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Biomedicines
Special Issues
Sepsis: From Pathophysiology to Novel Therapeutic Approach
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Sepsis: From Pathophysiology to Novel Therapeutic Approach

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Microbiology in Human Health and Disease".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 2748

Special Issue Editor

Dr. Alessandro Russo

E-Mail Website
Guest Editor
Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences, ‘Magna Graecia’ University of Catanzaro, Catanzaro, Italy
Interests: septic shock; multidrug-resistant pathogens; severe infections; hospital infections; antimicrobials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The dysregulated host response to infection leading to sepsis and septic shock is a life-threatening event that, despite advances in organ support and antimicrobial therapy, is associated with a mortality rate of >30%. Despite implementation of international guidelines supporting early-goal directed therapy, data about pathophysiology, management, and treatment of septic patients are evolving.

On this basis, knowledge about molecular mechanisms underlying clinical response in patients with sepsis or septic shock and new therapeutic approaches are mandatory for an early and appropriate management of critically ill patients. Then, data about the intricate interplay between host defense, infection, and pathogen virulence as well as timing and type of interventions that are most effective according to the personal characteristics of individual patients are mandatory. Thus, data about mechanisms related to progression from sepsis to septic shock and adequate management of patients, including choice and dosages of antimicrobials, are crucial for improving the outcome of septic patients.

This Special issue aims to expand the current knowledge on sepsis and septic shock in different stages and on its possible therapeutic exploitation, including new therapies. Experimental studies in in vitro and in vivo models, review articles, and clinical studies are welcome for consideration.

Dr. Alessandro Russo
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 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

  • septic shock
  • sepsis
  • immune response
  • pharmacokinetic and pharmacodynamic of antimicrobials
  • multidrug-resistant pathogens
  • antimicrobial therapies
  • adjunctive therapies

Published Papers (2 papers)

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Research

14 pages, 3141 KiB  
Article
Whole Blood Reactivity to Viral and Bacterial Pathogens after Non-Emergent Cardiac Surgery during the Acute and Convalescence Periods Demonstrates a Distinctive Profile of Cytokines Production Compared to the Preoperative Baseline in Cohort of 108 Patients, Suggesting Immunological Reprogramming during the 28 Days Traditionally Recognized as the Post-Surgical Recovery Period
by Krzysztof Laudanski, Da Liu, Lioudmila Karnatovskaia, Sanghavi Devang, Amal Mathew and Wilson Y. Szeto
Biomedicines 2024, 12(1), 28; https://doi.org/10.3390/biomedicines12010028 - 21 Dec 2023
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Abstract
The release of danger signals from tissues in response to trauma during cardiac surgery creates conditions to reprogram the immune system to subsequent challenges posed by pathogens in the postoperative period. To demonstrate this, we tested immunoreactivity before surgery as the baseline (t [...] Read more.
The release of danger signals from tissues in response to trauma during cardiac surgery creates conditions to reprogram the immune system to subsequent challenges posed by pathogens in the postoperative period. To demonstrate this, we tested immunoreactivity before surgery as the baseline (tbaseline), followed by subsequent challenges during the acute phase (t24h), convalescence (t7d), and long-term recovery (t3m). For 108 patients undergoing elective heart surgery, whole blood was stimulated with lipopolysaccharide (LPS), Influenza A virus subtype N2 (H3N2), or the Flublok™ vaccine to represent common pathogenic challenges. Leukocytosis, platelet count, and serum C-reactive protein (CRP) were used to measure non-specific inflammation. Cytokines were measured after 18 h of stimulation to reflect activation of the various cell types (activated neutrophils–IL-8; activated T cells-IL-2, IFNγ, activated monocyte (MO)-TNFα, IL-6, and deactivated or atypically activated MO and/or T cells–M-CSF, IL-10). IL-2 and IL-10 were increased at t7d, while TNFα was suppressed at t24h when LPS was utilized. Interestingly, M-CSF and IL-6 production was elevated at seven days in response to all stimuli compared to baseline. While some non-specific markers of inflammation (white cell count, IL-6, and IL-8) returned to presurgical levels at t3m, CRP and platelet counts remained elevated. We showed that surgical stimulus reprograms leukocyte response to LPS with only partial restoration of non-specific markers of inflammation. Full article
(This article belongs to the Special Issue Sepsis: From Pathophysiology to Novel Therapeutic Approach)
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19 pages, 3974 KiB  
Article
Cyclic GMP–AMP Synthase (cGAS) Deletion Reduces Severity in Bilateral Nephrectomy Mice through Changes in Neutrophil Extracellular Traps and Mitochondrial Respiration
by Nattavong Suksawad, Kanyarat Udompornpitak, Natchapon Thawinpipat, Pichaya Korwattanamongkol, Peerapat Visitchanakun, Pornpimol Phuengmaung, Wilasinee Saisorn, Patipark Kueanjinda and Asada Leelahavanichkul
Biomedicines 2023, 11(4), 1208; https://doi.org/10.3390/biomedicines11041208 - 18 Apr 2023
Cited by 1 | Viewed by 1551
Abstract
Uremia-induced systemic inflammation is partly caused by the dissemination of microbial molecules such as lipopolysaccharide and bacterial double-stranded DNA from leaked gut damaged by immune cells in response to the microbial molecules. Cyclic GMP–AMP synthase (cGAS) can recognize fragmented DNA and induce cGAMP [...] Read more.
Uremia-induced systemic inflammation is partly caused by the dissemination of microbial molecules such as lipopolysaccharide and bacterial double-stranded DNA from leaked gut damaged by immune cells in response to the microbial molecules. Cyclic GMP–AMP synthase (cGAS) can recognize fragmented DNA and induce cGAMP synthesis for the activation of the stimulator of interferon genes (STING) pathway. To study the effect of cGAS in uremia-induced systemic inflammation, we performed bilateral nephrectomy (BNx) in wild-type and cGAS knock-out mice and found that the gut leakage and blood uremia from both groups were similar. However, serum cytokines (TNF-α and IL-6) and neutrophil extracellular traps (NETs) decreased significantly in cGAS−/− neutrophils after stimulation with LPS or bacterial cell-free DNA. Transcriptomic analysis of LPS-stimulated cGAS−/− neutrophils also confirmed the down-regulation of neutrophil effector functions. The extracellular flux analysis showed that cGAS−/− neutrophils exhibited a higher respiratory rate than wild-type neutrophils despite having similar mitochondrial abundance and function. Our results suggest that cGAS may control effector functions and the mitochondrial respiration of neutrophils in response to LPS or bacterial DNA. Full article
(This article belongs to the Special Issue Sepsis: From Pathophysiology to Novel Therapeutic Approach)
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