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Special Issue "Sepsis: Immunopathology, Patient Classification and Clinical Management"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: 15 October 2019

Special Issue Editor

Guest Editor
Dr. Brendon P. Scicluna

1. Amsterdam UMC, University of Amsterdam, Center for Experimental Molecular Medicine, Amsterdam Infection and Immunity, Amsterdam, The Netherlands
2. Amsterdam UMC, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam, The Netherlands
Website | E-Mail
Interests: genomics; immunity; sepsis; infectious diseases; precision medicine; computational biology

Special Issue Information

Dear colleagues,

Sepsis is a multifaceted syndrome that is understood to be initiated by an abnormal reaction to infection, leading to life-threatening organ dysfunction. Despite empirical antimicrobial therapy and advances in intensive care, it is expected that sepsis will remain a major healthcare problem (it was recently recognized by the World Health Assembly and WHO, who made it a global health priority in 2017). More than 100 clinical trials have evaluated drugs targeting specific components of the host immune response to infection but to no avail. Those failures have been ascribed to the marked heterogeneity in the clinical presentation and immunopathology of sepsis, which hinders the identification of patients who would benefit from specific treatment. For decades, an abnormal inflammatory response to infection was considered to be central to the pathogenesis of sepsis. It is now evident that the host response is altered in a more complex way, involving persistent excessive inflammation, immune suppression, and a failure to restore normal homeostasis. It may be argued that those alterations may reflect a fundamental reorganization of immune and metabolic cell processes; however, it remains difficult to create an overarching framework of the key drivers in sepsis immunopathology versus changes that are secondary and less decisive to patient outcome. Improving our understanding of sepsis pathophysiology is critical for the development of precise therapeutics and patient management. Therefore, this Special Issue is dedicated to advances in sepsis immunopathology, patient classification, and clinical management. 

Dr. Brendon P Scicluna
Guest Editor

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 papers will be 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. Journal of Clinical Medicine 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 1800 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
  • immunopathology
  • heterogeneity
  • risk stratification
  • diagnosis

Published Papers (2 papers)

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Research

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Open AccessArticle
Lack of an Association between the Functional Polymorphism TREM-1 rs2234237 and the Clinical Course of Sepsis among Critically Ill Caucasian Patients—A Monocentric Prospective Genetic Association Study
J. Clin. Med. 2019, 8(3), 301; https://doi.org/10.3390/jcm8030301
Received: 1 February 2019 / Revised: 25 February 2019 / Accepted: 27 February 2019 / Published: 3 March 2019
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Abstract
Sepsis is a life-threatening condition and a significant challenge for those working in intensive care, where it remains one of the leading causes of mortality. According to the sepsis-3 definition, sepsis is characterized by dysregulation of the host response to infection. The TREM-1 [...] Read more.
Sepsis is a life-threatening condition and a significant challenge for those working in intensive care, where it remains one of the leading causes of mortality. According to the sepsis-3 definition, sepsis is characterized by dysregulation of the host response to infection. The TREM-1 gene codes for the triggering receptor expressed on myeloid cells 1, which is part of the pro-inflammatory response of the immune system. This study aimed to determine whether the functional TREM-1 rs2234237 single nucleotide polymorphism was associated with mortality in a cohort of 649 Caucasian patients with sepsis. The 90-day mortality rate was the primary outcome, and disease severity and microbiological findings were analyzed as secondary endpoints. TREM-1 rs2234237 TT homozygous patients were compared to A-allele carriers for this purpose. Kaplan–Meier survival analysis revealed no association between the clinically relevant TREM-1 rs2234237 single nucleotide polymorphism and the 90-day or 28-day survival rate in this group of septic patients. In addition, the performed analyses of disease severity and the microbiological findings did not show significant differences between the TREM-1 rs2234237 genotypes. The TREM-1 rs2234237 genotype was not significantly associated with sepsis mortality and sepsis disease severity. Therefore, it was not a valuable prognostic marker for the survival of septic patients in the studied cohort. Full article
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Review

Jump to: Research

Open AccessReview
Advance in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation
J. Clin. Med. 2019, 8(5), 728; https://doi.org/10.3390/jcm8050728
Received: 5 May 2019 / Revised: 17 May 2019 / Accepted: 20 May 2019 / Published: 22 May 2019
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Abstract
Coagulopathy commonly occurs in sepsis as a critical host response to infection that can progress to disseminated intravascular coagulation (DIC) with an increased mortality. Recent studies have further defined factors responsible for the thromboinflammatory response and intravascular thrombosis, including neutrophil extracellular traps, extracellular [...] Read more.
Coagulopathy commonly occurs in sepsis as a critical host response to infection that can progress to disseminated intravascular coagulation (DIC) with an increased mortality. Recent studies have further defined factors responsible for the thromboinflammatory response and intravascular thrombosis, including neutrophil extracellular traps, extracellular vesicles, damage-associated molecular patterns, and endothelial glycocalyx shedding. Diagnosing DIC facilitates sepsis management, and is associated with improved outcomes. Although the International Society on Thrombosis and Haemostasis (ISTH) has proposed criteria for diagnosing overt DIC, these criteria are not suitable for early detection. Accordingly, the ISTH DIC Scientific Standardization Committee has proposed a new category termed “sepsis-induced coagulopathy (SIC)” to facilitate earlier diagnosis of DIC and potentially more rapid interventions in these critically ill patients. Therapy of SIC includes both treatment of the underlying infection and correcting the coagulopathy, with most therapeutic approaches focusing on anticoagulant therapy. Recently, a phase III trial of recombinant thrombomodulin was performed in coagulopathic patients. Although the 28-day mortality was improved by 2.6% (absolute difference), it did not reach statistical significance. However, in patients who met entry criteria for SIC at baseline, the mortality difference was approximately 5% without increased risk of bleeding. In this review, we discuss current advances in managing SIC and DIC. Full article
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J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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