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Biomedicines
Special Issues
Recent Advances and Future Perspectives in Sepsis Translational Research
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Recent Advances and Future Perspectives in Sepsis Translational Research

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 4896

Special Issue Editors

Dr. Kazumichi Fujioka

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Guest Editor
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
Interests: sepsis; shock; translational research; animal model; therapeutics
Dr. Manabu Kinoshita

E-Mail Website
Guest Editor
Department of Immunology and Microbiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
Interests: sepsis; shock; translational research; animal model; therapeutics
Prof. Dr. Shigeaki Inoue

E-Mail Website
Guest Editor
Department of Disaster and Emergency Medicine, Kobe University Graduate School of Medicine, Kusunoki-cho 7-5-2, Chuo-ward, Kobe, Japan
Interests: post-intensive care syndrome; ICU-acquired weakness; aging; immunosenescence; sepsis; end-of life
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sepsis is a severe medical condition affecting all age groups, with approximately 50 million annual cases resulting in 11 million deaths worldwide. As sepsis is an enduring global health priority, researchers have worked over the decades to understand its underlying pathophysiology in hopes of developing safe and effective therapeutics. Additionally, establishing optimal animal sepsis models and designing well-designed clinical trials are essential for translating therapeutics from the research laboratory to patient care.

This Special Issue welcomes all manuscripts providing insight into basic, translational, and applied clinical investigation in sepsis research. Manuscripts discussing new animal models to test potential therapeutics and reports exploring the molecular mechanisms of sepsis are of particular interest. We are also interested in sepsis-related conditions and complications, such as sepsis-associated encephalopathy, immunosenescence, muscle atrophy, and secondary infection. In this Special Issue, we will detail both the cutting edge of current sepsis research and related conditions and provide a road map for the next generation of doctors and scientists on the challenges that still lie ahead for the field.

Dr. Manabu Kinoshita
Dr. Kazumichi Fujioka
Prof. Dr. Shigeaki Inoue
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sepsis
  • shock
  • septic shock
  • translational research
  • animal model
  • immune response
  • inflammation
  • infection
  • oxidative stress
  • therapeutics

Published Papers (4 papers)

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Research

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13 pages, 1453 KiB  
Article
Evaluation of the Kinetics of Pancreatic Stone Protein as a Predictor of Ventilator-Associated Pneumonia
by Adrian Ceccato, Marta Camprubí-Rimblas, Lieuwe D. J. Bos, Pedro Povoa, Ignacio Martin-Loeches, Carles Forné, Aina Areny-Balagueró, Elena Campaña-Duel, Luis Morales-Quinteros, Sara Quero, Paula Ramirez, Mariano Esperatti, Antoni Torres, Lluis Blanch and Antonio Artigas
Biomedicines 2023, 11(10), 2676; https://doi.org/10.3390/biomedicines11102676 - 29 Sep 2023
Viewed by 941
Abstract
BACKGROUND: Ventilator-associated pneumonia (VAP) is a severe condition. Early and adequate antibiotic treatment is the most important strategy for improving prognosis. Pancreatic Stone Protein (PSP) has been described as a biomarker that increases values 3–4 days before the clinical diagnosis of nosocomial sepsis [...] Read more.
BACKGROUND: Ventilator-associated pneumonia (VAP) is a severe condition. Early and adequate antibiotic treatment is the most important strategy for improving prognosis. Pancreatic Stone Protein (PSP) has been described as a biomarker that increases values 3–4 days before the clinical diagnosis of nosocomial sepsis in different clinical settings. We hypothesized that serial measures of PSP and its kinetics allow for an early diagnosis of VAP. METHODS: The BioVAP study was a prospective observational study designed to evaluate the role of biomarker dynamics in the diagnosis of VAP. To determine the association between repeatedly measured PSP and the risk of VAP, we used joint models for longitudinal and time-to-event data. RESULTS: Of 209 patients, 43 (20.6%) patients developed VAP, with a median time of 4 days. Multivariate joint models with PSP, CRP, and PCT did not show an association between biomarkers and VAP for the daily absolute value, with a hazard ratio (HR) for PSP of 1.01 (95% credible interval: 0.97 to 1.05), for CRP of 1.00 (0.83 to 1.22), and for PCT of 0.95 (0.82 to 1.08). The daily change of biomarkers provided similar results, with an HR for PSP of 1.15 (0.94 to 1.41), for CRP of 0.76 (0.35 to 1.58), and for PCT of 0.77 (0.40 to 1.45). CONCLUSION: Neither absolute PSP values nor PSP kinetics alone nor in combination with other biomarkers were useful in improving the prediction diagnosis accuracy in patients with VAP. Clinical Trial Registration: Registered retrospectively on August 3rd, 2012. NCT02078999. Full article
(This article belongs to the Special Issue Recent Advances and Future Perspectives in Sepsis Translational Research)
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14 pages, 1931 KiB  
Article
The Role of Mesenchymal Stem Cell Secretome in the Inflammatory Mediators and the Survival Rate of Rat Model of Sepsis
by Mutiara Indah Sari, Nelva Karmila Jusuf, Delfitri Munir, Agung Putra, Tatang Bisri, Syafruddin Ilyas, Farhat Farhat, Adi Muradi Muhar, Muhammad Rusda and Mustafa Mahmud Amin
Biomedicines 2023, 11(8), 2325; https://doi.org/10.3390/biomedicines11082325 - 21 Aug 2023
Viewed by 1389
Abstract
In sepsis, simultaneously elevated levels of pro-inflammatory cytokines and interleukin (IL)-10 indicate immune response dysregulation, increasing the mortality of the host. As mesenchymal stem cell (MSC) secretome is known to have immunomodulatory effects, we aim to assess the role of MSC secretome in [...] Read more.
In sepsis, simultaneously elevated levels of pro-inflammatory cytokines and interleukin (IL)-10 indicate immune response dysregulation, increasing the mortality of the host. As mesenchymal stem cell (MSC) secretome is known to have immunomodulatory effects, we aim to assess the role of MSC secretome in the inflammatory mediators (NF-κB p65 and p50, TNF-α, IL-10) and the survival rate of a rat model of sepsis. In this study, forty-eight male Rattus norvegicus rats were divided into one sham group and three groups with sepsis induction: the control group and the sepsis-induced rat groups treated with 150 μL (T1) and 300 μL (T2) of secretome. The survival rate was observed per 6 h for 48 h and plotted using the Kaplan–Meier method. Compared to the control group, T2 showed a significant decrease in the relative expression of NF-κB and the serum TNF-α level, and a significant increase in the serum IL-10 level. Meanwhile, T1 showed a significant decrease in the serum TNF-α level compared to the control group. The Kaplan–Meier Log Rank test did not show significance in the distribution of survival between T1, T2, and the control group. However, from the 18th to the 36th hour, the survival rate of T2 was lower than the survival rate of the control group and T1, with a noticeable difference between T2 and the control group, as well as T1 at the 36th hour. At the 42nd hour, the survival rate of T2 was the same as the control group and remained lower than T1. In conclusion, MSC secretome regulated the inflammatory mediators in rat model of sepsis, with a dose of 150 μL being more effective. Full article
(This article belongs to the Special Issue Recent Advances and Future Perspectives in Sepsis Translational Research)
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11 pages, 590 KiB  
Article
Differences in Mortality and Sepsis-Associated Organ Dysfunction between Surgical and Non-Surgical Sepsis Patients
by Caspar Mewes, Julius Runzheimer, Carolin Böhnke, Benedikt Büttner, Marcus Nemeth, José Hinz, Michael Quintel and Ashham Mansur
Biomedicines 2023, 11(8), 2233; https://doi.org/10.3390/biomedicines11082233 - 9 Aug 2023
Cited by 1 | Viewed by 716
Abstract
(1) Background: Patients with sepsis following surgical intervention may exhibit fundamental distinctions from those experiencing sepsis without prior surgery. Despite the potential clinical importance of distinguishing these two sepsis subpopulations, dissimilarities, particularly in outcome, between surgical and non-surgical patients have been subject to [...] Read more.
(1) Background: Patients with sepsis following surgical intervention may exhibit fundamental distinctions from those experiencing sepsis without prior surgery. Despite the potential clinical importance of distinguishing these two sepsis subpopulations, dissimilarities, particularly in outcome, between surgical and non-surgical patients have been subject to limited scientific investigations in the existing literature. This study aimed to investigate the differences in mortality and sepsis-associated organ dysfunction between these two groups. (2) Methods: A retrospective analysis was conducted using data from a large cohort of prospectively enrolled patients with sepsis (n = 737) admitted to three intensive care units at University Medical Center Goettingen; patients were categorized into surgical (n = 582) and non-surgical sepsis groups (n = 155). The primary outcomes assessed were 28- and 90-day mortality rates, and secondary endpoints were multiple clinical parameters and measures of sepsis-associated organ dysfunction. (3) Results: Non-surgical patients presented a significantly higher 90-day mortality (37%) compared to surgical sepsis patients (30%, p = 0.0457). Moreover, the non-surgical sepsis group exhibited increased sepsis-associated organ dysfunction, as evidenced by higher average SOFA scores (p < 0.001), elevated levels of serum Procalcitonin (p = 0.0102), and a higher utilization of organ replacement therapies such as ventilation (p < 0.001), vasopressor treatment (p < 0.001), and renal replacement therapy (p = 0.0364). Additionally, non-surgical sepsis patients had higher organ-specific SOFA respiratory (p < 0.001), cardiovascular (p < 0.001), renal (p < 0.001), coagulation (0.0335), and central nervous system (p = 0.0206) subscores. (4) Conclusions: These results suggested that patients with non-surgical sepsis may face distinct challenges and a higher risk of adverse outcomes compared to patients with sepsis following surgical intervention. These findings have important implications for clinical decision-making, patient management, and resource allocation in sepsis care. Full article
(This article belongs to the Special Issue Recent Advances and Future Perspectives in Sepsis Translational Research)
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Review

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10 pages, 266 KiB  
Review
Lactate: The Fallacy of Oversimplification
by Jiri Müller, Jaroslav Radej, Jan Horak, Thomas Karvunidis, Lenka Valesova, Miroslav Kriz and Martin Matejovic
Biomedicines 2023, 11(12), 3192; https://doi.org/10.3390/biomedicines11123192 - 1 Dec 2023
Cited by 2 | Viewed by 1290
Abstract
Almost a quarter of a millennium after the discovery of an acidic substance in sour milk by Swedish chemist Carl Wilhelm Scheele and more than 100 years after the demonstration of a tight connection between this lactic acid and tissue hypoxia in shock, [...] Read more.
Almost a quarter of a millennium after the discovery of an acidic substance in sour milk by Swedish chemist Carl Wilhelm Scheele and more than 100 years after the demonstration of a tight connection between this lactic acid and tissue hypoxia in shock, we are still surrounded by false beliefs and misunderstandings regarding this fascinating molecule. Common perceptions of lactate, the conjugate base of lactic acid, as a plain waste product of anaerobic metabolism and a marker of cellular distress could not be further from the truth. Lactate is formed and utilized continuously by our cells, even under fully aerobic conditions, in large quantities, and although marked hyperlactatemia is always a red flag in our patients, not all these conditions are life-threatening and vice versa—not all critically ill patients have hyperlactatemia. Lactate also does not promote acidosis by itself; it is not toxic, nor is it a metabolic renegade. On the contrary, it has many beneficial properties, and an interpretation of hyperlactatemia might be trickier than we tend to think. The aim of this article is to debunk some of the deeply rooted myths regarding this fascinating molecule. Full article
(This article belongs to the Special Issue Recent Advances and Future Perspectives in Sepsis Translational Research)
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