Sepsis affects approximately 50 million people worldwide, resulting in 11 million deaths annually. Conflicting results and insufficient evidence comparing performance biomarkers exist. The study aimed to comprehensively compare available biomarkers and clinical scores for detecting sepsis since its redefinition in 2016 with this systematic review and Bayesian diagnostic test accuracy network meta-analysis.

We conducted searches in the PubMed, EMBASE, and Scopus databases between January 2016 and December 2023. Eligible studies assessed the diagnostic accuracies of biomarkers, the quick Sequential Organ Failure Assessment (qSOFA) score, or Systemic Inflammatory Response Syndrome (SIRS) criteria in detecting sepsis. Bivariate hierarchical random effects arm-based beta-binomial models were used for quantitative synthesis (PROSPERO Registration Number: CRD42018086545).

We included 78 studies representing 34,234 patients and compared qSOFA score, SIRS criteria alongside seven of the most studied biomarkers: procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), presepsin (cluster of differentiation 14 subtypes), CD64, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), and lipopolysaccharide-binding protein (LBP). CD64 demonstrated the highest superiority index, followed by sTREM-1 and presepsin (diagnostic odds ratio: 20.17 vs 18.73 and 10.04, 95 % credible interval [CrI]: 8.39-38.61 vs 1.31-83.98 and 6.71-14.24; quality of evidence: moderate vs low and low). Multivariable meta-regression analysis identified significant sources of heterogeneity, including study design, proportion of sepsis, sample size, and the risk of bias (patient selection).

The best diagnostic accuracy for sepsis was shown by CD64, with a moderate quality of evidence. Compared to CD64, sTREM-1 and presepsin provided suboptimal and low evidence. These biomarkers were more effective at identifying updated sepsis than clinical scores. We recommend re-considering the addition of biomarkers in screening for sepsis or sepsis-related conditions, as this could lead to more accurate and timely decisions for future clinical interventions.

Inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are often elevated in liver cancer, making it difficult to monitor for bacterial infection. Hence, it is tempting to use more bacterial-specific sepsis markers such as procalcitonin (PCT) during immunosuppressive chemotherapy. This case study highlights the challenges of interpreting clinical chemistry sepsis biomarkers in patients with advanced cholangiocarcinoma (CCA).

A 55-year-old man presented with a liver mass on routine ultrasonography. MRI and CT showed multiple liver and bone metastases. The immunohistochemistry findings were consistent with an adenocarcinoma of the pancreaticobiliary system. After the diagnosis of primary hepatic CCA (NTM stage IV; FGFR2-SHROOM3 translocation) and 14 months of chemotherapy, the patient developed progressive liver lesions and new lung metastases.

During the last chemotherapy, PCT was highly elevated (>100 ng/mL), usually observed in severe sepsis or septic shock, whereas CRP was moderately elevated (<50 mg/L). The patient had mild leukopenia but no fever, systemic infection or septic shock. Blood and urine cultures were negative.

After referral to best supportive care, the patient died of liver failure. Retrospective blood analysis revealed high levels of soluble CD14 subtype, a bacterial sepsis marker known as presepsin. Calcitonin and IL-6 levels were above normal, consistent with advanced CCA, but not with a PCT/calcitonin-secreting tumor or systemic inflammation.

Oncologists are aware that CRP and IL-6 values can be elevated in liver cancer. Here, we further demonstrate that highly elevated, septic shock-like PCT values can occur even in the absence of bacterial sepsis. In addition, presepsin may be elevated, although mechanistically unrelated to PCT. Therefore, sepsis markers should be interpreted with caution and in the clinical context, not only in patients with neuroendocrine or hepatocellular carcinoma, which are known to secrete PCT and calcitonin, but also in patients with advanced CCA.

Community-acquired Roseomonas mucosa sepsis can lead to significant morbidity and mortality if not diagnosed promptly. We report a case of a 59-year-old woman with community-acquired Roseomonas mucosa sepsis who presented with persistent fever progressing to septic shock, despite repeatedly negative host-response biomarker results. Initial metagenomic analysis of peripheral blood suggested Pseudomonas aeruginosa infection. However, a peripheral blood culture identified Roseomonas mucosa as the causative pathogen. She was cured after switching to meropenem according to blood cultures and antimicrobial susceptibility testing.

Sepsis is a prevalent and critical condition triggered by an exaggerated immune response to specific infectious agents. The classification of the severity of sepsis plays a fundamental role in early identification and structured management, aiding in the prediction of increased risk of mortality. Despite the utilization of numerous biomarkers in sepsis diagnosis and treatment guidance, the early identification and prediction of sepsis still pose significant challenges.

To assess the prognostic value of vasoactive-inotropic score (VIS), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and 6 h blood lactate after admission in adult sepsis patients.

177 adult sepsis patients were enrolled in a cross-sectional study. Based on their 28-day outcome upon admission, patients were divided into a death group (n = 52) and a survival group (n = 125). Clinical data from both groups were collected. Univariate analysis and binary logistic regression were employed to identify independent risk factors for poor prognosis in adult sepsis patients. Receiver operating characteristic curve (ROC) analysis was performed to determine the predictive value of VIS, NT-proBNP, and blood lactate level at 6 h after admission for adult sepsis patients. Kaplan-Meier method was utilized to analyze the relationship between VIS, NT-proBNP, blood lactate level at 6 h after admission, and survival prognosis among adult sepsis patients.

1. VIS (OR: 7.117; 95 % CI: 1.648-30.738; P = 0.009), NT-proBNP (OR: 1.296; 95 % CI: 1.026-1.637; P = 0.030), SOFA score (OR:1.232; 95 % CI: 1.031-1.473; P = 0. 02) and blood lactate at 6 h after admission (OR: 3.484; 95 % CI: l.416-8.573; p = 0.007) were independent risk factors for poor prognosis of adult sepsis. 2. VIS, NT-proBNP, and blood lactate at 6 h after admission were positively correlated with SOFA scores (r = 0 0.255, 0.388, and 0.l89 respectively, P < 0.05). 3. ROC curve analysis showed that the area under the curve (AUC) of VIS, NT-proBNP, and blood lactate at 6 h after admission for predicting poor prognosis in adult sepsis patients was 0.673, 0.790, and 0.702 respectively. When the cut-off values were 3.86, l.69,and 3.35, the sensitivity was 40.5 %, 71.8 %, and 59.3 %, the specificity was88.2 %, 65.8 %, and 72.9 %, and the Youden index was 0.288, 0.501, and 0.324, respectively. 3. Kaplan-Meier analysis revealed statistically significant differences in survival prognosis between patients with VIS >1.69 and VIS ≤1.69 (Log-rank χ2 = 18.404, P < 0.001), NT-proBNP >3.86 and NT-proBNP ≤3.86 (Log-rank χ2 = 38.282, P < 0.001), as well as blood lactate >3.35 and blood lactic acid ≤3.35 after a duration of 6 h from admission (Log-rank χ2 = 11.776, P < 0.001).

VIS, NT-proBNP, and blood lactic acid levels 6 h post-admission independently contributed to the poor prognosis observed in adult sepsis patients; thus serving as valuable prognostic indicators for this population.

Sepsis and septic shock are common conditions evaluated and managed in the emergency department (ED), and these conditions are associated with significant morbidity and mortality. There have been several recent updates in the literature, including guidelines, on the evaluation and diagnosis of sepsis and septic shock.

This is the first paper in a two-part series that provides emergency clinicians with evidence-based updates concerning sepsis and septic shock. This first paper focuses on evaluation and diagnosis of sepsis and septic shock.

The evaluation, diagnosis, and management of sepsis have evolved since the first definition in 1991. Current guidelines emphasize rapid diagnosis to improve patient outcomes. However, scoring systems have conflicting data for diagnosis, and sepsis should be considered in any patient with infection and abnormal vital signs, evidence of systemic inflammation (e.g., elevated white blood cell count or C-reactive protein), or evidence of end-organ dysfunction. The clinician should consider septic shock in any patient with infection and hypotension despite volume resuscitation or who require vasopressors to maintain a mean arterial pressure ≥ 65 mmHg. There are a variety of sources of sepsis but the most common include pulmonary, urinary tract, abdomen, and skin/soft tissue. Examples of other less common etiologies include the central nervous system (e.g., meningitis, encephalitis), spine (e.g., spinal epidural abscess, osteomyelitis), cardiac (e.g., endocarditis), and joints (e.g., septic arthritis). Evaluation may include biomarkers such as procalcitonin, C-reactive protein, and lactate, but these should not be used in isolation to exclude sepsis. Imaging is a key component of evaluation and should be based on the suspected source.

There have been several recent updates in the literature including guidelines concerning sepsis and septic shock; an understanding of these updates can assist emergency clinicians and improve the care of these patients.

Antibiotic overtreatment in infants is a significant problem, due to lack of accurate diagnostic tools for late-onset neonatal sepsis (LONS). We aimed to investigate the diagnostic accuracy of presepsin for LONS at initial suspicion.

In this multicenter prospective observational cohort study, we consecutively included all term and preterm infants who started on antibiotics empirically for a nosocomial LONS suspicion. Presepsin concentrations were determined at initial LONS suspicion before antibiotic initiation (t = 0), and 12 and 24 h afterwards. Diagnostic accuracy measures for LONS were calculated.

A total of 63 episodes of suspected LONS (32 classified as LONS, including 23 culture-positive and 9 culture-negative episodes) in 50 infants were included. Presepsin concentrations were significantly higher in LONS cases compared with non-LONS at all time-points. The AUC for all LONS cases at t = 0 was 0.77 (95% CI 0.66-0.89) and 0.80 (95% CI 0.67-0.92) for culture-positive LONS cases only.

Presepsin seems to have insufficient accuracy as single biomarker to serve as a biomarker for ruling out LONS in infants suspected of LONS. Future larger studies are warranted to validate our findings and to investigate the clinical impact of presepsin, in combination with other biomarkers, as diagnostic tool to facilitate decision-making regarding the initiation of antibiotics, thereby supporting antibiotic stewardship.

Presepsin seems to have insufficient accuracy as single biomarker for the decision to treat or not at initial suspicion of late-onset neonatal sepsis. This is the first prospective observational cohort study on the diagnostic accuracy of presepsin for late-onset neonatal sepsis consecutively recruiting all infants suspected of late-onset neonatal sepsis, minimizing bias. Future larger studies are warranted to investigate the clinical impact of presepsin in facilitating decision-making regarding the initiation of antibiotics in infants, thereby supporting antibiotic stewardship.

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.

Procalcitonin is a useful biomarker for infection. Over the past two decades, there has been much research on the clinical applications of procalcitonin, yet the majority of these studies have been conducted in the intensive care setting. Despite the extensive use of procalcitonin in emergency departments, there have been no guidelines focusing specifically on these clinical settings. Additionally, previous guidelines were predominantly shaped by expert consensus and rarely incorporate evidence-based medicine concepts. To address these shortcomings, the current guideline adopts a novel approach. Initially, we identified the most critical questions regarding the use of procalcitonin in emergency settings through expert voting. This was followed by a systematic literature review and the evaluation of evidence levels using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. Key characteristics of individual studies will be summarized and evaluated by the guideline development group to determine the overall quality of evidence. The GRADE working group's categorization system will be employed to rate evidence quality into four levels. Recommendations will be formulated based on explicit consideration of established criteria. This structured approach ensures that guideline recommendations are founded on robust evidence and transparently assessed for strength and potential caveats. This is the first guideline on the use of procalcitonin to be applied in emergency departments that adopts the principles of evidence-based medicine and encompasses the up-to-date literatures, and it marks an advancement in providing guidance on the utilization of procalcitonin in emergency departments.

Diagnosing bacterial infections (BI) in patients with cirrhosis can be challenging because of unclear symptoms, low diagnostic accuracy, and lengthy culture testing times. Various biomarkers have been studied, including serum procalcitonin (PCT) and presepsin. However, the diagnostic performance of these markers remains unclear, requiring further informative studies to ascertain their diagnostic value.

To evaluate the pooled diagnostic performance of PCT and presepsin in detecting BI among patients with cirrhosis.

We performed a systematic search of the MEDLINE, EMBASE, and Scopus databases for studies that evaluated the diagnostic role of PCT and presepsin from inception to June 2024. Sensitivity and specificity values were pooled using a random effects model. BI was diagnosed based on clinical manifestations, physical examination, laboratory data, and radiological findings.

Of the 6639 articles retrieved, 28 met the inclusion criteria and included 4287 patients with 1789 cases of BI (41.7%). The bivariate pooled sensitivity and specificity estimates of PCT for BI diagnosis were 0.73 [95% confidence interval (CI): 0.64-0.81] and 0.83 (95%CI: 0.79-0.87), respectively. The diagnostic odds ratio (DOR) of PCT was 17.21 (95%CI: 9.57-30.95). Presepsin showed a pooled sensitivity of 0.75 (95%CI: 0.60-0.86), specificity of 0.80 (95%CI: 0.68-0.88), and DOR of 12.33 (95%CI: 5.10-29.83) for diagnosing BI. The pooled sensitivity and specificity of PCT for diagnosing spontaneous bacterial peritonitis (SBP) were 0.76 (95%CI: 0.67-0.84) and 0.87 (95%CI: 0.78-0.92), respectively. The positive likelihood ratio of PCT was 5.57 (95%CI: 3.34-9.29), which was sufficiently indicative of SBP. The DOR of PCT was 29.50 (95%CI: 12.30-70.80).

PCT and presepsin have high sensitivity and specificity for detecting BI in patients with cirrhosis. Furthermore, PCT has good diagnostic value as a rule-in test for SBP diagnosis.

Sepsis is a global health challenge, characterized by a dysregulated immune response, leading to organ dysfunction and death. Despite advances in medical care, sepsis continues to claim a significant toll on human lives, with mortality rates from 10-25% for sepsis and 30-50% for septic shock, making it a leading cause of death worldwide. Current diagnostic methods rely on clinical signs, laboratory parameters, or microbial cultures and suffer from delays and inaccuracies. Therefore, there is a pressing need for novel diagnostic tools that can rapidly and accurately identify sepsis. This review highlights advances in biosensor development that could ultimately lead to faster and more accurate sepsis diagnostics. The focus is on nanomaterial-based optical approaches that promise rapid diagnostics without the need for large equipment or trained personnel. An overview of sepsis is provided, highlighting potential molecular targets and the challenges they present for assay development. The requirements for an ideal point-of-care test (POC) are discussed, including speed, simplicity, and cost-effectiveness. Different nanomaterials suitable for various optical detection methods are reviewed and innovative nanosensors are discussed for sepsis diagnostics, focusing on chemical design and approaches to increase selectivity by multiplexing.

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.

Background/Objectives: Cutaneous leishmaniasis (CL) is a skin disease caused by Leishmania parasites. Presepsin, irisin, and apelin are biomarkers that are involved in the inflammatory response. The aim of this study was to investigate the association between serum levels of specific biomarkers, such as presepsin, apelin, and irisin, and the clinical features, location, number, and size of lesions in patients with CL. Methods: This study is a single-centre, prospective cohort study involving a total of 30 patients with skin lesions compatible with CL and 30 healthy matched controls. Age, sex, type of skin lesion, location of skin lesion, number of skin lesions, and diameter of skin lesions were recorded. The levels of presepsin, irisin, and apelin measured in the blood samples of the patient group were analysed in comparison to those in the healthy control group. Results: The findings revealed that presepsin levels were significantly elevated in the patient group compared to the controls (p = 0.000). However, no statistically significant differences were observed between the groups for irisin and apelin levels (p-values 0.096 and 0.836, respectively). A negative correlation was identified between presepsin levels and the number of skin lesions, the diameter of the largest lesion, and the total diameter of the lesions (p = 0.000). Conclusions: It appears that measuring presepsin levels in patients with CL may be beneficial. Presepsin has the potential to serve as a prognostic marker in CL, offering significant benefits in guiding clinicians in assessing disease progression and response to treatment.

Sepsis is a pervasive condition that affects individuals of all ages, with significant social and economic consequences. The early diagnosis of sepsis is fundamental for establishing appropriate treatment and is based on warning scores and clinical characteristics, with positive microbiological cultures being the gold standard. Research has yet to identify a single biomarker to meet this diagnostic demand. Presepsin is a molecule that has the potential as a biomarker for diagnosing sepsis. In this paper, we present a narrative review of the diagnostic and prognostic performance of presepsin in different age groups. Given its particularities, it is identified that presepsin is a potential biomarker for sepsis at all stages of life.

Background: Sepsis is defined as life-threatening organ dysfunction caused by an abnormal host response to infection. The study aimed to evaluate the utility of presepsin (P-SEP) in predicting the risk of death in patients with sepsis at the time of intensive care unit (ICU) admission. Methods: Adult patients were included in the study if they met SEPSIS-3 criteria at ICU admission. Demographic and clinical data were collected. The following inflammatory parameters were determined: C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and presepsin (P-SEP). Material was collected for microbiological testing depending on the suspected source of infection. The primary endpoint was patient death before ICU discharge. The secondary endpoint was a positive microbiological test result. Results: Eighty-six patients were included in the study. Thirty patients (35%) died before discharge from the ICU. There was no difference in P-SEP, CRP, PCT, and IL-6 values between patients who survived and those who died (p > 0.05 for all). P-SEP, CRP, PCT, and IL-6 were determined at ICU admission and did not accurately predict the risk of death in ROC curve analysis (p > 0.05 for all). Confirmation of the location of the focus of bacterial infection by microbiological testing was obtained in 43 (49%) patients. P-SEP, PCT, CRP, and IL-6 were significantly higher in patients with positive microbiological findings. Conclusions: In patients with suspected sepsis admitted to the Intensive Care Unit, presepsin does not accurately predict the risk of in-hospital death, but it can predict a positive microbiological culture.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels, and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510-0.802) and Day 3 (AUC 0.698; 95% CI: 0.559-0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572-0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 μg/L on Day 3, resulting in R2 of about 31% (p < 0.001). Conclusions: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.

Sepsis is a heterogeneous syndrome often misdiagnosed. Point-of-care (POC) diagnostic tests are commonly used to guide decision and include host biomarkers and molecular diagnostics.

The diagnostic and prognostic accuracy of established and emerging biomarkers for sepsis, including procalcitonin (PCT) soluble urokinase plasminogen activator receptor (suPAR), presepsin, TRAIL/IP-10/CRP, MxA, and MxA-CRP, are analyzed in this review. The clinical utility of the two prevalent molecular techniques for pathogens identification using polymerase chain reaction (PCR) assays is also presented: FILMARRAY and QIAstat-Dx RP.

The rising benefits of the combined use of POC biomarkers with molecular diagnostics in daily clinical routine appear to outperform conventional practices in terms of reduced turnaround time, timely diagnosis, and prompt administration of the appropriate treatment. Yet, this must be further demonstrated in future investigations. However, the cost-effectiveness of POC tests and the high rate of false positive and negative results, indicate the need for a comprehensive clinical evaluation.

Sepsis is a medical emergency resulting from a dysregulated response to an infection, causing preventable deaths and a high burden of morbidity. Protocolized and accurate interventions in sepsis are time-critical. Therefore, earlier recognition of cases allows for preventive interventions, early treatment, and improved outcomes. Clinical diagnosis of sepsis by clinical scores cannot be considered an early diagnosis, given that underlying molecular pathophysiological mechanisms have been activated in the preceding hour or days. There is a lack of a widely available tool enhancing preclinical diagnosis of sepsis. Sophisticated technologies for sepsis prediction have several limitations, including high costs. Novel technologies for fast molecular and microbiological diagnosis are focusing on bedside point-of-care combined testing to reach most settings where sepsis represents a challenge.

Sepsis is described as a life-threatening organ dysfunction and a heterogeneous syndrome that is a leading cause of morbidity and mortality in intensive care settings. Severe sepsis could incite an uncontrollable surge of inflammatory cytokines, and the host immune system's immunosuppression could respond to counter excessive inflammatory responses, characterized by the accumulated anti-inflammatory cytokines, impaired function of immune cells, over-proliferation of myeloid-derived suppressor cells and regulatory T cells, depletion of immune effector cells by different means of death, etc. In this review, we delve into the underlying pathological mechanisms of sepsis, emphasizing both the hyperinflammatory phase and the associated immunosuppression. We offer an in-depth exploration of the critical mechanisms underlying sepsis, spanning from individual immune cells to a holistic organ perspective, and further down to the epigenetic and metabolic reprogramming. Furthermore, we outline the strengths of artificial intelligence in analyzing extensive datasets pertaining to septic patients, showcasing how classifiers trained on various clinical data sources can identify distinct sepsis phenotypes and thus to guide personalized therapy strategies for the management of sepsis. Additionally, we provide a comprehensive summary of recent, reliable biomarkers for hyperinflammatory and immunosuppressive states, facilitating more precise and expedited diagnosis of sepsis.

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.

Sepsis remains a leading cause of death worldwide. In this context, heparin-binding protein (HBP) has emerged as a possible biomarker, drawing significant attention for its diagnostic and prognostic usefulness in septic patients. Despite this advancement, the literature yields conflicting results. This study is intended to critically evaluate the diagnostic and prognostic value of HBP in critically ill septic patients.

We searched multiple databases, including PubMed, SCOPUS, Web of Science, and EBSCO, to identify relevant studies on April 27, 2023. We included studies investigating sepsis or its severe outcomes that reported HBP levels and the required data to create 2 × 2 tables. We used R version 4.2.2 and R Studio to analyze the pooled diagnostic accuracy outcomes. The diagmeta package was utilized to calculate the optimum cutoff value.

In our meta-analysis, we incorporated 28 studies including 5508 patients. The analysis revealed that HBP has a sensitivity of 0.71 (95% CI: 0.60; 0.79) and a specificity of 0.68 (95% CI: 0.51; 0.81) in diagnosing sepsis, respectively. HBP demonstrated moderate prognostic accuracy for mortality at a cutoff value of 161.415 ng/mL, with a sensitivity and specificity of 72%, and for severe sepsis outcomes at a cutoff value of 58.907 ng/mL, with a sensitivity and specificity of 71%.

Our findings indicate a relatively moderate diagnostic and prognostic accuracy of HBP for sepsis. Future studies are required to verify the accuracy of HBP as a biomarker for sepsis.

The accurate identification of infections is critical for effective treatment in intensive care units (ICUs), yet current diagnostic methods face limitations in sensitivity and specificity, alongside cost and accessibility issues. Consequently, there is a pressing need for a marker that is economically feasible, rapid, and reliable. Presepsin (PSP), also known as soluble CD14 subtype (sCD14-ST), has emerged as a promising biomarker for early sepsis diagnosis. PSP, derived from soluble CD14, reflects the activation of monocytes/macrophages in response to bacterial infections. It has shown potential as a marker of cellular immune response activation against pathogens, with plasma concentrations increasing during bacterial infections and decreasing post-antibiotic treatment. Unlike traditional markers such as procalcitonin (PCT) and C-reactive protein (CRP), PSP specifically indicates monocyte/macrophage activation. Limited studies in critical illness have explored PSP's role in sepsis, and its diagnostic accuracy varies with threshold values, impacting sensitivity and specificity. Recent meta-analyses suggest PSP's diagnostic potential for sepsis, yet its standalone effectiveness in ICU infection management remains uncertain. This review provides a comprehensive overview of PSP's utility in ICU settings, including its diagnostic accuracy, prognostic value, therapeutic implications, challenges, and future directions.

Due to variability in pharmacokinetics and pharmacodynamics, clinical outcomes of antimicrobial drug therapy vary between patients. As such, personalised medication management, considering both pharmacokinetics and pharmacodynamics, is a growing concept of interest in the field of infectious diseases. Therapeutic drug monitoring is used to adjust and individualise drug regimens until predefined pharmacokinetic exposure targets are achieved. Minimum inhibitory concentration (drug susceptibility) is the best available pharmacodynamic parameter but is associated with many limitations. Identification of other pharmacodynamic parameters is necessary. Repurposing diagnostic biomarkers as pharmacodynamic parameters to evaluate treatment response is attractive. When combined with therapeutic drug monitoring, it could facilitate making more informed dosing decisions. We believe the approach has potential and justifies further research.

It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT.

This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia.

In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia.

IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis.