69%, and the highest AUC (0.574, p = 0.005). At 72 h, TNF-alpha levels greater than 14.3 pg/mL showed further increased predictive accuracy (sensitivity of 87%, specificity of 72%, AUC of 0.593, p < 0.001). The NMR also emerged as a significant predictor, with a cutoff value of >5.3 yielding a sensitivity of 78% and specificity of 67% (AUC of 0.562, p = 0.029) at 24 h, and a cutoff of >6.1 showing a sensitivity of 76% and specificity of 68% (AUC of 0.567, p = 0.025) at 72 h. Conversely, CRP and procalcitonin showed limited predictive value at both time points. This study identifies TNF-alpha and NMR as robust early predictors of neurological complications in mechanically ventilated neonates, underscoring their potential utility in guiding early intervention strategies. These findings highlight the importance of incorporating specific biomarker monitoring in the clinical management of at-risk neonates to mitigate the incidence of neurological complications.

Neonatal sepsis, a formidable threat to newborns, is a leading cause of neonatal mortality, with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning. Pneumonia, a prevalent sepsis presentation, poses a significant risk, especially during the neonatal phase when lung defenses are compromised. Accurate diagnosis of pneumonia is imperative for timely and effective interventions. Saliva, a minimally invasive diagnostic medium, holds great promise for evaluating infections, especially in infants.

To investigate the potential of serum C-reactive protein (CRP), salivary CRP (sCRP), and mean platelet volume (MPV) as diagnostic markers for late-onset neonatal pneumonia (LONP).

Eighty full-term neonates were systematically examined, considering anthropometric measurements, clinical manifestations, radiology findings, and essential biomarkers, including serum CRP, sCRP, and MPV.

The study reveals noteworthy distinctions in serum CRP levels, MPV, and the serum CRP/MPV ratio between neonates with LONP and healthy controls. MPV exhibited a robust discriminatory ability [area under the curve (AUC) = 0.87] with high sensitivity and specificity at a cutoff value of > 8.8. Correlations between serum CRP, sCRP, and MPV were also identified. Notably, sCRP demonstrated excellent predictive value for serum CRP levels (AUC = 0.89), underscoring its potential as a diagnostic tool.

This study underscores the diagnostic promise of salivary and serum biomarkers, specifically MPV and CRP, in identifying and predicting LONP among neonates. These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.

Sepsis is a serious disease caused by an impaired host immune response to infection, resulting in organ dysfunction, tissue damage and is responsible for high in-hospital mortality (approximately 20%). Recently, WHO documented sepsis as a global health priority. Nevertheless, there is still no effective and specific therapy for clinically detecting sepsis. Nanomaterial-based approaches have appeared as promising tools for identifying bacterial infections. In this review, recent biosensors are introduced and summarized as nanomaterial-based platforms for sepsis management and severe complications. Biosensors can be used as tools for the diagnosis and treatment of sepsis and as nanocarriers for drug delivery. In general, diagnostic methods for sepsis-associated bacteria, biosensors developed for this purpose are presented in detail, and their strengths and weaknesses are discussed. In other words, readers of this article will gain a comprehensive understanding of biosensors and their applications in sepsis management.

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum and hematological biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM) and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided into two groups: group A, with PROM ≥ 18 h, and group B, with ROM < 18 h. Both groups were further split into subgroups: proven sepsis, presumed sepsis, and no sepsis. Descriptive statistics, analysis of variance (ANOVA) and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cell count from the first (p = 0.005) and third day (p = 0.028), and high C-reactive protein (CRP) values from the first day (p = 0.004). Procalcitonin (area under the curve-AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early-onset neonatal sepsis. (4) Conclusions: Our results outline the feasibility of using procalcitonin and CRP measured on the first day taken individually in order to increase the detection rate of early-onset neonatal sepsis, in the absence of positive blood culture.

Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combine multi-parameter flow cytometry, single-cell RNA sequencing and plasma analysis to longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identify a dynamically changing blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and myeloid cell HLA-DR expression, which characterizes sepsis even when the common clinical marker of inflammation, C-reactive protein, is not elevated. Furthermore, single-cell RNA sequencing identifies upregulation of amphiregulin in leukocyte populations during sepsis, which we validate as a plasma analyte that correlates with clinical signs of disease, even when C-reactive protein is normal. This study provides insights into immune pathways associated with early-life sepsis and identifies immune analytes as potential diagnostic adjuncts to standard tests to guide targeted antibiotic prescribing.

Interleukins (ILs) are signaling molecules that are crucial in regulating immune responses during infectious diseases. Pro-inflammatory ILs contribute to the activation and recruitment of immune cells, whereas anti-inflammatory ILs help to suppress excessive inflammation and promote tissue repair. Here, we provide a comprehensive overview of the role of pro-inflammatory and anti-inflammatory ILs in infectious diseases, with a focus on the mechanisms underlying their effects, their diagnostic and therapeutic potential, and emerging trends in IL-based therapies.

The expression "developmental hemostasis" indicates the age-related physiological changes occurring during the maturational process of the hemostatic system. Despite the quantitative and qualitative alterations, the neonatal hemostatic system is competent and well-balanced. Conventional coagulation tests do not provide reliable information as they only explore the procoagulants during the neonatal period. In contrast, viscoelastic coagulation tests (VCTs), such as viscoelastic coagulation monitoring (VCM), thromboelastography (TEG or ClotPro), and rotational thromboelastometry (ROTEM), are point-of-care assays that provide a quick, dynamic and global view of the hemostatic process, allowing prompt and individualized therapeutic intervention when necessary. Their use in neonatal care is on the increase and they could help monitor patients at risk of hemostatic derangement. In addition, they are crucial for anticoagulation monitoring during extracorporeal membrane oxygenation. Moreover, implementing VCT-based monitoring could optimize blood product use.

The purpose of the network meta-analysis was to make a more comprehensive comparison of different interleukins in the detection of neonatal sepsis and to pose clues in the field of clinical practice.

Electronic databases of PubMed, Web of Science and Embase were systematically searched. Eligible studies included diagnostic tests utilizing interleukins to detect neonatal sepsis. We calculated pooled sensitivity, specificity, positive Likelihood Ratio (PLR) and negative Likelihood Ratio (NLR), diagnostic odds ratio (DOR), and superiority index.

Fifteen studies including 1,369 neonates diagnosed of sepsis were included in this meta-analysis. For the detection of early-onset sepsis in neonates, the pooled sensitivity was 0.91 (95% CI: 0.81, 0.97; I2 = 0%, p = 0.946) and the pooled specificity was 0.98 (95% CI: 0.87, 0.97; I2 = 46.3%, p = 0.172) for IL-8. For the detection of late-onset sepsis in neonates. the sensitivity was 0.96 (95% CI: 0.85, 1.00; I2 = NA, p = NA) and the pooled specificity was 1.00 (95% CI: 0.92, 1.00; I2 = NA, p = NA) for IL-27. Results of ANOVA model revealed that the superiority index of IL-6, IL-8, IL-10, and IL-27 were 1.20 (0.14, 5.00), 5.14 (0.33, 7.00), 0.75 (0.14, 5.00), and 1.31 (0.14, 5.00) in the detection of early-onset neonatal sepsis. Superiority index of IL-8, IL-10, and IL-27 were 1.84 (0.20, 5.00), 1.04 (0.20, 5.00), and 2.21 (0.20, 5.00) in the detection of late-onset neonatal sepsis.

Findings of this network meta-analysis suggest that interleukins including IL-6, IL-8, IL-10, and IL-27 may have favorable performance in the detection of neonatal sepsis. IL-8 was more accurate in the detection of early-onset sepsis in neonates. IL-27 was more accurate in the detection of late-onset neonatal sepsis.

In fetal/neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies against paternal human platelet antigens (HPA) cross the placenta and lead to platelet destruction. The extent of thrombocytopenia varies among neonates, and inflammation may constitute an important trigger. A set of stable inflammatory markers was measured in serum samples from neonates with low platelet counts, of which n = 50 were diagnosed with FNAIT due to anti-HPA-1a antibodies and n = 50 were thrombocytopenic without detectable maternal HPA antibodies. Concentrations of C-reactive protein, soluble CD14, procalcitonin, and sFlt-1 did not differ between the two cohorts. There was no correlation between C-reactive protein or soluble CD14 and the platelet count, but a negative correlation between procalcitonin concentrations and the neonatal platelet count in both cohorts. sFlt-1 concentration and the platelet count were correlated in FNAIT cases exclusively. None of the inflammatory markers was statistically different between cases with and without intracranial haemorrhage. We were unable to identify systemic inflammation as a relevant factor for thrombocytopenia in FNAIT. The antiangiogenic enzyme sFlt-1, released by the placenta, did correlate with the platelet count in FNAIT cases. Our findings may give rise to the hypothesis that placental inflammation rather than systemic inflammation modulates disease severity in FNAIT.

Neonatal sepsis is a life-threatening condition associated with significant morbidity and mortality. Sepsis-induced coagulopathy is a well-recognized entity, signifying the strong cross-talk between inflammation and coagulation. The aim of the present study was to compare the coagulation profile between the acute phase of sepsis and recovery in term and preterm neonates. Additional comparisons to healthy neonates were undertaken. Levels of clotting, anti-clotting factors and ADAMTS-13 (A disintegrin and metalloprotease with thrombospondin type-1 motives), the cleaving protein of von Willebrand factor (VWF), were measured in 16 term and preterm neonates in the acute phase of infection and following recovery, as well as in 18 healthy neonates. Clotting times were prolonged, while levels of particular clotting factors were lower in the acute phase of infection compared to controls and recovery. On the other hand, levels of fibrinogen, factor VIII (FVIII) and VWF were significantly higher in the acute phase in comparison to controls and recovery, while they remained persistently higher in the infection group compared to controls. In regard to the anticlotting mechanism, a clear suppression was observed in septic neonates. ADAMTS-13 levels were significantly lower in the acute phase of infection in comparison to controls and recovery (p = 0.015 and 0.004, respectively), while a trend toward superimposed normalization was demonstrated post infection, as higher ADAMTS-13 levels were measured in recovered neonates compared to controls (p = 0.002). The coagulation profile is considerably deranged in neonatal sepsis. ADAMTS-13 deficiency in septic neonates is a novel finding with promising future implications, as ADAMTS-13 substitution may serve as a useful therapeutic option in neonatal sepsis, prompting further investigation in future studies.

To develop a C-reactive protein-to-albumin ratio (CAR)-based nomogram for predicting the risk of in-hospital death in sepsis patients. Sepsis patients were selected from the MIMIC-IV database. Independent predictors were determined by multiple Cox analysis and then integrated to predict survival. The performance of the model was evaluated using the concordance index (C-index), receiver operating characteristic curve (ROC) analysis, and calibration curve. The risk stratifications analysis and subgroup analysis of the model in overall survival (OS) were assessed by Kaplan-Meier (K-M) curves. A total of 6414 sepsis patients were included. C-index of the CAR-based model was 0.917 [standard error (SE): 0.112] for the training set and 0.935 (SE: 0.010) for the validation set. The ROC curve analysis showed that the area under the curve (AUC) of the nomogram was 0.881 in the training set and 0.801 in the validation set. And the calibration curve showed that the nomogram performs well in both the training and validation sets. K-M curves indicated that patients with high CAR had significantly higher in-hospital mortality than those with low CAR. The CAR-based model has considerably high accuracy for predicting the OS of sepsis patients.

There are approximately 1.3 million cases of neonatal sepsis reported worldwide with deaths occurring more commonly in preterm and low-weight newborns. Neonatal sepsis is the third major cause of neonatal deaths resulting in 203,000 deaths per year. It is divided into two subtypes based on time of occurrence: early-onset neonatal sepsis (ENS), occurring within the first 72 hours of birth usually due to perinatal risk factors, and late-onset neonatal sepsis (LOS) usually occurring after the first week of life and up to 28th day of life. There are many complications associated with neonatal sepsis including septic shock, multiple organ failure, and death. It is vital for clinicians to know the signs and symptoms of neonatal sepsis in order to diagnose it early. Preventive measures, early diagnosis, appropriate antibiotic administration, timely supportive management, and the establishment of efficient management are vital in the prevention of severe complications or death. In this review, we aim to provide the most up-to-date information regarding risk factors, pathophysiology, signs and symptoms, diagnosis, and treatment of neonatal sepsis. We discuss the maternal and neonatal risk factors involved in the pathogenesis of neonatal sepsis and the signs and symptoms of early and late neonatal sepsis. We focus on the different pathogens involved and the markers used in the diagnosis and treatments available for each.