Biomedicines

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17 pages, 2999 KiB

Open AccessArticle

Point-of-Care Serum Proenkephalin as an Early Predictor of Mortality in Patients Presenting to the Emergency Department with Septic Shock

by Christos Verras, Sofia Bezati, Vasiliki Bistola, Ioannis Ventoulis, Dionysis Matsiras, Sotirios Tsiodras, John Parissis and Effie Polyzogopoulou

Biomedicines 2024, 12(5), 1004; https://doi.org/10.3390/biomedicines12051004 - 2 May 2024

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Abstract

Background: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. Methods: Bedside PENK was measured [...] Read more.

Background: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. Methods: Bedside PENK was measured in consecutive patients presenting to the ED with septic shock according to the Sepsis-3 clinical criteria. The association of PENK with inflammatory and routine biomarkers, and its role as a predictor of in-hospital mortality, was examined. Results: Sixty-one patients with septic shock [53% females, median age 83 years (IQR 71–88)] were evaluated. Median (IQR) values of creatinine, plasma lactate, soluble urokinase plasminogen activator receptor (SuPAR), procalcitonin and PENK were 1.7 (1.0–2.9) mg/dL, 3.6 (2.1–6.8) mmol/L, 13.1 (10.0–21.4) ng/mL, 2.06 (0.84–3.49) ng/mL, and 205 (129–425) pmol/L, respectively. LogPENK significantly correlated with LogLactate (rho = 0.369, p = 0.004), LogCreatinine (rho = 0.537, p < 0.001), LogProcalcitonin (rho = 0.557, p < 0.001), and LogSuPAR (rho = 0.327, p = 0.011). During hospitalization, 39/61 (64%) patients died. In a multivariable logistic regression model, logPENK was an independent predictor of in-hospital mortality (OR 11.9, 95% CI: 1.7–84.6, p = 0.013). Conclusion: POC PENK levels measured upon presentation to the ED strongly correlated with metabolic, renal and inflammatory biomarkers, and may serve as a predictor of in-hospital mortality in patients with septic shock. Full article

(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis)

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14 pages, 2301 KiB

Open AccessArticle

Cell-Free Nuclear and Mitochondrial DNA as Potential Biomarkers for Assessing Sepsis Severity

by Felipe Silva de Miranda, Livia Maria A. M. Claudio, Dayanne Silva M. de Almeida, Juliana Braga Nunes, Valério Garrone Barauna, Wilson Barros Luiz, Paula Frizzera Vassallo and Luciene Cristina Gastalho Campos

Biomedicines 2024, 12(5), 933; https://doi.org/10.3390/biomedicines12050933 - 23 Apr 2024

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Abstract

Sepsis continues to be a significant public health challenge despite advances in understanding its pathophysiology and management strategies. Therefore, this study evaluated the value of cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) for assessing the severity and prognosis of sepsis. Ninety-four [...] Read more.

Sepsis continues to be a significant public health challenge despite advances in understanding its pathophysiology and management strategies. Therefore, this study evaluated the value of cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) for assessing the severity and prognosis of sepsis. Ninety-four patients were divided into three groups: infection (n = 32), sepsis (n = 30), and septic shock (n = 32). Plasma samples were collected at the time of diagnosis, and cfDNA concentrations were determined by qPCR assay. The results showed that plasma cfDNA levels increased with the severity of the disease. To distinguish between patients with infection and those with sepsis, the biomarker L1PA2₉₀ achieved the highest AUC of 0.817 (95% CI: 0.725–0.909), demonstrating a sensitivity of 77.0% and a specificity of 79.3%. When cf-nDNA was combined with the SOFA score, there was a significant improvement in the AUC (0.916 (0.853–0.979)), sensitivity (88.1%), and specificity (80.0%). Moreover, patients admitted to the ICU after being diagnosed with sepsis had significantly higher cf-nDNA concentrations. In patients admitted to the ICU, combining cf-nDNA with the SOFA score yielded an AUC of 0.753 (0.622–0.857), with a sensitivity of 95.2% and a specificity of 50.0%. cfDNA can differentiate between patients with infection and those with sepsis. It can also identify patients who are likely to be admitted to the ICU by predicting those with indications for intensive care, suggesting its potential as a biomarker for sepsis. Full article

(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis)

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12 pages, 2354 KiB

Open AccessArticle

In Vitro Simulated Hemoperfusion on Seraph^®-100 as a Promising Strategy to Counteract Sepsis

by Antonio Lacquaniti, Antonella Smeriglio, Susanna Campo, Erminia La Camera, Giovanni Lanteri, Elena Giunta, Paolo Monardo and Domenico Trombetta

Biomedicines 2024, 12(3), 575; https://doi.org/10.3390/biomedicines12030575 - 5 Mar 2024

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Abstract

Blood purification represents a treatment option for sepsis, improving inflammation and the hyper-activated immune system. This study investigates the binding efficacy of Seraph^®-100 against 10⁸ CFU/mL of Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and [...] Read more.

Blood purification represents a treatment option for sepsis, improving inflammation and the hyper-activated immune system. This study investigates the binding efficacy of Seraph^®-100 against 10⁸ CFU/mL of Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli) during a simulated hemoperfusion treatment. The fluorescence-activated cell sorting (FACS) technique was used to evaluate the bacteria reduction, whereas kinetic analysis and cultures revealed bacterial detection and counting at established time points. At the end of the experiment, the filter was cut at three different levels, obtaining suspensions for cultures and scanning electron microscopy (SEM) analyses. The FACS technique revealed a 78.77% reduction of the total bacterial load at the end of the treatment, with maximum filter sequestration occurring in the first 30 min of the treatment. Non-linear regression analysis of kinetic experiments (T_{0–240 min}) highlighted a lower growth rate of S. aureus than the other two Gram bacteria, demonstrating a greater affinity without influencing a reduction rate of 99% for all three bacteria. The analyses of the suspension aliquots of the filter sections confirmed these data, revealing 1 × 10⁸ CFU/mL, equal to the initial bacterial charge. Furthermore, the filter head adsorbed approximately 50% of bacteria, whereas the remaining amount was equally distributed between the body and the tail, as corroborated by SEM analysis. In conclusion, Seraph^®-100 adsorbed 10⁸ CFU/mL of S. aureus, E. coli, and P. aeruginosa during an in vitro simulated hemoperfusion session. Full article

(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis)

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11 pages, 1047 KiB

Open AccessArticle

ARDS Mortality Prediction Model Using Evolving Clinical Data and Chest Radiograph Analysis

by Ana Cysneiros, Tiago Galvão, Nuno Domingues, Pedro Jorge, Luis Bento and Ignacio Martin-Loeches

Biomedicines 2024, 12(2), 439; https://doi.org/10.3390/biomedicines12020439 - 16 Feb 2024

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Abstract

Introduction: Within primary ARDS, SARS-CoV-2-associated ARDS (C-ARDS) emerged in late 2019, reaching its peak during the subsequent two years. Recent efforts in ARDS research have concentrated on phenotyping this heterogeneous syndrome to enhance comprehension of its pathophysiology. Methods and Results: A retrospective study [...] Read more.

Introduction: Within primary ARDS, SARS-CoV-2-associated ARDS (C-ARDS) emerged in late 2019, reaching its peak during the subsequent two years. Recent efforts in ARDS research have concentrated on phenotyping this heterogeneous syndrome to enhance comprehension of its pathophysiology. Methods and Results: A retrospective study was conducted on C-ARDS patients from April 2020 to February 2021, encompassing 110 participants with a mean age of 63.2 ± 11.92 (26–83 years). Of these, 61.2% (68) were male, and 25% (17) experienced severe ARDS, resulting in a mortality rate of 47.3% (52). Ventilation settings, arterial blood gases, and chest X-ray (CXR) were evaluated on the first day of invasive mechanical ventilation and between days two and three. CXR images were scrutinized using a convolutional neural network (CNN). A binary logistic regression model for predicting C-ARDS mortality was developed based on the most influential variables: age, PaO₂/FiO₂ ratio (P/F) on days one and three, CNN-extracted CXR features, and age. Initial performance assessment on test data (23 patients out of the 110) revealed an area under the receiver operating characteristic (ROC) curve of 0.862 with a 95% confidence interval (0.654–0.969). Conclusion: Integrating data available in all intensive care units enables the prediction of C-ARDS mortality by utilizing evolving P/F ratios and CXR. This approach can assist in tailoring treatment plans and initiating early discussions to escalate care and extracorporeal life support. Machine learning algorithms for imaging classification can uncover otherwise inaccessible patterns, potentially evolving into another form of ARDS phenotyping. The combined features of these algorithms and clinical variables demonstrate superior performance compared to either element alone. Full article

(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis)

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12 pages, 912 KiB

Open AccessArticle

The Neutrophil/Lymphocyte Ratio and Outcomes in Hospitalized Patients with Community-Acquired Pneumonia: A Retrospective Cohort Study

by Aysun Tekin, Felix W. Wireko, Ognjen Gajic and Yewande E. Odeyemi

Biomedicines 2024, 12(2), 260; https://doi.org/10.3390/biomedicines12020260 - 24 Jan 2024

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Abstract

We aimed to assess the prognostic role of the neutrophil/lymphocyte ratio (NLR) in community-acquired pneumonia (CAP) via a single-center retrospective cohort of hospitalized adult patients from 1/2009 to 12/2019. Patients were dichotomized into lower NLR (≤12) and higher NLR (>12). The primary outcome [...] Read more.

We aimed to assess the prognostic role of the neutrophil/lymphocyte ratio (NLR) in community-acquired pneumonia (CAP) via a single-center retrospective cohort of hospitalized adult patients from 1/2009 to 12/2019. Patients were dichotomized into lower NLR (≤12) and higher NLR (>12). The primary outcome was mortality. ICU admission and hospital- and ICU-free days were secondary outcomes. The pneumonia severity index (PSI) and the NLR’s ability to predict outcomes was also tested. An NLR ≤12 was observed in 2513 (62.2%) patients and >12 in 1526 (37.8%). After adjusting for PSI, the NLR was not associated with hospital mortality (odds ratio [OR] 1.115; 95% confidence interval [CI] 0.774, 1.606; p = 0.559), but it was associated with a higher risk of ICU admission (OR 1.405; 95% CI 1.216, 1.624; p < 0.001). The PSI demonstrated acceptable discrimination for mortality (area under the receiver operating characteristic curve [AUC] 0.78; 95% CI 0.75, 0.82) which was not improved by adding the NLR (AUC 0.78; 95% CI 0.75, 0.82, p = 0.4476). The PSI’s performance in predicting ICU admission was also acceptable (AUC 0.75; 95% CI 0.74, 0.77) and improved by including the NLR (AUC 0.76, 95% CI 0.74, 0.77, p = 0.008), although with limited clinical significance. The NLR was not superior to the PSI for predicting mortality in hospitalized CAP patients. Full article

(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis)

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11 pages, 1152 KiB

Open AccessArticle

Analysis of Calprotectin as an Early Marker of Infections Is Economically Advantageous in Intensive Care-Treated Patients

by Aleksandra Havelka, Anders O. Larsson, Johan Mårtensson, Max Bell, Michael Hultström, Miklós Lipcsey and Mats Eriksson

Biomedicines 2023, 11(8), 2156; https://doi.org/10.3390/biomedicines11082156 - 1 Aug 2023

Viewed by 1247

Abstract

Calprotectin is released from neutrophil granulocytes upon activation. Several studies have indicated that plasma calprotectin is an early determinant of bacterial infections, which may serve as a diagnostic tool facilitating decision making on antibiotic treatment. The study objective was to explore the health [...] Read more.

Calprotectin is released from neutrophil granulocytes upon activation. Several studies have indicated that plasma calprotectin is an early determinant of bacterial infections, which may serve as a diagnostic tool facilitating decision making on antibiotic treatment. The study objective was to explore the health and economic implications of calprotectin as a predictive tool to initiate antimicrobial therapy in a cohort of critically ill patients. Thus, data obtained from a previously published study on calprotectin as a hypothetical early biomarker of bacterial infections in critically ill patients were evaluated regarding the potential cost-effective impact of early analysis of calprotectin on an earlier start of antibiotic treatment. Under the assumption that calprotectin is used predictively and comparators (white blood cells, procalcitonin, and C-reactive protein) are used diagnostically, a cost-effective impact of EUR 11,000–12,000 per patient would be obtained. If calprotectin would be used predictively and comparators would be used predictively for 50% of patients, it is hypothesized that cost-effectiveness would be between EUR 6000 and 7000 per patient, based on reduced stay in the ICU and general ward, respectively. Furthermore, predictive use of calprotectin seems to reduce both mortality and the length of hospital stay. This health economic analysis on the predictive use of plasma calprotectin, which facilitates clinical decision making in cases of suspected sepsis, indicates that such determination has a cost-saving and life-saving impact on the healthcare system. Full article

(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis)

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Review

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16 pages, 416 KiB

Open AccessReview

Recent Data about the Use of Corticosteroids in Sepsis—Review of Recent Literature

by Alexandra Lazar

Biomedicines 2024, 12(5), 984; https://doi.org/10.3390/biomedicines12050984 - 30 Apr 2024

Viewed by 473

Abstract

Sepsis, characterized by life-threatening organ dysfunction due to a maladaptive host response to infection, and its more severe form, septic shock, pose significant global health challenges. The incidence of these conditions is increasing, highlighting the need for effective treatment strategies. This review explores [...] Read more.

Sepsis, characterized by life-threatening organ dysfunction due to a maladaptive host response to infection, and its more severe form, septic shock, pose significant global health challenges. The incidence of these conditions is increasing, highlighting the need for effective treatment strategies. This review explores the complex pathophysiology of sepsis, emphasizing the role of the endothelium and the therapeutic potential of corticosteroids. The endothelial glycocalyx, critical in maintaining vascular integrity, is compromised in sepsis, leading to increased vascular permeability and organ dysfunction. Corticosteroids have been used for over fifty years to treat severe infections, despite ongoing debate about their efficacy. Their immunosuppressive effects and the risk of exacerbating infections are significant concerns. The rationale for corticosteroid use in sepsis is based on their ability to modulate the immune response, promote cardiovascular stability, and potentially facilitate organ restoration. However, the evidence is mixed, with some studies suggesting benefits in terms of microcirculation and shock reversal, while others report no significant impact on mortality or organ dysfunction. The Surviving Sepsis Campaign provides cautious recommendations for their use. Emerging research highlights the importance of genomic and transcriptomic analyses in identifying patient subgroups that may benefit from corticosteroid therapy, suggesting a move toward personalized medicine in sepsis management. Despite potential benefits, the use of corticosteroids in sepsis requires careful consideration of individual patient risk profiles, and further research is needed to optimize their use and integrate genomic insights into clinical practice. This review underscores the complexity of sepsis treatment and the ongoing need for evidence-based approaches to improve patient outcomes. Full article

(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis)

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27 pages, 2590 KiB

Open AccessReview

Immunosuppression in Sepsis: Biomarkers and Specialized Pro-Resolving Mediators

by Cristina M. Padovani and Kingsley Yin

Biomedicines 2024, 12(1), 175; https://doi.org/10.3390/biomedicines12010175 - 13 Jan 2024

Cited by 1 | Viewed by 2048

Abstract

Severe infection can lead to sepsis. In sepsis, the host mounts an inappropriately large inflammatory response in an attempt to clear the invading pathogen. This sustained high level of inflammation may cause tissue injury and organ failure. Later in sepsis, a paradoxical immunosuppression [...] Read more.

Severe infection can lead to sepsis. In sepsis, the host mounts an inappropriately large inflammatory response in an attempt to clear the invading pathogen. This sustained high level of inflammation may cause tissue injury and organ failure. Later in sepsis, a paradoxical immunosuppression occurs, where the host is unable to clear the preexisting infection and is susceptible to secondary infections. A major issue with sepsis treatment is that it is difficult for physicians to ascertain which stage of sepsis the patient is in. Sepsis treatment will depend on the patient’s immune status across the spectrum of the disease, and these immune statuses are nearly polar opposites in the early and late stages of sepsis. Furthermore, there is no approved treatment that can resolve inflammation without contributing to immunosuppression within the host. Here, we review the major mechanisms of sepsis-induced immunosuppression and the biomarkers of the immunosuppressive phase of sepsis. We focused on reviewing three main mechanisms of immunosuppression in sepsis. These are lymphocyte apoptosis, monocyte/macrophage exhaustion, and increased migration of myeloid-derived suppressor cells (MDSCs). The biomarkers of septic immunosuppression that we discuss include increased MDSC production/migration and IL-10 levels, decreased lymphocyte counts and HLA-DR expression, and increased GPR18 expression. We also review the literature on the use of specialized pro-resolving mediators (SPMs) in different models of infection and/or sepsis, as these compounds have been reported to resolve inflammation without being immunosuppressive. To obtain the necessary information, we searched the PubMed database using the keywords sepsis, lymphocyte apoptosis, macrophage exhaustion, MDSCs, biomarkers, and SPMs. Full article

(This article belongs to the Special Issue Molecular Biomarkers and More Efficient Therapies for Sepsis)

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