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Sepsis represents a critical medical condition stemming from an imbalanced host immune response to infections, which is linked to a significant burden of disease. Despite substantial efforts in laboratory and clinical research, sepsis remains a prominent contributor to mortality worldwide. Nanotechnology presents innovative opportunities for the advancement of sepsis diagnosis and treatment. Due to their unique properties, including diversity, ease of synthesis, biocompatibility, high specificity, and excellent pharmacological efficacy, peptides hold great potential as part of nanotechnology approaches against sepsis. Herein, we present a comprehensive and up-to-date review of the applications of peptides in nanosystems for combating sepsis, with the potential to expedite diagnosis and enhance management outcomes. Firstly, sepsis pathophysiology, antisepsis drug targets, current modalities in management and diagnosis with their limitations, and the potential of peptides to advance the diagnosis and management of sepsis have been adequately addressed. The applications have been organized into diagnostic or managing applications, with the last one being further sub-organized into nano-delivered bioactive peptides with antimicrobial or anti-inflammatory activity, peptides as targeting moieties on the surface of nanosystems against sepsis, and peptides as nanocarriers for antisepsis agents. The studies have been grouped thematically and discussed, emphasizing the constructed nanosystem, physicochemical properties, and peptide-imparted enhancement in diagnostic and therapeutic efficacy. The strengths, limitations, and research gaps in each section have been elaborated. Finally, current challenges and potential future paths to enhance the use of peptides in nanosystems for combating sepsis have been deliberately spotlighted. This review reaffirms peptides' potential as promising biomaterials within nanotechnology strategies aimed at improving sepsis diagnosis and management. Highlights: • Due to their unique characteristics, Peptides hold significant promise as part of nanotechnology approaches for diagnosing and treating sepsis, a current leading global killer. • Various diagnostic nanotools utilizing peptides as pathogen recognition moieties can improve the pathogen capturing efficiency for sepsis diagnosis. • Nano-delivery can overcome the limitations of bioactive peptides and enhance their antibacterial and anti-inflammatory efficacy in sepsis management. • Peptides offer significant capabilities as targeting moieties and nanocarriers to augment the effectiveness of antisepsis agents. • Future research identified can potentiate the applications of peptides for the diagnosis and treatment of sepsis. [ABSTRACT FROM AUTHOR]

Blood stream infections (BSIs) cause high mortality, and their rapid detection remains a significant diagnostic challenge. Timely and informed administration of antibiotics can significantly improve patient outcomes. However, blood culture, which takes up to 5 d for a negative result, followed by PCR remains the gold standard in diagnosing BSI. Here, we introduce a new approach to blood-based diagnostics where large blood volumes can be rapidly dried, resulting in inactivation of the inhibitory components in blood. Further thermal treatments then generate a physical microscale and nanoscale fluidic network inside the dried matrix to allow access to target nucleic acid. The amplification enzymes and primers initiate the reaction within the dried blood matrix through these networks, precluding any need for conventional nucleic acid purification. High heme background is confined to the solid phase, while amplicons are enriched in the clear supernatant (liquid phase), giving fluorescence change comparable to purified DNA reactions. We demonstrate single-molecule sensitivity using a loop-mediated isothermal amplification reaction in our platform and detect a broad spectrum of pathogens, including gram-positive methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteria, gram-negative Escherichia coli bacteria, and Candida albicans (fungus) from whole blood with a limit of detection (LOD) of 1.2 colony-forming units (CFU)/mL from 0.8 to 1 mL of starting blood volume. We validated our assay using 63 clinical samples (100% sensitivity and specificity) and significantly reduced sample-to-result time from over 20 h to <2.5 h. The reduction in instrumentation complexity and costs compared to blood culture and alternate molecular diagnostic platforms can have broad applications in healthcare systems in developed world and resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the predictive power of three different Sepsis Scoring Systems (SSSs), namely maternity Systematic Inflammatory Response Syndrome (mSIRS), quick Sepsis-related Organ Failure Assessment (qSOFA) and Modified Early Warning System (MEWS) in identifying sepsis by comparing them with positive culture. This study also sought to evaluate compliance with using the Sepsis Six Care Bundle (SSCB) operated in an individual health board.Methods: A retrospective cohort study was conducted in 3 maternity hospitals of a single Scottish health board that admitted 2690 pregnancies in a 12 weeks period in 2016. Data for study was obtained from medical notes, handheld and electronic health records for women who were prescribed antibiotics with a confirmed or suspected diagnosis of sepsis. Data on clinical parameters was used to classify women according to mSIRS, qSOFA and MEWS as having sepsis or not and this was compared to results of positive culture to obtain sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under Receiver Operating Characteristic curve (AUROC) along with their 95% confidence intervals. Data was also obtained on SSCB compliance.Results: A total of 89 women were diagnosed with sepsis, of which 14 had missing data, leaving 75 for final analysis. Sensitivity, specificity, PPV, NPV and AUROC of mSIRS and MEWS were almost similar with AUROC of both being around 50%. Only 33 (37.1%) had identifiable sepsis six sticker displayed on medical notes and only 2 (2.2%) had all elements of SSCB delivered within the recommended one-hour post-diagnosis period. Blood culture and full blood count with other lab tests had been performed for most women (97%) followed by intravenous antibiotics and fluids (93.9%).Conclusions: mSIRS and MEWS were quite similar in detecting sepsis when compared to positive culture, with their ability to detect sepsis being close to chance. This underlines the need for creating a valid SSS with high sensitivity and specificity for clinical use in obstetric settings. Clinical use of SSCB was limited despite it being a health board policy, although there is considerable possibility of improvement following detailed audits and removal of barriers for implementing SSCB. [ABSTRACT FROM AUTHOR]

Highlights • Wheat germ agglutinin lectin (WGA) was applied as a recognition agent for S. aureus enrichment. • The use of LMS method resulted in a high enrichment efficiency even at low concentrations (100–102 CFU/mL) of S. aureus. • A quantitative and specific detection strategy based on dsDNA stabilized AuNPs was developed for S. aureus detection. • The detection limit of this method was 3.5 × 100 CFU/mL. Abstract A novel 2-step lectin-magnetic separation (LMS) method combined with gold nanoparticle (AuNPs) -based colorimetric system for specifically and quantitatively detecting S. aureus in blood samples was established. In this study, wheat germ agglutinin lectin from Triticum vulgaris (wheat) (WGA) was applied for the first time as a recognition agent in a 2-step magnetic separation method using magnetic nanoparticles (MNPs) for effective and low-cost bacteria enrichment. A quantitative detection strategy based on the long dsDNA amplicons stabilized with AuNPs against salt-induced aggregation was investigated. The 2-step LMS method resulted in a high enrichment efficiency even at low concentrations (100–102 CFU/mL) of S. aureus in pure culture and blood samples. The AuNPs-based colorimetric system was applied for quantitative detection of S. aureus with a limit of detection (LOD) at 3.5 × 100 CFU/mL. The complete process starting with the blood samples treatment, 2-step LMS, and AuNPs-based colorimetric detection took only 7 h. The low cost and sensitive 2-step LMS combined with AuNPs-based colorimetric detection holds considerable potential for early sepsis diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Sepsis is a highly prevalent syndrome in the United States. The use of cell surface markers, as an effective tool to diagnosis sepsis, has been widely investigated. However, the study of the combination of multiple biomarkers to achieve higher diagnosis accuracy is rare. This study, the panel combined with CD25, CD64, and CD69 was constructed and better diagnosis ability was observed. Septic patients (n = 40), with the mean age of 61 ± 14, were enrolled in this study, along with healthy volunteers (n = 10), included as a control group. All blood samples were measured by flow cytometry based on different subtypes of leukocytes, including neutrophils, monocytes, and lymphocytes. Antigen expression and the antigen positive cell population were reported separately based on cell types. CD64 was the best biomarker in predicting sepsis. The area under Receiver Operating Characteristic (ROC) curve (AUC) was 0.928 and 0.934 for neutrophil CD64 expression and CD64 + neutrophil population, respectively, indicating an excellent diagnosis ability for sepsis. A significant increase was also observed in the populations of CD25 + lymphocytes and CD69 + lymphocytes (p = 0.02 and 0.042, respectively; 95% confidence interval). A panel of combined CD25, CD64, and CD69 was constructed. The parameters of neutrophil CD64 expression, CD64 + neutrophil population, CD25 + lymphocyte population, and CD69 + lymphocyte population were included. The AUC of the ROC curve for this new constructed panel was 0.978. This result indicated that the combination of CD25, CD64, and CD69 outperformed each one of the single parameters in predicting sepsis alone. Graphical abstract fx1 Highlights • 8 different parameters were evaluated for CD25, CD64, and CD69, separately. • The combined panel was constructed to achieve the best accuracy in predicting sepsis. • Each biomarker was evaluated individually and compared with combined biomarker panel. • Culture-negative sepsis was detected by our biomarker panel. [ABSTRACT FROM AUTHOR]

Fast determination of antibiotic resistance is crucial in selecting appropriate treatment for sepsis patients, but current methods based on culture are time consuming. We are developing a microfluidic platform with a monolithic column modified with oligonucleotides designed for sequence-specific capture of target DNA related to the Klebsiella pneumoniae carbapenemase (KPC) gene. We developed a novel single-step monolith fabrication method with an acrydite-modified capture oligonucleotide in the polymerization mixture, enabling fast monolith preparation in a microfluidic channel using UV photopolymerization. These prepared columns had a threefold higher capacity compared to monoliths prepared in a multistep process involving Schiff-base DNA attachment. Conditions for denaturing, capture and fluorescence labeling using hybridization probes were optimized with synthetic 90-mer oligonucleotides. These procedures were applied for extraction of a PCR amplicon from the KPC antibiotic resistance gene in bacterial lysate obtained from a blood sample spiked with E. coli . The results showed similar eluted peak areas for KPC amplicon extracted from either hybridization buffer or bacterial lysate. Selective extraction of the KPC DNA was verified by real time PCR on eluted fractions. These results show great promise for application in an integrated microfluidic diagnostic system that combines upstream blood sample preparation and downstream single-molecule counting detection. [ABSTRACT FROM AUTHOR]

Background: Several studies were published to validate the quick Sepsis-related Organ Failure Assessment (qSOFA), namely in comparison with the systemic inflammatory response syndrome (SIRS) criteria. We performed a systematic review and meta-analysis with the aim of comparing the qSOFA and SIRS in patients outside the ICU.Methods: We searched MEDLINE, CINAHL, and the Web of Science database from February 23, 2016 until June 30, 2017 to identify full-text English-language studies published after the Sepsis-3 publication comparing the qSOFA and SIRS and their sensitivity or specificity in diagnosing sepsis, as well as hospital and ICU length of stay and hospital mortality. Data extraction from the selected studies followed the recommendations of the Meta-analyses of Observational Studies in Epidemiology group and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Results: From 4,022 citations, 10 studies met the inclusion criteria. Pooling all the studies, a total of 229,480 patients were evaluated. The meta-analysis of sensitivity for the diagnosis of sepsis comparing the qSOFA and SIRS was in favor of SIRS (risk ratio [RR], 1.32; 95% CI, 0.40-2.24; P < .0001; I2 = 100%). One study described the specificity for the diagnosis of infection comparing SIRS (84.4%; 95% CI, 76.2-90.6) with the qSOFA (97.3%; 95% CI < 92.1-99.4); the qSOFA demonstrated better specificity. The meta-analysis of the area under the receiver operating characteristic curve of six studies comparing the qSOFA and SIRS favored the qSOFA (RR, 0.03; 95% CI, 0.01-0.05; P = .002; I2 = 48%) as a predictor of inhospital mortality.Conclusions: The SIRS was significantly superior to the qSOFA for sepsis diagnosis, and the qSOFA was slightly better than the SIRS in predicting hospital mortality. The association of both criteria could provide a better model to initiate or escalate therapy in patients with sepsis.Systematic Review Registration: PROSPERO CRD42017067645. [ABSTRACT FROM AUTHOR]

With the development of economic level and growth in the living standard, how to enhance the accuracy and efficiency of remote sepsis diagnosis has become the key issue and hot topic in the current medical research. As the traditional BP neural network is poor in the generalization ability and needs a large number of samples, we proposed the study on remote sepsis diagnosis by using the FOA-optimized BP neural network. Besides, based on the wireless sensor network and ZigBee network, we constructed the mathematical model of FOA BP remote sepsis diagnosis based on wireless sensor network. The sepsis data set of School of Medicine and Public Health, University of Wisconsinwas used as the object of study. The FOA-BP algorithm is significantly superior to the BP neural network algorithm in the diagnosis accuracy, verifying the validity and reliability of making a sepsis diagnosis with FOA BP. Therefore, the method can be popularized to other fields to solve other similar problems. [ABSTRACT FROM AUTHOR]

With the development of economic level and growth in the living standard, how to enhance the accuracy and efficiency of remote sepsis diagnosis has become the key issue and hot topic in the current medical research. As the traditional BP neural network is poor in the generalization ability and needs a large number of samples, we proposed the study on remote sepsis diagnosis by using the FOA-optimized BP neural network. Besides, based on the wireless sensor network and ZigBee network, we constructed the mathematical model of FOA BP remote sepsis diagnosis based on wireless sensor network. The sepsis data set of School of Medicine and Public Health, University ofWisconsinwas used as the object of study. The FOA-BP algorithm is significantly superior to the BP neural network algorithm in the diagnosis accuracy, verifying the validity and reliability of making a sepsis diagnosis with FOA BP. Therefore, the method can be popularized to other fields to solve other similar problems. [ABSTRACT FROM AUTHOR]

• A new probabilistic modeling approach is used for sepsis diagnosis. • The classifier built by the approach features a unique strong interpretability. • The new approach is helpful for diagnostic decision-making in sepsis diagnosis. Sepsis is a serious disease that can cause death. It is important to predict sepsis within the early stages after the presence of sepsis symptoms. In this paper, a new probabilistic modeling approach is used to establish classifiers for sepsis diagnosis. This approach is characterized by unique strong interpretability, which is reflected in three aspects: (1) evidence acquisition based on likelihood analysis, (2) probabilistic rule-based inference, and (3) parameters optimization using machine learning algorithms. Four-fold cross-validation is used to train and validate classifiers established by the new approach and alternative ones. Results show that in terms of classification capability, the classifier established by the new approach generally performs better than the majority of alternative classifiers for sepsis diagnosis, and close to the best one. As the classifier also features an inherent interpretability, it can be used as a tool for supporting diagnostic decision-making in sepsis diagnosis. [ABSTRACT FROM AUTHOR]

The article focuses on early recognition of serious infections in obstetrics and gynecology. Pelvic infections commonly occur in pregnant and postoperative women which can be diagnosed and treated. However, sometimes sever infections, septic shocks may occur and may even cause morbidity. In such severe cases, clinicians should go for antimicrobial therapy, source control, and monitoring to control and treat infection.

Introduction: Neonatal sepsis (NS) is a systemic infection exhibiting 25% lethality among infected children, and it poses a higher risk in preterm than in full-term neonates. Routine microbiological culture, hematological quantification, IL-6, IL-8, C-reactive protein and procalcitonin determinations are the most commonly used tests to diagnose sepsis. However, these methods have substantial limitations due to the associated variation, low degree of sensitivity and long period of time required for execution. These factors decrease the efficiency of an early diagnosis. T oll-like receptors are involved in native immunity recognition and the stimulation of antimicrobial mechanisms. Therefore, they may be altered early during the systemic infection and may be useful in the diagnosis of sepsis. Methods: In this work, we analyze the expression of TLR2 and TLR4 on CD14+ cells as early markers for sepsis in preterm neonates. Results: Our results show that the percentage of CD14int cells and their TLR2 expression were significantly altered in preterm infants with diagnosed infections and were not altered in the systemic inflammatory response syndrome (SIRS) patients. Discussion: These results suggest that TLR2 screening could be a helpful diagnostic test for bacterial infection in preterm infants. [ABSTRACT FROM AUTHOR]

To date, sepsis is still one of the most important causes of death due to the difficulties concerning the achievement of a correct diagnosis. As well as in a clinical context, also in a medico-legal setting the diagnosis of sepsis can reveal challenging due to the unspecificity of the signs detected during autopsies, especially when no ante-mortem clinical data, laboratory, and cultural results are available. Thus, a systematic review of literature was performed to provide an overview of the main available and updated forensic tools for the post-mortem diagnosis of sepsis. Moreover, the aim of this review was to evaluate whether a marker or a combination of markers exist, specific enough to allow a correct and definite post-mortem diagnosis. The review was conducted searching in PubMed and Scopus databases, and using variable combinations of the keywords "post mortem sepsis diagnosis", "macroscopic signs", "morphology", "histology", "immunohistochemical markers", "biochemical markers", and "forensic microbiology". The article selection was carried out following specific inclusion and exclusion criteria. A total of 44 works was identified, providing data on morphological aspects of the organs examined, histological findings, immunohistochemical and biochemical markers, and cultural assays. The review findings suggested that the post-mortem diagnosis of sepsis can be achieved by a combination of data obtained from macroscopic and microscopic analysis and microbial investigations, associated with the increased levels of at least two of three biochemical and/or immunohistochemical markers evaluated simultaneously on blood samples. [ABSTRACT FROM AUTHOR]

Successful treatment of sepsis begins from early diagnosis and prognosis. In last decades the number of sepsis cases is growing, so establishing early diagnosis of sepsis as well as effectiveness of treatment are very significant. That is why development of new diagnostic sepsis markers is important. In this review we evaluated a new sepsis marker Presepsin (sCD14) and compared it to other markers: Procalcitonin (PCT), C-reactive protein (CRP) and Interleukine-6 (IL-6). [ABSTRACT FROM AUTHOR]

Background: Sepsis biomarker panels that provide diagnostic and prognostic discrimination in sepsis patients would be transformative to patient care. We assessed the mortality prediction and diagnostic discriminatory accuracy of two biomarkers reflective of cell death (apoptosis), circulating cell-free DNA (cfDNA), and nucleosomes. Methods: The cfDNA and nucleosome levels were assayed in plasma samples acquired in patients admitted from four emergency departments with suspected sepsis. Subjects with non-infectious systemic inflammatory response syndrome (SIRS) served as controls. Samples were acquired at enrollment (T0) and 24 h later (T24). We assessed diagnostic (differentiating SIRS from sepsis) and prognostic (28-day mortality) predictive power. Models incorporating procalcitonin (diagnostic prediction) and APACHE II scores (mortality prediction) were generated. Results: Two hundred three subjects were included (107 provided procalcitonin measurements). Four subjects exhibited uncomplicated sepsis, 127 severe sepsis, 35 septic shock, and 24 had non-infectious SIRS. There were 190-survivors and 13 non-survivors. Mortality prediction models using cfDNA, nucleosomes, or APACHEII yielded AUC values of 0.61, 0.75, and 0.81, respectively. A model combining nucleosomes with the APACHE II score improved the AUC to 0.84. Diagnostic models distinguishing sepsis from SIRS using procalcitonin, cfDNA(T0), or nucleosomes(T0) yielded AUC values of 0.64, 0.65, and 0.63, respectively. The three parameter model yielded an AUC of 0.74. Conclusions: To our knowledge, this is the first head-to-head comparison of cfDNA and nucleosomes in diagnosing sepsis and predicting sepsis-related mortality. Both cfDNA and nucleosome concentrations demonstrated a modest ability to distinguish sepsis survivors and non-survivors and provided additive diagnostic predictive accuracy in differentiating sepsis from non-infectious SIRS when integrated into a diagnostic prediction model including PCT and APACHE II. A sepsis biomarker strategy incorporating measures of the apoptotic pathway may serve as an important component of a sepsis diagnostic and mortality prediction tool. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To study the potential of buffy coat culture as a diagnostic tool for neonatal late-onset sepsis. Methods: This was a study of diagnostic accuracy in newborn infants born at 28–41 weeks of gestation, weighing >800g, with ≥8 points on the NOSEP-1 scale. Paired samples for total blood culture (TBC) and buffy coat culture were drawn. We established the positivity rate, sensitivity, specificity, predictive values, and likelihood ratios, and compared time to positivity and contamination rates. Results: Fifty-two newborns were included in the study. Twenty-one TBC and 22 buffy coat cultures were positive. The positivity rate for TBC was 40.4% and for buffy coat culture was 42.3% (p =not significant). Three TBC were positive with negative buffy coat culture. Four buffy coat cultures were positive with negative TBC; Kappa agreement was 0.723, p <0.001. Buffy coat culture sensitivity was 86% (95% confidence interval (CI) 68.5–95.4%), specificity 87% (75.4–93.7%), positive predictive value 82% (65.4–91.1%), negative predictive value 90% (77.9–96.8%), positive likelihood ratio 6.64 (2.79–15.05), and negative likelihood ratio 0.16 (0.05–0.42). We found no difference in time to positivity in hours; Wilcoxon Z =1224, p =0.22. The contamination rate was 1.9% for both methods. Conclusions: Buffy coat culture is as good as TBC for the microbiological diagnosis of late-onset sepsis of the newborn. Buffy coat culture allows the use of remaining plasma for further analysis. [ABSTRACT FROM AUTHOR]