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Immunology in Critical Illness - Immune Response and Immunotherapy
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Immunology in Critical Illness - Immune Response and Immunotherapy

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

Deadline for manuscript submissions: closed (5 December 2021) | Viewed by 8722

Special Issue Editor

Prof. Dr. Tamas Szakmany

E-Mail Website
Guest Editor
Department of Anaesthesia, Intensive Care and Pain Medicine, Division of Population Medicine, Cardiff University, Cardiff, UK
Interests: ARDS; sepsis; epidemiology; haemodynamic monitoring; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the last several decades, mounting data have shown that substantial critical-illness-induced changes in the immune system can be observed in most ICU patients and that not only “hyper-inflammation” but also the persistence of an anti-inflammatory phenotype (as in sepsis-associated immunosuppression) is associated with increased morbidity and mortality. Despite common perception, changes in functional immunity cannot be adequately assessed by routine inflammatory cytokines, and a deeper understanding of cellular functions and new approaches to biomarkers are required to monitor the progress. Importantly, recent data demonstrate that critical-illness-associated immunosuppression can be reversed, opening up new therapeutic avenues in affected patients. The present Special Issue will examine the evidence for the epidemiology, monitoring aspects, and management of immune response in critical illness including novel cellular and humoral approaches to the prevention and management of the dysregulated immune response. We invite researchers and clinicians to submit their work, including original laboratory-based and clinical research studies, meta-analyses, and systematic reviews that will provide additional knowledge regarding the immune response and immunotherapy in critical illness.

Prof. Tamas Szakmany
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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly 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

  • immunology 
  • biomarkers 
  • critically ill 
  • immune response 
  • host response 
  • inflammation 
  • sepsis

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Published Papers (3 papers)

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Research

15 pages, 803 KiB  
Article
Plasma IgM Levels Differentiate between Survivors and Non-Survivors of Culture-Positive and Culture-Negative Sepsis and SIRS: A Pilot Study
by Navichandra Pathare, Tamas Szakmany, Judith E. Hall and Meike Heurich
J. Clin. Med. 2021, 10(22), 5391; https://doi.org/10.3390/jcm10225391 - 19 Nov 2021
Cited by 1 | Viewed by 2334
Abstract
Immunoglobulin IgM is important for controlling viral and bacterial infections, and low immunoglobulin levels have been found in sepsis. There is a clear need to stratify sepsis patients according to the presence of an invading organism, compared to no organism identified, and SIRS [...] Read more.
Immunoglobulin IgM is important for controlling viral and bacterial infections, and low immunoglobulin levels have been found in sepsis. There is a clear need to stratify sepsis patients according to the presence of an invading organism, compared to no organism identified, and SIRS patients, where organ dysfunction is a result of a non-infective process. The aim of this pilot study in a small cohort of patients with sepsis was to evaluate the association between IgM plasma levels and survival in 47 patients with sepsis and 11 patients diagnosed with organ failure without the identification of a pathogen (SIRS). Patients were admitted to the intensive care unit (ICU) at The Royal Glamorgan Hospital, Llantrisant, UK between 2010 and 2014. We found that low IgM levels were associated with sepsis, but not SIRS. IgM levels did not differ significantly for culture-positive (CP) compared with culture-negative (CN, no organism found) sepsis samples. Kaplan–Meier analysis was used to compare survival curves according to IgM levels, with no significant difference. We observed significantly higher survival in the CP samples when comparing with CN. Cut-off value for IgM (266 μg/mL) for diagnosis of sepsis patients was determined using receiver operator characteristic (ROC) curves with 70% sensitivity, 69% specificity and 92% negative predictive values (NPV), respectively. The corresponding area under the curve (AUC) for the discrimination of sepsis patients was AUC = 0.73, and in a subgroup analysis of CP was AUC = 0.77 and for CN was AUC = 0.79. We confirm IgM as a good diagnostic marker of sepsis. These findings indicate a difference in the pathology between culture-positive versus negative sepsis, SIRS and survival. This indicates that IgM is likely relevant to pathology, because of its role in the early immune response against pathogens, the potentially protective role of natural IgM antibodies, and supports its application in immunoglobulin therapy. Full article
(This article belongs to the Special Issue Immunology in Critical Illness - Immune Response and Immunotherapy)
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9 pages, 1003 KiB  
Article
Differences in Inflammatory Marker Kinetics between the First and Second Wave of COVID-19 Patients Admitted to the ICU: A Retrospective, Single-Center Study
by Tamas Szakmany, William Tuckwell, Elsa Harte, Nick Wetherall, Saraswathi Ramachandran, Shannon Price, Henry Breen, Charlotte Killick, Yusuf Cheema, Charles King and Owen Richards
J. Clin. Med. 2021, 10(15), 3290; https://doi.org/10.3390/jcm10153290 - 26 Jul 2021
Cited by 6 | Viewed by 3665
Abstract
Background: We sought to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels between the first and the second COVID-19 wave of ICU patients. Methods: In [...] Read more.
Background: We sought to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels between the first and the second COVID-19 wave of ICU patients. Methods: In a single-center retrospective observational study, ICU patients were enrolled during the first and second waves of the COVID-19 pandemic. Data were collected on patient demographics, comorbidities, laboratory results, management strategies, and complications during the ICU stay. The inflammatory response was evaluated using WBC count, CRP, PCT, and Ferritin levels on the day of admission until Day 28, respectively. Organ dysfunction was measured by the SOFA score. Results: 65 patients were admitted during the first and 113 patients during the second wave. WBC and ferritin levels were higher in the second wave. CRP and PCT showed markedly different longitudinal kinetics up until day 28 of ICU stay between the first and second wave, with significantly lower levels in the second wave. Steroid and immunomodulatory therapy use was significantly greater in the second wave. Mortality was similar in both waves. Conclusions: We found that there was a significantly reduced inflammatory response in the second wave, which is likely to be attributable to the more widespread use of immunomodulatory therapies. Full article
(This article belongs to the Special Issue Immunology in Critical Illness - Immune Response and Immunotherapy)
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12 pages, 2758 KiB  
Article
Complement Factor C5a Inhibits Apoptosis of Neutrophils—A Mechanism in Polytrauma?
by Christian Ehrnthaller, Sonja Braumüller, Stephanie Kellermann, Florian Gebhard, Mario Perl and Markus Huber-Lang
J. Clin. Med. 2021, 10(14), 3157; https://doi.org/10.3390/jcm10143157 - 17 Jul 2021
Cited by 5 | Viewed by 1836
Abstract
Life-threatening polytrauma results in early activation of the complement and apoptotic system, as well as leukocytes, ultimately leading to the clearance of damaged cells. However, little is known about interactions between the complement and apoptotic systems in PMN (polymorphonuclear neutrophils) after multiple injuries. [...] Read more.
Life-threatening polytrauma results in early activation of the complement and apoptotic system, as well as leukocytes, ultimately leading to the clearance of damaged cells. However, little is known about interactions between the complement and apoptotic systems in PMN (polymorphonuclear neutrophils) after multiple injuries. PMN from polytrauma patients and healthy volunteers were obtained and assessed for apoptotic events along the post-traumatic time course. In vitro studies simulated complement activation by the exposure of PMN to C3a or C5a and addressed both the intrinsic and extrinsic apoptotic pathway. Specific blockade of the C5a-receptor 1 (C5aR1) on PMN was evaluated for efficacy to reverse complement-driven alterations. PMN from polytrauma patients exhibited significantly reduced apoptotic rates up to 10 days post trauma compared to healthy controls. Polytrauma-induced resistance was associated with significantly reduced Fas-ligand (FasL) and Fas-receptor (FasR) on PMN and in contrast, significantly enhanced FasL and FasR in serum. Simulation of systemic complement activation revealed for C5a, but not for C3a, a dose-dependent abrogation of PMN apoptosis in both intrinsic and extrinsic pathways. Furthermore, specific blockade of the C5aR1 reversed C5a-induced PMN resistance to apoptosis. The data suggest an important regulatory and putative mechanistic and therapeutic role of the C5a/C5aR1 interaction on PMN apoptosis after polytrauma. Full article
(This article belongs to the Special Issue Immunology in Critical Illness - Immune Response and Immunotherapy)
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